Electrochemistry. Volume 15 978-1-78801-389-5, 1788013891, 978-1-78801-373-4, 978-1-78801-583-7

Citation preview

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP001

Electrochemistry Volume 15

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP001

View Online

View Online

A Specialist Periodical Report

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP001

Electrochemistry Volume 15

Editors Craig Banks, Manchester Metropolitan University, UK Steven McIntosh, Lehigh University, Bethlehem PA, USA Authors Prashanth S. Adarakatti, Indian Institute of Science, India Elena A. Baranova, University of Ottowa, Canada Lynn Dennany, University of Strathclyde, UK Suresh K. Kempahanumakkagari, Dayananda Sagar University, India Mona A. Mohamed, National Organization for Drug Control and Research, Egypt Evans A. Monyoncho, University of Ottowa, Canada Edward Randviir, Manchester Metropolitan University, UK Tom K. Woo, University of Ottowa, Canada

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP001

View Online

Print ISBN: 978-1-78801-373-4 PDF eISBN: 978-1-78801-389-5 ePUB eISBN: 978-1-78801-583-7 ISSN: 0305-9979 DOI: 10.1039/9781788013895 A catalogue record for this book is available from the British Library r The Royal Society of Chemistry 2019 All rights reserved Apart from fair dealing for the purposes of research for non-commercial purposes or for private study, criticism or review, as permitted under the Copyright, Designs and Patents Act 1988 and the Copyright and Related Rights Regulations 2003, this publication may not be reproduced, stored or transmitted, in any form or by any means, without the prior permission in writing of The Royal Society of Chemistry or the copyright owner, or in the case of reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK, or in accordance with the terms of the licences issued by the appropriate Reproduction Rights Organization outside the UK. Enquiries concerning reproduction outside the terms stated here should be sent to The Royal Society of Chemistry at the address printed on this page. Whilst this material has been produced with all due care, The Royal Society of Chemistry cannot be held responsible or liable for its accuracy and completeness, nor for any consequences arising from any errors or the use of the information contained in this publication. The publication of advertisements does not constitute any endorsement by The Royal Society of Chemistry or Authors of any products advertised. The views and opinions advanced by contributors do not necessarily reflect those of The Royal Society of Chemistry which shall not be liable for any resulting loss or damage arising as a result of reliance upon this material. The Royal Society of Chemistry is a charity, registered in England and Wales, Number 207890, and a company incorporated in England by Royal Charter (Registered No. RC000524), registered office: Burlington House, Piccadilly, London W1J 0BA, UK, Telephone: þ44 (0) 20 7437 8656. Visit our website at www.rsc.org/books Printed in the United Kingdom by CPI Group (UK) Ltd, Croydon, CR0 4YY, UK

Preface

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP005

DOI: 10.1039/9781788013895-FP005

We are pleased to introduce volume 15 of Specialist Periodical Reports in Electrochemistry, which presents comprehensive and critical reviews covering some of the most impactful areas of electrochemistry. In this volume, Randavir discusses electrochemical impedance spectroscopy as a quantitative tool for sensors for a wide variety of potential applications. Baranova and co-authors provide a comprehensive and critical discussion around our current state-of-the-art understanding of ethanol electrooxidation kinetics in alkaline media. They point to the excellent progress made to date, and the challenges remaining, as we move towards high performance direct ethanol fuel cells. Dennany contributes an extensive discussion of electrochemiluminescence sensors, from their fundamental principles to their application in analytic systems, particularly for medical diagnostics. The chapter discusses the development of the most commonly utilized ruthenium base systems, emerging new materials, and their incorporation in composite nanomaterials. Wearable electrochemical sensors are discussed in a chapter by Mohamed, with consideration of sensors that monitor sweat, breath, saliva, tears and skin to monitor our health and provide diagnostic signals. Finally, Adarakatti and Kempahanumakkagari consider techniques for electrode modification to enhance both kinetics and stability, and the characterization and application of the electrodes in electro-analysis. Craig Banks and Steven McIntosh

Electrochemistry, 2019, 15, v–v | v

c

The Royal Society of Chemistry 2019

Author biographies

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP006

DOI: 10.1039/9781788013895-FP006

Prashanth S. Adarakatti received an M.Sc. in Chemistry from P. C. Jabin Science College (Autonomous) at Karnatak University, Dharwad, India in 2012. He has recently obtained his PhD from Bangalore University, Bengaluru, India and has published over 20 papers and is currently a Postdoctoral Researcher at the Solid State and Structural Chemistry Unit, Indian Institute of Science (IISc), Bengaluru, India. His current research interests include electrochemical sensors, electroanalytical chemistry and materials chemistry for energy storage applications.

Elena Baranova is a Full Professor in the Department of Chemical and Biological Engineering at the University of Ottawa. She received her M.Sc. in Chemical Engineering (1999) and Ph.D in Chemistry (2003) from the Ukrainian State University of Chemical Engineering. She then pursued her graduate studies at EPFL, Switzerland, where she completed her Ph.D. in Chemical Engineering (2005). She became an NSERC postdoctoral fellow in 2005 and later a Research Associate at the National Research Council, Canada. She joined the University of Ottawa in 2008 as a tenure-track Assistant Professor. Her research interests are in the area of electrocatalysis and electrochemical promotion of catalysis.

vi | Electrochemistry, 2019, 15, vi–ix

c

The Royal Society of Chemistry 2019

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP006

View Online

Dr Lynn Dennany has attracted Bd1M in research funding to develop electrochemical sensors for chemical and biomedical sensor applications. She is making pioneering contributions to three core areas: (1) novel electrochemiluminescence (ECL) materials; (2) development of robust surface attachment strategies for enhanced ECL sensitivities and multiplexed detection; (3) devising of novel advanced methodologies for ultrasensitive disease biomarker detection, thus making an impact on improving clinical practice. In particular, the detection of oxidative stress leading to mutagenesis, neurological diseases and aging and the early detection of biomarkers for disease detection are continuing themes within her research. She is currently a Senior Lecturer in Chemistry at the University of Strathclyde, where she has established the electrochemical analytics group consisting of a postdoctoral fellow and 4 PhD students. Her vision is to establish rapid and portable electrochemical sensors for real world applications through understanding of electrochemical behaviour and event recognition events, particularly biochemical interactions. She has published over 40 publications and has successfully supervised 5 PhD students to completion.

Kempahanumakkagari Sureshkumar received BSc., MSc., and Ph.D. degrees (Chemistry) in the years 2004, 2006 and 2012 respectively from Bangalore University, Bengaluru, India. He then worked as postdoctoral fellow in Jain University, India from 2012–2014. He worked as postdoctoral fellow in Chungnam National University, South Korea, from 2014–2015. Then he worked as Research Assistant professor in Hyanyang University, South Korea from 2016–2017. Presently, he is working as assistant professor in School of Basic and Applied Sciences, Dayananda Sagar University, Bengaluru, India. His current research interests include development of electrochemical/optical sensors, fuel cells and synthesis of functional organic molecules for thermochromic applications.

Electrochemistry, 2019, 15, vi–ix | vii

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP006

View Online

Mona A. Mohamed received her PhD in Analytical Chemistry from Cairo University, Egypt in 2012. She is a researcher of analytical chemistry in the pharmaceutical chemistry department, National Organization for Drug Control and Research (NODCAR). She is now a postdoc researcher at institute of electronics microelectronics and nanotechnology (IEMN), France. Her current research interests are lap-on-chip applications, electrochemical sensors, and the preparation and characterization of new doped graphene based materials for electrochemical sensing.

Evans Monyoncho earned a PhD in Chemistry from the University of Ottawa under the co-supervision of Professors Tom Woo and Elena Baranova in 2017. The PhD project focused on the rational catalyst design for ethanol electrooxidation using in-situ and computational studies. Evans currently holds Mitacs Elevate Post-doctoral fellowship at the University of Ottawa working with Prof. Elena Baranova and GBatteries Energy Canada Inc. Evans is originally from Kenya where he earned a Diploma in Analytical Chemistry at The Kenya Polytechnic University College. He obtained Bachelors and Masters in Chemistry from Saint Mary’s University and University of Prince Edward Island, respectively.

viii | Electrochemistry, 2019, 15, vi–ix

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP006

View Online

Edward Randviir is a post-doctoral research fellow at Manchester Metropolitan University. His interests range from using analytical methods to inform public policy, through to the design of new processes to recycle waste materials, and the development of electrochemical sensors. Edward has contributed 21 academic articles in the field of electrochemical sensors and 4 book chapters since the beginning of his PhD in 2011. He has a h-index of 12.

Tom Woo received both his B.Sc. and Ph.D. (1998) in Chemistry at the University of Calgary in Canada. He did postdoctoral research at ETH Zurich and in 2000 started his independent career as an Assistant Professor of Chemistry at the University of Western Ontario in Canada. In 2005 he became a Canada Research Chair in Catalyst Modelling and Computational Chemistry at the University of Ottawa, where he continues his research today. His research has been recognized by several awards, including the 2016 Canadian Society of Chemistry’s Tom Ziegler Award in theoretical and computational chemistry.

Electrochemistry, 2019, 15, vi–ix | ix

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP006

View Online

CONTENTS

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP011

Cover

Preface

v

Author biographies

vi

Ethanol electrooxidation reaction in alkaline media for direct ethanol fuel cells Evans A. Monyoncho, Tom K. Woo and Elena A. Baranova

1

1 2 3 4 5

Introduction Direct ethanol fuel cells Catalyst design strategies Bimetallic catalysts Ethanol electrooxidation reaction mechanism in alkaline media 6 Summary of Issues to be addressed for DEFCs 7 Conclusions and outlook Appendix References

Modified electrodes for sensing

1 5 9 19 30 36 39 41 47

58

Prashanth Shivappa Adarakatti and Suresh Kumar Kempahanumakkagari 1 Introduction 2 Types of electrodes used for modification process

58 59

Electrochemistry, 2019, 15, xi–xii | xi

c

The Royal Society of Chemistry 2019

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-FP011

3 Chemical modification of electrodes 4 Modified electrodes for electrochemical sensing References

Electrochemiluminescence fundamentals and analytical applications Lynn Dennany 1 Introduction 2 Conclusions References

Wearable miniaturized electrochemical sensors: benefits and challenges Mona A. Mohamed 1 2 3 4 5 6 7

Introduction Sweat-based sensors Breath monitoring using miniaturized gas sensing Saliva-based sensors Tears-based sensors Skin fluid-based sensors Implemented materials for printed wearable electrochemical devices 8 Key challenges for wearable sensors implementations 9 Conclusion References

65 78 91

96

96 140 141

147

147 149 151 157 159 163 167 170 175 175

The application of electrochemical impedance spectroscopy to electrochemical sensor devices Edward Randviir

186

1 Electrochemical impedance spectroscopy 2 Information from Nyquist plots 3 EIS in the design of electrochemical sensors 4 The use of EIS in electrochemical sensor assays 5 Challenges facing EIS sensors References

186 190 193 196 203 204

xii | Electrochemistry, 2019, 15, xi–xii

Ethanol electrooxidation reaction in alkaline media for direct ethanol fuel cells

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

Evans A. Monyoncho,a,b Tom K. Wooa and Elena A. Baranova*b DOI: 10.1039/9781788013895-00001

1

Introduction

Fuel cell technology dates back to 1839 when Grove demonstrated that chemical energy from hydrogen and oxygen can be converted directly into electrical energy with high efficiency.1 Therefore, by principle, fuel cells represent a promising technology for clean generation of power from chemicals compared to combustion Carnot engines. Fuel cells convert chemical energy (fuel) into electrical energy with higher energy efficiencies, i.e., 45% in electrical energy, 90% in total energy (electricity and heat production) compared to combustion engines with total efficiency of up to 40%.2 In addition, fuel cells have low-to-none emission of pollutants.2,3 There are several good review articles4–12 and book chapters13–15 reporting the status of direct ethanol fuel cells (DEFCs) at different periods since 2000. By 2002 DEFCs were conceived based on the significant progress done on proton exchange membrane fuel cells (PEMFCs). The motivation was that direct alcohol fuel cells (DAFCs) were to eliminate the need for the bulky and expensive reformers hence allowing the deployment of the technology for mobile applications.12 However, this shift to DAFCs encountered other challenges such as: (i) the complex and incomplete oxidation of alcohols leading to low fuel efficiencies, (ii) the alcohol crossover, in particular methanol, through the proton exchange membrane, etc. These challenges became the focus of active research since then. Most investigators focused on direct methanol fuel cells (DMFCs) and DEFCs in acidic media. It was recognised that DEFCs were more promising than DMFCs if the C–C bond would be cleaved.12 Cleaving the C–C bond was found to be favourable in alkaline conditions than in acidic media because the OH species readily accepts a proton which facilitates ethanol dehydrogenation. This finding sparked interest for direct alcohol alkaline fuel cells (DAAFCs). In 2005, Varcoe and Slade reported alkaline anion-exchange membranes followed by reports on Platinum-free low temperature fuel cells by Tsivadze et al. in 2007.16,17 DEFCs have several advantages compared to the most studied hydrogen and methanol fuel cells:5,18 (i) ethanol is a non-toxic liquid, which a

Department of Chemistry and Biomolecular Sciences, University of Ottawa, Centre for Catalysis Research and Innovation (CCRI), 10 Marie-Curie Private, Ottawa, ON K1N 6N5, Canada b Department of Chemical and Biological Engineering, University of Ottawa, Centre for Catalysis Research and Innovation (CCRI), 161 Louis-Pasteur St., Ottawa, ON K1N 6N5, Canada. E-mail: [email protected] Electrochemistry, 2019, 15, 1–57 | 1  c

The Royal Society of Chemistry 2019

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

lowers the investment of handling facilities because the current infrastructure for gasoline can be largely used, (ii) ethanol can be conveniently produced from biomass, hence is carbon neutral which mitigates the increasing atmospheric CO2, (iii) ethanol is the smallest alcohol with the C–C bond, hence can serve as a model for the electro-oxidation of bigger compounds containing the C–C bonds, (iv) ethanol has a higher energy density than methanol if completely oxidized to CO2 since it can deliver 12 electrons per molecule following the anodic reaction in eqn (1):5 CH3CH2OH þ12OH-2CO2 þ 9H2O þ 12e

Eoa ¼þ 0.19 V/RHE (1)

In DEFCs, eqn (1) is counterbalanced at the cathode by the oxygen reduction reaction, generating a theoretical cell voltage of 1.14 V. However, in practice ethanol is known to be partially oxidized to acetic acid (acetate in alkaline media) giving a maximum of 4 electrons as shown in eqn (2): CH3CH2OH þ 5OH-CH3COO þ 4H2O þ 4e

Eoa ¼ 0.20 V/RHE (2)

The standard potential of acetic acid formation indicates that the reaction path leads to inevitable potential losses of about 0.4 V (the difference between ideal potential for CO2 and acetic acid ‘‘production’’).19 The progress in the development of DEFCs is well documented since the concept was conceived in earlier 2000. At that time, McLean et al. reviewed the state of the art of alkaline fuel cell (AFC) technology based on publications covering the past twenty five years up to 2002.20 Although popular in the 1970s and 1980s, the AFC had fallen out of favour with the technical community in the light of the rapid development of proton exchange membrane fuel cells (PEMFCs). AFCs had been shown to provide high power densities and achieve long lifetimes in certain applications, and appeared to compete favourably with ambient air PEMFCs. In the review, McLean et al. examined the overall technology of AFCs, i.e., the power density, the lifetime performance, and the potential solutions were discussed. They presented a rough cost comparison between ambient air AFCs and PEMFCs. Overall, they showed that AFCs had potential to succeed in certain market niche applications, but lacked research and development support to refine the technology into successful market offerings. The mechanistic understanding of ethanol electrooxidation reaction was reviewed in 2008 by Koper et al.15 They highlighted that the synergy between single-crystal in-situ studies and DFT calculations were beginning to unravel the kinetic and thermodynamic factors, the reaction pathways, and the structure sensitivity issues in electrocalysis with a special focus in their own work. Shortly after, Lamy et al. reviewed the working principles for DEFCs with a particular focus on solid alkaline membrane fuel cell.14 By 2010 there was realization in the community that direct alkaline fuel cells had many advantages compared to acidic counterparts.11 2 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

The success leading up to this major shift from acidic to alkaline was the development of alkaline anion-exchange membranes (AEMs).16,21–23 The use of AEMs have several advantages over conventional AFCs: (i) the enhanced electro-kinetics of the reaction, (ii) the potential to use nonnoble metal catalysts, (iii) the use of higher energy density fuels such as ethanol, ethylene glycol, and glycerol, (iv) no carbonate precipitation since there was no mobile cation (Na1 or K1) which mitigates the issue of progressive carbonation of the alkaline electrolyte, (v) no electrolyte weeping (flooding), (vi) the reduced alcohol crossover, (vii) the simplified water management due to the fact that the water is produced at the anode and consumed at the cathode, and (viii) the reduced corrosion when working in alkaline media compared to acidic media.11,24 Varcoe et al. have pointed out the importance and breakthrough of designing membrane electrode assembly (MEA) without metal cations (e.g. K1, Na1) present in alkaline fuel cells in which CO2 is supplied to or generated at the electrodes to avoid undesirable carbonate precipitation, a major problem with traditional aqueous potassium hydroxide (KOH) electrolyte AFCs.22 Antolini and Gonzalez reviewed the progress of the catalysts and membranes tested for alkaline direct alcohol fuel cells fuelled by methanol, ethanol, and ethylene glycol as of 2010.11 The same year (2010) Zhao et al. presented a comprehensive review on the development of AEM DEFCs including the aspects of catalysts design, AEMs, and single-cell design and performance.25 In 2012, Yu et al. reviewed developments in AFCs, considering different types of fuels, novel catalysts and AEM.9 They showed AFC systems and configurations particularly the new designs for portable devices. They pointed out that further development of DAFCs will rely on: (i) the improved AEMs with good ionic conductivity and stability, (ii) the low cost non-Pt catalysts with high activity, and (iii) the catalyst stability towards various fuels and oxidants. Rabis et al. presented a perspective summarizing the most outstanding contributions covering ten years (2002 to 2012) in terms of activity and durability of the catalyst materials for ethanol oxidation and oxygen reduction reaction, respectively.10 They provided an outlook towards the development of new catalyst support materials with improved performance/stability, the use of advanced characterization techniques, and the fundamental studies of reaction mechanisms and degradation processes as areas deserving attention from researchers.10 In 2013, Almeida and Andrade reviewed the trends in DEFCs with special attention to: (i) the systematic study toward the preparation of effective catalyst formulations by use combinatorial method, (ii) the oxidation of ethanol in amorphous alloys containing low amounts of Pt, and (iii) the use of non-noble materials as catalysts.13 Singh et al. reviewed the status of the efforts in developing low cost and efficient electrocatalysts (the preparation and structural characterization catalysts) so as to decrease the over-potential for alcohol oxidation reaction and oxygen reduction reaction.26 Brouzgou et al. reviewed the comparison in performance of PEM-DEFCs and AEM-DEFCs.8 They pointed out that Pt-containing or Pt-free PEM-DEFCs that use acid proton-exchange Electrochemistry, 2019, 15, 1–57 | 3

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

membranes (typically Nafion type) exhibited relatively low performance, while AEM-DEFCs exhibited better performance values. They noted that the best value ever reported (peak power density was 360 mW cm2 at 60 1C) had been obtained in a very promising alkaline-acid direct ethanol fuel cells (AA-DEFCs). In 2014, Rao et al. reviewed the progress in ethanol electrooxidation reaction focusing on the thermodynamic process, the reaction mechanism, and the advantages and disadvantages of different electrocatalysts.27 They discussed the factors affecting the reaction activity and selectivity such as supports, nanoparticle sizes, catalyst structure, and alloying of metals. Sharaf et al. although focusing on hydrogen fuel cells provided a very good and concise review of fuel cell ranging from the fundamentals, history developments, the competing technologies, to the system evaluation factors.6 They used the most current data from industry and academia to highlight the relations between fuel cell fundamentals and applications. In 2015, Wang et al. presented an overview of the advances in the study of ethanol electrooxidation mechanism and the electrocatalytic materials with a focus on Pt- and Pd-based catalysts.28 They discussed the mechanistic understanding of ethanol oxidation reaction (EOR) on Pt and Pd surfaces. They reported that consensuses from the mechanistic studies are that sufficient active surface sites to facilitate the cleavage of the C–C bond and the adsorption of water or water residue were critical for obtaining a higher activity. They showed how this understanding had been applied to achieve improved performance on various Pt- and Pd-based catalysts. This was achieved by optimization of electronic and bifunctional effects, as well as by tuning the surface composition and structure of the catalysts. Badwal et al. reviewed various types of DEFCs currently under development with emphasis on ethanol sources and production methods, the fuel cell construction materials and their operating regime, the performance and life time issues and market applications.29 An et al. reviewed the comparison of acidic and alkaline DEFCs, i.e., their working principles, cell performance, system efficiency, reaction products, and the cost.5 Similarly, recently Akhairi and Kamarudin published an overview of the acidic and alkaline DEFCs.4 The review focused on the work done on platinum and palladium as strong competitors and highlighted the outstanding problems such as the incomplete oxidation of ethanol to carbon dioxide, the need to optimize the performance of DEFCs at standard conditions, the discovery of suitable catalysts for higher tolerance to surface poison, the stability of the catalysts, the promotion of better diffusivity between the membranes and the electrodes, and the need to control the selectivity of the reaction. From the above quick survey, it is evident that alkaline DEFCs are superior to their acidic counterparts. Therefore, the detailed review and focus of this chapter is on alkaline DEFCs. The literature review starts with the various prototypes of DEFCs which have been proposed to highlight current state-of-the-art of DEFCs, followed by an overview of catalyst designs with a focus on monometallic, bimetallic catalysts and metal oxide supports. Then we review the current understanding of EOR 4 | Electrochemistry, 2019, 15, 1–57

View Online

mechanism with emphasis to the reaction in alkaline conditions. The review is ended with a summary of outstanding challenges for DEFCs and proposal(s) of the strategies to deal with them.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

2

Direct ethanol fuel cells

2.1 Fuel cell designs There have been five types of DEFC designs reported in the literature to date,5,8,30 (i) the proton-exchange membrane fuel cells (PEMFCs), (ii) the Anion-exchange membrane fuel cells (AEM-FCs), (iii) alkaline-anode membrane acid-cathode fuel cells (AA-FCs), (iv) direct alkaline fuel cells (DAFCs), and (v) direct ethanol solid oxide fuel cells (DE-SOFCs). The first three are shown in Fig. 1 and the last two are shown in Fig. 2 and 3, respectively. The reactions for PEM-based, AEM-based, and AA for DEFCs are shown in eqn (3–5), (6–8), and (9–11), respectively. PEM-based DEFCs Anode: C2H5OH þ 3H2O-2CO2 þ 12[H1 þ e]

(3)

Cathode: 3O2 þ 12[H1 þ e]-6H2O

(4)

Cell: C2H5OH þ 3O2-2CO2 þ 3H2O

(5)

AEM-based EOR Anode: C2H5OH þ 12OH-2CO2 þ 9H2O þ 12e

(6)

Cathode: 3O2 þ 6H2O þ 12e-12OH

(7)

Cell: C2H5OH þ 3O2-2CO2 þ 3H2O

(8)

AA based EOR Anode: C2H5OH þ 5MOH-CH3COOM þ 4[M1 þ e] þ 4H2O Cathode: 2H2O2 þ 2H2SO4 þ 4e-2SO42 þ 4H2O

(9) (10)

Cell: C2H5OH þ 5MOH þ 2H2O2 þ 2H2SO4 -CH3COOM þ 2M2SO4 þ 8H2O

(11)

where M ¼ Na or K 2.2 Cation/proton – exchange membranes (PEM) fuel cell designs Fig. 1a shows the working principle of the first conceived fuel cell directly fed with the alcohol at the anode. The design had the advantage of avoiding the use of the bulk fuel reformer used in PEMFCs.12 Typically an aqueous solution of ethanol is circulated through the anodic compartment, and oxygen (or air) is circulated in the cathodic compartment. Later, it was realized that there were several challenges for design such as:8 (i) the acidic electrolyte membranes (mostly Nafion-based) were Electrochemistry, 2019, 15, 1–57 | 5

Published on 15 October 2018 on https://pubs.rsc.org | d

6 | Electrochemistry, 2019, 15, 1–57 Fig. 1 Fuel cell design schematics for (a) Proton Exchange Membrane (PEM), (b) Anion Exchange Membrane (AEM), and (c) Alkaline anode – acid cathode (AA). Reproduced from ref. 5 with permission from Elsevier, Copyright 2015.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Fig. 2 Schematic for direct alkaline fuel cell. Reproduced from ref. 34 with permission from Elsevier, Copyright 2007.

Fig. 3 Schematic for a typical direct liquid SOFCs. Reproduced from ref. 38 with permission from the Royal Society of Chemistry.

expensive, (ii) the incomplete oxidation of ethanol to CO2, instead acetaldehyde and acetic acid which liberates only 2 and 4 electrons, respectively greatly reduced the Faradaic efficiency of the fuel cell, (iii) the sluggish reaction kinetics for EOR in acid media, leading to a large activation loss, (iv) ethanol crossover from the anode to the cathode Electrochemistry, 2019, 15, 1–57 | 7

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

within the PEM which lead to a parasitic current generation, (v) the need to use a cathode catalyst tolerant to ethanol, (vi) the durability of the state-of-the-art catalysts employed such as PtRu/C and PtSn/C was in question. Therefore, there was need to develop other fuel cell designs to avoid the use of acidic electrolyte as presented below. 2.3 Anion – exchange membranes (AEM) fuel cell designs The prospect of using an anionic membrane or a solid polymer electrolyte (SPE) in an alkaline fuel cell was first looked at by Agel et al. in 2000.31 Their goal was to extend the concept of using cheaper SPE which were well developed in lithium-ion batteries into the fuel cell design. They characterized SPE for ionic conductivity, transport numbers, water content and assembled a prototype alkaline fuel cell to show the viability of the new design. They reported that the performance of the prototype fuel cell was greatly improved while using an interfacial solution between the electrodes and the membrane.31 Fig. 1b shows the working principle for AEM-DEFCs. This concept was rapidly explored in the community as evidenced by the articles and patents reviewed by Varcoe and Slade in 2005.16 The advantages of this configuration are presented in the introduction. The challenges for AEM-based DEFCs are: (i) the incomplete oxidation of ethanol to CO2 remain an issue, (ii) the activity and durability of the Pd-based catalyst (the top candidates in the literature) for the EOR in alkaline media needs to be further enhanced, (iii) enhancing the catalytic activity of non-Pt catalysts at the cathode to make them comparable to that of Pt is required. Currently, Ag-based cathode catalysts for the ORR in alkaline media are the leading candidates, (iv) a significant improvement is needed to upgrade the OH conductivity, chemical, mechanical, and thermal stability of the existing AEMs. The OH conductivity can be improved by increasing the amount of charged groups in the membrane; however, there is a trade-off with the mechanical properties. A loss of the mechanical properties by promoting excessive water uptake is the result of increasing the concentration of the charged groups. The thinness of the AEM is an important requirement related to mechanical stability. To keep good mechanical stability when immersed in water, an AEM as thin as B50 mm is necessary. AEM suffers also of a poor chemical stability in alkaline media, stemming from the hydroxide attack on the cationic group. The result of this degradation is an important loss in the number of anionic exchange groups, and a decrease of the ionic conductivity. (v) Improvements of the ionic conductivity and the thermal and chemical stability of the ionomers present within the catalyst layers are required. 2.4 Alkaline anode – acid cathode (AA) fuel cell designs Fig. 1c shows the working principle for alkaline-acid DEFCs. It consist of an alkaline anode, a membrane, and an acid cathode employing hydrogen peroxide as oxidant which boost the theoretical voltage from 1.14 V to 2.52 V.30,32 Although, this design has been reported to deliver the highest power density (360 mW cm2), it has two major issues; (i) the species crossover, and (ii) the hydrogen peroxide decomposition.33 8 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

2.5 Direct alkaline fuel cells In direct alkaline fuel cell (DAFC) designs, an aqueous solution of ethanol and KOH/or NaOH is used in a flow type arrangement without the need for a membrane to separate the anode and the cathode as shown in Fig. 2.34 The electrode reactions are similar to AEM fuel cells, eqn. (2.6)–(2.8). This design has been mostly studied by Verma and Basu.34–37 The best performance for this system was obtained with electrolyte concentration of 3 M KOH and 2 M Ethanol. However, it was reported that ethanol oxidation in this configuration proceeded to only acetaldehyde which involves only two electron. Therefore, considerable effort is required to optimise this technology that is promising for stationary power supply. 2.6 Direct ethanol solid oxide fuel cells (DE-SOFCs) Last but not least is the direct ethanol solid oxide fuel cells (DE-SOFC) configuration shown in Fig. 3.38,39 This design marks the efforts towards using liquid fuels such as ethanol directly in the SOFCs.

3

Catalyst design strategies

The development and design of efficient catalysts for breaking the C–C bond during ethanol electrooxidation is a central question in electrocatalysis. Many factors are known to influence the catalyst activity and selectivity such as chemical composition, morphology, size and shape of the catalyst in addition to the reaction conditions.40–46 Therefore, the precise control of these parameters is crucial for the rational design of efficient and stable electrocatalysts for DEFCs. Fig. 4, gives a summary of the common factors/parameters that control the catalytic performance of the catalyst.43 The efforts in the rational catalyst design strategies include the search for optimal formulations, the catalyst supports, and in the methodologies for catalyst preparations to tune the sizes, the morphologies and the surface composition. In this section, we first give an overview of the various methodologies reported, followed by a review of mono-, and bi-metallic catalysts for EOR in alkaline media. 3.1 Methodologies for catalyst preparation There has been excellent progress in the synthesis of electrocatalysts with different morphologies, mono- and multi-metallic nanoparticles with various compositions and well-controlled shapes.41,47 It is now possible to rationally design catalysts at the atomic-level to enhance electrocatalytic performance, hence making it possible to correlate the nanoparticle structure with activity. Fig. 5 shows the facets for different nanoparticle structures accessible for Au and Pd bimetallics.47 During the nanoparticle synthesis, various approaches are used to reduce the metal ions as summarised in Table 1 (see Appendix) such as:13 sodium borohydride reduction, polyol (alcohol–reduction), formic acid Electrochemistry, 2019, 15, 1–57 | 9

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Fig. 4 A schematic illustration of the complex factors and parameters that control the catalytic performance. Reproduced from ref. 43 with permission from Elsevier, Copyright 2013.

reduction, tannic acid, zinc, sodium silicate (Na2SiO3), gas phase reduction, thermal decomposition of polymeric precursors (Pechini method), and microwave-assisted heating method. A number of synthesis methods have been adopted such as: (i) Impregnation, in which the support is mixed with a suitable metal precursor solution before the reduction of the metal ions. The method is best suited for monometallic catalysts.32,48,49 (ii) Sequential impregnation/Colloidal, in which a colloid precursor is first synthesised preferably in an organic solvent in the presence of a suitable surfactant before adding the supports.50 The approach is better suited for the synthesis of polymetallic systems of uniform composition. (iii) Micro-emulsion, in which the first step is the formation of the nanoparticles via a water-in-oil micro-emulsion reaction followed by a reduction step.51–53 A micro-emulsion is formed by vigorous stirring or sonication and is thermodynamically stable. Nano-sized particles can spontaneously form within the micron size water droplets as a thermodynamically stable microemulsion.26 This method provides the ability to control the metallic composition and particle size with a narrow distribution.53 (iv) Sol–Gel Derived, in which the catalysts are prepared by the hydrolysis of acetylacetonate of the metal salt precursors in the presence of tetra methyl ammonium hydroxide followed by solution evaporation to form xerogel then thermal treatment under controlled atmosphere.54 Examination of the available literature for EOR reveals that there are four strategies commonly adapted to design catalysts: (i) the use of high 10 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Fig. 5 Schematics showing (a) a triangular diagram correlating fcc metal polyhedrons with different crystallographic facets and (b) illustrating the reaction regions that form Au@Pd NPs with different polyhedral shapes and different high-index facets. Reproduced from ref. 47 with permission from American Chemical Society, Copyright 2010.

surface area carbon supports and/or reducible metal oxide supports, (ii) the tuning of the catalyst structure and morphology which includes mesoporous, two- and three-dimensional structures with preferential facets, (iii) the addition of the second or third ad-atoms on the catalyst surface, and (iv) the tuning of the reaction conditions such as electrolyte pH, cations and anions. Electrochemistry, 2019, 15, 1–57 | 11

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

3.2 Catalyst support materials Catalyst supports are reported to play a significant role towards morphology, dispersion, activity, and selectivity of the catalysts.55–57 Carbon is the most widely used support in the fuel cell research because it has high electrical conductivity and excellent structural properties which are important for fuel cell application.58 Carbon has been widely used in PEMFCs and alkaline fuel cells for fabrication of the bipolar plate, the gas-diffusion layer and as a support for the active metal in the catalyst layer. Antolini has reviewed the application of carbon supports for Pt-based catalysts in fuel cells.59 The novel carbon materials presented showed improved electrocatalytic properties and stability during fuel cells operation. Carbon nanotubes and aerogels have been investigated for use as catalyst support leading to the fabrication of more stable and active catalysts by reducing the undesirable carbon corrosion and degradation.60 Graphene or graphene oxide materials are attractive alternative supports for dispersion and stabilization of the catalyst nanoparticles. Graphene is one atom thick nano-carbon materials which has attracted considerable attention in various applications including electrocatalysis.61 There are several reports showing the application of metal oxide supports such as CeO2,62–73 SnO2,62,64,74–82 TiO2,62,64,83–86 MnxOy,70,71,87 WOx,64,88 MoOx,64,89 RuO2,78 ZrO2,64,90 CaSiO2,91 MgO,92,93 NiO/ foam,70,71,94–96 and CoOx70,71 as promising supports for EOR catalysts. These metal oxide supports have a significant effect on the catalytic activity of the catalysts because of the interaction phenomenon known as ‘‘strong metal-support interaction’’ which was recognized by Tauster et al.97,98 and advanced by Sanches and Gazquez.99

3.3 Monometallic catalysts 3.3.1 Platinum catalysts for ethanol electrooxidation reaction. Platinum is one of the default catalyst metals for many reactions, as such it has been considered for EOR. Katayama et al. investigated the role of adsorbed OH species on Pt catalyst for EOR.100 They did a comparative study between ionomer-coated Pt and highly oxophilic CeO2 modified Pt electrode using in situ ATR-FTIR to monitor adsorption behaviour of adsorbed OH. They observed a distinct change in adsorption behaviour of adsorbed OH in blank KOH solution, which was attributed to the activity enhancement for EOR. This activity increase was not observed under acidic conditions. Hence, the pH has a significant effect not only on the reaction kinetics but also on the equilibrium properties of both solution and surface species. During EOR in alkaline media, the OH species are consumed which alters the local pH at the electrode surface, decreasing the reaction kinetics. Figueiredo et al. have shown the evidence of the local changing pH for EOR on Pt electrodes in alkaline media.101 They used rotating ring-disc electrode experiments to monitor the local pH change during EOR. The current at the ring when polarized at the onset of hydrogen evolution (0.1 V vs RHE) served as a measure of the local pH in the vicinity of the 12 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

electrode. Their results showed that the current at the ring at 0.1V became more negative during EOR, owing to a change in the equilibrium potential of the hydrogen evolution reaction caused by a change in the local pH. Lai et al. investigated EOR on Pt in electrolytes of varying pH and composition using electrochemical and surface-enhanced Raman spectroscopy (SERS) techniques.102 The reaction activity increased significantly when the pH of the electrolyte was above 10 (as shown in Fig. 6). According to their report, the reaction selectivity strongly depends on the nature of the electrolyte, but to a smaller extent on the electrolyte pH.102 These findings opened up the door to exploration of various electrolyte compositions. Of great interest from Lai et al. investigations, was the observation that the cleavage of the C–C bond was only observed on Pt in the absence of strongly adsorbed anions, which was attributed to the competition for the active sites. A comparative study of EOR on Pt electrode in acidic and alkaline media using DEMS was conducted by Cremers et al.103 They reported that in the acidic environment the initial oxidation of ethanol was via acetaldehyde formation, which proceeded rather easily and was found to be highly reversible. They pointed out that

Fig. 6 CVs for EOR (0.5 M EtOH þ 0.1 M phosphate buffers) on polycrystalline Pt showing the effect of electrolyte pH. Reproduced from ref. 102 with permission from Elsevier, Copyright 2010. Electrochemistry, 2019, 15, 1–57 | 13

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

the challenge in implementing DEFCs was to consequently oxidize acetaldehyde, a step that was particularly difficult as it must not proceed via acetic acid which cannot be oxidized further to CO2.104 In alkaline media, they found EOR to proceed rather faster and lead to a complete oxidation to CO2, a promising approach for DEFCs. Electrochemically reduced Pt oxide films were reported to be 29 times more active for EOR than Pt films.105 The superior activity was attributed to higher electrochemical active surface area and the existence of residual oxygen based on CV and XPS measurements. The concentration dependence for EOR on Pt in alkaline medium was studied using electrochemical and DEMS techniques by Bayer et al.106,107 They showed that selectivity for EOR to CO2 was favoured at lower concentrations and was only observed during CV and not during CA, indicating that formed intermediate(s) were playing a key role. They did a comparison to ethylene glycol, which showed significant CO2 formation during CV and CA experiments with the tendency that low concentrations and low potentials yielded higher CO2 current efficiencies. Although in acidic medium both alcohols exhibited a comparable electrochemical performance, in alkaline medium the current densities for ethylene glycol were substantially higher.107 The single-crystal Pt structural effects on EOR have been studied by several authors.108–110 Buso-Rogero et al. used single-crystal Pt electrodes to show the effect of different facets (111, 110, and 100) for EOR using electrochemical and IRRAS techniques.108 Although, the Pt(111) electrode displayed the highest currents and also the highest onset potential in CV, the CA showed that the activity decreased in the order of 11041004111. Surprisingly, their IRRAS data showed that the C–C bond cleavage was not favoured in alkaline media. Lai and Koper studied irreversible adsorption of ethanol on Pt single crystal in alkaline solution using SERS.109 They reported that EOR was very sensitive to the electrode surface structure, i.e., a higher concentration of low-coordination sites increased the current, lowered the over-potential required and lowered the deactivation rate. They found that the terrace length affected the quantity and nature of the adsorbed species, i.e., on Pt(110) only adsorbed CO was observed whereas adsorbed CHx was only found on Pt(111) terrace sites.109 Tripkovic et al. studied EOR on Pt(111), Pt(755), and Pt(332) surfaces in NaOH solution with a special focus on the oxygencontaining species generated and adsorbed on the surface.110 They suggested the existence of reversible and irreversible adsorbed OH and PtO species in the potential region relevant for EOR. They suggested the role of these species in the reaction and proposed a dual path reaction mechanism as discussed in the mechanism section.110 There are studies which have looked at Pt nanoparticles for EOR in alkaline media.111,112 Buso-Rogero et al. investigated EOR on Pt nanoparticles with different shapes and loadings using electrochemical and spectroscopic techniques.111 The nanoparticles with a large amount of (100) ordered domains showed higher current densities compared to nanoparticles with higher (111) domains. They reported that acetate was the main product with negligible amounts of CO2, regardless of the type 14 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

of Pt nanoparticles used. Sun et al. investigated the nanoparticle size effect for Pt nanoparticles supported on sulfonated graphene (Pt/sG) for EOR in alkaline solution.112 They prepared five catalysts with various average particle sizes. They reported that 2.5 nm catalyst had the highest current density peak for EOR.112 The effect of the support on Pt activity has been explored by many research groups. Xu and Shen did a comparative study for Pt/C and Pt–CeO2/C.72,73 They reported that the electrode with a weight ratio of Pt to CeO2 of 1.3 to 2.1 and a Pt loading of 0.30 mg cm2 had the highest activity. Xu et al. studied EOR on MgO promoted Pt/C catalysts in alkaline media.93 The promoted electrocatalysts were superior to pure Pt and the electrode with a weight ratio of Pt to MgO of 4 : 1 showed the highest activity for EOR. Bai et al. compared EOR on Pt–ZrO2/C with Pt/C(20 wt.% E-TEK) using CV, Tafel plot, and impedance spectroscopy in alkaline conditions.90 They reported that molar ratio of Pt : ZrO2 of 1 : 4 had the best catalytic activity for EOR. Recently, a comparative study of the effect of metal oxide support (support ¼ TiO2/C, ZrO2/C, SnO2/C, CeO2/C, MoO3, and WO3) on Pt nanoparticles for EOR in alkaline media was reported.64 Godoi et al. used in-situ XAS to show that Pt-support interaction produces changes in the Pt 5d band vacancy, which correlated to the EOR catalytic activity.64 They observed the highest and lowest activities for Pt nanoparticles on TiO2/C and CeO2/C, respectively.64 Using the IRRAS technique, they reported that acetate was the main product and traces of CO2 with different amounts for each support. They showed good correlation between fuel cell performances with electrochemical data.

3.4 Palladium catalyst for ethanol electrooxidation Palladium is the strongest competitor to platinum catalysts so far based on reports in literature. In particular, Pd-based catalysts show high activity for EOR in alkaline media, hence has been extensively studied in the last decade. The influence of halide ions on EOR on Pd was reported by Kumar and Buttry, who found that halide ions decreased the peak currents monotonically as a function of increasing halide concentration.113 The extent of poisoning, which also shifted the oxidation peak potential in more positive direction, was in the order of I4Br4Cl. This study highlighted the importance of thoroughly cleaning the nanoparticles prepared from palladium halide salt precursors. The effect of concentration has been studied using 8 wt.% Pd, on Vulcan XC-72 in passive alkaline DEFC and it was reported that improved performance and stability was observed when the [hydroxyl]/[ethanol] ¼ 1.114 CarreraCerritos et al. investigated the performance and stability of Pd nanostructures (nanopolyhedral, nanobar and nano-rod particles) in DEFCs.115 They studied the effect of the operation parameters, i.e., temperature and ethanol concentration on the maximum power density (MPD) and open circuit voltage (OCV). They reported that OCV values increased with increasing temperature for all of the catalysts at low ethanol concentration. Although, the MPD increased with temperature for all of the catalyst independent of the ethanol concentration, the effect Electrochemistry, 2019, 15, 1–57 | 15

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

of the temperature on the MPD for each Pd structure results in different slopes due to the different crystal faces.115 A study on single crystal Pd has been reported by Wang et al. who demonstrated the effectiveness of an electrochemical treatment consisting in cycles of constant potential oxidation and reduction of polycrystalline Pd surface in the enhancement of EOR.116 The rise of the activity after the treatment was ascribed to the increase of both the surface area and density of low coordination surface atoms. With the aid of IRRAS, they showed that a change in the reaction products distribution also occurred, resulting in some cases, in an increased tendency to cleave the C–C bond. Most of the studies have focused on the use of Pd nanoparticles. Assaud et al., reported the use of three dimensional Pd clusters grown on TiO2 nanotubes by atomic layer deposition for EOR.117 They found that there existed not only a direct correlation between the catalytic activity and the particle size but also a steep increase of the response due to the enhancement of the metal-support interaction when the crystal structure of the TiO2 nanotubes was modified by annealing at 450 1C in air. Rohwer et al. have reported a comparison of microwave and non-microwave treated Pd nanoparticles for EOR in alkaline medium.118 Microwaved Pd nanocatalyst showed higher electrochemical active surface area, aggregation/uniformity dispersion, higher amounts of palladium oxides, and had remarkable activity for EOR. The morphological effect of Pd catalyst for EOR was investigated by Cerritos et al., who studied three different structures; nanoparticles (NP/C), nano-bars (NB/C) and nanorods (NR/C) with preferentially exposed crystal faces supported on carbon black.119 They reported considerable differences with the performance trend of peak oxidation potential of: NB/CoNP/CoNR/Cocommercial Pd/C, indicating that NB/C catalyst enclosed by Pd(100) facets was the best catalysts. Cherevko et al. used high surface area Pd foams with roughness factors of more than 1000 and a specific surface area of 60 m2 g1 obtained by electrodeposition and reported them to have high activity towards the EOR.120 The effect of the catalyst support for Pd has been shown is several studies. For instance, Monyoncho et al. reported the promotional role of metal oxide supports (CeO2, SnO2, TiO2) for EOR on Pd in alkaline media.62 They monitored in-situ electrooxidation products using the PM-IRRAS which revealed that the supports influence the selectivity the reaction. They reported superior selectivity towards breaking the C–C bond to produce CO2 on Pd/CeO2. Acetate was the major product evident on all the catalysts, but at different ratios.62 Safavi et al. have proposed the use of immobilized Pd nanoparticles in a well-structured composite of hydroxyapatite and carbon nanotubes EOR.121 They demonstrated that the use of hydroxyapatite-carbon nanotubes composites lead to remarkable enhancements in the electrocatalytic activity, the kinetic parameters, and the durability of the catalyst. They attributed catalytic improvements to the synergetic effects between the immobilized Pd nanoparticles and the functionalities on the carbon nanotube-hydroxyapatite.121 To avoid the use of metal oxides, 16 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Fig. 7 The structure of Pd(DBA)2 catalyst. Reproduced from ref. 122 with permission from Elsevier, Copyright 2014 Hydrogen Energy Publications, LLC.

Zhian et al. have conducted a study of EOR on bis(dibenzylidene acetone)palladium(0), Pd(DBA)2, complex shown in Fig. 7.122 They reported that Pd(DBA)2 had higher tolerance against poisoning intermediate/ products for EOR, which was successfully employed as an anode catalyst in a passive air breathing DEFCs achieving a maximum power densities of 30, 31, 25 and 18 mW cm2 for ethylene glycol, ethanol, glycerol and methanol, respectively.122 Chen et al. conducted a comparative study of DEFCs build with a 2 mm thick layer of TiO2 nanotube arrays doped with Pd nanoparticles (1.5 mg Pd cm2) and reported a maximum power densities were 210, 170, and 160 mW cm2 at 80 1C for fuel cells fed with 10 wt.% aqueous solutions of ethanol, ethylene glycol, and glycerol, respectively in 2 M aqueous KOH.123 The use of highly porous 3D-Graphene nanosheets synthesized using the sacrificial support method as a support for Pd nanoparticles was presented by Serov et al.124 Their approach allowed the preparation of nanoparticles with smaller particle size distribution, higher surface area and showed good electrochemical activity and durability for EOR. Silva et al. described the use of Pd nanoparticles supported on physical mixtures of C þ TiO2 for EOR in alkaline media.83 They prepared C/TiO2 mass ratios of 100 : 0, 80 : 20, 60 : 40, 40 : 60, 20 : 80, and 0 : 100. They reported that Pd/C þ TiO2 (40 : 60) as the most promising mixture ratio. Chen et al. studied EOR on Pd/C promoted with CaSiO3 in alkaline medium and demonstrate that the Pd/CaSiO3 and C in wt.% 50 : 50 had higher current density (1408 mA mg1) than that of the Pd/C catalyst (743 mA mg1).91 Li et al. investigated the effect of adding MgO to Pd/C catalyst for EOR in alkaline medium and reported a significant improvement in activity and in the poisoning resistance.92 They reported Electrochemistry, 2019, 15, 1–57 | 17

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

that a catalyst with a weight ratio of Pd to MgO of 2 : 1 had the best performance, the onset potential was negative shifted by 80 mV and the peak current density was 3.4 times higher than Pd/C.92 Li et al. reported EOR on Pd nanoparticles supported on multi-wall carbon nanotubes synthesized on a carbon fiber paper (MWCNTs/CFP) in alkaline media which gave higher activity and stable performance than the commercial Pd/C and Pd/CFP.125 The promotion role of oxide phases on Pd for the EOR was studied by Martinez et al. who presented the evidence for the difference between an intrinsic effect obtained from an alloyed system and a synergistic effect produced by the presence of an oxide phase (SnO2).74 They interestingly showed that at 1M KOH, SnO2 acted as a cocatalyst to provide OH ions to the interface layer which increased the turnover rate. However, acetate was reported to be the main product instead of the desired complete electrooxidation of ethanol to CO2.74 Pd nanoparticle-deposited MoOx/C catalyst (Pd–MO/C) were considered by Lim et al. who showed a 35% higher mass activity compared to Pd/C catalyst for EOR.89 They attributed the performance of Pd–MO/C to the high active surface area and the higher resistance to adsorbed CO. Uhm et al. synthesized well-ordered arrays of free-standing Pd–CeO2 nanobundles in an anodic alumina template via occlusion electrodeposition which showed dramatically enhanced activity for EOR compared to pure Pd.68 Chu et al. reported EOR activity enhancement on palladium-indium oxide supported on carbon nanotubes (Pd–In2O3/CNTs) composites prepared via chemical reduction and hydrothermal reaction process.126 The composite electrode with the mass ratio of Pd : In2O3 equals to 10 : 3 (with Palladium loading of 0.20 mg cm2) showed the highest electrocatalytic activity for EOR.126

3.5 Comparative studies between Pt and Pd catalysts for ethanol electrooxidation Comparative studies between Pt and Pd for EOR in alkaline media have been conducted to determine the best candidate.70,79,95,127–130 Xu et al. showed that Pd/C has a higher catalytic activity and better steady-state performance for EOR than Pt/C in alkaline media and the addition of oxides (CeO2, NiO) significantly promoted the activity.95 They found better performance for Pd or Pt supported on CeO2 and NiO with weight ratio of 2 : 1 and 6 : 1, respectively. In another study, they reported EOR Pt and Pd electrocatalysts supported on carbon microspheres (CMS).130 The results showed that nanoparticles supported on carbon microspheres gave better performance than those supported on carbon black and pointed out that although Pd was not a good catalyst for methanol oxidation; it was excellent catalyst for EOR in alkaline media than Pt. Hu et al. prepared Pt/C and Pd/C electrocatalysts supported on NiO by intermittent microwave heating (IMH) method and tested them for EOR in electrolyte with and without the presence of CO.96 They reported that EOR on Pd–NiO/C electrocatalyst was better than Pt–NiO/C electrocatalyst. Bayer et al. studied EOR on Pt and Pd in alkaline medium using DEMS.129 They reported that the reaction products and their current 18 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

efficiencies depended strongly on the metal used. Acetate was the major reaction product while the current efficiency for CO2 was low for both. However, the amount of acetate was higher for Pd electrode. At higher ethanol concentrations, ethyl acetate was formed on the Pt electrode but was absent on the Pd electrode. Cantane and Lima have studied EOR on electrodeposited layers of Pd and Pt in alkaline electrolyte and monitored reaction products by online DEMS.131 The DEMS evidenced similar amounts of CO2 for Pd and Pt but Pd presented a higher production of ethyl acetate (acetic acid) and EOR on the Pd surface occurred to a greater extent, in agreement with previous reports. They proposed a mechanism as presented in the study.

4 Bimetallic catalysts It is well known that bimetallic, trimetallic, and quaternary catalysts are better than monometallic catalysts.42,132–142 We are going to focus our attention on the bimetallic work to understand the synergetic effect of the metals involved to determine the rationally for catalyst optimization for EOR in alkaline media. Table 1 (appendix) gives a summary of bimetallic catalysts and their corresponding monometallic catalysts tested for alkaline DEFCs. 4.1 Bimetallic platinum catalysts for ethanol electrooxidation in alkaline media There are many reports that Pt–M (M ¼ Pd,143–150 Sn,151–158 Ru,60,155,158–164 Mo,159,165 W,158 Bi,166–168 Au,102,128,148,169–173 145,167,174–177 178,179 180 181 182,183 Pb, Rh, Cu, Co, and Ag, ) etc. catalysts are significantly more active for the EOR than Pt alone. Here we examine a number of these studies to highlight what has been done. Pt–Pd catalysts: The fabrication of Pt–Pd alloy nanoparticles on graphene nano-sheets (PtPdNPs/GNs) have been described by Chen et al.143 They reported that varying the molar ratio of the starting precursors, nanoparticles with different shapes such as spherical (Pt1Pd1NPs), nanoflowers (Pd@PtNFs) and nanodentrites (Pt3Pd1NPs) could be produced on graphene nanosheets. Based on these observations, they proposed a plausible growth mechanism of PtPdNPs/GNs as shown in Fig. 8.

Fig. 8 Proposed growth process for PtPdNPs on GNs. Reproduced from ref. 143 with permission from the Royal Society of Chemistry. Electrochemistry, 2019, 15, 1–57 | 19

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

The electrocatalytic properties of PtPdNPs/GNs for EOR exhibited higher activity and better tolerance to poisoning intermediates compared to PtPdNPs supported on carbon black (PtPdNPs/C).143 Zhu et al. reported 3D PdPt bimetallic alloy nano-sponges which exhibited enhanced activity and stability towards EOR in an alkaline medium.144,148 They developed a method to synthesize well-defined PdPt alloy nanowires, which exhibited significant activity enhancement towards EOR. Yang et al. reported an electrochemical method to synthesize PtPd alloy nanoparticles on Nafion-graphene film and demonstrated that the catalyst had good tolerance against poisoning by the reaction intermediates generated during EOR.146 Datta et al. used poly-vinyl carbazole (PNVC), a conducting polymer composite matrix, cross linked with vanadium pentoxide (V2O5) and embedded with PtPd nano-crystallites for EOR leading to higher currents compared to carbon supported counterpart.147 Lin et al. reported a spontaneous reduction method to prepare PtPd with high activity for EOR.149 They showed that Pd77Pt23 had the highest activity followed by Pd87Pt13, Pd, and Pt. Pt–Ru catalysts: PtRu bimetallic is the oldest and most studied in the literature. Therefore, it is more appropriate here to refer the interested reader to a comprehensive review by Petri who discusses the three periods of Pt–Ru research:162 (a) the initial period after discovery (1963– 1970); (b) the observation and classification of basic tendencies (like the effects of compound segregation, structural features on the activity; up to 1990); and (c) the nano-structural studies and molecular level consideration of electrocatalytic phenomena in combination with advanced applied studies of materials, mechanistic, and applied aspects (after 1990 to 2008). The review focuses on the balance of various aspects of Pt–Ru electrochemical related to material science and electrocatalysis as well as to remember the early basic results being of importance for future understanding of Pt–Ru functional properties.162 Gralec et al. have studied the role of the Kegging-type phosphomolybdate (PMo12O403) ions adsorbed on C-supported PtRu and PtRu/C for EOR using CV, DEMS, and XPS.159 They showed that modification of PtRu/C nanoparticles with phosphomolybdate ions lead to the suppression of the formation of surface Ru oxides which resulted into more than 40% activity increase for EOR at potentials 4700 mV.159 Pt–Sn catalysts: This bimetallic system has been extensively studied and here we mention a few selected studies. The structure-to-property relationship for EOR on PtSn in alkaline and acidic environments have been studied by Artyushkova et al.151 They observed that transitioning from acidic to an alkaline environment, changes the material structure and electrochemical reaction mechanisms. Electrocatalysts containing larger particles with larger relative amounts of metallic Pt and Sn performed better in acid media which they attributed to the inner-sphere electron transfer reaction on active PtSn alloy phase.151 PtSn electrocatalysts containing larger amounts of oxidized Pt and Sn performed better in alkaline, which they suggested indicated that hydroxyl species that are natively present on oxidized Pt and Sn were promoting an outersphere electron transfer. Du et al. sought to explain why Pt–Sn 20 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

nanoparticles are active electrocatalysts for EOR but inactive for splitting the C–C bond to CO2 using microelectrode to monitor the amount of CO2.152 They reported that the composition and crystalline structure of the Sn element played an important role in the CO2 generation. The non-alloyed Pt46–(SnO2)54 core/shell particles demonstrated a strong capability for breaking the C–C bond than pure Pt and intermetallic Pt/Sn. The effect of ethanol concentration on the DEFCs with PtSn anode performance and products distribution was studied by Assumpcao et al. using in-situ single fuel cell/ATR-FTIR setup.153 They performed experiments at 801 using commercial Pt3Sn/C as anodic catalyst and the concentrations of ethanol solution were varied from 0.1 to 2.0 M. An increase in power density was observed with the increase of ethanol concentration up to 1.0 M, and the FTIR spectra band intensities revealed an increase of acetic acid/acetaldehyde ratio with increasing concentration of ethanol. Baranova et al. studied EOR on PtSn/C nanoparticles in alkaline media synthesized using a polyol reduction method.154 They formed bi-phase PtSn electrocatalysts where one group was composed of disordered PtSn alloys and the other group composed of PtSn alloys intimately mixed with SnOx. They reported that all catalysts were active during CV experiments but the bi-phase PtSn þ SnOx nanoparticles had significantly higher current densities at lower over-potentials compared to the pure alloy PtSn catalysts.154 They correlated the catalyst bulk and surface structure with the observed EOR in alkaline media demonstrating that 1 M KOH was the best when electrocatalyst contained higher amounts of both Pt and oxides. They reported that alloying of Pt with Sn improves intrinsic Pt catalytic activity and plausibly prevents Pt oxidation.154 Pt–Rh catalysts: For these catalysts, Calderon-Cardenas et al. have studied the effect of the composition and thermal treatment in H2 of Pt–Rh/C materials with atomic ratios of Pt : Rh 3 : 1, 1 : 1 and 1 : 3 and metal loading of 40 wt.% for EOR in alkaline media.178 They reported that thermally treated Pt–Rh catalysts in a hydrogen atmosphere showed greater stability and higher current densities and suggested the necessity of exploring the effects of thermal treatments of the catalysts for EOR. Shen et al. prepared PtRh/C catalysts and compare their catalytic activities with that of Pt/C in alkaline media and reported that the peak current density on Pt2Rh/C was about 2.4 times of that on Pt/C.179 They ascribed the enhanced activity to the improved C–C bond cleavage in the presence of Rh and to the accelerated oxidation kinetics of adsorbed CO to CO2 in alkaline media. Pt–Pb catalysts: Gunji et al. synthesized Pt3Pb(core)–PtPb(shell) nanoparticles on carbon black by converting nano-crystalline Pt to an ordered intermetallic compound with the reduction of Pb ions and tested them for EOR in alkaline media.174 The nanoparticles exhibited enhanced catalytic activity and relatively stable cycle performance towards EOR in an alkaline solution. They attributed the improved performance to both the enhancement of ethanol dehydrogenation and the higher concentration of surface adsorbed OH on the modified PtPb surface in the Pt3Pb–PtPb core-shell NPs. The mechanism for EOR on a Pt electrode modified with an irreversibly-deposited layer of Pb in alkaline solution Electrochemistry, 2019, 15, 1–57 | 21

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Fig. 9 Schematic to show the noncovalent interactions with hydrate Pd cations that would lead to a preferred orientation of acetaldehyde and/or acetate anion with the CH3 end pointing toward the surface as it approaches the electrode surface. Reproduced from ref. 176 with permission from American Chemical Society, Copyright 2012.

was proposed by Christensen et al. based on in-situ IRRAS insights.145 He et al. described an approach for the selective cleavage of the C–C bond using a solution-born co-catalyst based on Pb(IV) acetate, which they suggested controlled the mode of ethanol adsorption so as to facilitate the direct activation of the C–C bond, as shown in Fig. 9.176 Matsumoto studied the electrocatalytic activities of a wide range of intermetallic bulk compounds for EOR in alkaline media including PtPb which had the lowest onset potential for ethanol oxidation of 20–30 mV less than that of pure Pt and Pd.167 The current densities for PtPb were Z17 times larger than those of pure Pt and Pd. Yang et al. synthesized Pt–PbOx nanocomposite catalyst with a mean size of 3.23 nm with a much higher catalytic activity and a longer durability than Pt nanoparticles and commercial Pt black catalysts for EOR in alkaline media.175 In-situ IRRAS data revealed that breaking the C–C bonds on Pt–PbOx was 5.17 times higher than that of the Pt nanoparticles. Pt–Au catalysts: Mourdikoudis et al. synthesized PtAu heteronanostructures comprising the dimer (Pt–Au) and core-satellite (Pt@Au) configurations by means of a seeded growth procedure using Pt nano-dendrites as seeds.169 They reported that the prepared PtAu bimetallic nanostructures were highly efficient catalysts for EOR in alkaline solution. Dutta et al. synthesized PtAu alloyed nanoparticles and reported improved half-cell activity for EOR and a considerable increase in the peak power density (4191%) in an in-house fabricated DEFCs.170 da Silva et al. tested PtAu/C electrocatalysts in different atomic ratios and reported that the 50 : 50 as the most promising ratio for half-cell tests for EOR in alkaline media, while single fuel cell suggested a 70 : 30 ratio.172 They attributed the discrepancy to the electrode architecture since 50 : 50 ratio yielded a much thicker electrode than the 70 : 30 catalyst because 22 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

the Pt load was the same. Song et al. reported the preparation of hollow Au@Pt core–shell nanoparticles and used them for EOR in alkaline media which showed high current density in the forward scans.173 Cherevko et al. prepared highly ordered Pt decorated Au nanowire arrays, Pt/Au NWA and studied the effect of shell materials for EOR in alkaline media and reported up to 4-fold increase in the ethanol oxidation peak current.128 Pt–Bi catalysts: Figueiredo et al. reported the enhancement of EOR activity on Pt/C by simple adsorption of Bi on the surface.166 They reported that Bi promoted the cleavage of the C–C bond. Matsumoto et al. reported PtBi and PtBi2 intermetallic compounds as promising electrocatalysts among the various bulk electrodes they examined which had lower onset potentials for the EOR and exhibited extremely stable oxidation currents of 4.8 and 3.3 mA cm2 during the constantpotential electrolysis.167 Tusi et al. prepared Pt/C, Bi/C and PtBi/C (Pt : Bi atomic ratios of 90 : 10, 70 : 30 and 50 : 50) electrocatalysts and showed that PtBi/C had significant increase of performance for EOR in alkaline compared to Pt/C.168 They noted that the performance of PtBi/C electrocatalysts for EOR was superior in alkaline medium compared to acid medium. Pt–others: Li et al. synthesized a series of Mo-doped Pt/C catalysts with a microwave assisted technology and investigated the effects of Mo content on using CV, CA, and EIS.165 They reported that the Pt2Mo/C showed the highest current density and the slowest deterioration from intermediates/products poisoning. Kepenier et al. fabricated graphene supported PtCo catalysts (Pt : Co ¼ 1 : 1, 1 : 7 and 1 : 44) by the rapid microwave heating method and reported that the molar ratio of 1 : 7 had highest activity.181 Jin et al. prepared Pt/C catalysts modified by the potentiostatic deposition of Ag and reported a significant improvement in the activity of PtAg/C for ethanol oxidation in alkaline solution.182 El-Maksoud et al. investigated the electrocatalytic effect of Pb, Tl, and Cd ad-atoms on Pt electrode for EOR in alkaline medium.177 They reported that all three metal ad-atoms enhanced activity and Pb and Tl ad-atoms increased the oxidation rate by a factor of about 15, whereas Cd ad-atoms shifted the polarization curves negatively by a factor of about 5 at lower over-potentials. 4.2 Bimetallic palladium catalysts for ethanol electrooxidation Pd is considered the most active metal for EOR in alkaline media; hence a lot of effort has been directed towards improving its catalytic activity as evidenced from recent reviews.1–4 Several bimetallic catalysts have been tested so far Pd–M (M ¼ Ni,17,184–203 Ru,17,60,204–209 Au,17,128,148,173,208,210–216 Ir,217,218 Bi,219–221 Sn,75,185,188,216,222 V,223 W,224,225 Ag,49–52 Cu,226–232 Co,17,233 Fe,17 Mn,57 Ti,234,235 Rh,236,237 Sb,238 Te,239 La,240 and Pb.241). Herein we highlight a few of them. Pd–Ni catalysts: PdNi combination has been extensively studied because Ni is very cheap. Obradovic et al. synthesized Pd–Ni/C using NaBH4 reduction method which they reported to be up to three times Electrochemistry, 2019, 15, 1–57 | 23

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

184

more active for the EOR compared to Pd/C. They found that maximum activity was attained after fifty cycles with the positive potential limit of 1.2 V/RHE regardless of whether they were performed in the electrolyte with or without ethanol, hence proposed that potential cycling induces reorganization of the catalyst surface bringing Pd and Ni sites to a more suitable arrangement for ethanol electrooxidation.184 Moraes et al. have reported performance enhancement for alkaline DEFCs using nonfunctionalized and functionalized Vulcan carbon supported Pd, PdNi, and PdNiSn anodic electrocatalysts produced by impregnationreduction.185 They reported that alkaline DEFCs with PdNiSn supported on functionalized Vulcan had the best performance which they attributed to improved textural properties.185 Chen et al. prepared PdNi nano-catalysts supported on multi-walled carbon nanotube (MWCNT) using a modified polyol method.187 They reported that the surface oxygen content in PdNi/MWCNT was higher than in Pd/MWCNT and Ni existed mainly in the form of hydroxides which were attributed to be responsible for the improved poison resistance. Wang and co-workers have demonstrated in a number of studies that de-alloying can be used to improve PdNi electrocatalysts.186,189,192 They used Pd–Ni–P film prepared via electro-deposition on Au substrate and de-alloyed it by repetitive potential cycling in acidic media to leach out most of the Ni and P components and the resulting film showed significantly enhanced and durable activity for EOR. They used in-situ ATR-SEIRAS for reaction insights which revealed that the enhanced electrocatalysis correlated well with the enhanced formation of adsorbed CO and acetate.186 This was an extension of their earlier work on Pd–Ni–P where they showed that Pd–Ni–P have double the number of electrocatalytically active sites (12.03%) compared with the Pd–Ni (6.04%) and Pd-black (5.12%) samples.192 Dutta and Datta have investigated EOR on PdxNiy/C in alkaline medium synthesized by simultaneous reduction of metal precursors using NaBH4 method.190 They attributed the improved catalytic activity on NiO present in the binary catalyst matrix. Ahmed and Jeon studied a series of graphene supported NixPdy binary alloyed catalysts for EOR and reported activities in the order Ni75Pd25/G4Ni0Pd100/G4Ni25Pd75/G4 Ni50Pd50/G as shown in Fig. 10.191 Sheikh et al. synthesized Pd–Ni/C catalysts by impregnation-reduction method and reported that Pd40Ni60/C had the best catalytic performance for EOR in alkaline medium, which they attributed to Ni hydroxides (Ni(OH)x).188 Lee et al. prepared highly monodisperse 5 nm Pd–Ni alloy nanoparticles by the reduction of Pd(acac)2/Ni(acac)2 mixtures with tertbutylamine-borane complex in the presence of oleic acid and oleylamine which exhibited higher activity and stability for EOR.196 Miao et al. used to electroless co-plating to coat Pd–Ni nanoparticles on Si nanowires for EOR.195,199 They reported that Pd–Ni/SiNWs electrode had higher activity and better long-term stability in an alkaline solution.195 The work was an extension of their previous work on using silicon microchannel plates modified with Ni–Pd nanoparticles.199 Shen et al. performed a quantitative product analysis of EOR in an anion-exchange membrane DEFC that consisted of a PdNi/C anode and 24 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Fig. 10 CVs of a series of graphene supported NixPd100x recorded in 1 M KOH in the absence (dotted lines) and presence of 0.1 M EtOH. Reproduced from ref. 191 with permission from American Chemical Society, Copyright 2014.

found that Pd2Ni3/C leads to a significant increase in the cell performance compared to Pd/C but did not improve the selectivity towards CO2.193,201 They observed that among the operating conditions tested (temperature, discharge current, and ethanol concentration) the operating temperature was the most significant parameter that affect the CO2 selectivity: increasing the temperature from 60 to 100 1C increased the CO2 current efficiency from 6.0% to 30.6% with the Pd/C. This work was an extension of their earlier studies.7 Roy et al. prepared spherical Pd nanoparticles and dip-coated them Ni-foil and found them to be superior electrocatalysts for EOR compared to the Ni-supported Pd electrode despite of them having less Pd0 loading.194 Qi et al. used de-alloying method to prepare Pd40Ni60 alloy from a ternary Al75Pd10Ni15 in a 20 wt.% NaOH solution under free corrosion conditions.198 They reported that Pd40Ni60 had enhanced electrocatalytic performance for EOR in alkaline media than nanoporous Pd. Zhang et al. prepared PdxNiy/C through a solution phase-based nanocapsule method and showed that onset potential for EOR on Pd4Ni5/C was negative shifted by 180 mV and the exchange current density was 33 times higher compared to Pd/C.197 They proposed that surface Ni promoted a refreshing of the Pd active sites, thus enhancing the overall reaction kinetics. Maiyalagan and Scott prepared Pd–Ni nanoparticles supported on carbon nanofibers by NaBH4 reduction method and reported negative onset potential shift of 200 mV and four times increased peak current density for EOR on Pd–Ni/CNF compared to Pd/C.202 Electrochemistry, 2019, 15, 1–57 | 25

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Pd–Ru catalyst: Monyoncho et al. prepared PdRu nanoparticles supported on carbon PdxRu1x/C (x ¼ 1, 0.99, 0.95, 0.90, 0.80, 0.50) using a polyol method and reported that the resulting bimetallic catalysts were primarily a mix of Pd metal, Ru oxides and Pd oxides.204 They found that addition of 1–10 at.% Ru to Pd not only lowered the onset oxidation potential for EOR but also produced higher current densities at lower potentials compared to Pd/C by itself. In particular, they singled out Pd90Ru10/C and Pd99Ru1/C which gave up to six times higher current densities than Pd/C at 0.96 V and 0.67 V vs MSE, respectively. Similarly, Ma et al. studied PdRu/C catalysts with various Pd : Ru atomic ratios synthesized by impregnation method and tested them in AEMDEFCs.205,206 They reported that the anode with Pd3Ru/C showed a maximum power density as high as 176 mW cm2 at 80 1C, which was about 1.8 times higher than that of the Pd/C catalyst. Anindita et al. reported that addition of Ru to a Pd-0.5wt%C composite electrode increased the electrocatalytic activity greatly, attaining a maximum at 20wt% i.e. (Pd-0.5wt%C-20wt% Ru) for EOR in alkaline media.207 Pd–Au catalysts: Cai et al. synthesized Pd nanotubes covered by highdensity Au-islands that increased the mass activity by up to six times for EOR in alkaline media compared to Pd/C as shown in Fig. 11.210 They proposed a model to explain the relationship between the structure and the catalytic activity. Hong et al. have demonstrated a rapid synthetic process for alloyed dendritic PdAu nanocrystals that are active for EOR in alkaline media.211 The process involves mixing Na2PdCl4, HAuCl4, polyvinylpyrrolidone and hydroquinone and heating at 50 1C for 15 min. Smiljanic et al. examined the catalytic properties of Pd/Au(111) nanostructures obtained by spontaneous deposition of Pd using PdSO4 and PdCl2 salts.212 They reported that Pd/Au(111) nanostructures obtained using PdCl2 salt had higher activity which they ascribed to the thinner and smoother Pd deposits on the surface, hence more convenient sites for the adsorption of ethanol and its subsequent oxidation steps. Song et al. prepared hollow Au@Pd core-shell nanoparticles using galvanic displacement with Ag which

Fig. 11 The controlled synthesis of Au-Island-covered Pd. Reproduced from ref. 210 with permission from American Chemical Society, Copyright 2016. 26 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

showed highest current density in forward scan for EOR in alkaline media.173 Xu et al. prepare Pd–Au alloy electrocatalysts using dimethylformamide co-reduction method under an ultrasonic process and reported Pd3Au/C exhibited an enhanced catalytic activity and stability for EOR compared to monometallic Pd/C catalyst.213 Cheng et al. prepared highly ordered PdAu nanowire arrays using a combination of anodized Al oxide template-electrodeposition and Pd nanowire arrays reacting with HAuCl4.214 They found that the PdAu nanowires shifted onset oxidation potential by 123 mV more negative compared with that on the Pd nanowires. Recently, Assaud et al. reported Pd nanoparticles of controlled particle size deposited by Atomic Layer Deposition (ALD) on electrochemically grown TiO2 nanotubes (TNTs).117,242 The particle size was controlled by the number of ALD cycles (Fig. 12). They showed by TEM that catalysts fully cover the inner and outer walls of the threedimensional nanostructured TiO2. The influence of TiO2 nanotube support was demonstrated through the modification of the crystalline structure of the TNTs anatase TiO2 phase obtained after annealing is more conductive than the amorphous TiO2. Catalysts with a different number of ALD cycles were prepared and studied for EOR. Among the prepared electrocatalysts (N ¼ 400–900 ALD cycles), the 500 ALD Pd/ TNTs system showed the best catalytic activity and satisfactory stability in alkaline media (Fig. 13). Zhu et al. decorated carbon-supported gold nanoparticles with monolayer of Pd atoms with different Pd : Au atomic ratios using chemical epitaxial seeded growth method and showed that PdAu nanoparticles had higher specific activities than Pd/C for EOR in alkaline media.215 He et al. prepared carbon-supported Pd4Au and Pd2.5Sn nanoparticles using a chemical reduction method and examined the kinetics for EOR using impedance spectroscopy and Tafel plots which showed that the reaction kinetics were somewhat more sluggish on the Pd-based alloy catalysts than on commercial Pt/C, but the alloy catalysts had higher tolerance to surface poisoning.216 Pd4Au/C displayed the best catalytic activity among the series of prepared catalysts for EOR in alkaline media. Pd–Cu catalysts: Serov et al. used a sacrificial support method in combination with the thermal reduction of metal precursors to prepare unsupported uniformly-distributed PdCu catalysts with ratios of 1 : 3, 1 : 1, and 3 : 1.226 They found that PdCu and Pd3Cu electrocatalysts showed improved EOR activity, which they attributed to the presence of surface Cu sites favouring adsorbed OH species as confirmed by their DFT calculations in the paper.226 Mao et al. prepared a series of surface Pd rich CuxPdy/ C catalysts and reported Cu1Pd2/C stood out from the four sets tested for EOR in alkaline.227 Cai et al. reported catalyst with Cu core-shell structure prepared by the galvanic replacement between Pd21 ions and Cu particles (Cu@PdCu/C) which showed greatly improved durability, poisoning tolerance, and current density of 2.78 times higher than Pd/C for EOR.230 Zhao et al. have demonstrated a one-pot, room temperature aqueous synthesis of submicrometer-sized PdCu networks as superior catalysts for EOR in alkaline medium.229 Their composition-optimized Pd73Cu27 Electrochemistry, 2019, 15, 1–57 | 27

Published on 15 October 2018 on https://pubs.rsc.org | d

28 | Electrochemistry, 2019, 15, 1–57 Fig. 12 SEM micrographs of TNTs coated by Pd nanoparticles with an increasing number of ALD cycles: (a) 400, (b) 500, (c) 600, (d) 700, (e) 800, and (f) 900 cycles. Insets show the size distribution estimated, for each N, from the SEM pictures. Reproduced from ref. 117 with permission from American Chemical Society, Copyright 2015.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Fig. 13 Cyclic voltammograms of Pd/TNTs with a varying number of Pd ALD cycles on annealed TNTs in 1 M KOH þ 1 M C2H5OH. The current density is given per geometrical area (a) and ECSA (b). The scan rate is 25 mV s1. Reproduced from ref. 117 with permission from American Chemical Society, Copyright 2015.

network showed superior performance for EOR and better tolerance of COlike poisoning species compared to commercial Pd/C. Wang & Kang et al. have worked on the development of high performance PdCu/C catalysts to enhance EOR performance.231,232 Pd–Sn catalysts: Mao et al. used impregnation reduction method to prepare carbon-supported PdSn–SnO2 with higher catalytic activity for EOR in alkaline solution compared to Pd–Sn/C and Pd/C catalysts.75 They attributed the higher activity to easy adsorption-dissociation of OH over the SnO2 surface which changed the electronic effect and accelerated the adsorption of ethanol on the surface of Pd. Du et al. prepared a series of carbon-supported Pd–Sn binary alloyed catalysts using a polyol method among which Pd86Sn14/C catalyst showed much enhanced current densities.8 They supplemented their study with DFT calculations, which confirmed that Pd–Sn alloy structures lead to lower reaction energies for ethanol dehydrogenation compared to pure Pd crystals. 4.3 Nickel-based and non-platinum group metal catalysts for ethanol electrooxidation Ni-based bimetallic catalysts without Pt or Pd have been tested for EOR in alkaline media.243–252 Zhan et al. synthesized well-dispersed mesoporous Electrochemistry, 2019, 15, 1–57 | 29

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

NiCo2O4 fibres using an easy-controlled template-free method with specific surface area of 54.469 m2 g1 and average pore size of 13.5 nm.243 The catalysts exhibited significantly high EOR activity with higher current densities and lower onset potential compared to those of Co3O4 and NiO. Ren et al. reported a three-dimensional free-standing Ni nanoparticle aerogel with a graphene sheet network formed through the self-assembly aggregation of graphene accompanied by nickel nanoparticle in-situ loading on the graphene sheet during the hydrothermal reduction of graphene oxide and Ni ions.244 The three-dimensional composite architecture revealed excellent EOR activity. Hassan and Hamid electrodeposited Ni–Cr2O3 nanocomposite supported on carbon electrodes for EOR and showed that the catalytic activity of the fabricated electrodes increased with increasing the volume fraction percent (Vf%) of Cr2O3 in the deposited film up to 7 Vf%.245 The Ni–Cr2O3/C (7 Vf%) electrode displayed significantly enhanced catalytic activity and stability towards EOR compared with Ni/C electrode. Yi et al. compared nanoporous Ni electrode synthesized by electrodeposition into alumina template with smooth Ni electrode and reported that nanoporous Ni electrode had dominant (111) facets and self-regulated NiOOH rich surface in KOH solution, which they ascribed to be active for EOR.246 Tarasevich, Tsivadze, and co-workers conducted studies on anodic (RuNi/C) and cathodic (PtCo/C and CoN4/C) catalysts, polybenzimidazole membrane, and membrane-electrode assemblies for alkaline ethanol-oxygen fuel cell.247,250 They reported optimized atomic percent of Ru : Ni ¼ 68 : 32 and the metal mass on carbonaceous support of 15–20% which was superior to commercial Pt/C and RuPt/C catalysts when calculated per unit mass of the precious metal. Using chromatographic analysis of the products, they reported the highest CO2 yield at low electrolysis overvoltage and elevated temperature. The use of non-platinum group metals such as Au102,208,253–258 and Rh259,260 have also received attention, especially Aubased, but they are expensive for commercial applications, hence will not be discussed further.

5 Ethanol electrooxidation reaction mechanism in alkaline media The understanding EOR mechanism is critical for the rational design of catalysts and in the reaction optimization for DEFCs. The synergy between experimental techniques and theoretical simulations has been employed to achieve this objective. A combination of pure electrochemical methods with state of the art in-situ analytical methods to monitor adsorbed intermediates/products is necessary to visualize the reaction paths. See the methodology chapter for more details on the techniques used. Ethanol electrooxidation mechanism has many pathways leading to controversial debates on the details in the literature. Nevertheless, there is a general consensus that EOR mechanism exhibits a ‘‘dual pathway’’.110,257,261,262 Several reaction mechanism schematics have been presented to explain the mechanistic details.102,110,145,155,170,176,261,263–272 Currently, there are two schematics, which in our opinion are inclusive of 30 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Fig. 14 The proposed general ‘‘dual pathway’’ EOR mechanism scheme. Reproduced from ref. 261 with permission from Springer Nature, Copyright 2013.

all the other schematics reported in the literature. One of the schematics is more general and is based on electrochemical experiments without proper identification of intermediates/products.110,261 The second schematic is more detailed and applicable to both acidic and alkaline conditions.155 The first and more general schematic is shown in Fig. 14 and shows a dual path reaction where in one path the reactive intermediates are weakly bound to the catalyst surface, which leads to incomplete oxidation ‘‘C2 pathway’’.110,261 The other pathway involves strong bond intermediates, which can be fully oxidized to CO2 in the ‘‘C1 pathway’’ if the right conditions are met, otherwise they can block the catalyst surface. The arrows in Fig. 14 show the interplay between the two pathways. In the dominant C2 pathway, the C–C bond does not break and ethanol is oxidized to products such as acetaldehyde, acetic acid, acetate, germinal diols etc. depending on the electrolyte used. In the C1 pathway, the C–C bond is broken and the fragments are oxidized into CO and eventually CO2. The second and more comprehensive schematic presented to date is shown in Fig. 15.155 It was based on cumulative experimental data from different groups and intuition. In the schematic, the lighter highlighted species were identified with NMR155,273 while the darker highlighted species had been identified by DEMS, chromatography, and infrared spectroscopy. The reaction steps marked with stars (*) are those in which OHads are involved and catalytic sites are regenerated due to reaction with OHads. Note that although, the schematics show the reaction paths in a stepwise manner it is possible some steps would happen in a concerted manner as suggested in literature.274 The schematic is universal in a sense that it can be used to explain observations in both acidic and alkaline conditions. Therefore, the schematic in Fig. 15 stands out among the many schematics102,110,145,155,170,176,261,263–272 in highlighting the experimental progress made in understanding EOR without theoretical insight. It is important to note that EOR intermediates/products are influenced by the nature of the catalyst, the electrolyte, and the applied potential. Therefore, not all the intermediates/products shown are observed in each reaction. The schematic in Fig. 15 tells us that there are three possible routes for ethanol electrooxidation. The first two pathways are due to Electrochemistry, 2019, 15, 1–57 | 31

Published on 15 October 2018 on https://pubs.rsc.org | d

32 | Electrochemistry, 2019, 15, 1–57 Fig. 15 Schematic for EOR pathways on Pt-based catalysts proposed on the basis of NMR data and literature prior to 2011. The chemical species in light grey were observed by NMR while those in dark grey were observed by other analytical techniques in previous studies. Reproduced from ref. 155 with permission from John Wiley & Sons, Copyright 2011 r WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

dehydrogenation which would lead either to adsorbed CH3CHOH or CH3CH2O in the first step. In the second pathway, acetaldehyde is the central molecule. Following the first steps in these two pathways in EOR, there are many other possibilities as shown in the schematic of which the details are not necessarily accurate as presented in the Fig. 15. The third pathway is due to loss of the water molecule to form adsorbed CH3CH2 which can be reduced to ethane. Path three is specific to acidic media where ethane was observed as one of the products in low/cathodic potential. The key points we would like to highlight from Fig. 15 are: (i) Acetyl (CH3CO) pathway leads to the cleaving of the C–C bond to form CO2 but it faces a strong competition to formation of acetic acid and/or ethyl acetate instead based on quantitative analysis of the products, (ii) the NMR technique was critical in identifying products such as ethyl acetate (CH3COOCH2CH3), germinal diol (CH3CH(OH)2), and CH3CH(OH)OCH2CH3, (iii) the link of the reactions leading to some products is not explicitly presented such as CH3CH(OH)2-CH3COOH, (iv) the schematic does not incorporate first-principle insights available in literature. The last two points represents the weaknesses of the schematic which will be addressed in a different forum. Herein we focus our attention to what has been done for EOR in alkaline media particularly in addressing the question as to why it is difficult to break the C–C bond. The understanding of EOR mechanism in alkaline conditions is in its infancy, for only a few studies provide molecular information.104,269,275–280 The reason for the scarcity of EOR mechanism details was the fact that the produced CO2 forms soluble carbonates in the presence of aqueous alkaline electrolyte, which makes it difficult to study using FTIR or model DEMS systems. Rao et al. overcame this obstacle by using alkaline polymer electrolyte membranes which gave them opportunity to observe CO2 produced during EOR using fuel cell effluents coupled to DEMS system.104,279 Hence, DEMS was the first technique to reveal that in alkaline conditions the C–C bond cleavage in ethanol is more efficient than in acidic media. Rao et al. demonstrated that CO2 current efficiency was around 55% at 0.8 V/RHE at 60 1C for alkaline MEA compared to only 2% for acidic MEAs.104,279 This fact was confirmed by Cremers et al. who reported that the kinetics for ethanol oxidation in alkaline media were higher than in acidic media under the same conditions.103 In a subsequent study, Cremers et al. made some interesting observations:281 (i) in alkaline medium ethanol adsorbates can only be desorbed in form of carbon dioxide and methane, (ii) preadsorbed CO could not be reduced to methane at Pt in alkaline conditions, hence they ascribed methane formation from ethanol adsorbates to an adsorbed CHx or COxHy species, (iii) ethanol adsorbates in alkaline media can be oxidized in two potential regions, i.e., below and above 0.9 V/RHE, (iv) the calculated number of electrons per molecule of CO2 evolved in the potential region below 0.9 V/RHE was found to be two, independent of the adsorption potential. They claimed that a form of adsorbed COads species was present on the electrode. They suggested that the higher calculated number of electrons per molecule of CO2 in the potential region above 0.9 V/RHE pointed to the co-existence of more Electrochemistry, 2019, 15, 1–57 | 33

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

than one adsorbate species. The deviation of the number of electrons per molecule of CO2 from the value of two in the potential region below 0.9 V/ RHE for stripping experiments started in cathodic direction indicated an alteration of the adsorbate in the form of COads, initially being present, or the co-existence of two adsorbate species. Their observation that no CO2 formation was observed in the potential region above 0.9 V/RHE for stripping experiments started in cathodic direction, lead to their conclusion that the adsorbates which are oxidized in the potential region above 0.9 V/RHE are the ones which can be reduced to methane.281 They later determined that in alkaline media CO2 was only formed in the potential region of the oxidation of adsorbed CO.107 Therefore, they inferred that in alkaline conditions, CO2 was produced from adsorbed ethanol and not from bulk ethanol. (v) The efficiency of breaking the C–C bond is lower with an increase in the concentration of ethanol,281 and comparison between Pd and Pt showed that on Pd, ethanol oxidation in alkaline media is almost selectively towards acetate formation. Similarly, on Au electrodes, acetate and ethyl acetate seemed to be the exclusive products with no cleaving of the C–C bond. They reported Ni to be a poor catalyst for EOR.129 It has been recognized that the inconsistencies of EOR details in literature both from experimental and computational studies were due to the sensitivities of the reaction to the surface structure of the electrode and the adsorbed ions.271 Melke et al. summarized the available literature data up to 2010 into the reaction schematic shown in Fig. 16.103,272,282–284

Fig. 16 Summary of the ethanol oxidation reaction (EOR) mechanism on Pt. Path on the left is preferred in Pt(111) and at high surface coverages and the path on right side is dominant at low coverages on stepped surfaces and defects. Adsorbates pictured in black were found experimentally and molecules in blue are present in solution. Reproduced from ref. 271 with permission from American Chemical Society, Copyright 2010. 34 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

Fig. 16, shows that there exist two main EOR paths governed by the reaction conditions and the structure/morphology of the catalyst used. Acetyl serves as a bridging intermediate between the two reaction paths, which means it will have a very small life-span once generated during the reaction due to the strong competition to either break the C–C bond or to the formation of acetic acid. The reaction path towards acetic acid (acetate in alkaline media) is preferred on close-packed surfaces such as Pt(111) and/or at high surface coverage (left side in Fig. 16). On the other hand, full oxidation to CO2 prefers open or stepped surfaces like Pt(110), Pt(100), and Pt(211) (right side in Fig. 16) and low surface coverage. It has been suggested that the bond breaking takes place either within adsorbed CHCO or CH2CO species,77 and CHx and CO are the strongly adsorbed intermediates.281 Fang et al. reported the mechanism for EOR on a Pd electrode in alkaline solution using cyclic voltammetry and in-situ infrared spectroscopy.285 They observed the best performance at the pH ¼ 14 (1M NaOH) and acetate was the main product for concentrations higher than 0.5 M NaOH. They reported that the C–C bond cleavage to form CO2 occurred at pHr13, which was in agreement with online massspectrometry results from Cantane and Lima evidencing CO2 production over Pt and Pd in 0.01 M NaOH where acetic acid formation was almost absent.131 Christensen et al. have shown that the interfacial pH drops at higher potentials due to the high consumption of OH which is not completely counterbalanced by the OH diffusion from the bulkphase.269,278,286 This phenomenon leads to a transition from alkaline to acidic conditions at the interphase. The transition potential varies with the diffusion rate of OH which is dependent on the temperature and mass flow-rate. They reported that during electrooxidation reaction, ethanol is converted to acetate in alkaline pH but above the transition potential, acetic acid and traces of CO2 are formed.287 A comparative study of EOR on Pd, Pt, and Rh in alkaline electrolyte through online DEMS experiments have shown similar amounts of CO2 for the three metals but Pd electrode produced higher amounts of ethyl acetate (which they attributed to acetic acid formation).131 The authors reported that on Pt and Rh the formation of CO2 occurred mainly via oxidation of either the adsorbed CO or CHx species formed after dissociative adsorption of ethanol or the oxidation of the ethoxy species that takes place only at low potentials. This argument was based on the observation of methane for Pt and Rh electrodes during potential excursions to lower potentials which was lacking for the case of Pd electrode. These insights implied that the dissociative adsorption of ethanol or ethoxy species is inhibited at higher potentials on Pt and Rh.131 For the case of Pd electrode, the reaction may be occurring via nondissociative adsorption of ethanol or ethoxy species at lower potentials followed by oxidation to acetaldehyde and to acetic acid. Alternatively, they proposed a parallel reaction path where acetaldehyde molecules adsorbed on the Pd surface can be deprotonated, yielding a reaction intermediate in which the C–C bond can be easily broken to produce CO2 after potential excursions to higher potentials.131 Electrochemistry, 2019, 15, 1–57 | 35

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

The question(s) on why it is difficult to break the C–C bond and at what intermediate does it occur during ethanol electrooxidation was recently tackled by the authors.288 We found that at lower potential (e.g. 0.56V/RHE), it is possible to break the C–C bond on Pd/C in alkaline media to form CO2 as shown in Fig. 17b. However, the selectivity is poor due to competition towards the formation of acetate and other side products. At higher potentials (e.g. 0.72 V/RHE), the selectivity towards C–C cleavage gets worse, as shown in Fig. 17e. In that work, DFT calculations were used to complete the reaction pathway details using the computational hydrogen electrode approach. The calculations highlighted the pivotal role of the CH3CO intermediate that can either undergo a C–C bond scission yielding CO and then CO2 or that can be oxidized towards CH3COO. The latter is a dead end in the reaction path towards CO2 production, since it cannot be easily oxidized or broken into C1 fragments in agreement with CV data provided therein showing that acetic acid in KOH was not active. Unfortunately, CH3CO is not the most favored intermediate formed during EOR on Pd, hence limiting the production of CO2. Strategies to overcome these limitations are discussed in the conclusions and outlook below.

6

Summary of issues to be addressed for DEFCs

The top priority challenge for the successful development of DEFCs depends on the detailed understanding of the reaction mechanism which would pave way for the rational design of the catalysts capable of cleaving the C–C bond in ethanol. A breakthrough in this endeavour will increase the overall DEFCs efficiency from the current 14% to 43%, hence making them the strongest competitor to hydrogen fuels cells, which have an efficiency of 54%.29 Other issues which are more in the engineering development part include: membrane and ionomer improvements, water and ethanol transport management, carbon dioxide regulation and electrolyte development. 6.1 Reaction mechanism and rational catalysts design strategies Although, ethanol electrooxidation reaction kinetics are faster in alkaline conditions, an efficient catalyst for the complete oxidation of ethanol to CO2 remains an outstanding challenge in the reviewed literature. Even after three decades of active research, there is still no selective catalyst for breaking the C–C bond. Therefore, efforts in the fundamental understanding of the reaction mechanism are required to pave the way for the rational design of efficient catalysts. On the cathode side, the challenge is how to enhance non-Pt catalysts to make them comparable to Pt for ORR. 6.2 Membranes improvements Anion-exchange membrane can be grouped into two categories: polyelectrolytes and alkali-doped polymer membranes.31 Membrane 36 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | d Electrochemistry, 2019, 15, 1–57 | 37

Fig. 17 PM-IRRAS spectra for ethanol electrooxidation products on Pd/C nanoparticles in 1M (KOH þ C2H5OH) at 0.56 V/RHE (a, b) and 0.72 V/RHE (d, e). The left panels show oxidation species on the catalyst surface and the right panels show oxidation species in the liquid-phase. The spectra show that at low potentials (0.56 V/RHE, c, d), the C–C bond is broken which desorbs from the catalyst surface into the liquid-phase. At higher potentials (0.72 V/RHE, e, f), the selectivity for cleaving the C–C bond is very poor. Reproduced from ref. 288 with permission from American Chemical Society, Copyright 2016.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

improvements in parameters such as composition, ionic conductivity, ethanol permeability, thermal and chemical stability are discussed elsewhere.16,25,289 The main challenges with alkaline anion-exchange membranes are the low stability in OH and low OH conductivities. Therefore, efforts are required not only in developing new membrane formulations, but also the development of tools for characterising membrane properties such as water uptake, ethanol permeability, water diffusivity, and electro-osmotic coefficient. 6.3 Ionomer improvements Ionomers are critical components of the fuel cell that help to bind discrete catalyst particles, which must form a porous conduction layer for the transfer of ions, electrons, and reactants/products.290 Therefore, similar to membranes, there is need to improve ionic conductivity, thermal and chemical stability, and make them soluble in nontoxic and cheap solvents. 6.4 Water transport management Water management is a critical requirement for the long-term operation of DEFCs. Water is produced at the anode and consumed at the cathode, leading to a high water crossover from the anode to the cathode. Although, the water crossover phenomenon has the advantage of improving the ionic conductivity, too much water crossover would lead to the cathode flooding and hinder oxygen transport. Similarly, a low water crossover can facilitate oxygen transport but leads to mass transport loss for ORR, which would result into high cathode activation loss. 6.5 Ethanol transport management Maintaining proper circulation of the fuel (ethanol) is critical to obtaining the optimum current density and avoiding fuel waste due to incomplete reaction.25 If ethanol concentration in the anode is too high will lead to the reduction of the coverage of OH and increase the anode activation loss. Secondly, high ethanol concentration will increase ethanol crossover that can reduce fuel utilization. On the other hand, too low ethanol concentration level in the anode will increase mass transport loss and reduce the optimum current. Therefore, efforts in the design of the anode flow field as well as determining the optimum operating conditions, such as ethanol concentration supplied to the flow field and the ethanol solution flow rate in the flow field and temperature are required. 6.6 Carbon dioxide regulation It is cheaper to use air rather than oxygen in the fuel cells but this presents a challenge for alkaline fuel cells because air contains around 0.039% (volume fraction) of CO2. Under standard conditions, this CO2 38 | Electrochemistry, 2019, 15, 1–57

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001



will react with the OH generated by the ORR to form carbonate (CO23), which may affect cell performance in two aspects:25 (i) by decreasing the pH level in the cathode, thus affecting the kinetic of the ORR, and (ii) by reducing the ionic conductivity in both the cathode and membrane, increasing the cell resistance. Hence, the problem associated with CO2 from air is an issue that needs to be addressed in the future. 6.7 Electrolyte (KOH, ionic liquids etc.) The fact that KOH reacts with CO2 produced at the anode or from the air at the cathode presents a serious challenge. As discussed above KOH reacts with CO2 to form carbonate which precipitates and blocks the pores of the membranes and the electrodes. At the cathode, KOH can reduce the hydrophobicity of the gas diffusion layer, thereby breaking the balance of mass transport between water and oxygen. Therefore, efforts in consideration of other possible electrolyte formulations such as ionic liquids to mitigate the use of the KOH will be welcomed in the future studies.

7

Conclusions and outlook

From the survey of the literature presented herein, it is clear that in the past two decades tremendous efforts have been devoted to developing DEFCs from both the fundamental understanding of the reaction to the prototype fuel cell design development. From a fundamental perspective, many analytical techniques have been extended towards insitu identification and quantification of the reaction products. This is a significant advance for they now provide the opportunity to visualize the progress of the reaction in real-time, hence providing much needed insight into understanding the reaction mechanism. A range of tools (electrochemical techniques, mass spectroscopy, surface enhanced Raman spectroscopy, sum frequency generation spectroscopy, X-ray absorption spectroscopy, chromatography, and nuclear magnetic resonance spectroscopy) and protocols for using them to probe electrocatalytic reactions in-situ are now available in the literature. Besides the electrochemical techniques, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and X-ray absorption/photoemission spectroscopy are recommended as complementary techniques to capture complete details of the reaction mechanism. To complement these experimental tools is the use of first-principles calculations such as DFT for atomic insights to facilitate the screening of the best candidate catalysts for experimental testing. Combining the contributions of these various techniques for the past two decades has provided good understanding of the EOR mechanism, although it is very complex. Special credit goes to the application of NMR,155,273 which has disclosed intermediates such as CH3CH(OH)2, CH3CH(OH)OCH3, CH3CH(OH)OCH2CH3, and CH3COOCH2CH3, which were impossible to distinguish with the other techniques used so far. Electrochemistry, 2019, 15, 1–57 | 39

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

View Online

When it comes to catalyst design, excellent progress has been made which allows tailoring the nanoparticle structures and morphology from the atomic level. Now it is possible to make nanoparticles with preferred facets (111, 100 etc.), dimensions (1D, 2D, 3D such as nanosheets, nano-wires, nano-tubes, nano-cages, nano-boxes, nano-spheres etc.), and compositions (mono- or multi-metallic). All these possible structures provide great opportunities for structure-activity relationship studies which are yet to be optimized for EOR. These possibilities also present a great challenge for there are many to be optimized. In addition to these possibilities, there is great consensus in literature that supports have a significant influence on the catalytic properties of the nanoparticles. Of particular interest are the metal-oxide supports such as SnO2, CeO2, NiO/foams, and TiO2. In terms of selectivity towards cleaving the C–C bond, CeO2 stands out as the best candidate support. On the other hand SnO2, although it significantly improves the reaction kinetics, the selectivity for breaking the C–C bond is very poor. However, it presents the opportunity of considering running the EOR in DEFCs with the benefit of getting value added chemicals instead of CO2. In designing the catalyst structures, it seems the efforts should be focused on 3D and/or mesoporous materials. This is because, from computational insights, ethanol is reported to preferentially adsorb via the oxygen lone pair of electrons, which allows the activation of the alphacarbon (a-C). Therefore, it would be interesting to confine ethanol molecule in thin-cavity catalysts, which would allow the beta-carbon (b-C) to be activated too. Five prototype DEFCs have been proposed and tested in literature to date. They are proton-exchange membrane fuel cells, anion-exchange membrane fuel cells, alkaline-anode acid-cathodes fuel cells, direct alkaline fuel cells without membranes, and solid oxide fuel cells. Each design has its own advantages and disadvantages which mean that there should be simultaneous development and optimization hence presents a great challenge. Nevertheless, these provide the opportunity to start identifying for what application each design is best suited for and the potential returns. Regardless of which prototype design is the best, the various components of the fuel cells still needs combined efforts of both scientists and engineers. These components include the development of membranes, ionomers, catalysts (anode and cathode), water transport and ethanol transport management, carbon dioxide management, and electrolyte formulations that favour the reaction selectivity towards complete oxidation. For the electrolyte formulations, there is need to use buffer solutions to mitigate the effect of the changing pH at electrolyte/electrode interfaces. Changing the pH when working, especially in alkaline conditions, alters the reaction kinetics, as reported in the literature. The other option would be to consider the use of ionic liquids with ions, which would not block the catalyst active sites for ethanol oxidation. Overall, the development of DEFCs looks promising in the near future.

40 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | d

Appendix Table 1 Summary of alkaline DEFCs tests showing the catalysts used, the operating conditions, and power density obtained.a

Electrochemistry, 2019, 15, 1–57 | 41

Anode

Synthesis

Support

Membrane (AEM)

Cathode

Pt

Commercial

Ni

Teflon

MnO2

NaBH4 reduction

C

A-600, Tokuyama

Pt/C

NaBH4 reduction

C

Nafions 117

Pt/C

Polyol and impregnation

C

Nafions 115

Pt/C

Polyol

C

Nafion 117, DuPont Pt/C

Pt–Pd

Polyol and impregnation

C

Nafions 115

Pt/C

PNVC– V2O5

A-006, Tokuyama

Pt/C

Pt–Au

Solid state polymerization (for PNVC–V2O5) and NaBH4 reduction NaBH4 reduction

C

Tokuyama (A-600)

Pt/C

NaBH4 reduction

C

Nafions 117

Pt/C

Pt–W

Polyol and impregnation

C

Nafions 115

Pt/C

Pt–Ru

Commercial

C

PBI/KOH

Pt/C

AAEM-C, AAEM-E, Nafions 115

Pt black

Commercial

Operating conditions/ temperature

Power (mW cm2)

Ref.

1 M Ethanol þ 3 M KOH/O2; T ¼ room temp 1 M Ethanol þ 0.5 M NaOH; T ¼ 20–80 1C JO2 ¼ 150 cm3 min1; 2 M Ethanol þ 2 M KOH; T ¼ 75 1C JO2 ¼ 120 cm3 min1; 1 M Ethanol; T ¼ 90 1C JO2 ¼ 45 cm3 min1; 1 M Ethanol; T ¼ 80 1C JO2 ¼ 120 cm3 min1; 1 M Ethanol; T ¼ 90 1C JO2 ¼ 100 sccm; 1 M Ethanol þ 0.5 M NaOH; T ¼ 40 1C 1 M Ethanol þ 0.5 M NaOH; T ¼ 20–80 1C JO2 ¼ 150 cm3 min1; 2 M Ethanol þ 2 M KOH; T ¼ 75 1C (room temperature) JO2 ¼ 120 cm3 min1; 1 M Ethanol; T ¼ 90 1C 2 M Ethanol þ 2 M KOH; T ¼ 75, 90 1C JO2 ¼ 2000 sccm; 2 M Ethanol/O2; T ¼ 50 1C

14.6

291

12

170

3

172

10.85

158

B21 mW

155

11.97

158

30

147

35

170

9 (PtAu 70 : 30)

172

15.88

158

49.20, 60.95

292

1.71, 2.09, 7.42

293

42 | Electrochemistry, 2019, 15, 1–57

Published on 15 October 2018 on https://pubs.rsc.org | d

Table 1 (Continued) Anode

Synthesis

Support

Membrane (AEM)

Cathode

Polyol and impregnation

C

Nafions 115

Pt/C

AAEM, Tokuyama

Pt black

Power (mW cm2)

Ref.

28.54

158

58

164

16

34

30

294

58.87

295

22.4

296

B50 mW

155

52.22

158

B67 mW

155

B1.2

153

61.2 (Pt2Sn1)

156

28

157

C

Nafions 117, DuPont Nafions 117

Pt/C

C

Nafions 115

Pt/C

JO2 ¼ 120 cm3 min1; 1 M Ethanol; T ¼ 90 1C Jo2 ¼ 100 cm3 min1; 1 M EtOH þ 0.5 M NaOH; T ¼ room temperature 2 M Ethanol þ 3 M KOH/O2; T ¼ 25 1C 2 M Ethanol þ 2 M KOH/air; T ¼ 60 1C 2 M Ethanol þ 2 M KOH/0.2 MPa O2; T ¼ 90 1C 1 M Ethanol þ 0.25 M KOH/O2; T ¼ 50 1C JO2 ¼ 45 cm3 min1; 1 M Ethanol; T ¼ 80 1C JO2 ¼ 120 cm3 min1; 1 M Ethanol; T ¼ 90 1C JO2 ¼ 45 cm3 min1; 1 M Ethanol; T ¼ 80 1C JO2 ¼ 100 cm3 min1; 1 M Ethanol; T ¼ 80 1C 1 M Ethanol; T ¼ 90 1C

C

Nafions 117

Pt/C

EtoH T ¼ 110 1C

Commercially

Pt–Sn

Operating conditions/ temperature

Commercially

C

KOH

MnO2

Commercial

C

PBI/KOH

MnO2/C

Commercial

C

Pt/C

Commercial

C

CEM (Na1) (Nafions 112) AEM (A-201)

Polyol reduction

C

Reducing metal precursors in EG and impregnation Polyol reduction process with EG *Commercial catalysts were used Mixing solution of metal precursors in EG with carbon slurry then acidifying Metal precursors in THF in the presence of a surfactant to form a colloidal precursor, which is then dispersed on carbon powder

C C

Nafions 117, DuPont Nafions 115

Pt/C Pt/C Pt/C Pt/C

Published on 15 October 2018 on https://pubs.rsc.org | d

Pd

Dimethylformamide co-reduction method THF added to a suspension of MWCNT and Pd metal precursor Impregnation/reduction method NaBH4 reduction

Impregnation and NaBH4 reduction Simultaneous reduction method NaBH4 reduction

Electrochemistry, 2019, 15, 1–57 | 43

Pd–Au Pd–Ir Pd–Sn Pd–Ni

C

A-201, Tokuyama

Acta Hypermect

MWCNT

A-600, Tokuyama

Acta Hypermect, K14

C

Pt/C

C

Nafions 117 (DuPont) A-201, Tokuyama

Acta Hypermect

C

A-201, Tokuyama

MnO2

C

AEM (A-201)

C

PBI/KOH

Fe–Co Hypermect, K14 MnO2/C

NaBH4 assisted EG reduction NaBH4 reduction

C

A-600, Tokuyama

TNTA

A-201, Tokuyama

Acta Hypermect, K-14 Fe–Co/C

Electroless method

C

A-600, Tokuyama

Fe–Co/C

Dimethylformamide coreduction method NaBH4 reduction

C

A-201, Tokuyama

C

Nafions 117

Acta HYMPERMECt Pt/C

Impregnation/reduction method

C

Nafions 117, DuPont CEM (Na1) (Nafions 211), A-201, Tokuyama

C

Pt/C Acta Hypermect, K14

JO2 ¼ 100 sccm; 3 M Ethanol þ 5 M KOH; T ¼ 40 1C JO2 ¼ 200 sccm; 10 wt% Ethanol þ 2 M KOH; T ¼20–22, 80 1C 2 M Ethanol þ 6 M NaOH; T ¼ 100 1C JO2 ¼ 100 sccm; 1, 3 M Ethanol þ 1, 5 M KOH/O2; T ¼ 60 1C JO2 ¼ 300 sccm; 3 M Ethanol þ 3 M KOH; T ¼ 60, 70, 80 1C JO2 ¼ 100 sccm; 1 M Ethanol þ 1 M KOH/O2; T ¼ 100 1C 2 M Ethanol þ 2 M KOH/air; T ¼ 60 1C 5 M Ethanol þ 5 M KOH; T ¼ 25 1C JO2 ¼ 100 cm3 min1; 10 wt% Ethanol þ 2 M KOH; T ¼ 80 1C JO2 ¼ 200 cm3 min1; 10 wt% Ethanol þ 2 M KOH; T ¼ 25, 80 1C JO2 ¼ 100 sccm; 3 M Ethanol þ 5 M KOH; T ¼ 40 1C JO2 ¼ 150 cm3 min1; 2 M Ethanol þ 2 M KOH; T ¼ 70 1C 2 M Ethanol þ 6 M NaOH; T ¼ 100 1C 3 M Ethanol þ 5 M NaOH/O2; T ¼ 60, 90 1C

56

213

18.4, 73

60

30.1

185

33, 67

201

67, 82, 98

205

40

193

16

294

16.8

114

335

123

18, 120

66

57.5

213

10 (70 : 30)

217

27.2

185

100, 135, 90, 115 297

Published on 15 October 2018 on https://pubs.rsc.org | d

44 | Electrochemistry, 2019, 15, 1–57

Table 1 (Continued) Anode

Synthesis

Support C C C

Impregnation/reduction method Simultaneous reduction method Mixing PdNi/C with PTFE in EtOH and brushing catalysts on surface of nickel foam

Membrane (AEM) 1

CEM (Na ) (Nafions 117) CEM (Na1) (Nafions 117) A-201, Tokuyama

C

Nafions 117 (DuPont) AEM (A-201)

C

A-201, Tokuyama

C

A-600, Tokuyama

Pd–Ru

PtRu black

Cathode Pt/C Au/Ni–Cr foam Acta Hypermect, K14 Pt/C Fe–Co Hypermect, K14 Fe–Co Hypermect, K14

NaBH4 reduction

C

A-201, Tokuyama

Acta Hypermect, K14 Acta Hypermect

Impregnation and NaBH4 reduction Impregnation method

C

A-201, Tokuyama

MnO2

C

A-201, Tokuyama

MnO2

Commercial

PVA/TiO2

MnO2/C

Commercial

AEM (A-201)

Pt black

PVA/HAP

MnO2

Commercial

C

Operating conditions/ temperature

Power (mW cm2)

Ref.

3 M Ethanol þ 5 M NaOH/4 M H2O2 þ 1 M H2SO4; T ¼ 60 1C 3 M Ethanol þ 5 M NaOH/4 M H2O2 þ 1 M H2SO4; T ¼ 60 1C 3 M Ethanol þ 5 M KOH/4 M H2O2; T ¼ 80 1C 2 M Ethanol þ 6 M NaOH; T ¼ 100 1C JO2 ¼ 100 sccm; 1 M Ethanol þ 1 M KOH/O2 JO2 ¼ 100 sccm; 3 M Ethanol þ 5 M KOH/O2; T ¼ 80 1C

240

30

200

32

160

33

19.8

185 193

130

Ethanol þ KOH/O2; T ¼ 60 1C JO2 ¼ 100 sccm; 1, 3 M Ethanol þ 1, 5 M KOH/O2; T ¼ 60 1C JO2 ¼ 300 sccm; 3 M Ethanol þ 3 M KOH; T ¼ 60, 70, 80 1C JO2 ¼ 300 sccm; 3 M Ethanol þ 3 M KOH; T ¼ 80 1C 2 M Ethanol þ 4 M KOH; T ¼ room temperature JO2 ¼ 100 sccm; 1 M Ethanol þ 0.5 M KOH/O2; T ¼ room temperature 2 M Ethanol þ 8 M KOH; T ¼ room temperature

200

298 44, 90

201

123, 151, 176

205

160

206

8.0

299

58

164

10.74

300

Published on 15 October 2018 on https://pubs.rsc.org | d

RuV

H2 reduction 430 1C

Pt black

Acta Hypermect

PBI/KOH

TMPhP/C

Commercial

Teflon

MnO2/C/Ni

Commercial

Teflon

MnO2

Commercial

KOH

MnO2

Commercial

A-201, Tokuyama

Commercial

PVA/TMAPS

Commercial

A-600, Tokuyama

Acta Hypermect, K14 Acta Hypermect, K14 Acta Hypermect, K14, Pt/C

NiCo RuNi Electrochemistry, 2019, 15, 1–57 | 45

Ni–Fe–Co HYPERMECt Au

PdNiSn PtRuW

H2 reduction at high temperature Heat treatment at 430 1C with H2 Synthesis on XC72 soot

C

C

Mg–Al CO32–LDH

FeCo/C

C

N4Co/C

C

CEM (Na1) (Nafion 117) PBI/KOH

C

PBI A-201, Tokuyama

Acetylene soot promoted by CoN4 Fe–Co Hypermect

CoN4/C

NaBH4 reduction

C

Nafions 117

Pt/C

Impregnation/reduction method Polyol impregnation

C

Nafions 117 (DuPont) Nafions 115

Pt/C

C

Pt/C

JO2 ¼ 200 cm3 min1; 2 M EtOH þ 3 M NaOH; T ¼ 80 1C 2 M Ethanol þ 3 M KOH/O2; T ¼ 25 1C 2 M Ethanol þ 3 M KOH/O2; T ¼ 45 1C 2 M Ethanol þ 3 M KOH/O2; T ¼ 25 1C JO2 ¼ 100 sccm; 3 M Ethanol þ 7 M KOH/O2; T ¼ 40 1C JO2 ¼ 50 sccm; 3 M Ethanol þ 5 M KOH/ O2; T ¼ 60 1C JO2 ¼ 150 cm3 min1; 10 wt% Ethanol þ 10 wt% KOH/O2; T ¼ 60 1C 10 wt% Ethanol þ 10 wt% KOH/ air; T ¼ 80 1C 2 M Ethanol þ 6 M NaOH/O2; T ¼ 60 1C 4 M Ethanol þ 8 M KOH/O2; T ¼ 60 1C 4 M Ethanol þ 8 M KOH; T ¼ 60 1C JO2 ¼ 100 sccm; 1 M Ethanol þ 1 M KOH; T ¼ 40 1C JO2 ¼ 150 cm3 min1; 2 M (1 M) Ethanol þ 2 M (1M) KOH; T ¼ 75 1C (room temperature) 2 M Ethanol þ 6 M NaOH; T ¼ 100 1C JO2 ¼ 120 cm3 min1; 1 M Ethanol; T ¼ 90 1C

100

301 36

55

35 34

60

302

50

303

80, 72

304

65

248

B40

250

B55

247

60

17 305

1.6 (PtAu 70 : 30)

172

27.1

185

38.54

158

Published on 15 October 2018 on https://pubs.rsc.org | d

46 | Electrochemistry, 2019, 15, 1–57

Table 1 (Continued) Anode

Synthesis

Support

Membrane (AEM)

Cathode

Pd–(Ni–Zn)

Spontaneous deposition

C

A-006, Tokuyama

Fe–Co Hypermect, K-14

PtRuMo

Polyol impregnation

C

Nafions 115

Pt/C

Pd–La(OH)3

Microwave

C

MnO2/C

Pd(DBA)2

Commercial

AEM, Qianqiu Corporation A-600, Tokuyama

Fe–Co Hypermect

Pd–CeO2

Electroless method

A-600, Tokuyama

Fe–Co/C

C

Operating conditions/ temperature

Power (mW cm2)

Ref.

Jo2 ¼ 200 cm3 min1; 10 wt% Ethanol þ 2 M KOH; T ¼ 20, 80 1C JO2 ¼ 120 cm3 min1; 1 M Ethanol; T ¼ 90 1C 6 M Ethanol þ 6 M KOH, T ¼ room temperature 5 wt% Ethanol þ 5 wt% KOH, T ¼ room temperature JO2 ¼ 200 cm3 min1; 10 wt% Ethanol þ 2 M KOH; T ¼ 25, 80 1C

58, 170

306

23.34

158 240

31

122

66, 140

66

a Legend: C ¼ carbon, CMS ¼ carbon microspheres, MWCNT ¼ multi-walled carbon nanotubes, EG ¼ ethylene glycol, TNTA ¼ titanium nanotube arrays, NP ¼ nanoparticles.

View Online

References

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

1 2

3

4 5 6 7 8 9 10 11 12 13 14

15 16 17 18 19 20 21 22 23 24 25 26

W. R. Grove, J. Franklin. Inst., 1843, 35, 277–280. A. Heinzel, M. Cappadonia, U. Stimming, K. V. Kordesch and J. C. T. de Oliveira, in Ullmann’s Encyclopedia of Industrial Chemistry, ed. Wiley-VCH Verlag GmbH & Co. KGaA, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2010. S. P. Jiang and X. Wang, in Solid State Electrochemistry II, ed. V. V. Kharton, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2011, pp. 179–264. M. A. F. Akhairi and S. K. Kamarudin, Int. J. Hydrogen Energy, 2016, 41, 4214–4228. L. An, T. S. Zhao and Y. S. Li, Renewable Sustainable Energy Rev., 2015, 50, 1462–1468. O. Z. Sharaf and M. F. Orhan, Renewable Sustainable Energy Rev., 2014, 32, 810–853. M. Z. F. Kamarudin, S. K. Kamarudin, M. S. Masdar and W. R. W. Daud, Int. J. Hydrogen Energy, 2013, 38, 9438–9453. A. Brouzgou, A. Podias and P. Tsiakaras, J. Appl. Electrochem., 2013, 43, 119– 136. E. H. Yu, X. Wang, U. Krewer, L. Li and K. Scott, Energy Environ. Sci., 2012, 5, 5668–5680. A. Rabis, P. Rodriguez and T. J. Schmidt, ACS Catal., 2012, 2, 864–890. E. Antolini and E. R. Gonzalez, J. Power Sources, 2010, 195, 3431–3450. ´ger, C. Lamy, A. Lima, V. LeRhun, F. Delime, C. Coutanceau and J.-M. Le J. Power Sources, 2002, 105, 283–296. T. D. S. Almeida and A. R. De Andrade, in New and Future Developments in Catalysis: Batteries, Hydrogen storage and Fuel Cells, Elsevier, 2013, pp. 429–452. C. Lamy, C. Coutanceau and J.-M. Leger, in Catalysis Sustainable Energy Production, ed. P. Barbaro and C. Bianchin, Wiley-VCH Verlag GmbH & Co. KGaA, 2009, pp. 3–46. M. T. Koper, S. C. Lai and E. Herrero, in Fuel Cell Catalysis, John Wiley & Sons, Inc., 2008, pp. 159–207. J. R. Varcoe and R. C. T. Slade, Fuel Cells, 2005, 5, 187–200. A. Y. Tsivadze, M. R. Tarasevich, V. N. Andreev and V. A. Bogdanovskaya, Russ. J. Gen. Chem., 2007, 77, 783–789. J. Goldemberg, Science, 2007, 315, 808–810. J. K. Nørskov, J. Rossmeisl, A. Logadottir, L. Lindqvist, J. R. Kitchin, ´nsson, J. Phys. Chem. B, 2004, 108, 17886–17892. T. Bligaard and H. Jo G. F. McLean, T. Niet, S. Prince-Richard and N. Djilali, Int. J. Hydrogen Energy, 2002, 27, 507–526. Z. Ogumi, K. Matsuoka, S. Chiba, M. Matsuoka, Y. Iriyama, T. Abe and M. Inaba, Electrochemistry, 2002, 70, 980–983. J. R. Varcoe, R. C. T. Slade and E. L. H. Yee, Chem. Commun., 2006, 1428– 1429. R. Zeng and J. R. Varcoe, Recent Pat. Chem. Eng., 2011, 4, 93–115. F. Bidault, D. J. L. Brett, P. H. Middleton and N. P. Brandon, J. Power Sources, 2009, 187, 39–48. T. S. Zhao, Y. S. Li and S. Y. Shen, Frontiers of Energy and Power Engineering in China, 2010, 4, 443–458. R. N. Singh, Madhu and R. Awasthi, in New and Future Developments in Catalysis: Batteries, Hydrogen Storage Fuel Cells, Elsevier B.V., 2013, pp. 453– 478.

Electrochemistry, 2019, 15, 1–57 | 47

View Online

27 28 29

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45

46

47 48

49 50 51 52 53 54 55 56 57

L. Rao, Y. Jiang, B. Zhang, L. You, Z. Li and S. Sun, Huaxue Jinzhan, 2014, 26, 727–736. Y. Wang, S. Zou and W.-B. Cai, Catalysts, 2015, 5, 1507–1534. S. P. S. Badwal, S. Giddey, A. Kulkarni, J. Goel and S. Basu, Appl. Energy, 2015, 145, 80–103. L. An, T. S. Zhao, R. Chen and Q. X. Wu, J. Power Sources, 2011, 196, 6219– 6222. E. Agel, J. Bouet and J. F. Fauvarque, J. Power Sources, 2001, 101, 267–274. L. An, T. S. Zhao and J. B. Xu, Int. J. Hydrogn Energy, 2011, 36, 13089–13095. L. An, T. S. Zhao, L. Zeng and X. H. Yan, Int. J. Hydrogen Energy, 2014, 39, 2320–2324. A. Verma and S. Basu, J. Power Sources, 2007, 174, 180–185. D. Gaurava, A. Verma, D. K. Sharma and S. Basu, Fuel Cells, 2010, 10, 591– 596. A. Verma and S. Basu, J. Power Sources, 2005, 145, 282–285. A. Verma, A. K. Jha and S. Basu, J. Fuel Cell Sci. Technol., 2005, 2, 234. K. T. Lee, C. M. Gore and E. D. Wachsman, J. Mater. Chem., 2012, 22, 22405– 22408. M. Cimenti and M. J. Hill, Energies, 2009, 2, 377–410. B. R. Cuenya, Thin Solid Films, 2010, 518, 3127–3150. Z. Yin, L. Lin and D. Ma, Catal. Sci. Technol., 2014, 4, 4116–4128. M. Bron and C. Roth, in New and Future Developments in Catalysis, Elsevier, Amsterdam, 2013, pp. 271–305. A. S. Bandarenka and M. T. M. Koper, J. Catal., 2013, 308, 11–24. F. Calle-Vallejo, M. T. M. Koper and A. S. Bandarenka, Chem. Soc. Rev., 2013, 42, 5210–5230. A. S. Bandarenka, A. S. Varela, M. Karamad, F. Calle-Vallejo, L. Bech, F. J. Perez-Alonso, J. Rossmeisl, I. E. L. Stephens and I. Chorkendorff, Angew. Chem., Int. Ed., 2012, 51, 11845–11848. F. Calle-Vallejo, J. Tymoczko, V. Colic, Q. H. Vu, M. D. Pohl, K. Morgenstern, D. Loffreda, P. Sautet, W. Schuhmann and A. S. Bandarenka, Science, 2015, 350, 185–189. Y. Yu, Q. Zhang, B. Liu and J. Y. Lee, J. Am. Chem. Soc., 2010, 132, 18258– 18265. ´n-Blas, C. L. Mene ´ndez, C. A. Ve ´lez, E. R. Fachini, R. Guzma A. Johnston-Peck, S. D. Senanayake, D. Stacchiola, K. Sasaki and C. R. Cabrera, Smart Grid Renewable Energy, 2013, 4, 1–9. H.-F. Wang, H. Ariga, R. Dowler, M. Sterrer and H.-J. Freund, J. Catal., 2012, 286, 1–5. J. Speder, L. Altmann, M. Roefzaad, M. Baumer, J. Kirkensgaard, K. Mortensen and M. Arenz, Phys. Chem. Chem. Phys., 2013, 15, 3602–3608. ´n, F. J. Vidal-Iglesias, M. Nisula, J. M. Feliu M. C. Figueiredo, J. Solla-Gullo and T. Kallio, Electrochem. Commun., 2015, 55, 47–50. R. A. Martinez-Rodriguez, F. J. Vidal-Iglesias, J. Solla-Gullon, C. R. Cabrera and J. M. Feliu, ChemPhysChem, 2014, 15, 1997–2001. Z. Liu, J. Y. Lee, M. Han, W. Chen and L. M. Gan, J. Mater. Chem., 2002, 12, 2453–2458. H. B. Suffredini, G. R. Salazar-Banda and L. A. Avaca, J. Power Sources, 2007, 171, 355–362. Z. Zhang, J. Liu, J. Gu, L. Su and L. Cheng, Energy Environ. Sci., 2014, 7, 2535. B. E. Hayden, Acc. Chem. Res., 2013, 46, 1858–1866. E. H. Yu, X. Wang, X. T. Liu and L. Li, RSC Energy Environ. Ser., 2012, 6, 227– 249.

48 | Electrochemistry, 2019, 15, 1–57

View Online

58 59 60

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

61 62 63 64 65 66

67 68 69 70 71 72 73 74 75 76 77 78 79 80

81 82 83 84 85 86 87 88

A. L. Dicks, J. Power Sources, 2006, 156, 128–141. E. Antolini, Appl. Catal., B, 2009, 88, 1–24. V. Bambagioni, C. Bianchini, A. Marchionni, J. Filippi, F. Vizza, J. Teddy, P. Serp and M. Zhiani, J. Power Sources, 2009, 190, 241–251. R. N. Singh and R. Awasthi, Catal. Sci. Technol., 2011, 1, 778. E. A. Monyoncho, S. Ntais, N. Brazeau, J.-J. Wu, C.-L. Sun and E. A. Baranova, ChemElectroChem, 2016, 3, 218–227. Y. Katayama, T. Okanishi, H. Muroyama, T. Matsui and K. Eguchi, ACS Catal., 2016, 6, 2026–2034. D. R. M. Godoi, H. M. Villullas, F.-C. Zhu, Y.-X. Jiang, S.-G. Sun, J. Guo, L. Sun and R. Chen, J. Power Sources, 2016, 311, 81–90. R. Maache, R. Brahmi, L. Pirault-Roy, S. Ojala and M. Bensitel, Top. Catal., 2013, 56, 658–661. V. Bambagioni, C. Bianchini, Y. Chen, J. Filippi, P. Fornasiero, M. Innocenti, A. Lavacchi, A. Marchionni, W. Oberhauser and F. Vizza, ChemSusChem, 2012, 5, 1266–1273. Y.-C. Wei, C.-W. Liu, W.-D. Kang, C.-M. Lai, L.-D. Tsai and K.-W. Wang, J. Electroanal. Chem., 2011, 660, 64–70. S. Uhm, Y. Yi and J. Lee, Catal. Lett., 2010, 138, 46–49. A. O. Neto, M. Linardi, D. M. dos Anjos, G. Tremiliosi-Filho and ´, J. Appl. Electrochem., 2009, 39, 1153–1156. E. V. Spinace C. Xu, Z. Tian, P. Shen and S. P. Jiang, Electrochim. Acta, 2008, 53, 2610– 2618. P. K. Shen and C. Xu, Electrochem. Commun., 2006, 8, 184–188. C. Xu, R. Zeng, P. K. Shen and Z. Wei, Electrochim. Acta, 2005, 51, 1031–1035. C. Xu and P. K. Shen, J. Power Sources, 2005, 142, 27–29. U. Martinez, A. Serov, M. Padilla and P. Atanassov, ChemSusChem, 2014, 7, 2351–2357. H. Mao, L. Wang, P. Zhu, Q. Xu and Q. Li, Int. J. Hydrogen Energy, 2014, 39, 17583–17588. P. A. Russo, M. Ahn, N. Pinna and Y.-E. Sung, RSC Adv., 2013, 3, 7001–7008. H. An, L. Pan, H. Cui, B. Li, D. Zhou, J. Zhai and Q. Li, Electrochim. Acta, 2013, 102, 79–87. R. B. Moghaddam and P. G. Pickup, Electrochim. Acta, 2012, 65, 210–215. T. Takeguchi, Y. Anzai, R. Kikuchi, K. Eguchi and W. Ueda, J. Electrochem. Soc., 2007, 154, 1132. L. Jiang, L. Colmenares, Z. Jusys, G. Q. Sun and R. J. Behm, ELECTROCATALYSIS THEORY Ind. Appl. Sel. Pap. 5th Int. Conf. ECS06 10–14 Sept. 2006 Kotor MontenegroELECTROCHEMICAL MICRO Nanosyst. Technol. Sel. Pap. 6th Int. Symp. EMNT 2006 22–25 August 2006 Bonn Ger., 2007, 53, 377–389. T. Okanishi, T. Matsui, T. Takeguchi, R. Kikuchi and K. Eguchi, Appl. Catal., A, 2006, 298, 181–187. M. Batzill and U. Diebold, Prog. Surf. Sci., 2005, 79, 47–154. ´, A. O. Neto and J. C. M. Silva, G. S. Buzzo, R. F. B. De Souza, E. V. Spinace ˜o, Electrocatalysis, 2015, 6, 86–91. M. H. M. T. Assumpça ´, A. O. Neto and R. F. B. De Souza, G. S. Buzzo, J. C. M. Silva, E. V. Spinace ˜o, Electrocatalysis, 2014, 5, 213–219. M. H. M. T. Assumpça S. T. Nguyen, Y. Yang and X. Wang, Appl. Catal., B, 2012, 113–114, 261–270. F. Hu, F. Ding, S. Song and P. K. Shen, J. Power Sources, 2006, 163, 415–419. Q. Liu, K. Jiang, J. Fan, Y. Lin, Y. Min, Q. Xu and W.-B. Cai, Electrochim. Acta, 2016, 203, 91–98. A. Lewera, L. Timperman, A. Roguska and N. Alonso-Vante, J. Phys. Chem. C, 2011, 115, 20153–20159. Electrochemistry, 2019, 15, 1–57 | 49

View Online

89 90 91

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116

117

E. J. Lim, H. J. Kim and W. B. Kim, Catal. Commun., 2012, 25, 74–77. Y. Bai, J. Wu, J. Xi, J. Wang, W. Zhu, L. Chen and X. Qiu, Electrochem. Commun., 2005, 7, 1087–1090. H. Chen, Y. Huang, D. Tang, T. Zhang and Y. Wang, Electrochim. Acta, 2015, 158, 18–23. N. Li, Y.-X. Zeng, S. Chen, C.-W. Xu and P.-K. Shen, Int. J. Hydrogen Energy, 2014, 39, 16015–16019. C. Xu, P. K. Shen, X. Ji, R. Zeng and Y. Liu, Electrochem. Commun., 2005, 7, 1305–1308. R. M. Modibedi, E. K. Louw, M. K. Mathe and K. I. Ozoemena, ECS Trans., 2013, 50, 9–18, 10. C. Xu, P. Kang Shen and Y. Liu, J. Power Sources, 2007, 164, 527–531. F. Hu, C. Chen, Z. Wang, G. Wei and P. K. Shen, Electrochim. Acta, 2006, 52, 1087–1091. S. Tauster, J. Catal., 1978, 55, 29–35. S. J. Tauster, S. C. Fung and R. L. Garten, J. Am. Chem. Soc., 1978, 100, 170–175. M. Sanchez, J. Catal., 1987, 104, 120–135. Y. Katayama, T. Okanishi, H. Muroyama, T. Matsui and K. Eguchi, ACS Catal., 2016, 6, 2026–2034. ´n-Ais, V. Climent, T. Kallio and J. M. Feliu, M. C. Figueiredo, R. M. Ara ChemElectroChem, 2015, 2, 1254–1258. ¨ ztu ¨rk, V. C. van Rees Vellinga, J. Koning, S. C. S. Lai, S. E. F. Kleijn, F. T. Z. O P. Rodriguez and M. T. M. Koper, Catal. Today, 2010, 154, 92–104. ¨bke, C. Cremers, D. Bayer, B. Kintzel, M. Joos, F. Jung, M. Krausa and J. Tu ECS Trans., 2008, 16, 1263–1273. V. Rao, Hariyanto, C. Cremers and U. Stimming, Fuel Cells, 2007, 7, 417– 423. H. Takahashi, M. Sagihara and M. Taguchi, Int. J. Hydrogen Energy, 2014, 39, 18424–18432. ¨bke, ECS Trans., 2010, 95–103. D. Bayer, S. Berenger, C. Cremers and J. Tu ¨bke, Int. J. Hydrogen D. Bayer, S. Berenger, M. Joos, C. Cremers and J. Tu Energy, 2010, 35, 12660–12667. ´-Rogero, E. Herrero and J. M. Feliu, ChemPhysChem, 2014, 15, 2019– C. Buso 2028. S. C. S. Lai and M. T. M. Koper, Phys. Chem. Chem. Phys., 2009, 11, 10446– 10456. A. V. Tripkovic´, K. D. Popovic´ and J. D. Lovic´, Electrochim. Acta, 2001, 46, 3163–3173. ´-Rogero, J. Solla-Gullo ´n, F. J. Vidal-Iglesias, E. Herrero and C. Buso J. M. Feliu, J. Solid State Electrochem., 2016, 20, 1095–1106. C.-L. Sun, J.-S. Tang, N. Brazeau, J.-J. Wu, S. Ntais, C.-W. Yin, H.-L. Chou and E. A. Baranova, Electrochim. Acta, 2015, 162, 282–289. A. Kumar and D. A. Buttry, Electrocatalysis, 2016, 7, 201–206. R. M. Modibedi, T. Mehlo, K. I. Ozoemena and M. K. Mathe, Int. J. Hydrogen Energy, 2015, 40, 15605–15612. ˜ iz, R. Carrera-Cerritos, R. Fuentes-Ramı´rez, F. M. Cuevas-Mun J. Ledesma-Garcı´a and L. G. Arriaga, J. Power Sources, 2014, 269, 370–378. L. Wang, M. Bevilacqua, Y.-X. Chen, J. Filippi, M. Innocenti, A. Lavacchi, A. Marchionni, H. Miller and F. Vizza, J. Power Sources, 2013, 242, 872–876. ¨cken, S. Ntais, E. A. Baranova L. Assaud, N. Brazeau, M. K. S. Barr, M. Hanbu and L. Santinacci, ACS Appl. Mater. Interfaces, 2015, 7, 24533–24542.

50 | Electrochemistry, 2019, 15, 1–57

View Online

118 119

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

120 121 122 123 124

125 126 127 128 129 130 131 132 133

134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150

M. B. Rohwer, R. M. Modibedi and K. I. Ozoemena, Electroanalysis, 2015, 27, 957–963. ´zar, R. F. Ramı´rez, J. Ledesma-Garcı´a and R. C. Cerritos, M. Guerra-Balca L. G. Arriaga, Materials, 2012, 5, 1686–1697. S. Cherevko, N. Kulyk and C.-H. Chung, Nanoscale, 2012, 4, 103–105. A. Safavi, A. Abbaspour, M. Sorouri and A. Mohammadi, ChemElectroChem, 2016, 3, 558–564. M. Zhiani, S. Majidi, H. Rostami and M. M. Taghiabadi, Int. J. Hydrogen Energy, 2015, 40, 568–576. Y. Chen, M. Bellini, M. Bevilacqua, P. Fornasiero, A. Lavacchi, H. A. Miller, L. Wang and F. Vizza, ChemSusChem, 2015, 8, 524–533. A. Serov, N. I. Andersen, S. A. Kabir, A. Roy, T. Asset, M. Chatenet, F. Maillard and P. Atanassov, J. Electrochem. Soc., 2015, 162, F1305– F1309. Y. Li, Q. Xu, Q.-Y. Li, H. Wang, Y. Huang and C. Xu, Electrochim. Acta, 2014, 147, 151–156. D. Chu, J. Wang, S. Wang, L. Zha, J. He, Y. Hou, Y. Yan, H. Lin and Z. Tian, Catal. Commun., 2009, 10, 955–958. L. Ma, D. Chu and R. Chen, Int. J. Hydrogen Energy, 2012, 37, 11185–11194. S. Cherevko, X. Xing and C.-H. Chung, Electrochim. Acta, 2011, 56, 5771– 5775. ¨bke, ECS Trans., 2011, 41, D. Bayer, C. Cremers, H. Baltruschat and J. Tu 1669–1680. C. Xu, L. Cheng, P. Shen and Y. Liu, Electrochem. Commun., 2007, 9, 997–1001. D. A. Cantane and F. H. B. Lima, Electrocatalysis, 2012, 3, 324–333. A. Chen and C. Ostrom, Chem. Rev., 2015, 115, 11999–12044. X. Teng, Anodic Catalyst Design for the Ethanol Oxidation Fuel Cell, in Materials and Processes for Energy: Communicating Current Research and Technological Developments, ed. A. Mendez-Vilas, Formatex Research Center, 2013, pp. 473–484. F. Liao, T. W. B. Lo and S. C. E. Tsang, ChemCatChem, 2015, 7, 1998–2014. ¨ller and Y. Lin, Chem. Rev. 2015, 115, 8896–8943. C. Zhu, D. Du, A. Eychmu ´ger, L. Dubau, S. Rousseau and C. Coutanceau, S. Brimaud, C. Lamy, J.-M. Le F. Vigier, Electrochim. Acta, 2008, 53, 6865–6880. E. Antolini, J. Power Sources, 2007, 170, 1–12. M. Weber, A. Mackus, M. Verheijen, C. van der Marel and W. Kessels, Chem. Mater. 2012, 24, 2973–2977. J. Park and S. Hong, Chem. Soc. Rev., 2012, 41, 6931–6943. J. Gu, Y.-W. Zhang and F. Tao, Chem. Soc. Rev., 2012, 41, 8050–8065. M. Sankar, N. Dimitratos, P. Miedziak, P. Wells, C. Kiely and G. Hutchings, Chem. Soc. Rev., 2012, 41, 8099–8139. H. Zhang, M. Jin and Y. Xia, Chem. Soc. Rev., 2012, 41, 8035–8049. X. Chen, Z. Cai, X. Chen and M. Oyama, J. Mater. Chem. A, 2014, 2, 315–320. C. Zhu, S. Guo and S. Dong, Chem. – Eur. J., 2013, 19, 1104–1111. P. A. Christensen, S. W. M. Jones and A. Hamnett, Phys. Chem. Chem. Phys., 2013, 15, 17268. X. Yang, Q. Yang, J. Xu and C.-S. Lee, J. Mater. Chem., 2012, 22, 8057. J. Datta, A. Dutta and M. Biswas, Electrochem. Commun., 2012, 20, 56–59. C. Zhu, S. Guo and S. Dong, Adv. Mater., 2012, 24, 2326–2331. S.-C. Lin, J.-Y. Chen, Y.-F. Hsieh and P.-W. Wu, Mater. Lett., 2011, 65, 215– 218. H. T. Zheng, S. Chen and P. K. Shen, Electrochem. Commun., 2007, 9, 1563– 1566. Electrochemistry, 2019, 15, 1–57 | 51

View Online

151 152

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

153

154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169

170 171 172

173 174

175 176 177

K. Artyushkova, B. Halevi, M. Padilla, P. Atanassov and E. A. Baranova, J. Electrochem. Soc., 2015, 162, H345–H351. W. Du, G. Yang, E. Wong, N. A. Deskins, A. I. Frenkel, D. Su and X. Teng, J. Am. Chem. Soc., 2014, 136, 10862–10865. ˜o, J. Nandenha, G. S. Buzzo, J. C. M. Silva, M. H. M. T. Assumpça ´, A. O. Neto and R. F. B. De Souza, J. Power Sources, 2014, 253, E. V. Spinace 392–396. E. A. Baranova, M. A. Padilla, B. Halevi, T. Amir, K. Artyushkova and P. Atanassov, Electrochim. Acta, 2012, 80, 377–382. I. Kim, O. H. Han, S. A. Chae, Y. Paik, S.-H. Kwon, K.-S. Lee, Y.-E. Sung and H. Kim, Angew. Chem., Int. Ed., 2011, 50, 2270–2274. W. J. Zhou, S. Q. Song, W. Z. Li, Z. H. Zhou, G. Q. Sun, Q. Xin, S. Douvartzides and P. Tsiakaras, J. Power Sources, 2005, 140, 50–58. ´ger, ElecC. Lamy, S. Rousseau, E. M. Belgsir, C. Coutanceau and J.-M. Le trochim. Acta, 2004, 49, 3901–3908. W. Zhou, Appl. Catal., B, 2003, 46, 273–285. B. Gralec, A. Lewera and P. J. Kulesza, J. Power Sources, 2016, 315, 56–62. L. Huang, E. G. Sorte, S.-G. Sun and Y. Y. J. Tong, Chem. Commun., 2015, 51, 8086–8088. A. Hajian, A. A. Rafati, O. Yurchenko, G. Urban, A. Afraz, M. Najafi and A. Bagheri, J. Electrochem. Soc., 2014, 162, B41–B46. O. A. Petrii, J. Solid State Electrochem., 2008, 12, 609–642. A. Ghumman, C. Vink, O. Yepez and P. G. Pickup, J. Power Sources, 2008, 177, 71–76. N. Fujiwara, Z. Siroma, S. Yamazaki, T. Ioroi, H. Senoh and K. Yasuda, J. Power Sources, 2008, 185, 621–626. L. Li, X.-X. Yuan, X.-Y. Xia, J. Du, M. Z. Ma and F. Zi, J. Inorg. Mater., 2014, 29, 1044–1048. ´n-Ais, J. M. Feliu, K. Kontturi and T. Kallio, M. C. Figueiredo, R. M. Ara J. Catal., 2014, 312, 78–86. F. Matsumoto, Electrochemistry, 2012, 80, 132–138. ´ and A. O. Neto, M. M. Tusi, N. S. O. Polanco, S. G. da Silva, E. V. Spinace Electrochem. Commun., 2011, 13, 143–146. S. Mourdikoudis, M. Chirea, D. Zanaga, T. Altantzis, M. Mitrakas, S. Bals, ´n, J. Pe ´rez-Juste and I. Pastoriza-Santos, Nanoscale, 2015, 7, L. M. Liz-Marza 8739–8747. A. Dutta, A. Mondal and J. Datta, J. Power Sources, 2015, 283, 104–114. W. Zhou, M. Li, L. Zhang and S. H. Chan, Electrochim. Acta, 2014, 123, 233– 239. ´, S. G. da Silva, J. C. M. Silva, G. S. Buzzo, R. F. B. De Souza, E. V. Spinace ˜o, Int. J. Hydrogen Energy, 2014, 39, A. O. Neto and M. H. M. T. Assumpça 10121–10127. H. M. Song, D. H. Anjum, R. Sougrat, M. N. Hedhili and N. M. Khashab, J. Mater. Chem., 2012, 22, 25003. T. Gunji, T. Tanabe, A. J. Jeevagan, S. Usui, T. Tsuda, S. Kaneko, G. Saravanan, H. Abe and F. Matsumoto, J. Power Sources, 2015, 273, 990– 998. W.-H. Yang, H.-H. Wang, D.-H. Chen, Z.-Y. Zhou and S.-G. Sun, Phys. Chem. Chem. Phys., 2012, 14, 16424. ´, P. Krtil, D. Ramaker and S. Mukerjee, J. Am. Q. He, B. Shyam, K. Macounova Chem. Soc., 2012, 134, 8655–8661. A. A. El-Shafei, S. A. A. El-Maksoud and M. N. H. Moussa, J. Electroanal. Chem., 1992, 336, 73–83.

52 | Electrochemistry, 2019, 15, 1–57

View Online

178

179

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

180 181

182 183 184

185

186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210

´n-Ca ´rdenas, J. E. Ortiz-Restrepo, N. D. Mancilla-Valencia, A. Caldero ˜os-Rivera, E. R. Gonzalez G. A. Torres-Rodriguez, F. H. B. Lima, A. Bolan and W. H. Lizcano-Valbuena, J. Braz. Chem. Soc. 2014, 25, 1391–1398. S. Y. Shen, T. S. Zhao and J. B. Xu, Int. J. Hydrogen Energy, 2010, 35, 12911– 12917. W. Hong, J. Wang and E. Wang, Nano Res., 2015, 8, 2308–2316. V. Kepeniene, L. Tama auskaite-Tama i naite, J. Jablonskiene, J. Vai i niene, R. Kondrotas, R. Ju kenas and E. Norkus, J. Electrochem. Soc., 2014, 161, F1354–F1359. C. Jin, X. Ma, J. Zhang, Q. Huo and R. Dong, Electrochim. Acta, 2014, 146, 533–537. K. Matsuoka, Y. Iriyama, T. Abe, M. Matsuoka and Z. Ogumi, J. Power Sources, 2005, 150, 27–31. ˇ . Lacˇnjevac, V. V. Radmilovic´, ˇic ´, U. C M. D. Obradovic´, Z. M. Stanc A. Gavrilovic´-Wohlmuther, V. R. Radmilovic´ and S. L. Gojkovic´, Appl. Catal., B, 2016, 189, 110–118. L. P. R. Moraes, B. R. Matos, C. Radtke, E. I. Santiago, F. C. Fonseca, S. C. Amico and C. F. Malfatti, Int. J. Hydrogen Energy, 2016, 41, 6457– 6468. Y. Wang, K. Jiang and W.-B. Cai, Electrochim. Acta, 2015, 162, 100–107. W. Chen, Y. Zhang and X. Wei, Int. J. Hydrogen Energy, 2015, 40, 1154–1162. A. M. Sheikh, E. L. Silva, L. Moares, L. M. Antonini, M. Y. Abellah and C. F. Malfatti, Am. J. Min. Metall., 2014, 2, 64–69. R. Jiang, D. T. Tran, J. P. McClure and D. Chu, ACS Catal., 2014, 4, 2577–2586. A. Dutta and J. Datta, J. Mater. Chem. A, 2014, 2, 3237–3250. M. S. Ahmed and S. Jeon, ACS Catal., 2014, 4, 1830–1837. Y. Wang, F.-F. Shi, Y.-Y. Yang and W.-B. Cai, J. Power Sources, 2013, 243, 369–373. S. Y. Shen, T. S. Zhao and Q. X. Wu, Int. J. Hydrogen Energy, 2012, 37, 575– 582. P. S. Roy, J. Bagchi and S. K. Bhattacharya, Catal. Sci. Technol., 2012, 2, 2302. F. Miao, B. Tao and P. K. Chu, Dalton Trans., 2012, 41, 5055. K. Lee, S. W. Kang, S.-U. Lee, K.-H. Park, Y. W. Lee and S. W. Han, ACS Appl. Mater. Interfaces, 2012, 4, 4208–4214. Z. Zhang, L. Xin, K. Sun and W. Li, Int. J. Hydrogen Energy, 2011, 36, 12686– 12697. Z. Qi, H. Geng, X. Wang, C. Zhao, H. Ji, C. Zhang, J. Xu and Z. Zhang, J. Power Sources, 2011, 196, 5823–5828. F. Miao and B. Tao, Electrochim. Acta, 2011, 56, 6709–6714. Y. S. Li and T. S. Zhao, Int. J. Hydrogen Energy, 2011, 36, 7707–7713. S. Y. Shen, T. S. Zhao, J. B. Xu and Y. S. Li, J. Power Sources, 2010, 195, 1001–1006. T. Maiyalagan and K. Scott, J. Power Sources, 2010, 195, 5246–5251. R. N. Singh, A. Singh and Anindita, Carbon, 2009, 47, 271–278. E. A. Monyoncho, S. Ntais, F. Soares, T. K. Woo and E. A. Baranova, J. Power Sources, 2015, 287, 139–149. L. Ma, H. He, A. Hsu and R. Chen, J. Power Sources, 2013, 241, 696–702. L. Ma, A. Hsu and R. Chen, ECS Trans., 2013, 58, 1321–1326. A. Anindita, Open Catal. J., 2011, 4, 88–99. Y. Chen, L. Zhuang and J. Lu, Chin. J. Catal., 2007, 28, 870–874. J. Bagchi and S. K. Bhattacharya, Transition Met. Chem., 2007, 32, 47–55. K. Cai, Y. Liao, H. Zhang, J. Liu, Z. Lu, Z. Huang, S. Chen and H. Han, ACS Appl. Mater. Interfaces, 2016, 8, 12792–12797. Electrochemistry, 2019, 15, 1–57 | 53

View Online

211 212 213

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

214 215 216 217

218 219 220 221

222 223 224 225 226

227 228 229 230 231 232 233 234 235 236 237

238

W. Hong, C. Shang, J. Wang and E. Wang, Electrochem. Commun., 2014, 48, 65–68. M. Smiljanic´, Z. Rakocˇevic´ and S. B. Strbac, Int. J. Electrochem. Sci., 2013, 8, 4941–4954. J. B. Xu, T. S. Zhao, S. Y. Shen and Y. S. Li, Int. J. Hydrogen Energy, 2010, 35, 6490–6500. F. Cheng, X. Dai, H. Wang, S. P. Jiang, M. Zhang and C. Xu, Electrochim. Acta, 2010, 55, 2295–2298. L. D. Zhu, T. S. Zhao, J. B. Xu and Z. X. Liang, J. Power Sources, 2009, 187, 80–84. Q. He, W. Chen, S. Mukerjee, S. Chen and F. Laufek, J. Power Sources, 2009, 187, 298–304. A. O. Neto, S. G. da Silva, G. S. Buzzo, R. F. B. de Souza, ˜o, E. V. Spinace ´ and J. C. M. Silva, Ionics, 2015, 21, M. H. M. T. Assumpça 487–495. S. Y. Shen, T. S. Zhao and J. B. Xu, Electrochim. Acta, 2010, 55, 9179–9184. P. Wang, X. Lin, B. Yang, J.-M. Jin, C. Hardacre, N.-F. Yu, S.-G. Sun and W.-F. Lin, Electrochim. Acta, 2015, 162, 290–299. J. Cai, Y. Huang and Y. Guo, Electrochim. Acta, 2013, 99, 22–29. A. O. Neto, M. M. Tusi, N. S. de Oliveira, Polanco, S. G. da Silva, M. Coelho, ´, Int. J. Hydrogen Energy, 2011, 36, dos Santos and E. V. Spinace 10522–10526. W. Du, K. E. Mackenzie, D. F. Milano, N. A. Deskins, D. Su and X. Teng, ACS Catal., 2012, 2, 287–297. Z. Yan, M. Zhang, J. Xie and P. K. Shen, J. Power Sources, 2013, 243, 336–342. Q. Liu, M. Liu, Q. Li and Q. Xu, Catalysts, 2015, 5, 1068–1078. J. Yang, Y. Xie, R. Wang, B. Jiang, C. Tian, G. Mu, J. Yin, B. Wang and H. Fu, ACS Appl. Mater. Interfaces, 2013, 5, 6571–6579. A. Serov, T. Asset, M. Padilla, I. Matanovic, U. Martinez, A. Roy, K. Artyushkova, M. Chatenet, F. Maillard, D. Bayer, C. Cremers and P. Atanassov, Appl. Catal., B, 2016, 191, 76–85. H. Mao, T. Huang and A. Yu, Electrochim. Acta, 2015, 174, 1–7. H. Liu, R. R. Adzic and S. S. Wong, ACS Appl. Mater. Interfaces, 2015, 7, 26145–26157. X. Zhao, J. Zhang, L. Wang, Z. Liu and W. Chen, J. Mater. Chem. A, 2014, 2, 20933–20938. J. Cai, Y. Zeng and Y. Guo, J. Power Sources, 2014, 270, 257–261. K.-W. Wang, W.-D. Kang, Y.-C. Wei, C.-W. Liu, P.-C. Su, H.-S. Chen and S.-R. Chung, ChemCatChem, 2012, 4, 1154–1161. W.-D. Kang, Y.-C. Wei, C.-W. Liu and K.-W. Wang, Electrochem. Commun., 2011, 13, 162–165. A.-L. Wang, X.-J. He, X.-F. Lu, H. Xu, Y.-X. Tong and G.-R. Li, Angew. Chem., Int. Ed., 2015, 54, 3669–3673. M. del, C. Aguirre, A. S. Fuentes and A. F. Filippin, Procedia Mater. Sci., 2015, 9, 3–12. J. Liu, J. Ye, C. Xu, S. P. Jiang and Y. Tong, Electrochem. Commun., 2007, 9, 2334–2339. ´, Z. Rakocˇevic´ and S. ˇ A. Maksic´, M. Smiljanic´, ˇ S. Miljanic Strbac, Electrochim. Acta, 2016, 209, 323–331. B. T. Sneed, C. N. Brodsky, C.-H. Kuo, L. K. Lamontagne, Y. Jiang, Y. Wang, F. (Feng) Tao, W. Huang and C.-K. Tsung, J. Am. Chem. Soc., 2013, 135, 14691–14700. J. Cai, Y. Huang and Y. Guo, Int. J. Hydrogen Energy, 2014, 39, 18256–18263.

54 | Electrochemistry, 2019, 15, 1–57

View Online

239 240 241 242

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

243 244 245 246 247 248 249

250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270

J. Cai, Y. Huang and Y. Guo, Appl. Catal., B, 2014, 150–151, 230–237. H. Yu, D. Zhou and H. Zhu, J. Solid State Electrochem., 2014, 18, 125–131. Y. Wang, T. S. Nguyen, X. Liu and X. Wang, J. Power Sources, 2010, 195, 2619–2622. ¨cken, S. Ntais, L. Santinacci M. K. S. Barr, L. Assaud, N. Brazeau, M. Hanbu and E. A. Baranova, J. Phys. Chem. C, 2017, 121, 17727–17736. J. Zhan, M. Cai, C. Zhang and C. Wang, Electrochim. Acta, 2015, 154, 70– 76. L. Ren, K. S. Hui and K. N. Hui, J. Mater. Chem. A, 2013, 1, 5689–5694. H. B. Hassan and Z. A. Hamid, Int. J. Hydrogen Energy, 2011, 36, 5117–5127. Y. Yi, S. Uhm and J. Lee, Electrocatalysis, 2010, 1, 104–107. M. R. Tarasevich, V. A. Bogdanovskaya and P. V. Mazin, Russ. J. Electrochem., 2010, 46, 542–551. A. Hayashi, M. Tatsumisago, K. Tadanaga and Y. Furukawa, Adv. Mater., 2010, 22, 4401–4404. W. S. Cardoso, V. L. N. Dias, W. M. Costa, I. Araujo Rodrigues, E. P. Marques, A. G. Sousa, J. Boaventura, C. W. B. Bezerra, C. Song, H. Liu, J. Zhang and A. L. B. Marques, J. Appl. Electrochem., 2009, 39, 55–64. A. Y. Tsivadze, M. R. Tarasevich, B. N. Efremov, N. A. Kapustina and P. V. Mazin, Dokl. Phys. Chem., 2007, 415, 234–236. J.-W. Kim and S.-M. Park, J. Electrochem. Soc., 2003, 150, E560–E566. I. G. Casella, T. R. I. Cataldi, A. M. Salvi and E. Desimoni, Anal. Chem., 1993, 65, 3143–3150. Z. Jin, Q. Wang, W. Zheng and X. Cui, ACS Appl. Mater. Interfaces, 2016, 8, 5273–5279. A. Leelavathi, G. Madras and N. Ravishankar, J. Am. Chem. Soc., 2014, 136, 14445–14455. M. T. M. Koper, Y. Kwon and P. Rodriguez, Nat. Chem., 2012, 4, 177–182. R. B. de Lima and H. Varela, Gold Bull., 2008, 41, 15–22. G. Tremiliosi-Filho, E. R. Gonzalez, A. J. Motheo, E. M. Belgsir, J.-M. Leger and C. Lamy, J. Electroanal. Chem., 1998, 444, 31–39. M. Avramov-Ivic, V. Jovanovic, G. Vlajnic and J. Popic, J. Electroanal. Chem., 1997, 423, 119–124. F. Zhang, D. Zhou, Z. Zhang, M. Zhou and Q. Wang, RSC Adv., 2015, 5, 91829–91835. A. Resta, J. Blomquist, J. Gustafson, H. Karhu, A. Mikkelsen, E. Lundgren, P. Uvdal and J. N. Andersen, Surf. Sci., 2006, 600, 1136–1141. M. R. Tarasevich and O. V. Korchagin, Russ. J. Electrochem., 2013, 49, 600–618. M. T. M. Koper and S. C. S. Lai, Faraday Discuss., 2009, 140, 399–416. H. A. Asiri and A. B. Anderson, J. Electrochem. Soc., 2015, 162, F115–F122. T. Sheng, W.-F. Lin, C. Hardacre and P. Hu, J. Phys. Chem. C, 2014, 118, 5762–5772. D. D. Hibbitts and M. Neurock, J. Catal., 2013, 299, 261–271. C. Buso-Rogero, V. Grozovski, F. J. Vidal-Iglesias, J. Solla-Gullon, E. Herrero and J. M. Feliu, J. Mater. Chem., A, 2013, 1, 7068–7076. J. Melke, A. Schoekel, D. Gerteisen, D. Dixon, F. Ettingshausen, C. Cremers, C. Roth and D. E. Ramaker, J. Phys. Chem. C, 2012, 116, 2838–2849. R. Kavanagh, X.-M. Cao, W.-F. Lin, C. Hardacre and P. Hu, Angew. Chem., Int. Ed., 2012, 51, 1572–1575. P. A. Christensen, S. W. M. Jones and A. Hamnett, J. Phys. Chem. C, 2012, 116, 24681–24689. B. N. Zope, D. D. Hibbitts, M. Neurock and R. J. Davis, Science, 2010, 330, 74–78. Electrochemistry, 2019, 15, 1–57 | 55

View Online

271 272

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

273 274 275

276 277 278 279 280 281 282 283 284 285 286 287 288 289

290 291 292 293 294 295 296 297 298 299

J. Melke, A. Schoekel, D. Dixon, C. Cremers, D. E. Ramaker and C. Roth, J. Phys. Chem. C, 2010, 114, 5914–5925. ´, E. Herrero and F. Colmati, G. Tremiliosi-Filho, E. R. Gonzalez, A. Berna J. M. Feliu, Faraday Discuss., 2008, 140, 379–397, 37. Y. Paik, S.-S. Kim and O. H. Han, Electrochem. Commun., 2009, 11, 302–304. H.-F. Wang and Z.-P. Liu, J. Phys. Chem. C, 2007, 111, 12157–12160. A. N. Geraldes, D. Furtunato da Silva, J. C. Martins da Silva, ´, E. V. Spinace ´, A. O. Neto and M. Coelho dos Santos, O. Antonio de Sa J. Power Sources, 2015, 275, 189–199. Y.-Y. Yang, J. Ren, Q.-X. Li, Z.-Y. Zhou, S.-G. Sun and W.-B. Cai, ACS Catal., 2014, 4, 798–803. Z.-Y. Zhou, Q. Wang, J.-L. Lin, N. Tian and S.-G. Sun, Electrochim. Acta, 2010, 55, 7995–7999. P. A. Christensen, A. Hamnett and D. Linares-Moya, Phys. Chem. Chem. Phys., 2011, 13, 11739–11747. V. Rao, C. Cremers, U. Stimming, L. Cao, S. Sun, S. Yan, G. Sun and Q. Xin, J. Electrochem. Soc., 2007, 154, 1138. Z.-Y. Zhou and S.-G. Sun, Electrochim. Acta, 2005, 50, 5163–5171. D. Bayer, C. Cremers, H. Baltruschat and J. Tuebke, ECS Trans., 2010, 25, 85–93. X. H. Xia, H.-D. Liess and T. Iwasita, J. Electroanal. Chem., 1997, 437, 233– 240. D. J. Tarnowski and C. Korzeniewski, J. Phys. Chem. B, 1997, 101, 253–258. H.-F. Wang and Z.-P. Liu, J. Am. Chem. Soc., 2008, 130, 10996–11004. X. Fang, L. Wang, P. K. Shen, G. Cui and C. Bianchini, J. Power Sources, 2010, 195, 1375–1378. P. A. Christensen and D. Linares-Moya, J. Phys. Chem. C, 2010, 114, 1094– 1101. P. A. Christensen and S. W. M. Jones, J. Phys. Chem. C, 2014, 118, 29760– 29769. E. A. Monyoncho, S. N. Steinmann, C. Michel, E. A. Baranova, T. K. Woo and P. Sautet, ACS Catal., 2016, 6, 4894–4906. J. R. Varcoe, P. Atanassov, D. R. Dekel, A. M. Herring, M. A. Hickner, P. A. Kohl, A. R. Kucernak, W. E. Mustain, K. Nijmeijer, K. Scott, T. Xu and L. Zhuang, Energy Environ. Sci., 2014, 7, 3135–3191. R. Zeng, J. Handsel, S. D. Poynton, A. J. Roberts, R. C. T. Slade, H. Herman, D. C. Apperley and J. R. Varcoe, Energy Environ. Sci., 2011, 4, 4925–4928. A. Verma, A. K. Jha and S. Basu, J. Power Sources, 2005, 141, 30–34. H. Hou, G. Sun, R. He, Z. Wu and B. Sun, J. Power Sources, 2008, 182, 95–99. J. R. Varcoe, R. C. T. Slade, E. L. H. Yee, S. D. Poynton and D. J. Driscoll, J. Power Sources, 2007, 173, 194–199. H. Hou, S. Wang, Q. Jiang, W. Jin, L. Jiang and G. Sun, J. Power Sources, 2011, 196, 3244–3248. H. Hou, S. Wang, W. Jin, Q. Jiang, L. Sun, L. Jiang and G. Sun, Int. J. Hydrogen Energy, 2011, 36, 5104–5109. M. Unlu, D. Abbott, N. Ramaswamy, X. Ren, S. Mukerjee and P. A. Kohl, J. Electrochem. Soc., 2011, 158, B1423–B1431. L. An and T. S. Zhao, Energy Environ. Sci., 2011, 4, 2213–2217. Y. S. Li, T. S. Zhao and R. Chen, J. Power Sources, 2011, 196, 133–139. C.-C. Yang, S.-J. Chiu, K.-T. Lee, W.-C. Chien, C.-T. Lin and C.-A. Huang, J. Power Sources, 2008, 184, 44–51.

56 | Electrochemistry, 2019, 15, 1–57

View Online

300 301

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00001

302 303 304 305 306

C.-C. Yang, Y.-J. Lee, S.-J. Chiu, K.-T. Lee, W.-C. Chien, C.-T. Lin and C.-A. Huang, J. Appl. Electrochem., 2008, 38, 1329–1337. A. D. Modestov, M. R. Tarasevich, A. Y. Leykin and V. Y. Filimonov, J. Power Sources, 2009, 188, 502–506. Y. S. Li, T. S. Zhao and Z. X. Liang, J. Power Sources, 2009, 187, 387–392. E. D. Wang, T. S. Zhao and W. W. Yang, Int. J. Hydrogen Energy, 2010, 35, 2183–2189. M. Zhiani, H. A. Gasteiger, M. Piana and S. Catanorchi, Int. J. Hydrogen Energy, 2011, 36, 5110–5116. Y. S. Li, T. S. Zhao and Z. X. Liang, J. Power Sources, 2009, 190, 223–229. C. Bianchini, V. Bambagioni, J. Filippi, A. Marchionni, F. Vizza, P. Bert and A. Tampucci, Electrochem. Commun., 2009, 11, 1077–1080.

Electrochemistry, 2019, 15, 1–57 | 57

Modified electrodes for sensing Prashanth Shivappa Adarakatti*a and Suresh Kumar Kempahanumakkagari*b Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

DOI: 10.1039/9781788013895-00058

1

Introduction

The development of new electrochemical sensors is one of the continuously growing areas in electrochemistry. Electrochemical sensor systems are extensively used in our daily lives, in places such as chemical laboratories, industries and health care centers. Furthermore, the research studies of electrochemical/biochemical sensors during analysis provide information that is helpful for understanding and solving problems regarding environmental pollution, biogeochemical cycles and fundamental environmental chemical process.1 Electrochemical sensor systems are more popular compared to other instrumental techniques. This may be due to their field portable abilities, and simpler instrumentation requirements, which in turn results in less cost. The development of a good electrochemical sensor requires knowledge of fundamental electrochemistry such as mass transfer, thermodynamics and kinetics of electron transfer, and finally the most important thing, the surface properties of the electrode. The performance of electrochemical sensors also highly depends on the type of electrode materials used during the analysis. The types of unmodified electrodes used for electro analysis include carbon (C), Au, Hg and Pt. However, these electrodes are found to be sensitive to some extent but some of the consequences of these electrodes due to their inherent properties limit their use in electro analysis and other electrochemical applications. These include, fouling of the electrode surface due to adsorption/unwanted precipitation process, and slow reaction rates for particular electrochemical reaction, which requires to apply higher over potentials. The other main drawback of above mentioned conventional electrodes is their nonspecific redox behavior i.e., these electrodes serve as heterogeneous electron transfer sites. In order to meet the new challenges during the electroanalysis of complex medical and environmental matrix, it is very much necessary to improve the stability, sensitivity, and selectivity of electrochemical sensors. The best approach to date in order to achieve the above said goals during electroanalysis is electrode surface modification. Deliberate and controlled electrode surface modification results in interesting charge transfer as well as charge transport properties, enhances specific redox process, avoids electrode fouling, retardation/acceleration of electrochemical reaction rates, reduces the over a

Solid State and Structural Chemistry Unit, Indian Institute of Science, Bengaluru, India. E-mail: [email protected] b School of Basic and Applied Sciences, Dayananda Sagar University, Kumarswamy Layout, Bengaluru, India. E-mail: [email protected] 58 | Electrochemistry, 2019, 15, 58–95  c

The Royal Society of Chemistry 2019

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

potentials of the redox process and results in a better electro-optical phenomenon.2 Furthermore, the intrinsic properties of the surface modified species for specific electrochemical reaction, exhibited a significantly improved response over the unmodified electrode. The electrode surface bound species exhibits a synergetic effect along with the electrode over the catalytic effect, conductivity, biocompatibility which helped in accelerating the signal transduction electrochemical biosensors.3 In addition to this, modified species also enhance bio recognition events using specific signal tags, which results in enhanced bio sensing. The above said improved properties of surface modified electrodes makes them useful for a variety of electrochemical applications such as studying the electrochemical behavior of surface modified species, electocatalysis, electro-organic synthesis, semiconductor stabilization, photosensitization, photo electrochemical energy conversion, electrochromism along with earlier mentioned electroanalysis.2 A variety of approaches has been reported for the surface modification of electrodes. All these approaches can be broadly grouped into four types namely (i) electrostatic approach, (ii) non-specific adsorption, (iii) non covalent approach and finally covalent approach.4 Among these, covalent surface modification is found to exhibit better selectivity, and reproducibility and also completely avoids unspecific adsorption, as in the case of other approaches. The present report illustrates different methods of electrode surface modification, characterization, and applications of these modified electrodes in electroanalysis, and finally, their advantages as well as their drawbacks.

2

Types of electrodes used for the modification process

Carbon based solid electrodes are of current widespread use within electroanalysis owing to their broad potential window, low background current, low cost, chemical inertness and suitability for various sensing applications.5 Carbon is one of the most abundant nonmetallic elements and is found uniformly distributed throughout the globe.6 The uniqueness of carbon is due to its catenation property i.e. the property of an element to form bonds with similar or different kinds of atoms. Because of its catenation property, carbon mainly exists in two different allotropic forms, crystalline and amorphous carbon. The crystalline form has an ordered arrangement which includes diamond (sp3), graphite (sp2), carbine (sp1) and fullerenes (distorted sp2). In its crystalline form, only diamond and graphite are found in nature and the remaining are synthetic. Each and every allotropic form of carbon exhibits different physical properties as a result of this, and these substrate materials can be tailored for various application.7,8 The properties of different types of carbon electrodes are discussed below. 2.1 Glassy carbon electrode Glassy carbon is a class of carbon prepared by the controlled charring of polymeric resins such as polyacrylonitrile or phenol/formaldehyde in an inert atmosphere at high temperature i.e. about 1000 to 3000 1C. It has a Electrochemistry, 2019, 15, 58–95 | 59

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

ribbon like structure wherein the graphitic sheets are cross-linked, hence it is harder and robust than the graphite.9 It is one of the most widely used electrode materials in electroanalytical chemistry with the advantage of excellent mechanical and electrical properties along with its wide working potential window in both anodic as well as cathodic reactions.10,11 It is well accepted that the electron transfer reactions on the surface of GCE mainly depend on the surface structure, which in turn is related to surface pretreatment protocols. Many methods are available in the literature for pretreatment such as chemical, electrochemical, heat and laser irradiation.12 In addition to these procedures, the most common and popular method is simple mechanical polishing of the surface to a shiny mirror like appearance using an alumina slurry of different particle sizes followed by sonication in deionized water or cyclohexane. The improved electron transfer kinetics can be ascribed to the removal of impurities and exposure of the fresh surface.13

2.2 Carbon paste electrodes Carbon paste electrodes consist of graphite powder and organic solvents such as Nujol, mineral oil, paraffin oil, silicone grease, and bromonaphthalene as binders. The carbon paste electrodes offer easy renewable surfaces, low cost and low background current within electroanalysis.5 Further, CPEs can be prepared by mixing a modifier material with graphite powder and binder material which further acts as working electrodes for electrochemical measurements. However, these electrodes are beneficial from the point of surface renewability but suffer from stability due to continuous leaching of modifier molecules during prolonged electrochemical measurements and also the presence of binder hinders the electrode kinetics, which in turn limits the long term usage, storage and operational stability. In recent years, F. Karimi et al. have employed an amplified sensor for epirubicin by using CoFe2O4 nanoparticles (CoFe2O4/NPs) for the modification of a carbon paste electrode using paraffin oil and 1,3-dipropylimidazoliumbromide (1,3-DPIBr) as binders. The modified electrode showed an improved catalytic activity for the electro-oxidation of epirubicin under biological conditions. Further, the modified electrode was applied in the analysis of epirubicin in injection and serum samples.14 M. Roushani et al. fabricated an electrochemical sensor for the efficient determination of cadmium ions by using a metal–organic framework such as TMU-16-NH2([Zn2(NH2-BDC)2(4-bpdh)]  3DMF) as a modifier for the first time.15 Temerk et al. have modified a carbon paste electrode with glassy carbon powder and indium doped cerium oxide nanoparticles and successfully applied it in the determination of uric acid in biological samples at trace levels.16 Paulo R O et al. measured copper ions using biochar as an electrochemical modifier interface utilizing a differential pulse adsorptive stripping voltammetric technique in spirit drink samples for the first time.17 Azam et al. reported the preparation of a voltammetric sensor for the selective recognition and sensitive determination of lead ions using a carbon paste electrode impregnated 60 | Electrochemistry, 2019, 15, 58–95

View Online 21

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

with novel Pb ion imprinted polymeric nanobeads (IIP) based on dithizone, as a suitable ligand for complex formation with Pb21 ions.18 The electroanalytical features of the carbon paste electrodes are given in Table 2. 2.3 Screen-printed electrodes (SPEs) Screen-printed electrodes (SPEs) have been extensively utilized in the field of electroanalysis.19 SPEs constitute a three electrode configuration, namely working, counter and reference electrodes. All three electrodes were printed on a single strip, which offers wide potential window, easy to fabricate, low cost and needs low sample volume for analysis.20 Furthermore, the target specific electrodes can be fabricated using various commercially available inks for the preparation of reference, counter and working electrodes. Moreover, SPEs have the advantage of being one-shot disposable sensor strips and furthermore require no polishing or smoothening of the electrode surface, as is often the case for more conventional solid electrodes.21 The different steps involved in construction of SPEs have been given Fig. 1. The constriction of SPEs involves printing the thixotropic fluid (it includes graphite, carbon black, solvents and polymeric binder) through a mesh screen. The size and shape of the constructed electrode depends on the above step. Two kinds of substrate materials can be used for construction which includes, ceramic and plastic materials. The plastic materials were found to be cheaper and also the carbon ink adheres strongly with plastic surface compared to the ceramic surface. The sensitivity and the selectivity can be enhanced via chemical modification of these carbon based SPEs with suitable functional motifs. Several reports have appeared recently on the application of various forms of sensing tools for trace metal quantification such as functional nucleic acids, carbon nanotubes and DNA-based biosensors.22–24 2.4 Basal and edge plane pyrolytic graphite electrodes Pyrolytic graphite is an electrode material which contains both basal plane and edge plane surfaces, with the graphite nanocrystal size and basal/edge ratio depending on the quality of the used pyrolytic graphite.25 In highly ordered pyrolytic graphite (HOPG) electrodes (Fig. 1), the basal plane surface consists of layers of graphite parallel to the surface and with an interlayer spacing of 3.35 Å. Surface defects occur in the form of steps exposing the edges of the graphite layers. Due to the nature of the chemical bonding in graphite, the two planes, edge and basal, can exhibit completely different electrochemical properties (Fig. 1 and 2).25,26 For a large variety of redox couples, electron-transfer rate constants at edge plane graphite have been found to be over 103 times faster than for basal plane graphite.25 The edge plane pyrolytic graphite electrode gives low background currents and improved electrocatalytic signals in comparison with those obtained by use of basal plane pyrolytic graphite, boron doped diamond, glassy carbon or carbon-nanotube-modified basal plane pyrolytic graphite electrodes.26,27 Electrochemistry, 2019, 15, 58–95 | 61

Published on 15 October 2018 on https://pubs.rsc.org | d

62 | Electrochemistry, 2019, 15, 58–95

Table 1 MOF modified electrodes for electrochemical sensing of different analytes.a

Electrode/modifier

Oxidation/reduction potential(V)

Analyte

Selectivity

[Cu3(BTC)2] MOF CPE

0.489(Oxidation)

2,4,6-Trichlorophenol

3D-KSC/PCN-333 (Al)@MP-11

(Reduction)-0.1

H2O2

Au/hemin@Fe–MIL-88-TBA II– GOD/GCE Tyrosinase@MOF/GCE

NA

Thrombin

NA

GOD–MIL-100(Fe)–Pt NP/CIE Cu-hemin MOFs/GCE

0.5(Oxidation) NA

Bisphenol A, F, E, B, and Z Glucose Glucose

Porphyrin@MOF/ Streptavidin/GCE

NA

DNA

HP3/AuNPs/Cu-MOFs/GCE

NA

Lipopolysacharide

No interference from 2-nitrophenol,4nitrophenol,2,4,6-trinitrophenol,2chlorophenol,3-chlorophenol,4chlorophenol,2,3-dichlorophenol,2,4dichlorophenol,2,5-dichlorophenol and 2,6-dichlorophenol. Slight interference from 2,3-methylphenol and 2,4-methylphenol. No interference from glu, lac and Na1. 5% interference from UA and 22% from AA. No interference from Ap0A1, Hb and L-Cys No interference from Hg21, Pd21, Cu21, Fe21, Co21, Ba21, Zn21, Cd21, and Ni21. No interference from AA, UA, and DA. No interference from Fru, Gal, Man, AA, and UA. No interference from SBMM DNA, TBMM DNA, ThBMM DNA, and random DNA. No interference from HSA, PCT, and CRP.

a

Application studies

Reference

Reservoir water analysis

123

NA

124

Serum samples

90

Serum samples

125

NA Human Serum samples Spiked clinical Serum samples

126 127

NA

129

128

3D-KSC/PCN-333 (Al)@MP-11 Kenaf stem-derived porous carbon, PCN-Porous coordination network, MP-11-Microperoxidase 11,TBA-Thrombin binding aptamer, GOD-Glucose oxidase. AA-Ascorbic acid, PtNP-Platinum nanoparticles, CIE-Carbon ink electrode, HP3-Hairpin probe 3,UA-Uric acid, DA-Dopamine, BSA-Bovine serum albumin, Hb-Hemoglobin, L-Cys-Cysteine, Fru-Fructose, Gal-Galactose, Man-Mannose, SBMM-Single base mismatch, HSA-Human serum albumin, CRP-Creactive protein, PCT-Procalcitonin.

Published on 15 October 2018 on https://pubs.rsc.org | d

Table 2 The modified Carbon paste electrode based electrochemical sensors and their electrochemical sensing studies.a

Electrochemistry, 2019, 15, 58–95 | 63

Sl. No.

Modifier

Binder

Analyte

Real samples

Reference

1 2 3 4 5 6 7 8

Cd-IIP/CPE CoFe2O4 NPs/IL/CPE IIP/MWCNT-CPE IIP/CNT-CPE Ce-IIP/MWCNT/CPE MOF/CPE (TMU–16-NH2) Zn4O(BDC)3/CPE (MOF-5) In-CeO2/GCPE

Mineral oil Paraffin Paraffin n-Eicosane n-Eicosane Mineral oil Mineral oil Mineral oil

Cd(II) Epirubicin Pb(II) Bi(III) Cerium(III) Cd(II) Pb(II) Uric acid

Water samples Injection and serum samples NA Environmental, pharmaceutical and biological samples Spiked samples of drinking water and sea water NA Real water samples and standard reference materials Human blood serum and urine samples

130 14 131 132 133 15 134 16

a Cd-IIP/CPE ¼ Cadmium ion imprinted polymer/carbon paste electrode; CoFe2O4 NPs/IL/CPE ¼ CoFe2O4 nanoparticles/ionic liquid/carbon paste electrode; IIP/CNTCPE ¼ Ion imprinted polymer/carbon nanotube-carbon paste electrode; IIP/MWCNT-CP ¼ Ion imprinted polymer/multi walled carbon nanotube-carbon paste electrode; Ce-IIP/MWCNT ¼ Cerium ion imprinted polymer/multi walled carbon nanotube-carbon paste electrode; MOF/CPE ¼ Metal organic framework (TMU–16-NH2) ¼ ; Zn4O(BDC)3/CPE ¼ 1,4-benzenedicarboxylate/carbon paste electrode; In-CeO2/GCPE ¼ Indium doped cerioum oxide nanoparticles/glassy carbon paste electrode.

Published on 15 October 2018 on https://pubs.rsc.org | d

64 | Electrochemistry, 2019, 15, 58–95 Fig. 1 Various types of electrodes and their structures used for modification in sensing applications. Adapted from ref. 25 with permission from John Wiley & Sons, Copyright r 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 2 Cyclic voltammograms of ferricyanide in aqueous solutions with basal plane, edge plane electrodes and MWCNTs modified electrodes. Adapted from ref. 25 with permission from John Wiley & Sons, Copyright r 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

2.5 Noble metal electrodes Nobel metals with nano size particles have received great interests due to their attractive electronic, optical, and thermal properties as well as catalytic properties and potential applications in the fields of physics, chemistry, biology, medicine, and material science and their different interdisciplinary fields and have been intensively studied as electrode materials for electrocatalytic purposes. As compared to bulk materials, metallic nanoparticles have widespread attention to researcher due to attractive physical and chemical properties such as surface and quantum confinement effects. These properties lead to improving the conductivity, optical properties, magnetic properties, catalytic activity, etc. For e.g. bulk gold is inactive, but nano gold acts as a very good catalyst for the oxidation of carbon monoxide and hydrocarbons, reduction of nitrogen oxides and also for the hydrogenation reactions. For e.g. Au, Pt and Pd are non-magnetic in the bulk form, but when they reduce to nano size, they behave as magnetic materials. In gold, one can make it ferromagnetic by capping with suitable molecules as the charge on the surface of the materials make ferromagnetic.

3

Chemical modification of electrodes

The design of electrochemical devices and systems has become a significant technical aspect due to the applications in number of domains like chemical sensing, energy conversion & storage, molecular electronics, electrochromic displays, corrosion protection and electro-organic synthesis.28 Especially, in electrochemical sensing applications, chemically modified electrodes (CMEs) comprises a relatively modern approach to electrode systems that finds utility in a wide spectrum of basic electrochemical investigations. These modified electrodes have gained much interest within the area of electroanalysis from past decades, due to the possibility of having direct control over the surface Electrochemistry, 2019, 15, 58–95 | 65

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 3 Illustrating the functionalization of SnO2 electrode with amine groups. Reproduced from ref. 30 with permission from American Chemical Society, Copyright 1980.

structure of the electrode.29 Royce Murray first introduced the concept of chemically modified electrodes (CMEs) in the year 1970 from his pioneering work in the modification of SnO2 electrode with amine groups. The amine modified electrode surface has been used for functionalization with various electroactive organic moieties through coupling reactions30 Fig. 3. The covalent or non-covalent anchoring of the modifier/ indicator molecules onto the surface of substrate material with the aid of binder gives the CMEs. Anchoring of modifier molecule on the surface of the carbon substrate by specific functional groups provide a pathway for the interaction with the target analyte. CMEs comprise two components, one is the substrate material and the other modifier molecule. The importance of these two components depends upon the nature of the analytical investigation. All electrochemical reactions occur at the electrode/solution interface. Hence, the surface structure of the electrode at the interface plays a distinct role in the electrode reaction and it promotes the pathway for the transfer of electrons at the interface which in turn gives the better electrode kinetics.31 The electrodes normally used in this phenomenon are carbon based substrate materials. However, these electrodes show some limitations over modified carbon electrodes due to sensitivity, selectivity and high over potentials. These electrodes require certain chemical and physical properties which do not usually exist on the carbon based electrodes. Hence the modification of carbon electrodes with suitable indicator molecules having functional groups within its structural framework indeed enhances the electro-analytical signal through complexation/chelation or enhances the electro catalytic activity which causes the facile electron transfer at the electrode interface.32 CMEs have been extensively used in the metal ion quantification due to their tailor made properties such as selectivity and sensitivity towards the target analytes. It can be illustrated with an example involving the electrochemical quantification of lead ion using graphene oxide (GO) modified electrode.33 The presence of GO on the electrode surface will reduce the over potential required for the redox process of lead ions on the carbon surface. Similarly, mercury quantification can be achieved using thiol containing functional groups on the carbon surface due to their strong binding interaction.34 The principal electrode modification routes include electrochemical and chemical modifications. The former modification technique can be popularly called as electrografting/electro polymerization. 66 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

3.1 Electrochemical modification Electrochemically assisted covalent modification of carbon substrate material with suitable modifier molecules has become one of the fascinating approaches in the area of development of chemically modified electrodes. This type of modification mainly involves two strategies, one is reductive and the other is oxidative strategy.35–37 In the oxidative grafting the electrode surface can be modified with amines and alcohols, whereas by reductive grafting results in functionalization with aryldiazonium diaryliodonium and triarylsulfonium salts.35 The reductive strategy was initially developed by Jean Pinson in 1990 and later developed by a number of workers including McCreery and Downard group.35,38,39 The mechanism involved in this modification is the generation of aryl radical at the electrode/solution interface by one electron electro reduction of corresponding diazonium salt and its subsequent attachment on the surface of carbon substrate. This attachment, results in the formation of a covalent bond between carbon atom of substrate and carbon atom of the modifier molecule38 (Fig. 4). This type of modification can be easily accomplished using cyclic voltammetry or controlled potential electrolysis either in aqueous or in non-aqueous medium.40–42 The thickness of the modifier molecule at the interface plays very important role in the area of electroanalysis as it decides the electrode kinetics of a particular redox reaction. It can be achieved by optimizing the experimental parameters like applied potential or current, length of modifier molecule, concentration of the diazonium salt and scan rate. McCreery et al. has observed the formation of monolayer when the concentration of modifier molecule is less than 1 mM and multilayer formation when it is above 1 mM concentration.36,43 Very low reduction potentials have to be applied typically around 0 V vs. SCE, to generate radical because of the electron withdrawing nature of diazonium group of the modifier molecule.44 The electrochemically generated aryl radicals are captured by the carbon surface, a fraction of aryl radicals generated in the reaction may bound to the carbon surface and rest of them goes into the solution.44 Another route of electrochemical modification involves the oxidation of the modifier molecules like amines, alcohols and aryl acetates. The carbon substrate surfaces like CNTs, graphitic carbon, carbon fibers and glassy carbon spheres were functionalized with amines by their oxidation

Fig. 4 Schematic representation of carbon surface modification by electrochemical reduction of aromatic diazonium salt. Adapted from ref. 122 with permission from American Chemical Society, Copyright 2005. Electrochemistry, 2019, 15, 58–95 | 67

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 5 A and B representing carbon modification through amine oxidation. Reproduced from ref. 38 with permission from ECS – The Electrochemical Society, Copyright 1990.

which forms surface attached layers on the electrode surface. Several mechanisms pertaining to the modification of carbon surfaces by the oxidation of amines have been reported in the literature. One such modification proceeds through stepwise manner wherein the proton loss occur after amine gets attached to the surface (Fig. 5A) and the other involves the loss of proton before the amine gets anchored onto the surface of carbon (Fig. 5B).38 Primary amines are more frequently used as modifier molecules when compared to secondary and tertiary amines. This is because the tertiary amines undergo oxidation easily due to the stabilization of amine cation radical by the presence of alkyl substituents. Although the oxidation of tertiary amine is comparably high, the oxidation of primary amines results highest modifier surface concentration. This might be due to the stearic hindrance of bulky substituents at the nitrogen atom of the tertiary amine which prevents facile oxidation.44,45 In recent years, polymers have been considered as the most exciting class of materials due to its low cost, easy preparation and availability in various chemical forms.46 As a result of this, the combination of polymer and the graphene produce synergetic effect which can be essentially tuned in sensors and actuators based on the modulation of functional properties.47 Qiu et al. has described an electrochemical grafting of graphene nano platelets (GNP) with 3,5-dichlorophenyl diazonium tetrafluoroborate and 4-nitrobenzene diazonium tetrafluoroborate.47,48 Mohamadi et al. have prepared the graphene nanoplatelets covalently functionalized polymetha acrylic anhydride chains by the introduction of vinyl groups onto the surface of graphene via simple esterification reaction between its hydroxyl groups and methacrylic anhydride.49 Thomas et al. has proposed a conducting electrospun fibre mat, surface-grafted with poly(acrylic acid) brushes and a conducting polymer sensing 68 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 6 Scheme illustrating the fabrication of the electrospun PEDOT gene sensor. Reproduced from ref. 50 with permission from Elsevier, Copyright 2017.

element with covalently attached oligonucleotide probes for the determination of non-Hodgkin lymphoma gene utilizing electrochemical impedance spectroscopy (Fig. 6).50 The electro analytical features of covalent modification techniques were given in Table 3. Belhousse et al. has reported on the preparation of a porous silicon (PSi)/poly(3-hexylthiophene) hybrid structure and its application in gas sensing. The poly (3-hexylthiophene) was covalently grafted on the PSi surface in a stepwise process. Electropolymerizable thiophene groups were covalently linked to an azide-terminated PSi surface using ‘click chemistry’ approach. Poly(3-hexylthiophene) films were grown on the thiophene-terminated PSi interface using electropolymerization in acetonitrile in the presence of 3-hexylthiophenemonomer51 (Fig. 7A). Chen et al. has described sensitive and selective electrochemical sensor based on molecular imprinting polymers grafted graphene (MIPs-G) was developed for simultaneous measurement of 4,4-Methylene diphenylamine (MDA) and aniline by differential pulse voltammetry (DPV). MIPs-G was synthesized via free radical polymerization reaction using MDA and 4-vinylpyridine as template molecule and functional monomer respectively52 (Fig. 7B). Babu et al. has been proposed an electrochemical sensing of dopamine at the surface of a dopamine grafted graphen oxide/poly(methylene blue) composite modified electrode. Further the grafting of dopamine on the surface of the modified interface was confirmed using FT-IR spectroscopy and XPS techniques53 (Fig. 7C). Cha and coworkers have been reported the use of poly (thiophen-3-yl-acetic acid 1,3-dioxo-1,3-dihydro-isoindol-2-yl ester (PTAE) for application to electrochemical hybridization sensor. In this strategy 3-thiophene acetic acid and N-hydroxyphthalimide (NHP) was stirred in chloroform at ambient temperature to synthesize thiophen-3-yl-acetic acid 1,3-dioxo-1,3-dihydro-isoindol-2-yl ester (TAE). The resulting product was formed with the aid of 1,3-dicyclohexylcarbodiimide (DCC). Further, poly (thiophen-3-yl-acetic acid Electrochemistry, 2019, 15, 58–95 | 69

Published on 15 October 2018 on https://pubs.rsc.org | d

70 | Electrochemistry, 2019, 15, 58–95

Table 3 The covalent modified electrodes obtained by reducing diazonium salts using hypophosphorous acid, amide bond formation through microwave, and ball milling.a Sl. No.

Modifier

Electrode

Analyte

Stability

Reference

1

2-Hydroxybenzoic acid functionalized glassy carbon spheres

Robust composite

Pb(II) and Cd(II)

60

2 3

GCE BPPG

Hg(II) NH3

4

MWCNT/Fast Violet B Anthraquinone functionalized glassy carbon spheres Pt/Gr Nanocomposite

Long term stability without much decrease (Decreased by 13% compared to freshly prepared electrode) in peak currents over 6 months NA NA

GCE

H2O2

5 6 7 8

AgNPs/GN rGO/ZnO composites Sulfur-doped graphene (SG) pulverized graphite (pGr)

ITO GCE GCE GCE

H2O2 Glucose H2O2 Dopamine

9

CuO–ZnO nanocomposite

10

Glassy carbon spheres modified with 4-amino benzamide

Transparent conducting oxide (TCO) GCE

112 129 135

H2O2 and NH3

Stable at room temperature for about one week with retaining 91.8% peak currents with freshly prepared electrode NA — — Stable for about 30 days with 90% response compared to freshly prepared electrode NA

Hg(II)

NA

113

136 137 138 139

a MWCNT ¼ Multiwalled carbon nanotubes; Pt/Gr ¼ Platinum graphene; AgNPs/GN ¼ Silver nanoparticles/graphitic nitride; rGO/ZnO ¼ reduced graphene oxide/zinc oxide; CuO-ZnO ¼ Copper oxide-zinc oxide; CPE ¼ Carbon paste electrode; GCE ¼ Glassy carbon electrode; BPPG ¼ Basal plane pyrolytic graphite electrode.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 7 A. Illustrating the preparation of conducting poly (3-hexylthiophene) polymer covalently bonded onto thiophene-terminated Psi surface, B. The synthesis route for MIPs-G via FRP and the electrochemical sensing of MDA and aniline, C. General reaction pathway of electrochemical polymerization and the grafting of dopamine. Reproduced from ref. 53 with permission from the Royal Society of Chemistry.

Fig. 8 Illustrating the synthesis of poly (thiophen-3-yl-acetic acid 1,3-dioxo-1,3-dihydroisoindol-2-yl ester on electrode by chemical and electro chemical reactions. Reproduced from ref. 54 with permission from Elsevier, Copyright 2003.

1,3-dioxo-1,3-dihydroisoindol-2-yl ester, TAE) (PTAE) was easily formed by electro polymerization onto an chip electrode as a highly electroactive film (Scheme)54 (Fig. 8). Electrochemistry, 2019, 15, 58–95 | 71

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

Table 4 The Electro grafting/electro polymerization mediated modified electrodes.a Sl. No. Modifier

Oxidation/Reduction Electrode potential Scan cycles

1 2 3 4 5 6 7 8 9

Au PGE GCE CPE Au GCE GCE GCE GCE

MIP/AuNPs MIP/PGE Poly-FA/MWCNT NR/MCPE MIP/PoPD Poly(CTAB)/GCE AuNPs/MIP/MWCNTs AuNPs/MIP MWCNT/MIP

0 and þ 1.3 V 1.0 V and 2.0 V 0.25 to þ 0.75 V 0.8 V to 1.0 V 0.0 and 1.0 V 0.8 V to 1.2 V 1.0 and þ1.0 V 0.2 to 0.6 V 0.00 to þ0.80 V

Reference

30 140 16 141 10 142 15 143 20 144 Multi cycles 145 NA 146 NA 147 NA 148

a MIP/AuNPs ¼ Molecular imprinted polymer/gold nanoparticles; MIP/PGE ¼ Molecular imprinted polymer/pencil graphite electrode; IIM/PC ¼ Ion imprinted polymer/polycatechol; poly-FA/MWCNT ¼ Poly-ferulic acid/Multiwalled carbon nanotube; NR/ CPE ¼ Neutral red/carbon paste electrode; MIP/PoPD ¼ Molecularly imprinted polymer/ poly(o-phenylenediamine); Poly(CTAB) ¼ Poly (cetyltrimethylammonium bromide); AuNPs/ MIP/MWCNTs ¼ gold nanoparticles/molecularly imprinted polymer/Multiwalled carbon nanotube; AuNPs/MIP ¼ Gold nanoparticles/molecularly imprinted polymer; MWCNT/ MIP ¼ Multiwalled carbon nanotube/molecularly imprinted polymer; GCE ¼ Glassy carbon electrode; CPE ¼ Carbon paste electrode; PGE ¼ Pencil graphite electrode; Au ¼ Gold electrode.

Some of the reported CMEs based on above techniques and the parameters used during modifications procedures were given in Table 4. 3.2 Chemical modification Several strategies have been reported for chemical modifications of electrodes. They include physisorption of the electrode substrate material with modifier along with binder (carbon paste electrodes), covalent modification of electrode substrate material via diazonium salt reduction using hypo phosphorus acid as the reducing agent, and solvent less green approaches like ball milling and microwave methods. 3.2.1 Physical Immobilization. Yihua Zhu et al. has constructed the Graphene-Fe3O4 composite using solvothermal method for the immobilization of horseradish peroxidase (HRP) to construct a mediator free H2O2 biosensor. Eelectrochemical impedance spectroscopy and cyclic voltammetry technique has been used to decipher the direct electron transfer of HRP and electrocatalytic reduction of H2O2 at biocomposite. Here the proposed platform has showed high sensitivity and a lower detection limit.55 The same group has described the H2O2 biosensor, graphene and horseradish peroxidase (HRP) were co-immobilized into biocompatible polymer chitosan (CS), and then a glassy carbon electrode (GCE) was modified by the biocomposite, followed by electrodeposition of Au nanoparticles on the surface to fabricate Au/graphene/ HRP/CS/GCE. The newly developed biosensor showed good performances such as high sensitivity, selectivity, improved stability and mainly short response time and wide linear range.56 Wu Zhao-yang et al. has proposed the disposable biosensor for determination of hydrogen peroxide (H2O2) based on Fe3O4–Au magnetic nanoparticles coated 72 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

horseradish peroxidase (HRP) and graphene sheets (GS)–Nafion film modified screen-printed carbon electrode (SPCE) was fabricated. To construct the H2O2 biosensor, GS–Nafion solution was first dropped onto the surface of SPCE. Subsequently, the bio composites of Fe3O4–Au magnetic nanoparticles coated HRP were adsorbed on the surface with the aid of an external magnetic field to fabricate the SPCE GS–Nafion/Fe3O4–Au-HRP electrode.57 Weihua Tang et al. has developed a biosensor for the quantification of H2O2 based on immobilizing hemoglobin on gold/graphene–chitosan nanocomposite as an efficient electrochemical interface58 (Fig. 9). Xiaoyu Cao et al. has proposed a highly sensitive hydrogen peroxide (H2O2) biosensor based on immobilization of hemoglobin (Hb) at Au nanoparticles (AuNPs)/flower-like zinc oxide/graphene (AuNPs/ZnO/Gr) composite modified glassy carbon electrode (GCE) was constructed, where ZnO and Au nanoparticles were modified through layer-by-layer onto Gr/GCE. Flower-like ZnO nanoparticles could be easily prepared by adding ethanol to the precursor solution having higher concentration of hydroxide ions. Further, the fabricated electrode was employed for determination of H2O2 in real samples with quick response, good sensitivity, high selectivity, and acceptable recovery.59 However, electrodes suffer from leaching of indicator molecules into the bulk of the electrolytic solution and the electrode interface need to regenerate by coating or insertion of the modifier into the electrodes (carbon paste electrodes). In order to overcome these potential drawbacks, covalent modification of substrate with suitable indicator molecules with specific functional groups on it, can be achieved using several approaches like physical adsorption (physisorption), chemical adsorption (chemisorption), covalent attachment, electrochemical and solvent free approaches like ball milling as well as microwave assisted covalent modification procedures.35 However, different carbon substrates like graphite, glassy carbon, carbon nanotubes (both multi walled and single walled) and screen-printed electrodes (SPEs) have been used as electrode materials for the modification purpose. Raghu et al. has modified the glassy carbon spheres with aryl diazonium salt in the presence of

Fig. 9 Lay-by-layer assembly preparation of Hb/Au/GR–CS/GCE. Reproduced from ref. 58 with permission from Elsevier, Copyright 2014. Electrochemistry, 2019, 15, 58–95 | 73

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 10 Schematic representation of the covalent bulk modification process. (a) Generation of aryl radical, (b) covalent attachment of aryl radical on the carbon surface. Reproduced from ref. 60 with permission from Springer Nature, Copyright 2011.

chemical reducing agent for the simultaneous measurement of lead and cadmium ions (Fig. 10).60 Prashanth Adarakatti et al. has used calixarene based screen-printed electrodes as one shot disposable sensor for the simultaneous determination of lead, copper and mercury ions and have been applied to industrial and environmental samples. In this strategy the authors have aimed at utilizing calixarene moiety upon the polyester strips as a one-shot disposable electrochemical sensor as in the form of screen printed calixarene carbon electrode (SPCCE) in the simultaneous measurement of lead(II), copper(II) and mercury(II) that require no polishing and smoothening61 (Fig. 11). All electrochemical reactions occur at the electrode/solution interface. Hence, the surface structure of the electrochemical interface where the electrochemical reaction proceeds will play decisive importance in the electrode reaction and also its facile kinetics.31 Carbon based substrate materials can be used as an electrode material in various potential applications. However, these electrodes suffer from sensitivity, selectivity and high over potentials. i.e. the potential required for the oxidation or reduction of a particular species is much more positive or negative than the expected thermodynamic potential. This behavior of the unmodified carbon is due to the absence of specific interaction of the functional groups of the modifier molecule with target analyte. In order to solve these problems associated with unmodified carbon electrodes, efforts have been directed towards altering the surface structure in such a way that it should selectively interact with target analyte. Using chemically modified surface, it is possible to achieve the selectivity, sensitivity as well as electrode kinetics.62 It can be illustrated with an example involving the electrochemical determination of lead ions using graphene oxide modified glassy carbon electrode. Here 74 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 11 Representation of binding and complexation mode of metal ions with modifier molecule (calixarene) present on the surface of SPCCE. Reproduced from ref. 61 with permission from Elsevier, Copyright 2017.

the presence of GO reduces the over potential required for the redox process of lead ions when compared to the bare glassy carbon electrode. The reduction in over potential as well as the increased peak currents are attributed to the selective interaction of ionizable oxygen containing functional groups of GO with lead ions because these functional groups are well known to show potential affinity towards lead ions.63 Among these, modified carbon material can be compressed into pellet without using any binder in the fabrication of electrode into robust pellet electrode and its surface renewability can be easily achieved by simple mechanical polishing and smoothening.64 Recently, Suresh kumar et al., reported in situ diazotization assisted functionalization of graphitic carbon using hypophosporous acid.65 In this method authors generated diazonium ion in situ, where as in other covalent modification strategies, diazonium salts are used along with carbon substrate and hypophosphorous acid. However, the covalent modification involves various organic solvents as reagents (dichloromethane, acetonitrile)/coupling agents (DCC, EDC, SOCl2)/reducing agents (H3PO2) are found to be toxic and should be avoided. As an alternative to above discussed strategies, solventless green approaches like ball milling and microwave methods have been reported. 3.2.1.1 Ball milling. The ball milling approach has been considered as a green protocol as this method offers surface modification of carbon based substrate materials in absence of solvents. The ball milling methodology make the synthesis simple and very efficient and it generates the active centers on the surface of substrate materials during functionalization course under solvent free condition. The basic principle behind this process is the grinding phenomenon facilitates the activation of substrate material which modifies the substrate with potential indicator material by the collision between the surface of the reactants which increases the internal energy, temperature and pressure as this often can be used in inorganic and material chemistry for the preparation and modification of solids.66 The mechanism of modification takes place either by changing the reactivity of the reagents or by breaking the molecular bonds.67 Pierard et. al. have evaluated the Electrochemistry, 2019, 15, 58–95 | 75

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

effect of grinding on the structure of single walled carbon nanotubes and found the decrease in the length and increase in the surface area which is a necessary condition for heterogeneous catalytic supports.68 Welham et al. have examined the effect of extended ball milling on the chemisorption of gases and its dependence on the extent of milling.69 Li et al. have reported the functionalization of SWCNTs with alkyl and aryl groups using the high speed vibration mill which have showed, that the modified carbon surfaces with long alkyl chains are remarkably soluble in common organic solvents.70 3.2.2 Microwave assisted covalent modification. Microwaves form a new alternative source of heat energy which are having the frequency range between 0.3 to 300 GHz and are situated between infrared radiation and radio waves in the electromagnetic spectrum. Microwaves have been widely used in synthetic organic chemistry to synthesize wide variety of reagents through different reaction pathways. Later on it has been extended to heterocyclic, organometallic, combitorial chemistry, synthetic transformations, radical reactions, organocatalysis, cycloaddition, metathesis and metal mediated transformations due to the possibility of controlling the reaction conditions by tuning the pressure and temperature. The basic principle lying in this strategy is when the molecules with permanent dipole moment are subjected to the electric field, the molecules get aligned with respect to the field. Molecular oscillations result as soon as the field oscillations begins and the molecules align and realign continuously giving rise to an intense internal heat energy which in turn agitates the molecules leading to the formation of desired product.71 Pandurangappa et al. has modified the graphitic carbon with the 4amino salicylic acid for the simultaneous determination of lead and cadmium ions from environmental samples.64 In this strategy, the functionalization was done in two steps. In the former step the graphitic carbon was oxidized with conc. HNO3 followed by amidation in the next step by adding amino salicylic acid. These two steps were performed using microwave irradiation.64 Similar to last method, Adarakatti et al. has explored a novel way to covalently anchor the aminocalixarene molecule with graphitic carbon as an electrochemical interface for the simultaneous determination of lead and cadmium ions utilizing electrochemical techniques.72 Further, the same group has been used the amino-thiacalix[4]-arene derivatized graphitic carbon in the quantification of mercury ions from real sample matrices. In this approach the presence of functional motifs (CONH groups) on the surface of thia[4]calixarene-graphite composite provides a good sensing ability in presence of mercury(II) ion73(Fig. 12). C. L. Sun et al. synthesized the graphene oxide nanoribbons (GONRs) from the facile unzipping of multiwalled carbon nanotubes (MWCNTs) with the help of microwave energy. A core–shell MWCNT/GONR-modified glassy carbon (MWCNT/GONR/GC) electrode was used to electrochemically detect ascorbic acid (AA), dopamine (DA), and uric acid (UA).74 F. Faranak et al., has developed the electrochemical sensing platform based on CuO and graphene modified CuO nanoparticles (NPs)/glassy carbon electrode which were fabricated by 76 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | d Electrochemistry, 2019, 15, 58–95 | 77

Fig. 12 Representation of the microwave irradiation assisted oxidation of graphitic carbon, amide bond formation between oxidized graphitic carbon and modifier and complexation mode of the modifier with the analyte. Reproduced from ref. 73 with permission from the Royal Society of Chemistry.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

microwave-assisted synthesis. Further, they employed in the determination of glucose. The modified GCE has exhibited a fast and selective linear response towards glucose at pH 13 that covers the 0.21 mM to 12 mM concentration range, with a 0.21 mM low detection limit. However, Ascorbic acid, dopamine, uric acid, sucrose, maltose and fructose do not interfere with the proposed sensing tool.75 This simple and convenient approach opens up a new way to scalable the synthesis of CNT based heterostructures that could be used in developing devices, novel catalysts and composites. Gao et al. has been used the carbon nanotubes to covalently immobilize the proteins in presence of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). In this strategy EDC first reacts with a carboxyl group, forming an amine-reactive O-acylisourea intermediate which subsequently reacts with an amine group to produce a stable amide bond76 (Fig. 13). Chen et al. has described the synthesis of the porphyrin–graphene nanohybrid. In this strategy the carboxylic acid groups at the edge sites were activated into acyl chloride using thionyl chloride as an activating agent. Then the resulting acyl chloride was coupled with 4,5 (aminophenyl)-10, 15, 20-triphenyl porphyrin (TPP) selectively at amine position through the formation of an amide bond77 (Fig. 14).

4 Modified electrodes for electrochemical sensing One of the advancement in electrochemical techniques includes using of CMEs in electroanalytical techniques which are proved to be sensitive and selective during electrochemical sensing application studies. The CMEs were also called as tailor made electrode materials, because of its inducible specific properties necessary for the user by modification of electrode surface. One of the distinguishable property exhibited by CMEs is electro catalytic activity, which will be beneficial for electro analysis involving sluggish electrode kinetics analytes. The decrease in overpontetial of electro catalytic reaction using CMEs has been illustrated in Fig. 15. The electro catalytic oxidation of A to B1 was carried out on electrode modified with reversible redox mediator R/S with standard potential E0R/S. From Fig. 15, it was clear that the oxidation potential was relatively high for the reaction A to B1, while it was low with redox mediator(R/S) functionalized electrode/ presence of redox mediator(R/S) in solution along with reactant A. This may be due to the redox mediation of the oxidation reaction by R/S redox couple.78 The numerous CMEs have been synthesized by following the various modification strategies discussed in the earlier sections. These CMEs were used for electroanalysis of environmentally important metal ions, anions, pesticides, insecticides, and biomolecules.78–81 Other than decreasing over potentials CMEs also exhibits preconcentration abilities towards given analytes from the bulk to the electrode surface which in turn increases the sensitivity of the method. This may be due to the chelating group present on the CMEs.82 Similarly, the noble metal composites modified electrodes helps to reduce over potentials of analytes with sluggish electrode kinetics like hexavalent chromium, where 78 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | d Electrochemistry, 2019, 15, 58–95 | 79

Fig. 13 Theoretical conjugation of proteins to carboxylated CNTs using EDC in the presence or absence of sulfo-NHS. Reproduced from ref. 76 with permission from American Chemical Society, Copyright 2008.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 14 Representation of part of the structure of the covalent TPP-NHCO-SPF graphene. (SPF – Solution processable functionalized graphene). Reproduced from ref. 77 with permission from John Wiley & Sons, Copyright r 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

it’s not possible to reduce on bare electrode.83 In the case of biosensors, where the electrode surface has been modified by enzymes exhibits specific electro catalytic activity towards their corresponding substrates makes them sensitive and selective methods. However, the enzymes are highly fragile and susceptible to various drastic environments during sensing studies limits their use as electrode modifiers in electro analysis. As an alternatives, so many enzyme less electrochemical sensors are reported based metal oxide nanoparticle composite modified electrodes.84–86 These kind of modified electrodes catalyzed the oxidation/ reduction of analytes resulted in lowering the over potentials but they lack selectivity. The researchers started using the enzyme composites as electrode modifiers to increase sensitivity and selectivity along with 80 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 15 Schematic representation showing the electrolytic oxidation of A to B on (A) Bare electrode (B) Bare electrode with mediator in the solution (C) Modified electrode. Reproduced from ref. 29 with permission, from John Wiley & Sons, Copyright r 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

improved operational stability of these enzyme modified electrodes.87 These composites include immobilizing agent, redox electron mediator and enzyme. The metal organic frame works (MOFs) proved as best immobilizing agents due to their large surface, porous, and crystalline nature. The MOFs serves as good adsorbing agents for electron mediators as well as enzymes through physical/electrostatic interactions between functional groups of MOFs and enzymes/redox mediators.88 The MOFs also helps in preconcentration of analyte on to the electrode surface through p–p interactions between aromatic groups of the ligands of MOFs and aromatic groups of analytes.89 The researchers reported multifunctional bio conjugate material (Au/hemin@MOF–TBA II (thrombin binding aptamer)–GOx (glucose oxidase)) modified electrode based sensor for thrombin.90 In the present material hemin is an naturally occurring metalloporphyrin which acts as both redox mediator (due to the reverse redox activity of Fe13–Fe21) and catalytic material (due to peroxidase activity).90 The MOFs in the present bioconjugate serves as immobilizing material which increases the operational stability of the material. Another interesting material MOF ((PCN-333(Fe)) encapsulated horse radish peroxidase (HRP) modified glassy carbon electrode (GCE) was reported for sensing of H2O2.91 The MOF showed maximum loading capacity of HRP due to size match of HRP (4.04.46.8 nm) and meso cages of MOFs (5.5 nm of diameter) Fig. 16. The encapsulation of HRP into MOF minimized its leaching and aggregation. In addition, the operational stability like thermal and stable acidic environments of HRP were achieved by encapsulation. Finally, the conformational changes of the HRP were also minimized due to encapsulation. The Fig. 16 illustrates the encapsulation of HRP into ((PCN-333(Fe)), its modification on to GCE and electro catalytic activity of the sensing system.91 Similar, MOF enzyme conjugates modified electrodes were reported for sensing materials and listed in Table 1. On the other hand, non-enzymatic electrochemical sensor were also reported using CMEs. The electrode Electrochemistry, 2019, 15, 58–95 | 81

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 16 Schematic representation of HRP encapsulation into mesocages of PCN-333(Fe), its casting on GCE and electro catalytic reduction of H2O2 . Reproduced from ref. 91 with permission from the Royal Society of Chemistry.

modifiers in these studies includes various nanomaterials (metal nano particles and metal oxide nanoparticles) and their composites with conducting materials like PANI, CNTs, graphene oxide and graphene. The nanomaterial composite modified electrodes enhances the sensitivity by assisting in redox activities of the analytes due to their unique electronic structures. In a typical example where the Au electrode has been modified by carbon nano cages decorated with Pt nanoparticles and used for sensing thrombin.92 In this case the authors used carbon nano cages (CNCs) as carriers for the Pt nanoparticles and thrombin capture probe (TCP). The large surface areas of CNCs helped in immobilizing large number of Pt nanoparticles as well as TCP molecules due to which the sensitivity increases. The mechanism of thrombin detection using above aptamer has been given in Fig. 17. Carbon nanotubes were extensively used as electrode modifiers for construction of electrochemical sensor systems.93 These CNTs were used as electrode materials due to their attractive electron transfer abilities during electrochemical reactions involving large and small biologically important molecules.94 In addition CNTs exhibited good chemical stabilities in both aqueous and non-aqueous environments.95 The carbon atoms of CNTs present at side walls will behavior differently with that of carbon atoms at edges. The behavior of carbon atoms of CNTs can be similar to the basal plane, and edge plane of highly oriented pyrolytic graphite (HOPG).96 The redox reactions of ferricayanide with CNTs modified electrodes reveals similar electron transfer rates with that of the edge plane HOPG electrodes.97 The electron transfer rates for the redox processes of Fe(CN)64 and Ru(NH3)631 were found to be better with the electrodes modified with MWCNTs with edge site defect.98 These results confirm the presence of electroactive sites at the tube ends of the MWCNT. Similarly, the redox process of ferricayanide redox couple were studied using the aligned and randomly dispersed acid treated single 82 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | d Electrochemistry, 2019, 15, 58–95 | 83

Fig. 17 Schematic representation of the sensing of thrombin by the PtNPs@CNCs modified electrodes. Reproduced from ref. 92 with permisison from Elsevier, Copyright 2016.

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

99

walled carbon nanotubes modified electrodes. The redox process were better with aligned acid treated SWCNTs modified electrodes (the peak separation and half-wave potentials were 59 mV and 0.231 V) than with acid treated randomly dispersed SWCNTs modified electrodes (the peak separation was 99 mV and 0.231 V). The above results with MWCNTs and SWCNTs revealed the fact that the electrochemical properties of the CNTs will be greatly depends on the carbon atoms present at the ends of the tubes rather than the carbon atoms present at the side walls.99 Furthermore, electron transfer ability of the aligned CNTs depends on their mean lengths (Reaction rates were inversely related to their mean lengths). This was proved by comparing the reaction rates obtained for redox process of ferrocenemethylamine with the vertically aligned CNTs (with varied mean lengths) modified electrodes.100 The rate constant was better (459  132 s1) with shorter mean length CNTs (257 nm) than that rate constants (98  25 s1) of CNTs with higher mean lengths (1175 nm).100 Furthermore, electron transfer ability of the CNTs modified electrodes were also depend on the metal content of CNTs [Imparted during acid treatment (con. HNO3 and con. H2SO4) process].101 The metal content of CNTs will tend to decease the electron transfer ability of the CNTs. In order to regain the original electron transfer ability, after acid treatment CNTs should dialyze against Tritons X-100 solution.101 The electro catalytic activity of the CNTs also depends on the technique used for their production. The CNTs produced by chemical vapor deposition method (CVD) exhibited superior electro catalytic activity compared to the CNTs produced by ARC method.102 The reason for this may be due to the fact that the CNTs produced by CVD technique has large density of edge defect sites.102 Whereas CNTs produced by ARC process little exposed edge plane sites. Furthermore, the electro catalytic activity of the CNTs produced by ARC process can be improved by pre-anodization.103 This preanodization cuts the end caps of CNTs, so that the new edge plane sites are exposed which obviously increases the electro catalytic activity.103 As discussed in electrode modification sections, numerous CNTs composite modified electrodes were reported as electrochemical sensors. The various CNTs and CNTs composites modified electrodes reported for sensing were given in Table 3. However, there are some drawbacks regarding CNTs which includes difficulty in production of pure form, minimizing aggregation, obtaining uniform length tubes etc., Furthermore, the toxic effects of CNTs limits their use in bioelectronics applications. Another carbon substrate used as electron transport material for electro catalytic material includes graphene and its derivatives like graphene oxide, reduced graphene oxide. In order to further increase its electro catalytic activity, the composites of graphene with metal and metal oxide nano particles were also reported. CuO–graphene composites modified GCE had been reported for non-enzymatic glucose sensing.85 Ag doped TiO2 nanoparticles synthesized ionothermally were used for sensing catechol, resorcinol and hexavalent chromium.83,104 Similarly, screen printed TiO2 electrode modified with Ag nanoparticles was reported for photoelectrical detection of hexavalent chromium105 (Fig. 18). The LODs obtained for hexavalent Cr detection with the discussed 84 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 18 Schematic diagram illustrating the photoelectrocatalytic reduction of Cr(VI) over Au-TiO2 under simulated sunlight irradiation and photocurrent responses of TiO2 and Au-TiO2 in the absence and presence of 100 mM Cr(VI). Reproduced from ref. 105 with permission from Elsevier, Copyright 2015.

electrode were far less that of other electrodes (0.004 mM) like Au nanoparticles on TiO2 nano arrays (0.03mM),106 Au nanoparticles on ITO electrodes (0.1 mM),107 and Au screen-printed macro electrode (4.4 mM).108 The electrode can be employed for monitoring Cr (VI) in drinking water due to its LOD lower than that of WHO guide line limit (1 mM).109 However, the metals like Au and Pt are expensive, the researchers also used inexpensive metals like Cu, Fe, Ti, and Ni for nanoparticle synthesis and their composites preparation with graphene had been used as electrode modifiers for electrochemical sensing. Ionothermally synthesized TiO2 nanoparticles modified GCE and hematite nanoparticles synthesized by Electrochemistry, 2019, 15, 58–95 | 85

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

sol–gel, solution combustion and molten salt methods were applied for dopamine sensing.84,86 Nickel Nitroprusside Coordination Nanoparticles synthesized by drop-by drop and bulk mixing methods were used for sulfide monitoring.110 The electrochemical sensing of toxic heavy metal ions like Pb, As, and Hg by CMEs is significantly increased from last two to three decades. The modifiers includes organic chelating agents, nanoparticles, aptamers and their composites. As discussed in electrode modification section numerous CMEs have been reported for toxic metal ion monitoring. The glassy carbon spheres covalently modified with 2-hydroxy benzoic acid The covalently modified glassy carbon spheres were then used for modification of GCE and used for monitoring Pb21 and Cd21 ions.60 The presence of 2-hydroxy benzoic acid helps in concentrating the analyte on to electrode surface (through interactions between hydroxyl and carboxyl groups of the modifier molecule) and induces selectivity as well as sensitivity during electrochemical monitoring. Another CME i.e., salicylic acid functionalized graphitic carbon pellet electrode had been reported for the same analytes as discussed earlier. The present modifier contains similar functional groups (OH– and COOH groups) with the earlier discussed modifier.64 Similarly, the Hg21 ions linker molecules (organic ligands) functionalized carbon substrates modified electrodes were reported for electrochemical monitoring of Hg21 ions.111–113 The linker organic molecules used in these studies include Fast violet B salt, 4aminobenzamide and mercaptobenzothizole diazonium compound. The corresponding functional groups acting as linker to Hg21 ions in these molecules were amide groups (Fast violet B salt), carbonyl and amine groups (4-aminobenzamide) and thiol group (mercaptobenzothizole diazonium compound). The fashion of coordination to metal ions with the functional groups present in modifier molecules were as given in Fig. 19. Recently calixarenes and their derivatives dragged attention of electroanalytical chemists with their unique properties like cavity size, complexing ability and specific surface binding sites. Some of the calixarenes modified electrodes for electrochemical sensing are discussed in the electrode modification section.61,72,73,114 The modifiers (calixarenes) includes aminothiacalix[4]arene, amino calix[4]arene and tetrahydroxy-calixarene. The amino-thiacalix[4]arene modified electrode was used for electrochemical sensing of Hg21 ions due to the presence of amide and thio groups, which will be specifically binds to Hg21 ions.73 Similarly, amino calix[4]arene modified electrodes were used for mercury determination and simultaneous determination of Pb21 and Cd21 ions.72,114 The tetrahydroxycalixarene modified electrode had been used for simultaneous determination of Pb21 Cu21and Hg21 ions.61 The coordination fashion of metal ions with the functional groups were similar to that of the earlier section. Some of authors reported CMEs for simultaneous electrochemical determination of more than two metal ions.82,115–117 The L-cysteine functionalized rGO composites modified electrode had been reported for simultaneous electrochemical determination of Cd21, Pb21,Cu21, and Hg21 ions.82 In the present modifier four different functional groups (carbonyl, amide, hydroxyl and thiol) are available for coordination with 86 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

Fig. 19 The coordination of Hg21 ions with various donar atoms present on covalently functionalized carbon substrates. A. Coordination of Hg21 ions with deprotonated thiol group sulpher and lone pair of electrons present on nitrogen atoms present on mercaptobenzothiozole covalently functionalized with exfoliated graphite. B. Coordination of Hg21 ions with lone pair of electrons present on amine group nitrogen and carbonyl oxygen of benzamide covalently functionalized glassy carbon spheres. C. Coordination of Hg21 ions with lone pair of electrons present on amine group nitrogen and carbonyl oxygen of fast violet B salt functionalized Single walled carbon nano tubes. Figure A reproduced from ref. 111 with permission from Elsevier, Copyright 2013. Figure B reproduced from ref. 113 with permission, from Elsevier, Copyright 2014. Figure C reproduced from ref. 112 with permission from Elsevier, Copyright 2012.

metal ions. In another CME the modifier composites consist of poly furfural film.115 The coordination interaction occurs between d electrons of metal ions and the p electron back bone of furfural groups. In other two reported simultaneous determination methods the modifier matrix includes N doped graphene and alkaline-Ti3C2.115,117 These substrates helps in increasing the sensitivity by their unique surface structures and electronic properties. Some of the miscellaneous modified electrode materials reported for sensing were discussed here. S. Nantaphol et. al. has reported the boron Electrochemistry, 2019, 15, 58–95 | 87

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

doped diamond paste electrode (BDDPE) coupled with microfluidic paper-based low cost and highly sensitive electrochemical sensing platform for the measurement of biological samples such as norepinephrine and serotonin and also employed in the determination of heavy metals like lead and cadmium ions. In this strategy, the proposed sensor shown a wider potential window, lower capacitive current, and were able to circumvent the fouling of serotonin118 (Fig. 20A). B. Cheng and coworkers have proposed indium tin oxide coated glass (ITO) decorated with vertically ordered mesoporous silica film (VMSF/ITO) and employed as electrochemical sensor for the simultaneous detection of lead, copper and cadmium ions in human serum and soil leaching solution using differential pulse voltammetry and the electrochemical detection consists of electrodeposition of metal species and subsequent anodic stripping in the silica nano channels119 (Fig. 20B). K. Vinod et al. has prepared the aptamer-functionalized black phosphorous nanostructured electrodes for the electrochemical detection of

Fig. 20 A. Boron Doped Diamond paste electrode, B. Illustration of the preparation of vertically ordered mesoporous silica film VMSF decorated ITO electrode and its simultaneous detection of Pb21, Cu21 and Cd21. Figure A reproduced from ref. 118 with permission from American Chemical Society, Copyright 2017. Figure B reproduced from ref. 119 with permission from Elsevier, Copyright 2017. 88 | Electrochemistry, 2019, 15, 58–95

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

View Online

myoglobin by measuring direct electron transfer. In this strategy, black phosphorus nano sheets have been functionalized with poly-L-lysine to facilitate binding with generated anti-Mb DNA aptamers on nanostructured electrodes. The sensing platform has exhibited low detection limit and sensitivity toward myoglobin and further employed in the serum samples120 (Fig. 21A). Satish K. Tuteja et al. has developed the ultrasensitive platform for the detection of cardiac marker Troponin I using bifunctionalized rebar graphene modified gold electrode. In this strategy, the functionalized rebar graphene has been synthesized by onestep microwave-assisted synthetic protocol and fabricated the gold electrodes by standard lithography procedure on a silicon chip28 (Fig. 21B). R. Hao et al. has described the Bipolar Electrochemistry on a NanoporeSupported Platinum Nanoparticle Electrode. In which the authors fabricated the nanopore-supported Pt nanoparticle electrodes and investigated their use in bipolar electrochemistry. Further, a Pt nanoparticle is deposited on the orifice of a solid-state nanopore inside a focused-ion beam (FIB) system121 (Fig. 22A and B).

Fig. 21 A. Black phosphorus functionalized poly-L-lysine decorated anti-Mb DNA aptamers on nanostructured electrodes for myoglobin sensing. B. Microwave-induced electromagnetic transformation of MWCNTs to form functionalized rebar graphene (f-RG). Figure A reproduced from ref. 120 with permission from American Chemical Society, DOI: 10.1021/acsami.6b06488, under the terms of a CC-BY License, https://pubs.acs.org/ page/policy/authorchoice_ccby_termsofuse.html, Copyright 2016. Figure B reproduced from ref. 28 with permission from American Chemical Society, Copyright 2014. Electrochemistry, 2019, 15, 58–95 | 89

Published on 15 October 2018 on https://pubs.rsc.org | d

90 | Electrochemistry, 2019, 15, 58–95 Fig. 22 A. Illustration of fabricating the Pt nanoparticles inside a nanopore by a FIB-assisted deposition process, and the coupled electrochemical reactions on it. B. A schematic illustration of a nanopore-supported nanoparticle electrode used in an electrochemical cell. C. Steady-state cyclic voltammograms of a dual Pt nanoparticle electrode [Electrochemical cell: Quartz nanopipette, Electrolyte: 0.1 M Perchloric acid (Inside) and 5.0 mM ferrocene, 0.2 M TBAPF6 in acetonitrile solution (Outside), Scan rate: 100 mV s1]. The insert shows an SEM image of the electrode. The scale bar represents 1 mm. Reprinted from ref. 121 with permission from American Chemical Society, Copyright 2017.

View Online

References 1

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

2

3 4 5 6 7 8

9 10 11 12 13 14 15 16 17

18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33

K. K. Ligia Moretto, Environmental Analysis by Electrochemical Sensors and Biosensors, Springer, US, 1 edn, 2014. R. A. Durst, E. A. Blubaugh, Chemically Modified Electrode Sensors, in: Fundamentals and Applications of Chemical Sensors, American Chemical Society, 1986, pp. 245–255. C. Zhu, G. Yang, H. Li, D. Du and Y. Lin, Anal. Chem., 2015, 87, 230–249. H. Randriamahazaka and J. Ghilane, Electroanalysis, 2016, 28, 13–26. J. Wang, Analytical Electrochemistry, 3rd edition, John Wiley & Sons, Inc., 2006. E. Butter, Cryst. Res. Technol., 1985, 20, 662. T. D. Burchell, Carbon Materials for Advanced Technologies, 1999. H. O. Pierson, Hand book of carbon, Graphite, Diamond and Fullerenes: Properties, Processing and Applications, Noyes Publications, Noyes New Jersey, 1993. J. C. Bokros, Carbon, 1977, 15, 353–371. R. C. Engstrom, Anal. Chem., 1982, 54, 2310–2314. D. T. Fagan, I. F. Hu and T. Kuwana, Anal. Chem., 1985, 57, 2759–2763. W. E. Van der Linden and J. W. Dieker, Anal. Chim. Acta, 1980, 119, 1–24. P. Chen, M. A. Fryling and R. L. McCreery, Anal. Chem., 1995, 67, 3115–3122. F. Karimi, A. F. Shojaei, K. Tabatabaeian and S. Shakeri, J. Mol. Liq., 2017, 242, 685–689. M. Roushani, A. Valipour and Z. Saedi, Sens. Actuators, B, 2016, 233, 419–425. Y. Temerk and H. Ibrahim, Sens. Actuators, B, 2016, 224, 868–877. P. R. Oliveira, A. C. Lamy-Mendes, E. I. P. Rezende, A. S. Mangrich, L. H. Marcolino Junior and M. F. Bergamini, Food Chem., 2015, 171, 426–431. A. Bahrami, A. Besharati-Seidani, A. Abbaspour and M. Shamsipur, Electrochim. Acta, 2014, 118, 92–99. O. D. Renedo, M. A. Alonso-Lomillo and M. J. A. Martı´nez, Talanta, 2007, 73, 202–219. J. P. Metters, R. O. Kadara and C. E. Banks, Analyst, 2011, 136, 1067–1076. A. P. Ruas de Souza, C. W. Foster, A. V. Kolliopoulos, M. Bertotti and C. E. Banks, Analyst, 2015, 140, 4130–4136. S. Zhan, Y. Wu, L. Wang, X. Zhan and P. Zhou, Biosens. Bioelectron., 2016, 86, 353–368. E. E. Ferapontova, Electroanalysis, 2017, 29, 6–13. M. R. Saidur, A. R. A. Aziz and W. J. Basirun, Biosens. Bioelectron., 2017, 90, 125–139. C. E. Banks, A. Crossley, C. Salter, S. J. Wilkins and R. G. Compton, Angew. Chem., Int. Ed., 2006, 45, 2533–2537. R. R. Moore, C. E. Banks and R. G. Compton, Analyst, 2004, 129, 755–758. C. E. Banks and R. G. Compton, Anal. Sci., 2005, 21, 1263–1268. S. K. Tuteja, P. Sabherwal, A. Deep, R. Rastogi, A. K. Paul and C. R. Suri, ACS Appl. Mater. Interfaces, 2014, 6, 14767–14771. J. M. Zen, A. S. Kumar and D. M. Tsai, Electroanalysis, 2003, 15, 1073–1087. R. W. Murray, Acc. Chem. Res., 1980, 13, 135–141. R. L. McCreery, K. K. Cline, C. A. McDermott and M. T. McDermott, Colloids Surf., A, 1994, 93, 211–219. A. J. Bard, J. Chem. Educ., 1983, 60, 302. R. L. McCreery, Chem. Rev., 2008, 108, 2646–2687.

Electrochemistry, 2019, 15, 58–95 | 91

View Online

34 35 36

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

E. F. S. Vieira, J. de, A. Simoni and C. Airoldi, J. Mater. Chem., 1997, 7, 2249– 2252. A. J. Downard, Electroanalysis, 2000, 12, 1085–1096. S. E. Kooi, U. Schlecht, M. Burghard and K. Kern, Angew. Chem., Int. Ed., 2002, 41, 1353–1355. J. Pinson and F. Podvorica, Chem. Soc. Rev., 2005, 34, 429–439. B. Barbier, J. Pinson, G. Desarmot and M. Sanchez, J. Electrochem. Soc., 1990, 137, 1757–1764. Y.-C. Liu and R. L. McCreery, J. Am. Chem. Soc., 1995, 117, 11254–11259. M. Khoshroo and A. A. Rostami, J. Electroanal. Chem., 2008, 624, 205–210. S. Mahouche Chergui, N. Abbas, T. Matrab, M. Turmine, E. Bon Nguyen, R. Losno, J. Pinson and M. M. Chehimi, Carbon, 2010, 48, 2106–2111. ´sarmot, O. Fagebaume, R. Hitmi, J. Pinsonc and M. Delamar, G. De ´ant, Carbon, 1997, 35, 801–807. J. M. Save A. O. Solak, L. R. Eichorst, W. J. Clark and R. L. McCreery, Anal. Chem., 2003, 75, 296–305. P. Allongue, M. Delamar, B. Desbat, O. Fagebaume, R. Hitmi, J. Pinson and ´ant, J. Am. Chem. Soc., 1997, 119, 201–207. J.-M. Save S. Ssenyange, F. Anariba, D. F. Bocian and R. L. McCreery, Langmuir, 2005, 21, 11105–11112. L. M. Santos, J. Ghilane, C. Fave, P.-C. Lacaze, H. Randriamahazaka, L. M. Abrantes and J.-C. Lacroix, J. Phys. Chem. C, 2008, 112, 16103–16109. Z. Qiu, J. Yu, P. Yan, Z. Wang, Q. Wan and N. Yang, ACS Appl. Mater. Interfaces, 2016, 8, 28291–28298. M. Lillethorup, M. Kongsfelt, M. Ceccato, B. B. E. Jensen, B. Jørgensen, S. U. Pedersen and K. Daasbjerg, Small, 2014, 10, 922–934. S. Mohamadi, N. Sharifi-Sanjani and H. Mahdavi, J. Macromol. Sci., Part A: Pure Appl.Chem., 2011, 48, 577–582. ¨m, T. E. Kerr-Phillips, N. Aydemir, E. W. C. Chan, D. Barker, J. Malmstro C. Plesse and J. Travas-Sejdic, Biosens. Bioelectron., 2018, 100, 549–555. S. Belhousse, R. Boukherroub, S. Szunerits, N. Gabouze, A. Keffous, S. Sam and A. Benaboura, Surf. Interface Anal., 2010, 42, 1041–1045. N. Chen, L. Chen, Y. Cheng, K. Zhao, X. Wu and Y. Xian, Talanta, 2015, 132, 155–161. D. B. Gorle and M. A. Kulandainathan, RSC Adv., 2016, 6, 19982–19991. J. Cha, J. I. Han, Y. Choi, D. S. Yoon, K. W. Oh and G. Lim, Biosens. Bioelectron., 2003, 18, 1241–1247. K. Zhou, Y. Zhu, X. Yang and C. Li, Electroanalysis, 2011, 23, 862–869. K. Zhou, Y. Zhu, X. Yang, J. Luo, C. Li and S. Luan, Electrochim. Acta, 2010, 55, 3055–3060. Y. Xin, X. Fu-bing, L. Hong-wei, W. Feng, C. Di-zhao and W. Zhao-yang, Electrochim. Acta, 2013, 109, 750–755. L. Zhang, G. Han, Y. Liu, J. Tang and W. Tang, Sens. Actuators, B, 2014, 197, 164–171. L. Xie, Y. Xu and X. Cao, Colloids Surf., B, 2013, 107, 245–250. G. K. Raghu, S. Sampath and M. Pandurangappa, J. Solid State Electrochem., 2012, 16, 1953–1963. P. Shivappa Adarakatti, C. W. Foster, C. E. Banks and A. K. N. S. P. Malingappa, Sens. Actuators, A, 2017, 267, 517–525. M. P. Somashekarappa and S. Sampath, Chem. Commun., 2002, 1262–1263. G. K. Ramesha and S. Sampath, Sens. Actuators, B, 2011, 160, 306–311. R. Gunigollahalli Kempegowda and P. Malingappa, Anal. Chim. Acta, 2012, 728, 9–17.

92 | Electrochemistry, 2019, 15, 58–95

View Online

65 66

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

67

68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84

85 86 87 88 89 90 91 92

S. K. Kempahanumakkagari, P. S. Adarakatti and P. Malingappa, J. Environ. Chem. Eng., 2018, 6, 2674–2683. B. Rodrı´guez, A. Bruckmann, T. Rantanen and C. Bolm, Adv. Synth. Catal., 2007, 349, 2213–2233. E. Gaffet, F. Bernard, J.-C. Niepce, F. Charlot, C. Gras, G. Le Caer, J.-L. Guichard, P. Delcroix, A. Mocellin and O. Tillement, J. Mater. Chem., 1999, 9, 305–314. N. Pierard, A. Fonseca, J. F. Colomer, C. Bossuot, J. M. Benoit, G. Van Tendeloo, J. P. Pirard and J. B. Nagy, Carbon, 2004, 42, 1691–1697. N. J. Welham, V. Berbenni and P. G. Chapman, Carbon, 2002, 40, 2307– 2315. X. Li, J. Shi, Y. Qin, Q. Wang, H. Luo, P. Zhang, Z.-X. Guo, H.-S. Woo and D.-K. Park, Chem. Phys. Lett., 2007, 444, 258–262. P. L. Spargo, Org. Process Res. Dev., 2005, 9, 697. P. S. Adarakatti and P. Malingappa, J. Solid State Electrochem., 2016, 20, 3349–3358. P. S. Adarakatti, C. E. Banks and P. Malingappa, Anal. Methods, 2017, 9, 6747–6753. C.-L. Sun, C.-T. Chang, H.-H. Lee, J. Zhou, J. Wang, T.-K. Sham and W.-F. Pong, ACS Nano, 2011, 5, 7788–7795. F. Foroughi, M. Rahsepar, M. J. Hadianfard and H. Kim, Microchim. Acta, 2017, 185, 57. Y. Gao and I. Kyratzis, Bioconjugate Chem., 2008, 19, 1945–1950. Y. Xu, Z. Liu, X. Zhang, Y. Wang, J. Tian, Y. Huang, Y. Ma, X. Zhang and Y. Chen, Adv. Mater., 2009, 21, 1275–1279. J.-M. Zen, A. Senthil Kumar and D.-M. Tsai, Electroanalysis, 2003, 15, 1073– 1087. S. Kempahanumakkagari, V. Kumar, P. Samaddar, P. Kumar, T. Ramakrishnappa and K.-H. Kim, Biotechnol. Adv., 2018, 36, 467–481. S. Kempahanumakkagari, K. Vellingiri, A. Deep, E. E. Kwon, N. Bolan and K.-H. Kim, Coord. Chem. Rev., 2018, 357, 105–129. S. Kempahanumakkagari, A. Deep, K.-H. Kim, S. Kumar Kailasa and H.-O. Yoon, Biosens. Bioelectron., 2017, 95, 106–116. S. Muralikrishna, K. Sureshkumar, T. S. Varley, D. H. Nagaraju and T. Ramakrishnappa, Anal. Methods, 2014, 6, 8698–8705. T. N. Ravishankar, S. Muralikrishna, K. Suresh kumar, G. Nagaraju and T. Ramakrishnappa, Anal. Methods, 2015, 7, 3493–3499. A. K. Ramasami, T. N. Ravishankar, K. Sureshkumar, M. V. Reddy, B. V. R. Chowdari, T. Ramakrishnappa and G. R. Balakrishna, J. Alloys Compd., 2016, 671, 552–559. S. Muralikrishna, K. Sureshkumar, Z. Yan, C. Fernandez and T. Ramakrishnappa, J. Braz. Chem. Soc., 2015, 26, 1632–1641. T. N. Ravishankar, K. Sureshkumar, J. Dupont, T. Ramakrishnappa and G. Nagaraju, J. Exp. Nanosci., 2015, 10, 1358–1373. S. Kempahanumakkagari, V. Kumar, P. Samaddar, P. Kumar, T. Ramakrishnappa and K.-H. Kim, Biotechnol. Adv., 2018, 36, 467–481. W. Ma, Q. Jiang, P. Yu, L. Yang and L. Mao, Anal. Chem., 2013, 85, 7550–7557. X. Wang, X. Lu, L. Wu and J. Chen, Biosens. Bioelectron., 2015, 65, 295–301. S. Xie, J. Ye, Y. Yuan, Y. Chai and R. Yuan, Nanoscale, 2015, 7, 18232–18238. W. Chen, W. Yang, Y. Lu, W. Zhu and X. Chen, Anal. Methods, 2017, 9, 3213– 3220. F. Gao, L. Du, Y. Zhang, F. Zhou and D. Tang, Biosens. Bioelectron., 2016, 86, 185–193. Electrochemistry, 2019, 15, 58–95 | 93

View Online

93 94 95

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

96 97 98 99 100 101 102 103 104 105 106 107 108 109 110

111 112 113 114 115 116 117 118 119 120

121

J.-J. L. A. J. Saleh Ahammad and Md. Aminur Rahman, Sensors, 2009, 9, 2289–2319. N. Sato and H. Okuma, Sens. Actuators, B, 2008, 129, 188–194. P. Santhosh, K. M. Manesh, A. Gopalan and K.-P. Lee, Sens. Actuators, B, 2007, 125, 92–99. C. E. Banks and R. G. Compton, Analyst, 2006, 131, 15–21. C. E. Banks, T. J. Davies, G. G. Wildgoose and R. G. Compton, Chem. Commun., 2005, 829–841. A. F. Holloway, G. G. Wildgoose, R. G. Compton, L. Shao and M. L. H. Green, J. Solid State Electrochem., 2008, 12, 1337. A. Chou, T. Bocking, N. K. Singh and J. J. Gooding, Chem. Commun., 2005, 842–844. J. J. Gooding, A. Chou, J. Liu, D. Losic, J. G. Shapter and D. B. Hibbert, Electrochem. Commun., 2007, 9, 1677–1683. ¨cking, R. Liu, N. K. Singh, G. Moran and J. J. Gooding, J. Phys. A. Chou, T. Bo Chem. C, 2008, 112, 14131–14138. N. S. Lawrence, R. P. Deo and J. Wang, Electroanalysis, 2005, 17, 65–72. M. Musameh, N. S. Lawrence and J. Wang, Electrochem. Commun., 2005, 7, 14–18. T. N. Ravishankar, K. Suresh Kumar, S. R. Teixeira, C. Fernandez and T. Ramakrishnappa, Electroanalysis, 2016, 28, 452–461. R. Siavash Moakhar, G. K. L. Goh, A. Dolati and M. Ghorbani, Electrochem. Commun., 2015, 61, 110–113. W. Jin, G. Wu and A. Chen, Analyst, 2014, 139, 235–241. M.-C. Tsai and P.-Y. Chen, Talanta, 2008, 76, 533–539. J. P. Metters, R. O. Kadara and C. E. Banks, Analyst, 2012, 137, 896–902. W. Jin and K. Yan, RSC Adv., 2015, 5, 37440–37450. J. M. Samrat Devaramani, S. Kempahanumakkagari, Ramakrishnappa Thippeswamy and P. Mahalingappagari, Int. J. Electrochem. Sci., 2014, 9, 4692–4708. R. G. Kempegowda and P. Malingappa, Sens. Actuators, B, 2013, 186, 478–485. R. G. Kempegowda and P. Malingappa, Electrochem. Commun., 2012, 25, 83–86. R. G. Kempegowda and P. Malingappa, Talanta, 2014, 126, 54–60. S. A. Prashanth and M. Pandurangappa, Mater. Lett., 2016, 185, 476–479. J. Huang, S. Bai, G. Yue, W. Cheng and L. Wang, RSC Adv., 2017, 7, 28556– 28563. H. Xing, J. Xu, X. Zhu, X. Duan, L. Lu, W. Wang, Y. Zhang and T. Yang, J. Electroanal. Chem., 2016, 760, 52–58. X. Zhu, B. Liu, H. Hou, Z. Huang, K. M. Zeinu, L. Huang, X. Yuan, D. Guo, J. Hu and J. Yang, Electrochim. Acta, 2017, 248, 46–57. S. Nantaphol, R. B. Channon, T. Kondo, W. Siangproh, O. Chailapakul and C. S. Henry, Anal. Chem., 2017, 89, 4100–4107. B. Cheng, L. Zhou, L. Lu, J. Liu, X. Dong, F. Xi and P. Chen, Sens. Actuators, B, 2018, 259, 364–371. V. Kumar, J. R. Brent, M. Shorie, H. Kaur, G. Chadha, A. G. Thomas, E. A. Lewis, A. P. Rooney, L. Nguyen, X. L. Zhong, M. G. Burke, S. J. Haigh, A. Walton, P. D. McNaughter, A. A. Tedstone, N. Savjani, C. A. Muryn, P. O’Brien, A. K. Ganguli, D. J. Lewis and P. Sabherwal, ACS Appl. Mater. Interfaces, 2016, 8, 22860–22868. R. Hao, Y. Fan, C. Han and B. Zhang, Anal. Chem., 2017, 89, 12652–12658.

94 | Electrochemistry, 2019, 15, 58–95

View Online

122 123 124

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00058

125 126 127 128 129 130

131 132 133 134 135 136 137 138 139 140 141 142

143 144 145 146 147 148

B. P. Corgier, C. A. Marquette and L. J. Blum, J. Am. Chem. Soc., 2005, 127, 18328–18332. S. Dong, G. Suo, N. Li, Z. Chen, L. Peng, Y. Fu, Q. Yang and T. Huang, Sens. Actuators, B, 2016, 222, 972–979. C. Gong, Y. Shen, J. Chen, Y. Song, S. Chen, Y. Song and L. Wang, Sens. Actuators, B, 2017, 239, 890–897. X. Lu, X. Wang, L. Wu, L. Wu, Dhanjai, L. Fu, Y. Gao and J. Chen, ACS Appl. Mater. Interfaces, 2016, 8, 16533–16539. S. Patra, T. Hidalgo Crespo, A. Permyakova, C. Sicard, C. Serre, A. Chausse, N. Steunou and L. Legrand, J. Mater. Chem. B, 2015, 3, 8983–8992. J. He, H. Yang, Y. Zhang, J. Yu, L. Miao, Y. Song and L. Wang, Sci. Rep., 2016, 6, 36637. P. Ling, J. Lei, L. Zhang and H. Ju, Anal. Chem., 2015, 87, 3957–3963. W.-J. Shen, Y. Zhuo, Y.-Q. Chai and R. Yuan, Anal. Chem., 2015, 87, 11345–11352. M. K. L. Coelho, H. L. De Oliveira, F. G. De Almeida, K. B. Borges, C. R. T. Tarley and A. C. Pereira, Int. J. Environ. Anal. Chem., 2017, 97, 1378–1392. T. Alizadeh, N. Hamidi, M. R. Ganjali and F. Rafiei, J. Environ. Chem. Eng., 2017, 5, 4327–4336. T. Alizadeh, N. Hamidi, M. R. Ganjali and P. Nourozi, Sens. Actuators, B, 2017, 245, 605–614. T. Alizadeh, M. R. Ganjali, M. Akhoundian and P. Norouzi, Microchim. Acta, 2016, 183, 1123–1130. Y. Wang, Y. Wu, J. Xie and X. Hu, Sens. Actuators, B, 2013, 177, 1161–1166. Y. Z. Z. W. Fengyuan Zhang, Z. Zheng, C. Wangv, Y. Du and W. Ye, Int. J. Electrochem. Sci., 2012, 7, 1968–1977. M. Sreejesh, S. Dhanush, F. Rossignol and H. S. Nagaraja, Ceram. Int., 2017, 43, 4895–4903. Y. Liu, Y. Ma, Y. Jin, G. Chen and X. Zhang, J. Electroanal. Chem., 2015, 739, 172–177. A. Ramachandran, S. Panda and S. Karunakaran Yesodha, Sens. Actuators, B, 2018, 256, 488–497. S. Chabri, A. Dhara, B. Show, D. Adak, A. Sinha and N. Mukherjee, Catal. Sci. Technol., 2016, 6, 3238–3252. S. Menon, S. Jesny and K. Girish Kumar, Talanta, 2018, 179, 668–675. A. Nezhadali, L. Mehri and R. Shadmehri, Mater. Sci. Eng., C, 2018, 85, 225–232. L. V. da Silva, C. B. Lopes, W. C. da Silva, Y. G. de Paiva, F. d. A. d. S. Silva, P. R. Lima, L. T. Kubota and M. O. F. Goulart, Microchem. J., 2017, 133, 460–467. T. S. Sunil Kumar Naik and B. E. Kumara Swamy, J. Electroanal. Chem., 2017, 804, 78–86. K. Kor and K. Zarei, Talanta, 2016, 146, 181–187. Y. J. Yang, L. Guo and W. Zhang, J. Electroanal. Chem., 2016, 768, 102–109. M. B. Gholivand and N. Karimian, Sens. Actuators, B, 2015, 215, 471–479. X. Zhang, Y. Peng, J. Bai, B. Ning, S. Sun, X. Hong, Y. Liu, Y. Liu and Z. Gao, Sens. Actuators, B, 2014, 200, 69–75. Y. Peng, Z. Wu and Z. Liu, Anal. Methods, 2014, 6, 5673–5681.

Electrochemistry, 2019, 15, 58–95 | 95

Electrochemiluminescence fundamentals and analytical applications Lynn Dennany Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

DOI: 10.1039/9781788013895-00096

1

Introduction

Electrochemiluminescence (ECL) or electrogenerated luminescence continues to develop as an effective electroanalytical tool ever since its introduction by Tokel and Bard.1 However, unlike chemiluminescence, ECL does not require an external light source. This combination of electrochemistry and chemiluminescence affords many potential benefits.2 These include the fact that some reactants can be electrochemically generated and regenerated at the electrode surface. This often results in many photons produced per measurement cycle and can therefore, enhance the observed sensitives. Since the often unstable chemiluminescence reagents or intermediates are generated in situ, this provides another advantage over traditional chemiluminescence. The electrochemical generation of reactants at the electrode surface also means that it is possible to generate species that may not take part in a chemiluminescent reaction. As the reactants are electrochemically generated, it allows greater control over the position of emission that can be beneficial for sensitivity, selectivity, the detection of multi-targets as well as for imaging analysis. There is also control over the time of these reactions, which can improve reproducibility and often simplify operation. Since both current and light signals are obtained simultaneously, investigations into the electrochemical reactions as well as the ECL detection can be monitored. Although ECL also has some limitations including weaker luminescent signals produced at the electrode surface, a requirement for frequent renewal of the electrode surface to ensure good reproducibility and specialised setup, its many advantages has lent itself to applications in numerous fields including immunoassays, DNA detection, nucleic acid sensors, biosensors, and forensic analysis to name but a few. Although tris(2,2 0 -bipyridine)ruthenium(II) ([Ru(bpy)3]21) based ECL continues to lead the way in terms of research and applications due to its high sensitivity, wide dynamic range, simplicity and stable labels for coupling with immunoassays and DNA probe assays, more and more research into alternative ECL materials has been undertaken. 1.1 Fundamentals of ECL ECL is a unique type of electron transfer that generates excited states, namely by the reaction of radical ions (or highly reduced or oxidised WestCHEM, Department of Pure & Applied Chemistry, University of Strathclyde, Technology & Innovation Centre, 99 George Street, Glasgow G1 1RD, UK. E-mail: [email protected] 96 | Electrochemistry, 2019, 15, 96–146  c

The Royal Society of Chemistry 2019

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

3

species). The emission of light is produced as a result of the formation of electrogenerated species through a heterogeneous electron transfer at the vicinity of the electrode, followed by the interaction of these precursor ions to generate an excited state through homogeneous electron transfer.4 An ECL response is detected as these excited states relax to a lowerlevel state; emission of a photon is detected at a particular wavelength controlled by the energy gaps between the two states.5,6 The excited state formation, as a result of electron transfer involves a kinetic manifestation of the Franck–Condon principle.7,8 The light is produced as a result of the formation of electrogenerated precursors (usually radical ions in organic systems and oxidised/reduced species in inorganic systems) through heterogeneous electron transfer at an electrode, followed by the interaction of these precursor ions to produce an excited state via rapid (B1010 M1 s1), energetic (2–4 eV), homogeneous electron transfer reactions (Fig. 1).4 Three fundamental factors are required for the production of an efficient ECL signal, specifically, the generation of stable precursor species within the system, sufficient energetics of the homogeneous electron transfer reactions to create an excited state and good photoluminescent efficient of this excited state. Both organic and inorganic ECL systems exist, which differ in their respective precursor species. In organic ECL systems the precursors participating in the homogeneous electron transfer, are often in the form of oxidised and reduced radical ions, whereas in inorganic systems they are typically the reduced and/or oxidised forms of the parent complex. The oxidised precursor represents a ‘hole’ in the HOMO which enhances its oxidation properties while the reduced form represents an electron in the LUMO, which enhances its capacity for reduction. The key element dictating the efficient of ECL production is the kinetics of the electron transfer reactions leading to precursor and excited state formation. The energetics of these processes are also important to consider when investigating the ECL behaviour of a system.

Fig. 1 Outline of the ECL process.2 Electrochemistry, 2019, 15, 96–146 | 97

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

1.2 Heterogeneous electron transfer – precursor formation ECL can be instigated in a number of different ways with the electrogeneration of precursor species resulting from an annihilation or coreactant pathway.4 1.2.1 Annihilation pathway. This mechanism usually involves the sequential generation of the oxidised and reduced forms of a radical ion or parent molecule through the application of a potential, at which these processes can occur. Initially, the electrode potential is stepped to produce a radical cation, eqn (1), (or anion) within the system, which remains in the diffusion layer surrounding the electrode. The potential is then rapidly switched to a voltage capable of producing the corresponding radical anion, eqn (2), (or cation), which diffuses away from the electrode following Fick’s first law as its concentration at the electrode surface increases. At this secondary potential, the radical cations within the immediate vicinity of the electrode are reduced and thus its concentration at the electrode diminishes. This results in back diffusion of the same species from within the diffusion layer towards the electrode surface. These then interact with the electrogenerated anions that are diffusing in the opposite direction. A-A 1 þ e

(1)

A-A   e

(2)

A 1 þ A -1A*

(3)

A 1 þ A -A þ 3A*

(4)

23A*-A þ 1A*

(5)

A*-A þ hn

(6)

Here, the excited singlet state is either formed directly by the interaction of the two electrogenerated species (eqn (3)) or through triplet– triplet annihilation following the formation of two excited triplet states (eqn (5)). Radiative relaxation of the excited state is accompanied by the emission of light, eqn (6), at the characteristic wavelength of the emitting species. Alternatively, the precursors can be created at two different electrodes in close proximity using rotating ring – disk electrodes, with one species formed at the ring and the other at the disk. These species are then swept together by diffusion and convection, allowing them to react.11,12 The major advantage of the annihilation pathway is that only the ECL species, solvent and electrolyte are required to generate light and the system is therefore simple and cost-effective. However, this system also has some limitations, namely, for emissions in the visible region (B400– 700 nm), the excited singlet energy lies between 1.8 and 3.1 eV (from the Planck relation, E ¼ hn ¼ hc/l) and therefore, for annihilation ECL to occur, the potential window of the system must be sufficiently large to 98 | Electrochemistry, 2019, 15, 96–146

View Online 2

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

allow the generation of stable radical anions and cations. Organic solvents are often required as the potential window of aqueous media is often insufficient to satisfy these criteria. Additionally, quenching of excited states by dissolved oxygen9 can significantly affect the annihilation ECL response and as such these must be removed from the system prior to analysis. 1.2.2 Co-reactant pathway. The co-reactant mechanism involves the addition of a reagent, often referred to as the co-reactant, to the system. The co-reactant must satisfy particularly criteria to be suitable for co-reactant ECL to occur. It must be both soluble and stable (ideally within aqueous media), be easily oxidised and reduced, and be able to form strongly oxidising or reducing intermediates. The kinetics of these processes should be rapid and none of the species involved should themselves generate ECL or quench the ECL signal of the luminophore. A potential is applied at an electrode causing the oxidation or reduction (depending on the polarity of the potential) of both the luminophore and the co-reactant to form radicals using a one-directional voltage scan. The electrogenerated co-reactant species then immediately decomposes to form a powerful reducing or oxidizing intermediate, which has a standard redox potential that permits fast electron or hole injection into the electrogenerated luminophore species with sufficient energy to generate the excited state. Following the emission of light, the luminophore can often be regenerated, whilst the co-reactant is usually consumed during this reaction. The co-reactant pathway has four main stages as outlined in Table 1. The oxidative route involves initial oxidation of the luminophore and co-reactant to create radical cations, with excited state formation following homogeneous electron transfer reactions, as outlined in Table 1. A common co-reactant used for oxidation is tri-n-propylamine (TPrA),10 shown in eqn (7–12), which produces strong reductants upon oxidation. A potential is applied at the electrode causing either oxidation or reduction of both the electroluminescent material and the co-reactant to form radicals. TPrA produces a strong reducing agent TPrA, whereas Table 1 The co-reactant mechanism.a Reaction process Redox reactions at electrode. Homogeneous electron transfer reactions. Excited state formation. Light emission.

Oxidative–reduction ECL

Reductive–oxidation ECL

R  e-R 1 C  e-C 1 R 1 þ C-R þ C 1 C 1-CaRed CaRed þ R-R  þ P R 1 þ R -R þ R* R 1 þ CaRed-R* þ P R*-R þ hn

R þ e-R  C þ e-C  R  þ C-R þ C  C -CaOx CaOx þ R-R 1 þ P R 1 þ R -R þ R* R  þ CaOx-R* þ P R*-R þ hn

a R ¼ luminophore; C ¼ co-reactant; Ca ¼ co-reactant intermediate, subscript ‘‘Red’’ for reducing agent, ‘‘Ox’’ for oxidizing agent; P ¼ product associated with Ca reactions.

Electrochemistry, 2019, 15, 96–146 | 99

View Online 

2

oxalate C2O4 produces a strong reductant, CO2 . These strong reducing or oxidising intermediates can then react with the oxidised or reduced electroluminescent species, respectively, to produce an excited state, followed by ECL emission.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

1

H3NCRHCO2 þ OH2H2NCRHCO2 þ H2O

(7)

H2NCRHCO2 þ Ru(bpy)331-H2N 1RHCO2 þ Ru(bpy)321

(8)

H2N 1CRHCO2-H2NC RCO2 þ H1

(9)

3þ 2þ *  H2 NC RCO þ Hþ 2 þ Ruðbpy Þ3 ! HNCRCO2 þ Ruðbpy Þ3

(10)

HNCRCO2 þ H2O-RCOCO2 þ NH3

(11)

RuðbpyÞ32þ * ! RuðbpyÞ32þ þhn

(12)

Danielson et al. have looked at a large number of amines with respect to their potential for producing ECL.11 They found a strong inverse correlation between ECL intensity and first ionisation potential, and also noted that the loss of a non-bonding electron for the electron transfer reaction leading to ECL was favoured. Knight and Greenway have reviewed the relationship between structural attributes of tertiary amines and ECL activity with Ru(bpy)321.12 Among the most important features were as follows; a hydrogen atom attached to the a-carbon is usually essential. Electron withdrawing or donating substituents close to the radical centre tend to modulate ECL intensity due to a stabilising or destabilising effect on the radical intermediate (which participates in the reaction leading to the excited state). Resonance stabilisation of the radical intermediate reduces its reactivity and thus ECL intensity (as is the case with aromatic amines), the molecular geometry and the radical species may also be a factor. The reductive ECL process involves reduction of the luminophore and co-reactant, which can generate the excited state following interaction of the oxidising co-reactant intermediate with the reduced luminophore (Table 1). An example of this is the ruthenium/persulfate system. Reduction of both the ruthenium and persulfate occurs at the electrode surface with the strong oxidising agent SO4  formed from the decomposition of S2O8 31. This is capable of removing an electron from the ruthenium tris(2,2 0 -bipyridine)ruthenium(II) species to generate the excited state that can emit an ECL signal. The major benefit of this co-reactant pathway is that it allows ECL generation in aqueous solution as the luminophore and the co-reactant can be reduced or oxidised during the same potential step, so a solvent with a wide potential window (i.e. an organic solvent) is not required. This is a benefit for clinical and biomedical applications, which require analysis in aqueous media and also physiological pH environments to aid biocompatibility.13,15 Additionally, co-reactants also allow production of 100 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

an ECL signal from systems where either the radical cation or anion of the luminophore is unstable, which would prevent annihilation ECL from occurring.2 It show also be noted that ECL intensity in such systems is often affected by dissolved O2. This can interact with the excited state causing nonradiative relaxation to the ground state thereby quenching the ECL signal. However, heavy metal complexes, such as ruthenium and osmium) usually generate strong ECL signals with shortened excited state lifetimes, which limits the impact of quenching by interfering species. 1.2.3 Homogeneous electron transfer – excited state formation. Homogeneous electron transfer resulting in excited state formation and subsequently relax resulting in light generation is essential for the observation of an ECL signal. This can be achieved via two alternative routes, A or B. Route A involves the transfer of an electron from the lowest unoccupied molecular orbital (LUMO) of the reduced precursor to the LUMO of the oxidized precursor, Fig. 2. This results in the

Fig. 2 Molecular orbital diagram showing two alternative pathways for electron transfer between oxidised and reduced precursors R  and R þ . (A) Formation of an excited state and (B) direct population of ground state products. Electrochemistry, 2019, 15, 96–146 | 101

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

formation of one ground state molecule and one excited state molecule, which can then relax, via the emission of a photon, to the ground state. Route B involves electron transfer from the LUMO of the reduced precursor to the highest occupied molecular orbital (HOMO) of the oxidised precursor to produce two molecules in the ground state. This pathway is favoured thermodynamically; as it results in two ground state molecules. However, if electron transfer is rapid enough, a large amount of energy has to be dissipated in vibrational modes over a very short period of time, which is unfavourable. Here a kinetic manifestation of the Franck–Condon principle is observed. The Franck–Condon principle states that the relative positions and momenta of atoms involved in a specific transition are preserved because of the movement of an electron is exponentially faster than that of a nucleus. Thus, the most probably transition will obey this principle and will be that with the fastest electron transfer. Relating this to the ECL process, route B results in the formation of two ground state molecules and therefore is thermodynamically favourable as a large amount of energy is released from the system. However, this energy must be dissipated vibrationally, which isn’t favourable due to the disruption of the system. Route A produces an excited state molecule and one in the ground state which is a less exergonic process overall and so is less thermodynamically favoured. The route means less energy must be dissipated through vibrational modes, which makes this process the more kinetically favourable route and electron transfer occurs more rapidly. Therefore, the path to electronically excited products becomes relatively attractive, because its demand for mechanical accommodation is not nearly so great.4,8 The requirements for reactions leading to ECL have also been explained within the frame work of the Marcus theory of electron transfer,14 which correlates the electron transfer to both electronic and nuclear considerations through eqn (13).   DG  KET ¼ n exp  RT

(13)

Where KET is the rate of electron transfer, n is the frequency factor, DG8 is the Marcus free energy of activation, R is the gas constant and T is the absolute temperature. DG8 can then be related to the standard free energy of the reaction, DG0, through eqn (14).15 DG  ¼

ðDG0 þ lÞ 4l

2

(14)

Where l is the total reorganisation energy, which is the energy required to distort the system to attain the equilibrium configuration of the product state. This includes an outer sphere component and an inner sphere component. The outer sphere comprises the reorganisation of solvent and surrounding media while the inner sphere comprises the reorganisation of the molecular geometry of the reactant as it reaches the product state. 102 | Electrochemistry, 2019, 15, 96–146

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

8

This equation predicts a parabolic relationship between DG and DG0 that can be used to explain the rate of electron transfer in relation to the standard free energy of the reaction. It predicts that as DG0 increases so does the rate of electron transfer. KET reaches a maximum when l ¼ DG0 and DG8 ¼ 0, with any further increases in DG0 resulting in a decrease in the electron transfer rate in the inverted Marcus region.15 This can be applied to the processes outlined in Fig. 2 where the highly exergonic nature of route B means that it lies in the inverted region and thus the rate of electron transfer is slower than for route A. Therefore, route A will experience a more instantaneous type electronic transition and according to the Franck–Condon principle, will be the most probably transition.7,8 1.2.4 Energetics of homogeneous electron transfer. The nature of the formed excited state is dependent upon the energy that is available in the system and the energies of the excited states, which is dictates where a singlet or triplet route is followed. The energy available in the system is governed by the energetics of the ion-annihilation reaction, which can be determined using eqn (15):2  DH0 ¼ Ep(D 1/D)  Ep(A/A )  TDS0 0

(15) 1

Where DH is the enthalpy for electron transfer reaction eV, Ep(D /D) and Ep(A /A) are the peak potentials for reduction of the precursor D and precursor A, in volts, respectively. TDS0 is an entropy term that is estimated at 0.1 eV (at 25 1C)16,17 and combined with the peak separation of a reversible redox couple (0.057 eV for a one electron transfer process) to give a final value of 0.16 eV.18 The reaction is said to be energy sufficient when DH0 of the system is greater than the energy required to promote an electron into the lowest excited singlet state. As such, excited singlet states are produced directly from electron transfer between ECL precursors and the mechanism of excited state formation is said to follow the S route. An example of this route is the DPA, 9, 10-diphenylanthracene, system shown in eqn (16)–(19).19 DPA-DPA 1 þ e

(16)

DPA þ e-DPA 

(17)

DPAþ þ DPA ! DPA*1

(18)

DPA*1 ! DPA þ hn

(19)

If there is insufficient enthalpy in the system to generate excited singlet states, then another mechanism is responsible for creating the ECL signal. Provided the free energy of the system is greater than that for the production of the excited triplet state, an ECL signal can be generated via the T route – the triplet–triplet annihilation of triplet species formed during the ion-annihilation reaction to produce an emissive singlet state. Generally, ECL emission directly from a triplet state will be low due to Electrochemistry, 2019, 15, 96–146 | 103

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

quenching of the long lived states by O2 and other quenching species in solution.12,19 An example of this is the TMPD (N, N, N 0 , N 0 -tetramethyl-pphenylenediamine)/DPA system shown in eqn (20)–(23).19 TMPD-TMPD 1 þ e

(20)

TMPDþ þ DPA ! TMPD þ DPA*3

(21)

2DPA*3 ! DPA þ DPA*1

(22)

DPA*1 ! DPA þ hn

(23)

Fig. 3 illustrates the energetics of the DPA and TMPD/DPA systems. It can be seen that eqn (18) is capable of populating the excited singlet state directly; however, eqn (21) only has sufficient energy to generate an excited triplet state. In general, the energy gap between the triplet state and the ground state is greater than the energy gap between the triplet and singlet states. As such, the interaction between two of these triplet species should provide sufficient electronic energy to create one excited singlet species, provided the second species relaxes to the ground state.20 An alternative mechanism of excited state generation is the ST route, which combines both the S and T-routes. When the available energy in the system is close to that of the excited singlet state, both the S and T routes contribute to the formation of the excited singlet species. An example of this is the Rubrene anion–cation annihilation.21 Ion annihilation reactions can also result in the formation of excited dimers

Fig. 3 Energy level diagram for DPA and DPA-TMPD ECL systems. 104 | Electrochemistry, 2019, 15, 96–146

View Online

(excimers) and excited complexes (exciplexes), as shown in eqn (24) and (25).2 Aþ þ A ! A*2

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

A 1 þ D -(AD)*

Excimer formation Exciplex formation

(25) (26)

These excimers and exciplexes can then emit light directly, with these types of reactions said to follow the E route. The E route emission is broad, featureless and lower in energy than the corresponding singlet emission.2 An example of this type of emission occurs in the pyrene/TMPD system (eqn. 30–32).22 Where 1Py* and 3Py* represent the excited singlet and triplet states of pyrene respectively and Py2* represents the eximer. The emission profile contains a double peak, one atB400 nm corresponding to the singlet and one at B480 nm corresponding to the excimer. 1.3 ECL systems 1.3.1 Ruthenium based ECL systems. Ruthenium based ECL systems have traditionally represented the majority of ECL systems and are the most successful ECL luminophore with a broad range of applications, indeed [Ru(bpy)3]21 was the first inorganic ECL luminophore. This achievement is ascribed to the excellent chemical, electrochemical and ECL properties of ruthenium complexes. Ruthenium based ECL complexes typically have a lmax between 600 and 650 nm and this is often difficult to tune owing to the limited ligand-field spitting energies of the central metal ions of these ruthenium complexes. [Ru(bpy)3]21 and its analogues have been widely used for the detection and quantitation of a wide variety of co-reactant targets such as oxalate,1 alkyamines, amino acids,23–25 ascorbic acid,26 DNA bases, and many pharmaceutical compounds. Developments to improve the recognition ability of ruthenium based ECL systems has examined the modulation of the ruthenium ligands to achieve the desired specificity. The modulation of ruthenium ligands also allowed for more efficient and effective coupling to recognition elements such as antibodies, DNA sequences or aptamers. The combination of [Ru(bpy)3]21 with antibodies, aptamers or DNA sequences and exploit the selectivity of these recognition elements with the inherent advantages of ECL based sensors.27 This facilitated the use of [Ru(bpy)3]21/TPrA ECL systems within sensitive label detection system at subpicomolar concentration while providing a wide dynamic range as shown in Fig. 4.27,28 This have expanded the application of [Ru(bpy)3]21/TPrA label co-reactant ECL into the commercial arena as well as for DNA analyses. The first attempts at improving molecular recognition through modulation of the ligands of the ruthenium complexes investigated the incorporation of crown ether moieties convalently bonded to the bipyridyl or phenathroline ligands to facilitate metal-cation sensing.29–32,58 The effects of cation binding on the ECL were investigated via both the annihilation and co-reactant pathways. These modifications resulted in a 20-fold enhancement of the ECL response in some instances. Selectivity Electrochemistry, 2019, 15, 96–146 | 105

Published on 15 October 2018 on https://pubs.rsc.org | d

106 | Electrochemistry, 2019, 15, 96–146 Fig. 4 (a) Schematic illustration of the fabrication of recombinant antibody based biosensor for the detection of C-Reactive protein. The stepwise fabrication of the sensor is highlighted, scFv immobilization onto electrode or electrochemical probe, binding of pentameric CRP followed by binding of metal labeled ScFv fragments. (b) Dependence of the ECL emission intensity on the CRP concentration. From top to bottom at þ1.2 V, the concentrations of CRP range from 600 ng mL1 to 5 fg mL1. The inset shows dependence of the logarithm of the maximum ECL intensity on log[CRP]. The error bars are comparable to, or smaller than, the size of the symbols. Reproduced from ref. 27 with permission of the Royal Society of Chemistry.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 5 (A) Scheme of ECL switch based on [Ru(bpy)2dppz]21 and DNA. (B) ECL intensities in 5 mM pH 5.5 oxalate solution containing 0.1 mM [Ru(bpy)2dppz]21 (curve a) and 0.1 mM [Ru(bpy)2dppz]21 þ 0.16 mM DNA (curve b). Reproduced from ref. 33 with permission from American Chemical Society, Copyright 2009.

was also shown to improve, with the ECL emission of guanidinium 3,3 0 functionalised bipyridyl ruthenium selectively increased in the presence of dihydrogenphosphate (Fig. 5).33 Many of these modified ruthenium ligands have been found to intercalate into DNA with a high affinity due to the extended aromatic structure. This property can be utilised in a popular ‘‘light switch’’ molecule that displays intense photoluminescence only in the presence of DNA. This has allowed for the dramatic enhancement of ECL responses upon intercalation with DNA.33 The ability of [Ru(bpy)2dppz]21 to act as a molecular switch is ascribed to the intercalation that shielded the phenazine nitrogens from the solvent and resulted in a luminescent excited state. The dramatic increase in ECL intensity upon intercalation has allowed [Ru(bpy)2dppz]21 to be exploited as an ECL probe. Indeed this strategy has been utilised for a label-free ATP aptamer sensor,34 and shown to be a highly selective method with low detection limits (0.016 pg mL1 for cardiac troponin I (cTnI)),35 although this proposed sensing platform (see Fig. 6) only demonstrated the applicability to cTnI it illustrated the potential for this method to be applied to a wide range of targets including other proteins and DNA by changing the molecular recognition element as required. This approach was exploited with great success to monitor the expression of P-glycoprotein in cells that could be used to demonstrate the drug resistance of cancer cells. A competitive method based ECL Electrochemistry, 2019, 15, 96–146 | 107

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 6 Principles of the switched ECL ‘‘off-on’’ strategy. Adapted from ref. 35 with permission from the Royal Society of Chemistry.

assays allowed for concentration ratio of two proteins to be estimated; and when compared to more conventional technologies showed improved sensitivity and accuracy with a correlation of 0.9928 and a detection limit of 0.52%.36 The advantages of this low cost, label free approach was further combined with paper-based biopolar electrodes, (see Fig. 7), to fabricate a highly sensitive, simple, rapid and robust method for bacterial identification.37 This was extremely effective detecting as little as 10 copies mL1 of the genomic DNA of Listeria monocytogenes. In addition, it could also specifically distinguish Listeria monocytogenes from Salmonella, Escherichia coli O267:H7, and Staphylococcus aureus. This simple application of ECL based sensors based on quite a traditional ECL generating mechanism while illustrating the potential this technique has in point-of-care applications for pathogen recognition and detection. [Ru(bpy)3]21-containing supramolecular microstructures can be formed via a single process via a solution-based self-assembly strategy by directly mixing [Ru(bpy)3]21 with a metal salt such as K3[Fe(CN)6]38 or H2PtCl6.39 Fig. 8 typical SEM images of the supramolecular microstructure. It consists of a large quantity of rod-shaped microstructures. It is believed that electrostatic attractions between the positively charged [Ru(bpy)3]21 and the negatively charged salt drive the formation of micrometre-scale supramolecular microstructures and that both the molar ratio and concentration of reactants influence the morphologies of 108 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 7 Scheme of the pBPE-ECL molecular switch system. (A) Analysis principle of the pBPE-ECL molecular switch system. (B) Workflow for the pBPE-ECL molecular switch system; the expanded schematic shows the construction of the pBPE chip. Reproduced from ref. 37 with permission from American Chemical Society, Copyright 2016.

these structures. More importantly, such microstructures exhibit excellent ECL behaviours and therefore hold great promise as new luminescent materials. ECL has also been reported from self-enhanced ECL nanorods based upon the covalent linking of [Ru(bpy)2(mcbpy)]21 with tris(3-aminopropyl)amine (TAPA) resulting in high luminous efficiency.40 Interestingly, it was also noted that using the ECL Ru complex as a precursor to directly prepare the nanostructure with a high electro-active area was a more effective method for enhancing the immobolised amount of Ru(II) within the construction of the biosensor compared to traditional immobolisation methods (see Fig. 9). The improved luminescence was attributed to the shorter electron transfer path and less energy loss from the intramolecular ECL reaction between the [Ru(bpy)2(mcbpy)]21 and the coreactive tertiary amine group in the TAPA. Solid-state [Ru(dpp)3][(4-Clph)4B]2 nanoislands can be assembled spontaneously on indium-doped tin oxide (ITO) and this is a simple and amenable way to mass produce solid-state ECL active electrodes.41 Although, large-scale production with real world applications has not yet been realised. Electrochemistry, 2019, 15, 96–146 | 109

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 8 (a) Low-magnification SEM and (b) high-magnification SEM, and (c) TEM image of the resulting precipitate of sample 1. Reproduced from ref. 39 with permission from American Chemical Society, Copyright 2007.

To expand the usefulness of ruthenium based ECL sensors, researchers have examined the potential of multi-metallic ruthenium complexes.42–44 These often resulted in more intense ECL emission, both via the annihilation and co-reactant pathways.41 More, importantly these multi-metallic complexes opened up the possibilities of multi-analyte detection.40,42 Although these primarily focused on multi-ruthenium complexes, studies into mixed metal supramolecular complexes were also undertaken.45,46 The trinuclear, mixed-metal supramolecular complex, [((phen)2-Ru(dpp))2RhCl2]51 (phen ¼ 1,10-phenanthroline, dpp ¼ 2,3-bis(2-pyridyl)pyrazine) has been studied.44 Its ECL spectrum showed a B55 nm blue shift compared to its fluorescence in acetonitrile with DBAE as the co-reactant, indicating that the ECL emissive state is rather different from the photoluminescent state. Indeed, it should be noted that within these mixed systems the intermolecular interactions influence the emission colour, and these are easily affected by numerous factors including molar ratio between the ECL labels, co-reactant, working electrode, solvent system etc.45 These factors often make applying these to real applications difficult. However, it was demonstrated that the ECL emission could be tuned based upon the applied potential. This on–off switching phenomenon was dependent on the applied scanning potential and illustrates the important implications for multiplexed ECLbased assays as it enables the selective excitation of intramolecular 110 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 9 (a) Preparation of [[Ru(bpy)2(mcbpy)]21-TAPA]NRs]; (b) Fabrication of the immunosensor and the reacted mechanism. Reproduced from ref. 40 with permission from American Chemical Society, Copyright 2016.

luminophores based on scanning potential without interference from intermolecular interactions.45 Alternatives to improve tunability, ECL efficiency, applicability etc. have focused on the addition of an enhancing agent, such as quantum dots,47 graphene, or CNTs.48 For example, the incorporation of 4-(N,N 0 dimethylamino) pyridine protected gold nanoparticles, DMAP–AuNPs, was shown to enhance the ECL response of a ruthenium complex by a factor of seven through the enhancement of the rate of electroregeneration of the Ru31 species, as shown in Fig. 9.49 This resulted in the improvement of the detection limit of nicotinamide adenine dinucleotide, down to 5 fM (Fig. 10). However to demonstrate a real improvement in sensitivities, an understanding of ECL efficiency is essential. For bio-sensing and diagnostic applications current research strategies for ruthenium based platforms focus on optimising the ECL efficiency, i.e., photons emitted per electron passed.24,50,51 Important approaches include new coreactants and altering the electrochemical characteristics of the Electrochemistry, 2019, 15, 96–146 | 111

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 10 ECL response of thin films of ruthenium metallopolymer and metallopolymer–gold nanocomposite films where the mole ratios of DMAP–AuNP: , 4.1  103 and 1.23  102 . The co-reactant is Ru21 are 1.025  102 3 mM NADH. The intensity is reproducible to within 5% between individual layers. The inset shows the TEM image of the as synthesized DMAP–AuNPs and their size distribution. Reproduced from ref. 49 with permission from Elsevier, Copyright 2012.

material itself so as to increase the charge transfer rate to produce more luminophores per unit time. To this end, attempts to improve efficiency by immobilising the ruthenium species within or by tethering to an electroactive polymeric backbone capable of mediating charge transfer between metal centres have been explored.52 Although this approach has exhibited significantly enhanced rates of charge transport in the ground state giving more intense ECL49 a decrease in ECL efficiency and therefore ECL signal is observed when analyte/co-reactant concentrations are low. This highlights the requirement to understand the ECL efficiency and mechanism to ensure an improvement in the signal to noise ratio as well as enhance electron movement to enhance sensitivities. Innovative methods for ECL enhancement for ruthenium-based systems include the development of hollow porous polymeric nanospheres of self-enhanced ruthenium (Ru-HPNSs).53 This approach was shown to decrease the inner filter effect and minimise inactive emitters within the nanosphere. This was then utilised as an ECL tag within an aptamer based hairpin strategy for the detection of mucin 1 showing linear responses over the concentration range 1 fg mL1 to 100 pg mL1 with a limit of detection of 0.31 fg mL1. This novel work highlights the continuing development of ruthenium based ECL sensors for applications in ultrasensitive bioassays for clinical and biochemical analysis. Although TPrA is a typical and successful co-reactant for ECL production, it does have some limitations. These include the fact that TPrA itself can be toxic, corrosive and volatile; and often high concentrations 112 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

are needed to obtain suitable sensitivities which can led to high to high backgrounds.54 Therefore, much effort has focused on the development and exploitation of new co-reactants to enhance the ECL produced from [Ru(bpy)3]21. Most recently, due to the functional groups on the surface of QDs, which could act as active sites for catalysing the reaction of coreactant ECL based systems, investigations into the exploitation of boron nitride QDs (BNQDs) have been undertaken. These showed that a 400fold enhancement could be obtained.55 This enhancement was hypothesised to be from the catalytic oxidation of surface functional groups of BNQDs to the [Ru(bpy)3]21. The reaction mechanism proposed that the [Ru(bpy)3]21 was oxidised to the 3 þ species via a one-electron oxidation at the electrode surface, while the BNQDs with a rich amino group were oxidised to produce BNQDs-NH1 , which underwent a deprotonation process to generate a reductive intermediate BNQD-N in alkaline conditions which could then react with the [Ru(bpy)3]31 to form the excited 2 þ species emitting an anodic ECL signal. Utilising this knowledge, a signal-off sensor was constructed for the determination of dopamine with good stability as well as excellent selectivity. This opens up new opportunities for a wide range of new applications for ruthenium based ECL sensors. 1.3.2 Iridium based ECL systems. Other luminescent complexes have been evaluated for their ECL properties. These include osmium(II)56,57 and platinum(IV)58 complexes, however, it has been cyclometalated iridium(III) complexes which have emerged in the past few years as the strongest contender to [Ru(bpy)3]21. This is primarily due to their often higher photoluminescence quantum yields and longer luminescent lifetimes as well as the capability to tune ECL emission.59 The capacity to tune emission is because the HOMO is frequently delocalised over the ligand framework unlike ruthenium complexes where the HOMO is mostly metal based. This means that the energies of the frontier orbitals (both HOMO and LUMO) can be easily modulated. More importantly for ECL applications, this independent control over the HOMO and LUMO energies allows for optimisation of the redox potentials.60 Initial studies into the ECL of cyclometaled iridium(III) complexes showed intense annihilation ECL intensities but quite weak co-reactant based ECL intensities.61,62 This was attributed to the weak oxidising power of the iridium complex and the higher energy of its emission.63,64 Nevertheless, insights by Kapturkiewicz illustrated the promise of ECL from iridium complexes if the thermodynamic and mechanistic aspects of electron transfer within a co-reactant system are considered.65 The first efficient iridium based co-reactant ECL systems were reported by Kim et al. who reported extremely high ECL responses from co-reactant systems using (pq)2Ir(acac) and (pq)2Ir(tmd) (see structures (g) and (h) in Fig. 11).60 Although these achieved an extremely high ECL response, this came at the cost of tenability with all having lmax values in the range 606–618 nm which limited their application to multiplexed analysis. Electrochemistry, 2019, 15, 96–146 | 113

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 11 Intense ECL-emitting iridium complexes with 2-phenylpyridine or 2phenylquinoline cyclometallating ligands and a variety of ancillary ligands reported by Kim et al.,60 (a) [Ir(ppy)2(bpy)]1, (b) Ir(pq)2(3-iq), (c) Ir(pq)2(pic) (d) Ir(pq)2(quin), (e) [Ir(ppy)2(phen)]1, (f) Ir(pq)2(dbm), (g) Ir(pq)2(tmd), (h) Ir(pq)2(acac). Adapted from ref. 64 with permission from American Chemical Society, Copyright 2005.

Following on from these fundamental insights, Zhou et al. using [Ir(ppy)2(dcbpy)]1 (ppy, 2-phenylpyridyl and dcbpy, 4,4 0 -dicarboxy-2,2 0 bipyridyl) for the potential biosensing applications by monitoring carbohydrate expression on cell surfaces.66 However to exploit the full range of applications, new analogues were developed which had their emission and redox properties tuned to facilitate multiplexed detection. Two main strategies to achieve this were examined. The first strategy investigated the lowering of the HOMO by attaching electronwithdrawing groups to the phenyl ring of the ppy ligand while the second strategy examined the raising of the LUMO by either attaching an electron-donating group to the pyridyl ring or replacing the pyridyl moiety with an electron-rich heterocycle.67,68 These studies proved to be the foundations for the advent of ECL systems based on iridium complexes facilitated by the unprecedented opportunity to tune both the photophysical and electrochemical properties of the ECL luminophore. This paved the way for potential-resolved ECL which is a technique that can be utilised to probe a system with two or more luminophores in a mixture.69–71 These studies illustrated how iridium based complexes could be utilised for multi-analyte detection systems as well as demonstrating the potential to resolve spectral overlap from multiple emitters. The ability to resolve spectral overlap from multiple emitters using a combination of wavelength and potential is shown in Fig. 12.67 This demonstrates the potential of ECL based systems for multi-analyte detection. More recently, Haghighatbin et al. have demonstrated the capacity to modulate the emission state based upon the applied potential.72 This is the first reported system to show a multi-coloured ECL emission from a single component system. This was achieved using a homoleptic aryl(1,2,4)triazole-based iridium(III) complex, [Ir(mptz)3]. Most notable, the emission showed a dependence on the mode of ECL production. 114 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 12 3D-ECL plot of a mixture of three metal complexes: Ir(dfppy)2(ptp) (blue emission at high potentials), Ir(ppy)3 (green emission at low potentials) and [Ru(bpy)2(dm-bpy-dc)]21 (red emission at intermediate and high potentials) in acetonitrile, using TPrA as the coreactant. Adapted from ref. 69 with permission from John Wiley & Sons, Copyright r 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

This work highlights the capabilities of 3D-ECL for mechanistic investigations as well as for multiplex detection applications. The capacity to selectively excite different emissive states by using differing redox potentials was purposed by Li et al. to be another advantage of these systems.73 By allowing for simultaneous rather than sequential excitation through the utilisation of a potential gradient, the authors suggested that instrumental complexity could be reduced making ECL systems based upon bipolar electrochemistry more suitable for low-cost sensing applications. This bipolar ECL approach has also be utilised within an immunodiagnostics platform (see Fig. 13)74 for the detection of prostate-specific antigen in human blood illustrating the Electrochemistry, 2019, 15, 96–146 | 115

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 13 Multi-colour bipolar ECL immune-detection concept. In this closed bipolar system, the selective response of the immunosensor governed the resistance between the poles of the bipolar electrodes, which determined the interfacial potential. This was then indicated by the colour of the ECL from a mixture of two luminophores, one with a high and one with a low oxidation potential. Reproduced from ref. 74 with permission from American Chemical Society, Copyright 2017.

successful application of bipolar ECL to biomedical diagnostics. These new developments open up new avenues of research and display the advantages of ECL for widespread adoption for analytical applications including multiplexed analysis. 1.4 Quantum dot based ECL Following the discovery of ECL emission from Si QDs,75 and the first reports of ECL from CdSe76,77 and CdTe nanocrystals,78 there has been continuing interest in the application of QDs for ECL systems. This is in part due to the ability for size-tunable emission and enhanced optical and electronic properties.79 The vast majority of these works focused on materials that emitted in the visible region, resulting in a good understanding of the ECL behaviour of these materials. Indeed the analytical applications of ECL from QDs have dramatically increased.80 This is primarily due to the significant advantages of the ECL over conventional spectroscopic techniques, in particular, low background signals and the ability to control accurately, both time and position of the light emitting reactions.5,6,81 ECL of QDs involves the emission of light by species that undergo highly energetic electron-transfer reactions that are potentially controlled. These follow the same fundamental ECL mechanisms of annihilation ECL, co-reactant ECL and cathodic luminescence.75 However, as with other ECL systems the most widely studied ECL system for analytical applications is the co-reactant ECL mechanism. Co-reactant ECL is usually generated through the reaction between an oxidised or reduced ECL generating molecule or compound and a 116 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

reduced or oxidised co-reactant. Depending on the polarity of the applied potential, the ECL reaction can be described as either ‘‘oxidative reduction’’ ECL or ‘‘reductive oxidation’’ ECL, respectively.82 Common coreactants for QD ECL include peroxydisulfate, tri-n-propylamine as well as hydrogen peroxide, to name but a few.5,77 Most of the ECL QD biosensors are based upon the quenching, or enhancement of the ECL intensities via these well-established co-reactant ECL systems.77,83,84 The common ECL processes corresponding to the production of ECL through the interaction with the co-reactant H2O2 is as follows:77,85,86 QDs þ 1e-QDs(e 1Se)

(27)

QDs(e 1Se) þ H2O2-QDs þ OH þ OH

(28)

OH þ QDs-OH þ QDs(h1 1Sh)

(29a)

QDs(e 1Se) þ OH -OH þ QDs*

(29b)

QDs(e 1Se) þ QDs(h1 1Sh)-QDs*

(30)

QDs*-QDs þ hn (640 nm)

(31)

During the cathodic scan, electrons are injected into the QDs (eqn (27)), then the electrons-injected QDs (QDs(e 1Se)) reduce H2O2 to produce OH and OH (eqn (28)). OH is the ‘‘key’ species that can easily inject a hole into the 1Sh quantum confined orbital of QDs (eqn (29a)) giving to the formation of QDs(h1 1Sh). This process is possible because of the high standard redox potential of the OH/OH couple.75,87 At the same time, the excited states, QDs*, are formed by the reaction of the reduced QDs with OH or by the recombination of the injected electrons (e) with the injected holes (h1) of QDs (eqn (30)). Both the processes eqn (29b) and (30) lead to the formation of the luminophore, QDs*, even though the two processes are mechanistically different, i.e. a coreactant ECL process the former one and an annihilation process the latter one. QDs* will emit light at a wavelength that depends on the size of quantum dots.5,71–75 To date, various QDs including classical chalcogenide QDs,88 carbon nanodots,89 graphene QDs (GQDs),90 Si QDs,91 carbon nitride QDs92 and doped QDs93 have been employed as luminophores, co-reactants, or energy transfer donors/acceptors in ECL sensors as well as functional nanoparticles. These have led to QD ECL sensors flourishing as novel analytical tools and are playing an increasingly important role in analysis and sensor research.94,95 1.4.1 Silicon QDs. Silicon QD ECL was first reported by Bard in 200296 in which the significant red shift of the ECL emission, at 640 nm, as compared to the photoluminescence, 420 nm, was attributed to the greater significance of surface states for charge injection as opposed to photo injection.These QDs are formed from etching of a Si Electrochemistry, 2019, 15, 96–146 | 117

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

source and the photoluminescence is dependent upon the size of the Si QD. However the major limitation of Si QDs resulting in very limited application of their ECL is their unstable photoluminescence and poor stability. 1.4.2 Chalcogenide QDs. Chalcogenide QDs represent the largest and most dominant QD based ECL luminophores. They are comprised of elements from groups II–VI (e.g. CdSe, CdTe, CdS) or IV–VI (e.g. PbSe, PbS). As previously described, their ECL and photoluminescence is size dependant. This relates to the energy gaps and relative positions of their electronic levels that are responsible for their electronic properties. The ECL of these semi-conductor QDs have found numerous applications in the field of biosensors particularly where the sensitive measurement of proteins or other biomarkers is critical to the biomedical assay.5,89 ECL immune-sensors are often utilised for such applications as this approach combines the high sensitivity of the ECL detection with the specificity of the immunoreaction. These systems are generally based upon co-reactant ECL but the amount of co-reactant isn’t responsible for the generation of a concentration dependant response, rather the present and amount of QD is utilised to determine concentrations. To exploit these properties, numerous systems employing QDs have been utilised as labels within ECL detection systems.80,97–99 Liu et al.99 used CdSe QDs to detect a-fetoprotein (AFP), a specific biomarker for carcinoma of the liver. Anti-AFP was covalently linked to a gold electrode, with secondary AFP antibodies labelled with the CdSe QDs. The electrode bound antibodies captured AFP and then the QD labelled antibodies bound to the captured AFP (Fig. 14). This represents a common approach to the attachment of the QDs onto an antibody for subsequent analysis via a ‘‘sandwich’’ immunoreactions. Detection limits for AFP were improved further,100 where a CdS QDgraphene-agarose composite coated onto a glassy carbon electrode was used and no label was required. Anti-AFP was linked to modified electrode via glutaric dialdehyde. ECL was observed through the interaction of the reduced forms of CdS and the co-reactant, K2S2O8 (CdS  and SO4  respectively) to produce the excited state (CdS*) through electron transfer.101 The ECL intensity of the QD-graphene-agarose composite was 7 times greater than that of the pure CdS QD film, owing to the improved porosity and conductivity of the composite. Complexation of anti-AFP

Fig. 14 Biosensor fabrication for the detection of AFP using CdSe QDs. Reproduced from ref. 99 with permission from the Royal Society of Chemistry. 118 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

with AFP resulted in a logarithmic decrease in the ECL intensity, allowing the concentration of AFP to be determined with a detection limit of 0.2 fg mL1.96 A similar system was developed that used a CdS QD-graphene-alginate composite coated onto a glassy carbon electrode, however, in this case, CdSe/ZnS core shell QDs were utilised.102 Anti-AFP was attached to the QD-graphene-alginate system, with secondary AFP antibodies bound to the CdSe/ZnS QDs. AFP was allowed to complex with the composite bound anti-AFP and then the secondary antibodies were allowed to bind to the formed immunocomplex. The formation of this complex resulted in a decrease in the ECL intensity of the CdS QD-graphene-alginate composite owing to the scavenging of ECL energy by the CdSe/ZnS QD label, preventing the formation of excited states. CdSe/ZnS QDs have an absorption range of 240–620 nm, whilst the emission of the CdS QDs is between 500–700 nm and this spectral overlap allows the ECL resonance transfer process to occur, resulting in extremely efficient quenching of the ECL signal following binding of the anti-AFP CdSe/ZnS QD label.97 This allows very low limits of detection, down to 20 pg mL1 in this case, with a working range of 0.05 to 500 fg mL1. Each of these AFP detection systems were successfully used in the determination of AFP from clinical samples (serum and saliva) and were not affected by the presence of other biomarkers (carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG) and Hepatitis B surface antigen (HBsAg)), highlighting the specificity of this technique. This most sensitive system is 5 million times more sensitive for AFP detection than an equivalent system that does not use nanomaterials in its set-up.103 To facilitate more sensitive detection and reduce the time spent on the labelling process, Tu et al.104 purposed a novel and universal strategy for label-free and highly sensitive ECL biosensing based upone CdSe QD/ single walled carbon nanotubes (SWCNTs) in room temperature ionic liquids (RTILs) as shown in Fig. 15. The synergic effect of the SWCNTs and RTILs significantly improved the ECL response of the CdSe QDs as well as improving their stability. Using AFP as a model detection system, a detection limit of 3 ng mL1 at a signal to noise ratio of 3s, where s was the relative standard deviation of 10 parallel measurements when AFP concentration was zero. This highlights the potential benefits in combining QD ECL with immunosensor analysis, namely, fast electron transfer and high quantum yields that result in improve sensitivities. Their biocompatibility and size also make them ideal for immobolisation of biomolecules thereby improving specificity. Numerous ECL biosensors have been applied to cancer applications including carcinoembryonic antigen (CEA) and human chorionic gonadotropin (HCG). A further development described a system for the detection of CEA using a composite nanostructure comprising gold/silica/ CdSe–CdS core-shell QDs.105 CdSe–CdS QDs were surface passivated with silica coated gold nanoparticles and immobilised on an electrode. Antibody bound gold nanoparticles were subsequently attached. The ECL Electrochemistry, 2019, 15, 96–146 | 119

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 15 Schematic illustration of the label-free ECL biosensing platform. Reproduced from ref. 104 with permission from the Royal Society of Chemistry.

intensity of this nanostructure was 17 times greater than that of pure CdSe–CdS QDs. This amplification attributed to an increase in the rate of electron transfer in the ECL reaction due to the high concentration of gold nanoparticles coated onto the surface of the QDs and an improvement in structure porosity, allowing improved diffusion of the co-reactant, K2S2O8, towards the electrode.99 Formation of the immunocomplex in the presence of CEA resulted in a decrease in the ECL intensity due to an increase in steric hindrance, impeding electron transfer and diffusion of K2S2O8 in the ECL reaction. A linear working range for CEA of 0.32 pg mL1 to 10 ng mL1 was achieved, with a detection limit of 0.064 pg mL1. Following on from this, developments into combining QDs with other metals for enhanced ECL responses have also shown a major growth in recent years. One such example is a biosensor using CdTe QD functionalized Pt–Ru alloys for the detection of a-HCG.106 CdTe QDs were immobilized within the nanoporous structure of the Pt–Ru alloy followed by attachment of anti-HCG. Chitosan coated Fe3O4 magnetic nanoparticles were coated with primary anti-HCG and in the presence of HCG these formed an immunocomplex with the QD modified alloy (Fig. 16). The presence of HCG resulted in an increase in the ECL intensity as the formation of the immunocomplex allowed QD driven signal amplification to occur. ECL detection using a single QD label was 4.67 times less intense due to a decrease in signal enhancement associated with the decrease in QD loading. A working linear range of 0.005 to 50 ng mL1 and detection limit of 0.8 pg mL1 were obtained.100 This system was tested using human clinical samples (serum) and showed an improvement in sensitivity compared to a standard ELISA assay, which has a 120 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 16 Fabrication of the immunosensor based on QD modified Pt–Ru alloys and magnetic beads. Reproduced from ref. 106 with permission from the Royal Society of Chemistry.

detection limit of approximately 70 ng mL1 (Pishtaz Teb Diagnostics, Inc. – Rapid hCG ELISA kit). This highlights the commercial use of QD ECL systems which can now take place, due to the tremendous research into this exciting field of biosensor analytical applications. Aptamers are single stranded DNA or RNA molecules that can form tertiary structures following binding to a specific target (proteins, small molecules, metal ions).93 They are prepared by an in vitro method known as systematic evolution of ligands by exponential enrichment (SELEX) and have a number of advantages over natural receptors. These include simple synthesis and labelling, good chemical stability and excellent flexibility for biosensor design.107 As a result, aptamers lend themselves to incorporation into novel biosensors and, in combination with QDs, have seen much research and development in recent years. For example, Jie et al.108 have developed an ECL sensor for cancer cells using novel dendrimer/CdSe–ZnS QD nanoclusters. Gold nanoparticles were absorbed onto an electrode surface and then functionalized with the specifically designed aptamer. Dendrimer nanoclusters were loaded with CdSe–ZnS QDs, onto which a probe DNA strand was attached and these hybridized with the electrode bound aptamers, resulting in an ECL signal that was 13 times more intense than that of a film of pure QDs (Fig. 17). This was caused by the increase in the number of QDs that could be loaded onto the dendrimer nanoclusters, increasing the surface area and improving electron transfer rates. Aptamer recognition by target cells led to dehybridisation of the nanocluster/QD-DNA biocomplex, resulting in a decrease in ECL intensity that was proportional to the concentration of target cells. A working linear range of 400–10 000 cell mL1 and a Electrochemistry, 2019, 15, 96–146 | 121

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 17 Fabrication of a QD based apatsensor for the detection of cancerous cells. Reproduced from ref. 108 with permission from American Chemical Society, Copyright 2011.

detection limit of 210 cells mL1 was achieved. Incorporating two ECL generating complexes within dendrimer systems can facilitate multiplexed detection. This has most recently been show for the simultaneous detection of two different tumour markers, cancer antigen 153 and cancer antigen 125.109 Through the utilisation of dendrimer nanoclusters that incorporated both QD and ruthenium, the sensitivity and selective detection of both markers within a single scan was achieved as shown in Fig. 18. Shan et al.110 developed a thrombin sensor that uses the quenching of CdS–Mn nanocrystal ECL by CdTe QD-doped silica nanoparticles. CdS–Mn nanoparticles were immobilised on an electrode and then modified with the specific aptamer for thrombin. Silica nanoparticles were doped with CdTe QDs and then functionalized with a probe DNA strand that complemented the aptamer. Hybridisation of the QD-doped silica nanopartilces with the aptamer brought them within the effective distance of energy scavenging and as a result led to ECL signal reduction caused by quenching of CdS–Mn ECL (585–660 nm) by the QD-doped silica nanoparticles, which showed a wide absorption in the visible region (400–700 nm). Non-doped silica nanoparticles showed no signs of ECL quenching and therefore quenching was attributed to the presence of the CdTe QDs. ECL quenching efficiency was dependent on the number of doped CdTe QDs. ECL quenching was attributed to long distance (410 nm) energy scavenging as interactions with the co-reactant 122 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | d Electrochemistry, 2019, 15, 96–146 | 123

Fig. 18 Schematic representation of the multiplex ECL sandwich immunoassay for simultaneous detection of cancer antigen 123 and 153. Reproduced from ref. 109 with permission from Elsevier, Copyright 2017.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

and charge transfer between excited CdS–Mn states and CdTe QDs were ruled out. Thrombin selectively interacts with the electrode bound aptamers, displacing the QD-doped silica nanoparticles, thus inhibiting ECL quenching. Therefore, the ECL signal is related to the concentration of thrombin and a working linear range of 5 pmol L1 to 5 fmol L1 was reported for this system, with a detection limit of 1 pmol L1. This compares to a detection limit of B0.3 ng mL1 with a standard ELISA kit for thrombin (AssayMax Human Thrombin ELISA kit). QDs are often incorporated into biosensor platforms to amplify the ECL signal, however, in this case the QDs efficiently amplify ECL quenching, displaying the versatility and flexibility of these nanomaterials when used within ECL systems. An adenosine 5 0 -triphosphate (ATP) sensor has been developed by Huang et al.111 Anti-ATP aptamers were attached to a gold electrode surface and biotinylated complementary DNA strands were allowed to hybridise with the aptamers. Avidin-modified CdSe–ZnS QDs could then bind via the biotin-avidin system to these complementary DNA strands, resulting in ECL emission following the reaction of the reduced forms of the QDs and the co-reactant (K2S2O8) to produce excited QD states. ATP preferentially binds with the aptamers on the electrode surface, decreasing the number of QDs that can interact with the electrode, resulting in a decrease in ECL intensity that is related to ATP concentration. A working linear range of 0.018 to 90.72 mmol L1 was achieved, with a detection limit of 6 nmol L1. This assay was not as sensitive as a standard ELISA kit for ATP, which has a detection limit of approximately 1.5 nM (Antibodies Online ATP ELISA kit). A very similar system was developed by Yao et al.,112 however, a ruthenium complex was used as the light emitting species. This system had a detection limit of 0.02 nM and is clearly superior to both the QD based and ELISA systems. However, neither the QD nor ruthenium based systems were tested using human samples, whereas the ELISA kit was. The attractiveness of the QD system lies in the ability to modify such systems due to the flexibility and versatility of QDs and this is one of the reasons that QD based biosensors have received so much attention in recent years. An excellent example of this was the introduction of ECL detection via resonance energy transfer (RET), first utilised for immunosensors in 2012 by Wu et al.113 To optimise the ECL-RET efficiency, greater energy overlap between done and acceptor pairs is essential,114 as such energy tunable materials, like QDs, are appealing. The feasibility of ECL sensing in biological matrices also makes QDs attractive materials, as they can be tuned to emit in the near-infrared (NIR).93 Utilising ECL systems based on NIR ECL materials allows for lower background interference,115 however, this highlighted one of the main challenges in this field, namely, producing stable and strong ECL emitters. To this end, electron transfer (ET) ECL was examined and showed improved sensitivities in this region.116 These systems examined the effectiveness of ECL-ET through excellent overlap between donor emission and acceptor absorption. This allowed for efficient ECL-ET quenching which, in turn, resulted in improving the sensitivities of these type of systems. 124 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

1.4.3 Carbon nanomaterials. Since their discovery, carbon nanotubes (CNTs) with their enhanced mechanical and electrical conductivity properties have been widespread used in electroanalytical sensing applications.117–127 Single-wall carbon nanotubes (SWCNTs) are considered as a small graphene sheets rolled up to form single-wall carbon nano-cylinders. Graphene sheets can be rolled up in different ways, and this is represented by the variation of a pair of integers (n, m). The values of these integers relate to the structure of SWNTs, in terms of both its diameter and chirality. Depending on the value of such integers, SWNTs are classified as having metallic or semiconductor character. Instead, Multi-wall carbon nanotubes (MWCNTs) are regarded as co-axial assemblies of SWCNTs carbon cylinders placed within another. Clearly, for electroanalytical application, metallic CNTs are preferable. CNTs are entirely composed of carbon sp2-hybridized and this confers unique properties such as tensile strength, chemical stability, and electrical conductivity in metallic SWNTs.120,128 A key aspect on the utilisation of CNTs in electroanalysis is the functionalisation with metal nanoparticles, biomolecules, redox mediators and other molecules that confers to the composite material high selectivity and sensitivity properties. For sandwich-type immunoassays, signal amplification and noise reduction are key aspect in order to achieve detection limits at ultra-trace level and high sensitivity. In this respect, ECL detection using CNTs is a very exciting combination and in the last years interesting works on ECL immunoassays have been reported. For example, Sun et al. developed an ECL immunosensor for the detection of a protein marker (carcinoembryonic antigen, CEA) using L-cysteine and in situ generating co-reactant for signal amplification.129 A primary antibody anti-CEA (Ab1) was immobilized onto Au nanoparticles (AuNPs) produced by electrodeposition on glassy carbon electrode. Then, L-cysteine and AuNPs functionalized MWCNTs were utilised as a platform for the enzyme immobilisation (glucose oxidase, GOD, horseradish peroxidise, HRP, and secondary antibody, Ab2). The CEA antigen and MWCNTS-AuNPs-enzyme labelled Ab2 were conjugated to form a sandwich-type immunocomplex through the specific interaction between the antigen and the antibody. The whole procedure is highlighted in Fig. 19. The developed ECL immunosensor exhibited high sensitivity and specificity for CEA detection, with a linear concentration response in the range 0.02 ng mL1–80 ng mL1, and a low detection limit of 0.67 pg mL1. Using a similar approach and utilising MWNTs-functionalised carbon coated magnetic nanoparticles (MWNTs-Fe3O4-C), Chu et al. were able to achieve a very similar detection limit (0.7 pg mL1).130 However, in this study the ECL immunosensor was validated in the presence of other biomarkers as potential interferences, such as cancer antigen 125, human serum albumin, and prostate-specific antigen. The as-prepared ECL immunosensor showed excellent specificity and the measurements were not appreciably affected by the presence of such interefer.ences. Such detection limits were even decreased further by Cao et al. using a combination of metal Electrochemistry, 2019, 15, 96–146 | 125

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 19 Schematic for the preparation of the ECL immunosensor for CEA detection. Reproduced from ref. 129 with permission from Elsevier, Copyright 2013.

Fig. 20 Schematic for the preparation of the ECL immunosensor for CEA detection and proposed mechanism. Reproduced from ref. 131 with permission from Elsevier, Copyright 2013.

nanoparticles (Au, Pt, Pd) with SWNTs-graphene composite.131 However, in this case the authors used a different strategy based on amplified cathodic ECL of luminol at low potential, as highlighted in Fig. 20. The SWNTs-graphene-metal NPs composite material loaded with GOD promoted the cathodic ECL of luminol response by catalyzing the enzymatic reaction of GOD with the generation in situ of hydrogen peroxide as a co-reactant of the luminol reaction. The as-proposed ECL 126 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

immunosensor exhibited a highly sensitive response towards CEA detection in the concentration range of 0.1 pg mL1–160 ng mL1 with a detection limit of 0.03 pg mL1.124 Using a very similar approach, the same authors in another contribution, developed an ECL immunosensor based on a platform made of carboxylic-functionalised MWNTs as a label, on which Au NPs were deposited for further functionalisation with glucose oxidase.132 Then, a secondary antibody (Ab2) and glucose oxidase were bound to the Au NPsfunctionalised MWNTs. The enzymatic reaction produced hydrogen peroxide as a co-reactant that caused a dramatic increase of the luminol ECL signal. The as-prepared immunosensor exhibited a linear range of concentration for the detection of a-1-fetoprotein (AFP) from 0.1 pg mL1 to 80 ng mL1, with a detection limit as low as 0.3 pg mL1.125 Similar results but with a slightly higher detection limits were obtained by the same authors using a MWNTs-Nafion and Ru(bpy)3 composites.124 Instead, Yan et al. obtained very similar results in terms of sensitivity (linear range of concentration between 1 pg mL1–100 ng mL1, and a low detection limit of 0.3 pg mL1), however, in their work they used an ECL immunosensor based on a paper-based microfluidic origami and Au NPs grown on graphene layers.133 A different approach has been used instead by Deng et al. who developed an ECL immunoassay for CEA detection using a signal amplification strategy based on the adsorption-induced catalytic reduction of dissolved oxygen at the side wall of nitrogen doped-single walled carbon nanotubes (N-CNTs) that promoted ECL emission of CdS quantum dots.134 In this work, the N-SWNTs had been shown to strongly influence the chemisorptions of O2 from the usual monoatomic end-on adsorption at CNTs to a diatomic side-on adsorption at sidewalls. This fact facilitated the breaking of the O–O bonding to facilitate the reduction of O2 to a radical superoxide intermediate, O2 -that acted as a co-reactant for the ECL emission of CdS QDs. Firstly, polystyrene sulfonated (PSS)functionalised N-CNTs were used for labelling with the signal antibody (Ab2) and forming a sandwich immunocomplex on the CdS QDs-chitosan and a capture antibody (Ab1) modified electrode. The generation of the superoxide radical specie, O2 -was ‘‘key’’ to generate a strong ECL signal without the addition of any other strong oxidants as co-reactant. The asprepared CdS–N-CNTs ECL immunosensor showed very a very good sensitivity in the concentration range from 50 pg mL1–5 mg mL1, and a low detection limit for CEA of 2.4 pg mL1.127 Interestingly, the proposed method could decrease the detection of false positive that usually occur due to the steric hindrance resulting from the formation of the immunocomplex and the consumption of the co-reactant in the ECL reaction. As previously mentioned, aptamers as molecular recognition elements for proteins are now challenging the dominance of antibodies for specificity due to their ease of production in vitro, wide target range, reversible thermal denaturation, and extended shelf-life. In the ‘‘signal off’’ configuration, a thiolated capture probe (ss-DNA, 12-mer) was attached to Au NPs that were deposited on the Au electrode surface using a self-assembly method. The capture probe was then Electrochemistry, 2019, 15, 96–146 | 127

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

hybridized with a six-base segment of the ss-DNA sequence (Tgt-aptamer, 21-mer) containing a TBA-I (ss-DNA, 15-mer) previously tagged with a ruthenium complex. The probe tagged with the Ru complex produced a high ECL signal. The introduction of thrombin induced the dissociation of the Tgt-aptamer tagged with the ruthenium complex from the aptasensors, leading to significant quenching of the ECL signal. The quenching of the ECL signal was proportional to the concentration of thrombin in the range 2.7 pmol L1 to 2.7 nmol L1, with a detection limit of 0.8 pmol L1. In the ‘‘signal on’’ configuration, the thiolated TBA-I was self-assembled on the Au electrode surface. Then the TBA-II (ss-DNA, 29-mer) labelled with a SWNT-ECL tag was bound with an epitope of thrombin, producing a high ECL signal. The enhancement of the ECL intensity was linear with the concentration of thrombin in the range 0.01–10 pmol L1, with a detection limit of 3 fmol L1.135 The utilisation of antibodies in ECL immunosensing can sometimes be problematic because of their stability and modification. Aptamers are good candidates for ECL immunosensing. Aptamers are short singlestranded oligonucleotides and they possess high affinity and specificity to bind to proteins. Aptamers as molecular recognition substances for proteins appear to be an excellent alternative to antibodies due to their ease of production in vitro, wide target range, reversible thermal denaturation, and unlimited shelf life. An interesting ECL aptasensor for the detection of thrombin has recently been reported by Li et al.135 In this work, thrombin binding aptamer (TBA) is used as a molecular recognition element, while Au NPs and SWNTs are used as a carrier of the ECL capture/signal probe. Through the incorporation of ferroferric oxide on stannic oxide (Fe3O4@SnO2) onto the AuNPs, a further enhanced of this ‘‘signal off/on’’ ECL aptasensor principle was achieved as shown in Fig. 21.136 This displayed a wide linear range response for thrombin from 1105 to 10 nM with a 3 fM limit of detection. The feasibility was illustrated via reasonable recovery (91.5%–102.0%) within normal human serum. The proposed ECL enhancement process of ruthenium was formulated to be: Ru(II)  e-Ru(III)

(32)

Ru(III) þ Fe3O4@SnO2@AuNPs-Ru(II)*

(33)

Ru(II)*-Ru(II) þ hn

(34)

Composite materials based on MWNTs are an interesting platform for the development of sandwich-type ECL immunosensors. Wu et al. have recently reported an ECL-based immunosensor for the detection of retinol-binding protein (RBP).137 In this work, a primary antibody (antiRBP) was immobilised onto MWCNTs. A RBP antigen and a Ru(bpy)3– Nafion deposited on SiO2 nanosphere labelled secondary antibody were then successively conjugated to form a sandwich-type immunocomplex through the specific interaction between antigen and antibody. The asprepared ECL immunosensor was extremely specific and selective and worked linearly in the concentration range 78 ng mL1–5000 ng mL1 128 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 21 The fabrication process of the simple and sensitive signal-on ECL aptasensor. Reproduced from ref. 136 with permission from Elsevier, Copyright 2017.

with a low detection limit of 26 ng mL1. The sensor was successfully used with sample of urine with RSDs and recovery between 98–112% and 0.6–5.9%, respectively.129 Ink-jet carbon nanotubes forests arrays have been developed in the Forster’s lab to detect picomolar concentrations of immunoglobulin G (IgG) using ECL.138 Arrays of vertically aligned nanotube forest were grown on indium tin oxide electrodes. Then, via peptide bond formation, capture anti-IgG were coupled to the carboxylic groups of SWNTS. A ruthenium luminophore were then used to functionalise SiO2 nanoparticles and IgG labelled G1.5acid-terminated poly(amido amine) (PAMAM) dendrimers. In the presence of sodium oxalate as a co-reactant, a significant ECL signal was obtained that allowed the detection of IgG concentration in the range 20 pM–300 nM, with a low detection limit of 1.1 pM.130 In a similar approach but using graphene oxide rather than carbon nanotubes, Cheng et al. developed an ECL immunosensor for the detection of CEA.139 In this work, the fabricated a luminol ECL immunosensor using ZnO NPs and glucose oxidase decorated graphene as labels. The hydrogen peroxide generated in situ by the enzymatic reaction with glucose oxidase as a co-reactant for the ECL reaction, while the CEA antibody was anchored on Au NPs electrodeposited on glassy carbon electrodes. The proposed approach allowed the detection of CEA at ultratrace concentration level with a detection limit of 3.3 pg mL1 and a linear concentration range between 10 pg mL1–80 pg mL1.131 The suitability of SWNTs forests as a platform for ECL immunosensing was demonstrated previously by the same authors for the detection of PSA and IL-6.140 In this work, SWNTs forests were casted in the bottom of Electrochemistry, 2019, 15, 96–146 | 129

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

a 10 mL wells, with a hydrophobic polymer walls. Then, SiO2 nanoparticles were functionalised with [Ru(bpy)3]21 and secondary antibody (Ru(bpy)–SiO2–Ab2) were employed for two-analyte detection. Notably, the antibodies to prostate specific antigen (PSA) and interleukin-6 (IL-6) were attached to the same (Ru(bpy)–SiO2–Ab2) particle. The wells were patterned on conductive pyrolytic graphite chips to form an array. The antibodies were attached to the SWNTs forest in the wells to capture the analyte proteins. Then, to capture the binded proteins, (Ru(bpy)–SiO2– Ab2) was added. TPrA was added as a co-reactant for the ECL reaction with [Ru(bpy)3]21. The as-prepared ECL immunosensor were able to detect PSA and IL-6 at the same very efficiently, achieving a detection limit of 1 pg mL1 for PSA and 0.25 pg mL1 for IL-6.132 The obtained results in serum for the determination of PSA and IL-6 correlated very well with single-protein ELISA essays. Recently, fluorescent carbon nanocrystals (CNCs) have been shown to be a very promising material for ECL sensing. For example, CNCs have successfully been employed in ECL detection of K562 leukemia cells based on aptamers and ZnO-functionalised carbon nanocrystals.141 The aptamers were used for cell capture, and after conjugation of Concanavalin A with the ZnO nanosphere-functionalised CQDs, the composite material was used for selective recognition of the cell surface carbohydrate. The functionalisation of ZnO nanospheres with CNCs improved the ECL signal of about one order of magnitude compared to pristine ZnO nanospheres and of ca. 4-fold compared to the pristine CNCs. The high surface-to-volume ratio of ZnO nanospheres enhanced the loading of CQDs and Concanavalin A, leading to a significant ECL signal amplification. The as-prepared ECL sensor showed high specificity towards the detection of K562 cells in a range from 1102 cells mL1 to 2107 cells mL1 with a detection limit of 46 cells mL1.133 Wang et al. developed an ECL aptasensor for the detection of thrombin using graphene oxide with intercalated a [Ru(phen)3]21 probe.142 Graphene oxide (GO) was deposited on conducting electrode surfaces (glassy carbon and/or Au electrodes) through physical adsorption, while the amino-tagged aptamers were immobilised on the electrode surface via amide linkage between the amino group of the aptamer and the carboxyl groups of GO. Then, a functional oligonucleotide containing two parts, i.e. a complementary strand and an intermolecular duplex for the intercalation of [Ru(phen)3]21 as ECL probe, was introduced. The hybridisation between the aptamer and its complementary part at the functional oligonucleotide containing the [Ru(phen)3]21 probe allowed to detect the ECL emission. The hybridisation between the aptamer and thrombin led to the release of the functional oligonucleotide containing the intercalated [Ru(phen)3]21 probe, causing the quenching of the ECL signal. The quenching of the ECL signal is directly proportional to the concentration of thrombin. The as-prepared ECL aptamer sensor showed a linear response for the detection of thrombin in the range 0.90 pM– 226 pM with a low detection limit of 0.40 pM.134 Composite materials based on the combination from graphene and CdSe QDs have found exciting applications in ECL immunosensing. Li 130 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

et al. have developed a novel strategy to fabricate a polymer-based (poly(diallyldimethylammonium chloride) (PDDA)-protected graphene– CdSe (P-GR-CdSe) composite for ECL detection of human IgG.143 GQDs composites were prepared using electrostatic interactions between negatively charged thioglycolic-capped CdSe QDs and positively charged PDDA-graphene. The latter was prepared via non-covalent functionalisation of graphene oxide with PDDA. The ECL immunosensor showed enhanced sensitivity towards human IgG detection in the range of 0.02 pg mL1–2000 pg mL1 with a low detection limit of 5 fg mL1.135 This high sensitivity is particularly significant since it shows how ECL-based immunosensor could be a potential replacement to the ELISA-based methods currently used for the detection of proteins. With a different approach, Liu et al. developed an ECL immunosensor for the detection of IL-6, using a graphene oxide nanosheets-polyaniline nanowires-CdSe QDs composite material.144 After the synthesis of a graphenepolyaniline composite, this material was then mixed with L-cysteine capped CdSe QDs to produce the resulting final composite material, graphene oxide nanosheets-polyaniline nanowires-CdSe QDs. The antigen and antibody were then anchored to the CdSe QDs using conventional immobilisation methods. This ECL immunosensor showed high sensitivity towards IL-6 detection, achieving a linear range of concentrations between 0.5 pg mL1–10 ng mL1, and a low detection limit of 0.17 pg mL1.136 Another interesting work has recently been proposed by Jie et al.145 A very sensitive ECL immunoassay for the detection of human IgG using MWNTS-CdSe quantum dots composites.137 At first, MWNTs were functionalised by polymer wrapping with poly(diallyldimethylammonium chloride, PDDA). Then, thioglycolic acid capped CdSe QDs (CdSe/TGA) were dispersed into PDDA-functionalised MWNTs and deposited on a gold electrode. The immunosensor was completed by adding citrate capped Au NPs and dipped into the antibody (Ab) solution. In this work, the ECL signal was based on the fact that the increment of the steric hindrance that occurred after the immunoreaction, resulted in the quenching of the ECL signal. The ECL immunosensor showed high sensitivity for IgG in the linear range of 0.002 ng L1–500 ng L1 with a low detection limit of 0.6 pg mL1.137 Similarly, Wang et al. developed a ‘‘signal-on’’ ECL biosensor for the detection of choline and acetylcholine based on CdS–MWNTs composites.146 Carboxylated-MWNTs were treated with NaOH and after addition of CdCl2, Na1 ions were exchanged with Cd21 ions. By reaction with tioacetamide, then CdS QDs-functionalised MWNTs were formed. Choline oxidase (ChO) and acetycholine esterase (AChE) were deposited by cross-linking with glutaraldehyde on CdS QDs-functionalised MWNTs modified electrodes. Using H2O2 as a co-reactant, a strong and stable ECL signal was generated. The resulting ECL sensor showed linearity in two different concentration ranges, i.e. between 1.7 mM to 332 mM and 3.3 mM to 216 mM, with lower detection limits of 0.8 mM and 1.7 mM for choline and acetylcholine, respectively, even in the presence of common interferents such as ascorbic and uric acids. Electrochemistry, 2019, 15, 96–146 | 131

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 22 Schematic representation of the ECL aptamer ATP sensor. (A) Immobilization of ssDNA1 on the surfaces of Au electrode. (B) Treated with MCH to obtain a well-aligned DNA monolayer. (C) Hybridization of the two fragments in the presence of ATP. Reproduced from ref. 147 with permission from Elsevier, Copyright 2013.

Very recent works have seen the use of luminescent graphene quantum dots for ultrasensitive ECL immunosensing. For example, a considerable improvement in sensitivity has recently been obtained by using luminescent blue graphene quantum dots. Lu et al. developed a simple approach to prepare water soluble graphene quantum dots (GQDs) using exfoliating and disintegrating treatments for graphene oxide, followed by hydrothermal synthesis.147 The as-prepared GQDs were utilised to fabricate an ultrasensitive ECL immunosensor for the detection of ATP using the procedure highlighted in Fig. 22. While ssDNA1 was adsorbed on a clean Au electrode surface, then, by employing SiO2 nanospheres previously functionalised with an amino group as signal carrier, a novel SiO2/GQDs ECL signal amplification labels were synthesized and bioconjugated with a ssDNA2 for ultrasensitive ECL detection. Water soluble GQDs exhibited bright blue emission under irradiation at 365 nm (UV irradiation). Noticeably, in the presence of hydrogen peroxide as a co-reactant, the GQDs showed a strong anodic ECL signal at relatively low potentials (ca. 0.4 V vs. Ag/AgCl) and the following mechanism was proposed:139 GQDs  e-GQDs 1

(35)

H2O2-H1 þ HOO

(36)

HOO  e-HOO 2 O2

(37)

GQDs 1 þ O2 -GQDs*

(38)

GQDs*-GQDs þ hn

(39)

132 | Electrochemistry, 2019, 15, 96–146

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096



The formation of the superoxide radical O2 is crucial for the ECL emission, since this specie reacting with the radical cation GQDs 1 lead to the formation of GQDs* and consequent emission of light. Under optimised experimental conditions, the as-prepared ECL aptamer sensor exhibited excellent analytical performance for adenosine triphosphate (ATP) detection, within the linear concentration range of 5 pmol L1– 5 nmol L1 with a low detection limit of 1.5 pmol L1. Due to the low cytotoxicity and excellent biocompatibility, GQDs are highly promising for applications in ECL immunosensing.139 In another interesting application, Wu et al. have used carbon quantum dots as labels to develop an ECL immunosensor for tumor marker detection, for PSA.148 In this work, graphene was conjugated with Au NPs and deposited on the surface of a glassy carbon electrode, which provide a good matrix for the antibody immobilisation (Ab1). Luminescent carbon quantum dots (CQDs) were synthesised by electro-oxidation of graphite and immobilised onto highly porous Ag, which provided a highly accessible surface area. CQDs were labelled with Ab2 and immobilised onto the nanoporous Ag surface. CQDs were used as an ECL reagent. The ECL immunosensor displayed good analytical performance for the detection of PSA in the concentration range 1 pg mL1–50 ng mL1 with a low detection limit of 0.5 pg mL1.140 Composite materials obtained by the combination of graphene with magnetic nanoparticles, polymers and redox probes have been particularly effective for the development of highly sensitive ECL immunosensors. In this respect, Liao et al. recently reported the development of a reagentless ECL immunosensor for the detection of human total 3,3,5-triiodothyronine(T3), a biomarker involved in thyroid disease.149 In this work, they used a poly(L-lysine)-[Ru(bpy)3]21 composite material, as a co-reactant for signal amplification, and magnetic Fe3O4-functionalised graphene sheets as nanoprobe. The probe was prepared by immobilising [Ru(bpy)3]21 and T3 antibody on the surface of Fe3O4-functionalised graphene sheets, while the T3 capture antibody was immobilised on Au NPs-functionalised poly(Llysine) modified electrode. The as-prepared ECL immunosensor worked in the linear concentration range of T3 of 0.1 pg mL1–10 ng mL1, with a low detection limit of 0.03 pg mL1.141 Interesting works have seen the combination of magnetic nanoparticles and quantum dots to generate magnetic quantum dots that possess both magnetic and optical properties. Jie et al. fabricated magnetic Fe3O4-CdSe quantum dots based that were labelled with an a1/bbcQD signal probe.150 The as-prepared signal probe was immobilised on graphene-modified capture DNA (c-DNA1) deposited onto a gold electrode. The whole procedure is summarised in Fig. 23. An endonuclease-assisted amplification technique was used to amplify the change in the ECL signal induced by target cells. Specifically, the bifunctional Fe3O4-CdSe QDs composite QDs with excellent magnetic property can be conveniently labelled to obtain an ECL signal probe with high specificity and sensitivity. In order to evaluate the analytical performance of the ECL immunosensor for early diagnosis of cancer, a target and a control cells samples with a concentration of 2000 cells mL1 were Electrochemistry, 2019, 15, 96–146 | 133

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 23 Schematic representation of the ECL aptasensor for cell detection by DNA cyclic amplification technique using Fe3O4-CdSe QDs composite as signal probe. Reproduced from ref. 150 with permission from Elsevier, Copyright 2013.

spiked into two different clinical samples. The obtained results showed that the ECL signals of the target cells in clinical sample and in cell media were almost the same. The ECL signal of cell media was greater than that one obtained in the control cells, indicating the suitability of the proposed ECL immunoassay. The proposed ECL method showed linearity in the range of 300–24 000 cells mL1, with a low detection limit of 98 cells mL1.142 Another recent ECL immunosensor application has seen the use of graphene and luminol for cancer biomarker detection. Xu et al. obtained a multiple signal amplification strategy using functionalised graphene and Au nanorods multi-labelled with glucose oxidase and secondary antibody (Ab2).151 Graphene was used to increase the electron transfer as well as to attach the primary antibody (Ab1), while Au nanorods acted as a carrier of the secondary antibody as well as catalyse the ECL reaction of luminol in the presence of glucose oxidase and oxygen. The as-prepared ECL immunosensor showed high sensitivity and selectivity towards the detection of PSA with a linear concentration range of 10 pg mL1– 8 ng mL1, and a low detection limit of 8 pg mL1.143 134 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

A similar approach, but without the use of graphene, was later used by Cheng et al. to develop an ECL resonance energy transfer (ERET) based on CdTe QDs and Au nanoclusters.152 At first, Au nanoclusters were labelled with hairpin DNA and then attached to carboxylated CdTe QDs on glassy carbon electrodes via amide reaction. The interactions between Au nanorods and CdTe cause the quenching of the ECL signal. In addition of assistant DNA and miRNA, the ligase selectively bound both of them on the strand of the hairpin DNA to form DNA–RNA heteroduplexes. This causes the recovery of the ECL due to the blocking of the ERET signal. In comparison, the ECL emission signal was weak, when directly opening the hairpin DNA by the target. Based on the distancedependent ERET, a ‘signal on’ ECL system was utilized for the detection of miRNA with the advantages of 6 orders magnitude linear range and excellent sequence specificity. For instance, the ECL signal scaled linearly with the concentration of miRNA in the range of 100 fM–100 nM, with a low detection limit of 21.7 fM.144 By substituting the hairpin DNA with different sequences, this novel strategy can be extended for detection of other short miRNA and DNA. The potentiality of the ECL detection in biomedical diagnostics is clearly evident when ECL is integrated within microfluidic devices. In this regard, Sardesai et al. recently incorporated an ECL immunoassay within a prototype microfluidic device for highly sensitive protein detection.153 The prototype was demonstrated for detection of PSA and IL-6. The design of the microfluidic device is shown in Fig. 24.

Fig. 24 Design of microfluidic ECL array: (1) syringe pump, (2) injector valve, (3) switch valve to guide the sample to the desired channel, (4) tubing for inlet, (5) outlet, (6) poly(methylmethacrylate) (PMMA) plate, (7) Pt counter wire, (8) Ag/AgCl reference wire (wires are on the underside of PMMA plate), (9) polydimethylsiloxane (PDMS) channels, (10) pyrolytic graphite chip (PG) (2.5  2.5 cm) (black), with hydrophobic polymer (grey) to make microwells. Bottoms of microwells (red rectangles) contain primary antibody decorated SWCNT forests, (11) ECL label containing RuBPY-silica nanoparticles with cognate secondary antibodies is injected to bind to the capture protein analytes previously bound to cognate primary antibodies. ECL is detected with a CCD camera. Reproduced from ref. 153 with permission from Springer Nature, Copyright 2013. Electrochemistry, 2019, 15, 96–146 | 135

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

1.4.4 Polymer systems. Polymer systems for ECL have not received much attention and are often utilised as simple platforms for confinement of the luminophore to the electrode surface.154,155 Commonly polyaromatic hydrocarbons (PAHs), such as rubrene and DPA have been studied in detail because of their high fluorescence quantum yields and stable radical cations and anions in aprotic media for ECL. Many studies on PAHs followed, and other organic systems including luminol,156 acridinium esters,157 polymers,158–160 and siloles161 have also been extensively investigated.28 Fluorene-substituted PAHs with enhanced ECL efficiency and stability have been reported.162 Fluorene was used as a capping agent to produce the derivatives of DPA, pyrene, and anthracene as new compounds (Fig. 25). The introduction of fluorene groups imparts steric hindrance that prevents interchromophore interactions and blocks the active position of PAH cores subject to electrochemical decomposition. Therefore, these molecules have high photoluminescence quantum yields and can generate stable radical ions. Moreover, the C2 and C6 substitutions on the DPA core provide extra stabilization for the highly charged species

Fig. 25 Chemical structures of new ECL active aromatic compounds and model compounds. Reproduced from ref. 162 with permission from John Wiley & Sons, Copyright r 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 136 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

(dication and dianion), allowing the fluorene-substituted DPA to have highly efficient (F ¼ 0.90, F is the relative ECL quantum yields compared to DPA) and stable blue ECL for up to 20 000 pulses. In another approach, the enhancement of ECL and radical stability by peripheral multidonors on pyrene derivatives has been demonstrated.163 Although the pyrene molecule shows poor ECL properties because of the electrochemical instability of its cationic radical, the ECL efficiencies of pyrene derivatives increase in proportion to the number of peripheral N,N-dimethyl aniline donors, which suggests that this approach has some promise for the development of highly efficient ECL materials. The ECL of 2,2 0 -bis(10-phenylanthracen-9-yl)-9,9 0 -spirobifluorene that is a dichromophoric molecule composed of two phenylanthracenes linked by a spirobifluorene moiety was studied.164 Because there are two redox centers, di-ions are created during each potential pulse of an ECL experiment. Since annihilation occurs between di-ions, a single electron transfer to form an excimer should be quenched by intramolecular transfer of the other electron prior to emission. Therefore, the ECL of 2,2 0 -bis(10-phenylanthracen-9-yl)-9,9 0 -spirobifluorene is reasonably explained by a simultaneous two-electron transfer. ECL of 3,6-dispirobifluorene-N-phenylcarbazole which contains two spirobifluorene groups covalently attached to a N-phenylcarbazole core has also been reported.165 Semi-empirical MNDO (modified neglect of differential overlap) calculations of this compound demonstrate that the spirobifluorene is twisted relative to N-phenylcarbazole and shows a weak orbital overlap between these two groups. This molecular geometry favours the localization of negative charges on the individual spirobifluorene groups and of the positive charge of radical cation onto N-phenylcarbazole. Donor–acceptor architectures such as this may provide a general approach to design new materials exhibiting efficient ECL. A group of highly fluorescent 2,1,3-benzothiadiazole derivatives, including two fluorene derivatives, were synthesized. These compounds show strong and stable green ECL emission.166 Generally, the fluorene derivatives emit blue light due to their large energy gap. By introducing a unit with a narrower energy gap, the electron-deficient 2,1,3-benzothiadiazole group, into the fluorene backbone, the emission colour can be tuned to green region. The ability to tune the luminescence of these systems makes them of interest to achieve multiple wavelength ECL labels (Fig. 26). Electrochemistry, spectroscopy, and ECL of a series of extended silolebased chromophores were studied to understand the effect of structure on behaviour.151 By changing substituents attached to the chromophore, large variations in quantum efficiency, lmax for absorbance and photoluminescence, and radical ion stability were observed. The differences are related to the motion in the 2,5-substituents and the steric protection of both the chromophore and the reactive parts of the substituents. Very recently, efficient and stable ECL was obtained by tuning the electrochemical potentials of silole–thiophene hybrid chromophores.167 Stable radical cations favourable for ECL emission were generated by extending silole p conjugation with thiophene units and by constraining the applied Electrochemistry, 2019, 15, 96–146 | 137

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 26 (a) The EC cell includes a Ag-wire QRE, a Au planar counter electrode and a 50 nm conjugated polymer-coated ITO working electrode. (b) Images of free and pinned ECL waves triggered by 250 nm Au NPs with potential steps of 1.5 and 1.8 V, respectively. (c) Radius vs time for (b). (d) ECL images at (left) 0.3 and (right) 0.6 s after the potential step of 1.6 V. The integration time was 100 ms (free) and 12 ms (pinned) in (b) and 100 ms in (d). Scale bars are 20 mm. Reproduced from ref. 170 with permission from American Chemical Society, Copyright 2009.

potential range. This provides a new approach for acquiring efficient ECL materials. Organic polymers have also attracted attention. A recent example involved excimer emission from two linear, stereo-regular, and structurally defined polyphenylene vinylene (PPV) derivatives, poly[distyrylbenzene-b(ethylene oxide)]s, with 12 and 16 of ethylene oxide repeating units in the backbone, respectively.168 A one-electron transfer, reversible oxidation at B0.75 V vs. Ag/Ag1 was observed for both polymers in CH2Cl2 solution. ECL responses with a maximum emission at B1.10 V vs. Ag/Ag1 were obtained with the polymer cast film in MeCN in the presence of TPrA. The proposed mechanism for ECL involved the oxidised polymer species and the strongly reducing TPrA free radical (TPrA ). In another paper, strong blue photoluminescence and ECL from (NH4)2S2O8-treated OH-terminated polyamidoamine (PAMAM) dendrimers were reported.169 A considerable enhancement of the ECL signal was observed when 10 mM sodium oxalate was added as a co-reactant. This kind of blue-luminescent chemical species may have potential applications as a new fluorophore or in aqueous ECL. The soliton-like ECL waves in the electrochemical oxidation of thin films of the semiconducting conjugated polymerpoly(9,9-dioctylfluoreneco-benzothiadiazole) (F8BT) have been observed recently.170 The waves were triggered by AuNPs embedded in the film (Fig. 25). The ECL ‘‘wave fronts’’ were visualized and imaged in space and time by optical emission microscopy and observed to freely propagate parallel to the plane of an electrode. ECL free waves were also launched by a square-shaped scratch instead of an embedded NP. For a film with a shallow scratch, irregular 138 | Electrochemistry, 2019, 15, 96–146

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

patterns of ECL rather than a free wave were observed. Similarly, a dense array of triggering leaks for ultrathin films generates dendritic ECL filaments throughout the film as a result of drying cracks. The proposed soliton ECL wave mechanism, which is based on lateral wave propagation, anion-gated electrochemistry, and critical polymer swelling transitions, has important implications for the design and operation of electrochemical light-emitting diodes, chemically sensitive field-effect transistors, electrochromic window coatings, and certain types of solar cells. Particularly fascinating ECL properties have been discovered in recent years of various conjugated oligomers with fluorene derivatives as emitters. Oligofluoren-truxenetrigonal systems (Fig. 27) are a fascinating class of the efficient blue emitters with a virtually ‘‘no core’’star-shaped structure.171,172 The 2-D architecture of these molecules provides an excellent film forming properties upon solution processing with amorphous morphology of the film which render the material a high PLQY in a solid phase. Being trapped in isotropic amorphous state with glass-transition temperature above 100 1C, the T4 and T3 members of the series prove to be efficient optically pumped lasing media with a low lasing threshold173 and wide range of tunability.174 The C3 symmetry of these star shaped molecules provides an interesting example of electronic communication between the arms in the excited state.175 ECL studies of monodisperse oligofluorene-truxenes T1–T4 have been reported previously.176,177 The compound in this study differs from the original T4 structures, in that there are additional 2,1,3-benzothiadazole (BT) units inserted in the middle of each of the oligofluorene arms. The locations of the BT units have a fundamental influence on the optical characteristics of the compound and a series of isomers have been synthesized and studied, in which the BT units are incorporated at each of 5 possible positions in the structure (see Fig. 27). The ECL properties of trigonalquaterfluorene-truxeneoligomer with fused 2,1,3-benzothiadazole unit, (T4BT-B) showed good electrochemistry in CH2Cl2, with excellent stability properties of both the anion and cation radicals. T4BTB also shows a yellow emission when generated by reaction with TPrA consistent with its photochemical properties. The production of ECL from the reaction of T4BT-B with TPA was shown to be linearly dependant over a wide dynamic linear range with low limits of detection and good reproducibility. Significantly producing almost double the ECL intensity compared to [Ru(bpy)3]21 under the same experimental conditions. This work illustrates the proof of concept of the promising ECL sensing applications of this new family of compounds in a wide variety of applications ranging from biomedical diagnostics to forensic science. The possibilities for polymer based ECL systems are open due to the highly luminescent and fast charge transfer properties of these compounds that can be utilised to detect low levels of co-reactant without increasing the background noise levels thereby allowing of the development of an ultrasensitive and selective ECL sensor. However, there is still a large amount of research to be done to exploit the capabilities of these systems to truly apply them to analytical applications. Electrochemistry, 2019, 15, 96–146 | 139

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

View Online

Fig. 27 Chemical structure of truxenequarterfluorenes with BT (green) unit, n ¼ 1, m ¼ 3 for T4BT-B. Reproduced from ref. 177 with permission from the Royal Society of Chemistry.

2

Conclusions

This chapter describes the fundamentals of ECL and the wide range of applications of this technology. It is a commercially successful analytical technique as well as being extremely versatile, providing insights into fundamental chemical, biological and physical questions. The increase in research and subsequent applications of ECL drives the development of assays within clinical diagnostics, biodefense, drug screening, food and water safety, environmental monitoring etc. This intense research will further develop innovation towards overcoming current limitations and drive active research in the areas of high-throughput analysis, aptamer based sensors, the development of new ECL luminophores and co-reactants as well as inspiring new applications of ECL technology. The miniaturisation of instruments will lead to the development of 140 | Electrochemistry, 2019, 15, 96–146

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

point-of-care devices and assays within biomedical diagnostics and environmental monitoring. The extremely rapid process in all areas of ECL research highlights this dynamic area of research and demonstrates the potential of this field as an analytical technique capability of providing fundamental insights into electron transfer mechanisms.

References 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

N. E. Tokel and A. J. Bard, J. Am. Chem. Soc., 1972, 94, 2862–2863. W. Miao, Chem. Rev., 2008, 108(7), 2506–2553. K. M. Omer, A. L. Kanibolotsky, P. J. Skabara, I. F. Perepichka and A. J. Bard, J. Phys. Chem. B, 2007, 111, 6612–6619. A. J. Bard, Electrogenerated Chemiluminescence, CRC Press, 2004. P. Bertoncello, A. J. Stewart and L. Dennany, Anal. Bioanal. Chem., 2014, 406, 5573–5587. A. J. Stewart, J. Hendry and L. Dennany, Anal. Chem., 2015, 87(23), 11847– 11853. A. J. Bard, L. R. Faulkner, J. Leddy and C. G. Zoski, Electrochemical Methods: Fundamentals and Applications, Wiley, New York, 1980, vol. 2. A. J. Bard and L. R. Faulkner, Electrochemical Methods, 2nd edn, Wiley, New York, 2001. H. Zheng and Y. Zu, J. Phys. Chem. B, 2005, 109, 12049–12053. N. D. Danielson, Electrogenerated Chemiluminescence, 2004, pp. 397–444. J. N. Noffsinger and N. D. Danielson, Anal. Chem., 1987, 59, 865. A. W. Knight and G. M. Greenway, Analyst, 1996, 121, 101R. Y. P. Dong, H. Cui and Y. Xu, Anal. Chem., 2009, 81, 9710–9715. C. D. Jonah, M. S. Matheson and D. Meisel, J. Am. Chem. Soc., 1978, 100, 1449. ¨rsterling and D. H. Waldeck, Principles of Physical H. Kuhn, H. D. Fo Chemistry, Wiley, 2009. W. H. Koppenol and J. D. Rush, J. Phys. Chem., 1987, 91, 4429–4430. I. Rubinstein, C. R. Martin and A. J. Bard, Anal. Chem., 1983, 55, 1580–1582. M.-M. Chang, T. Saji and A. J. Bard, J. Am. Chem. Soc., 1977, 99, 5399–5403. A. W. Knight and G. M. Greenway, Analyst, 1994, 119, 879. N. J. Turro, V. Ramamurthy and J. C. Scaiano, Principles of Molecular Photochemistry: An Introduction, 2009, Univ Science Books. H. Tachikawa and A. J. Bard, Chem. Phys. Lett., 1974, 26(2), 246–251. A. K. Campbell, Chemiluminescence: Principles and Applications in Biology and Medicine, 1988. L. Dennany, E. J. O’Reilly, T. Keyes and R. J. Forster, Electrochem. Commun., 2006, 8, 1588–1594. E. J. O’Reilly, T. E. Keyes, R. J. Forster and L. Dennany, Electrochem. Commun., 2018, 86, 90–93. J. Li, Q. Yan, Y. Guo and H. Ju, Anal. Chem., 2006, 78, 2699. M. Zorzi, P. Pastore and F. Magno, Anal. Chem., 2000, 72, 4934–4939. E. J. O’Reilly, P. Conroy, T. E. Keyes, R. O’Kennedy, R. J. Forster and L. Dennany, RSC Adv., 2015, 5, 67874–67877. L. Hu and G. Xu, Chem. Soc. Rev., 2010, 39, 3275–3304. Electrogenerated Chemiluminescence, A. J. Bard, ed. 2004, Marcel Bekker, New York. R. Y. Lai, M. Chiba, N. Kitamura and A. J. Bard, Anal. Chem., 2002, 74, 551– 553. B. D. Muegge and M. M. Richter, Anal. Chem., 2002, 74, 547–550. Electrochemistry, 2019, 15, 96–146 | 141

View Online

32 33 34

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

35 36 37 38 39 40 41 42 43 44 45

46 47 48 49 50 51 52 53 54 55 56 57

M. J. Li, Z. F. Chen, N. Y. Zhu, V. W. W. Yam and Y. B. Zu, Inorg. Chem., 2008, 47, 1218–1223. L. Z. Hu, B. Zheng, H. J. Li, S. Han, Y. L. Yuan, L. X. Guo and G. B. Xu, Anal. Chem., 2009, 81, 9807–9811. R. Kurita, K. Arai, K. Nakamoto, D. Kato and O. Niwa, Anal. Chem., 2012, 84, 1799–1803. Z. Xu, Y. Dong, J. Li and R. Yuan, Chem. Commun., 2015, 51, 14369–14372. W. B. Liang, M. Z. Yang, Y. Zhou, Y. N. Zheng, C. Y. Xiong, Y. Q. Chai and R. Yuan, Chem. Sci., 2016, 7, 7094–7100. H. Liu, X. Zhou, W. Liu, X. Yang and D. Xing, Anal. Chem., 2016, 88, 10191– 10197. X. Sun, J. Du, L. Zhang, S. Dong and E. Wang, Chem. – Asian J., 2007, 2, 1137–1141. X. P. Sun, Y. Du, L. X. Zhang, S. J. Dong and E. K. Wang, Anal. Chem., 2007, 79, 2588–2592. H. Wang, Y. Yuan, Y. Zhou, Y. Chai and R. Yuan, Anal. Chem., 2016, 88, 2258–2265. Y. Chen, J. Mao, C. Liu, H. Yuan, D. Xiao and M. M. F. Choi, Langmuir, 2009, 25, 1253–1258. L. Dennany, R. J. Forster, B. White, M. R. Smyth and J. F. Rusling, J. Am. Chem. Soc., 2004, 126(28), 8835–8841. M. M. Richter, A. J. Bard, W. Kim and R. S. Schemhl, Anal. Chem., 1998, 70, 310–318. S. G. Sun, Y. Yang, F. Y. Li, Y. Pang, J. L. Fan, L. C. Sun and X. J. Peng, Anal. Chem., 2009, 81, 10227–10231. S. J. Wang, J. Milam, A. C. Ohlin, V. H. Rabaran, E. Clark, W. Ward, L. Seymour, W. H. Casey, A. A. Holder and W. J. Miao, Anal. Chem., 2009, 81, 4068–4075. W. Sun, S. Sun, N. Jiang, H. Wang and X. Peng, Organometallics, 2015, 34, 3385–3389. L. Zhang, K. J. Tian, Y. P. Dong, H. C. Ding and C. M. Wang, Analyst, 2018, 143, 304–310. R. F. Huang, L. T. Wang, Q. Q. Gai, D. M. Wang and L. Qian, Sens. Actuators, B, 2018, 256, 953–961. A. Devadoss, L. Dennany, C. Dickinson, T. E. Keyes and R. J. Forster, Electrochem. Commun., 2012, 19, 43–45. E. J. O’Reilly, T. E. Keyes, R. J. Forster and L. Dennany, Analyst, 2013, 138, 677–682. E. J. O’Reilly, L. Dennany, D. Griffith, F. Moser, T. Keyes and R. J. Forster, Phys. Chem. Chem. Phys., 2011, 13, 7095–7101. L. Dennany, E. J. O’Reilly, P. C. Innis, G. G. Wallace and R. J. Forster, Electrochim. Acta, 2008, 53, 4599–4605. A. Chen, M. Zhao, Y. Zhou, Y. Chai and R. Yuan, Anal. Chem., 2017, 89, 9232–9238. W. J. Miao, J. P. Choi and A. J. Bard, J. Am. Chem. Soc., 2002, 124, 14478–14485. H. Xing, Q. Zhai, X. Zhang, J. Li and E. Wang, Anal. Chem., 2018, 90, 2141–2147. L. Dennany, G. G. Wallace and R. J. Forster, Langmuir, 2009, 25(24), 14053– 14060. L. Dennany, R. J. Forster and J. F. Rusling, J. Am. Chem. Soc., 2003, 125(17), 5213–5218.

142 | Electrochemistry, 2019, 15, 96–146

View Online

58 59

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

60

61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89

S. Carrara, A. Aliprandi, C. F. Hogan and L. De Cola, J. Am. Chem. Soc., 2017, 139, 14605–14610. M. A. Haghighatbin, S. E. Laird and C. F. Hogan, Curr. Opin. Electrochem., 2018, 8, 52–59. S. E. Laird and C. F. Hogan, Electrochemiluminescence of iridium complexes, E. Zysman-Coleman, ed. Iridium (III) in Optoelectronic and Photonics Applications, John Wiley & Sons, Ltd, 2017, pp. 359–414. E. M. Gross, N. R. Armstrong and R. M. Wightman, J. Electrochem. Soc., 2002, 149, E137–E142. D. Bruce and M. M. Richter, Anal. Chem., 2002, 74, 1340–1342. B. D. Stringer, L. M. Quan, P. J. Barnard, D. J. D. Wilson and C. F. Hogan, Organometallics, 2014, 33, 4860–4872. J. I. Kim, I. S. Shin, H. Kim and J. K. Lee, J. Am. Chem. Soc., 2005, 127, 1614– 1615. A. Kapturkiewicz, Anal. Bioanal. Chem., 2016, 408, 7013–7033. H. Zhou, Y. Yang, C. Li, B. Yu and S. Zhang, Chemistry, 2014, 20, 14736–14743. K. N. Swanick, S. Ladouceur, E. Zysman-Colman and Z. Ding, Chem. Commun., 2012, 48, 3179–3181. S. Ladouceur, K. N. Swanick, S. Gallagher-Duval, Z. Ding and E. Zysman-Colman, Eur. J. Inorg. Chem., 2013, 5329–5345. E. H. Doeven, E. M. Zammit, G. J. Barbante, C. F. Hogan, N. W. Barnett and P. S. Francis, Angew. Chem., Int. Ed., 2012, 51, 4354–5357. M. Schmittel, Q. Shu and M. E. Cinar, Dalton Trans., 2012, 41, 6064–6068. E. H. Doeven, G. J. Barbante, E. Kerr, C. F. Hogan, J. A. Endler and P. S. Francis, Anal. Chem., 2014, 86, 2727–2732. M. A. Haghighatbin, S. C. Lo, P. L. Burn and C. F. Hogan, Chem. Sci., 2016, 7, 6974–6980. H. Li, L. Bouffier, S. Arbault, A. Kuhn, C. F. Hogan and N. Sojic, Electrochem. Commun., 2017, 77, 10–13. Y. Z. Wang, C. H. Xu, W. Zhao, Q. Y. Guan, H. Y. Chen and J. J. Xu, Anal. Chem., 2017, 89, 8050–8056. Z. Ding, B. M. Quinn, S. K. Haram, L. E. Pell, B. A. Korgel and A. J. Bard, Science, 2002, 296, 1293–1297. N. Myung, Z. F. Ding and A. J. Bard, Nano Lett., 2002, 2, 1315–1319. N. Myung, Y. Bae and A. J. Bard, Nano Lett., 2003, 3, 1053–1055. Y. Bae, N. Myung and A. J. Bard, Nano Lett., 2004, 4, 1153–1161. H. Qi, Y. Peng, Q. Gao and C. Zhang, Sensors, 2009, 9, 674–695. R. Russell, A. J. Stewart and L. Dennany, Anal. Bioanal. Chem., 2016, 408, 7129–7136. S. Wang, E. Harris, J. Shi, A. Chen, S. Parajuli, X. Jing and W. Miao, Phys. Chem. Chem. Phys., 2010, 12, 10073–10080. D. M. Hercules, Science, 1964, 145, 808–809. X. B. Yin and E. Wang, Anal. Chim. Acta, 2005, 533, 113–120. C. A. Marquette and L. J. Blum, Anal. Bioanal. Chem., 2008, 390, 155–168. L. Dennany, M. Gerlach, S. O’Carroll, T. E. Keyes, R. J. Forster and P. Bertoncello, J. Mater. Chem., 2011, 21, 13984–13990. A. J. Stewart, E. J. O’Reilly, P. Bertoncello, T. E. Keyes, R. J. Forster and L. Dennany, Electrochim. Acta, 2015, 157, 8–14. Y. Cao, R. Yuan, Y. Chai, L. Mao, X. Yang, S. Yuan, Y. Yuan and Y. Liao, Electroanalysis, 2011, 23, 1418–1426. L. Zhang and S. Dong, Electrochem. Commun., 2006, 8, 1687–1691. J. Mal, Y. V. Nancharaiah, E. D. van Hullebusch and P. N. L. Lens, RSC Adv., 2016, 6, 41477–41495. Electrochemistry, 2019, 15, 96–146 | 143

View Online

90 91 92

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130

S. Lim, W. Shen and Z. Gao, Chem. Soc. Rev., 2015, 44, 362–381. L. Lin, M. Rong, F. Luo, D. Chen, Y. Wang and X. Chen, TrAC, Trends Anal. Chem., 2014, 54, 83–102. B. L. Oliva-Chatelain, T. M. Ticich and A. R. Barron, Nanoscale, 2016, 8, 1733–1745. W. Wang, J. Yu, Z. Chen, D. K. L. Chan and T. Gu, Chem. Commun., 2014, 50, 10148–10150. X. Chen, Y. Liu and Q. Ma, J. Mater. Chem. C, 2018, 6, 942–959. L. Shaw and L. Dennany, Curr. Opin. Electrochem., 2017, 3(1), 23–28. Z. Ding, B. M. Quinn, S. K. Haram, L. E. Pell, B. A. Korgel and A. J. Bard, Science, 2002, 296, 1293–1297. D. Zhou and X. Xing, Anal. Chim. Acta, 2012, 725, 39–43. K. Muzyka, Biosens. Bioelectron., 2014, 54, 393–407. Q. Liu, M. Han, J. Boa, X. Jiang and Z. Dai, Analyst, 2011, 136, 5197–5203. Z. Guo, T. Hao, J. Duan, S. Wang and D. Wei, Talanta, 2012, 89, 27–32. G. Jie, P. Lui, L. Wang and S. Zhang, Electrochem. Commun., 2010, 12, 22–26. Z. Guo, T. Hao, S. Wang, N. Gan, X. Li and D. Wei, Electrochem. Commun., 2012, 14, 13–16. M. Xue, T. Haruyama, E. Kobatake and M. Aizawa, Sens. Actuators, A, 1996, 36(1), 458–462. W. Tu, X. Fang, J. Lou and Z. Dai, Analyst, 2015, 140, 2603–2607. G. F. Jie, G. P. Liu and S. S. Zhang, Chem. Commun., 2010, 8, 1323–1325. Y. Zhang, S. Ge, M. Yan, J. Yu, X. Song and W. Liu, Analyst, 2012, 137, 2176– 2182. S. D. Jayasena, Clin. Chem., 1999, 45, 1628–1650. G. Jie, L. Wang, J. Yuan and S. Zhang, Anal. Chem., 2011, 83, 3873–3880. B. Babamiri, R. Hallaj and A. Salimi, Biosens. Bioelectron., 2018, 99, 353–360. Y. Shan, J. J. Xu and H. Y. Chen, Nanoscale, 2011, 3, 2916–2923. H. Huang, Nanoscale, 2010, 2, 606–612. W. Yao, Biosens. Bioelectron., 2009, 24, 3269–3274. M. Wu, H. Shi, L. He and J. Xu, Anal. Chem., 2012, 84, 4207–4213. W. Qi, D. Wu, J. Zhao, Z. Liu, W. Zhang, L. Zhang and G. Xu, Anal. Chem., 2013, 85, 3207–3212. G. Liang, S. Liu, G. Zou and X. Zhang, Anal. Chem., 2012, 84, 10645–10649. Z. Li, Y. Wang, W. Kong, C. Li, Z. Wang and Z. Fu, Biosens. Bioelectron., 2013, 39, 311–314. S. Iijima, Nature, 1991, 314, 56–58. P. Ayajan, Chem. Rev., 1999, 99, 1787–1799. R. Baughman, A. Zakhidov and W. de Heer, Science, 2002, 297, 787–792. Y. Sun, K. Fu, Y. Lin and W. Huang, Acc. Chem. Res., 2002, 35, 1096–1104. M. S. Dresselhaus and H. Dai, MRS Bull., 2004, 29, 237–239. J. J. Gooding, Electrochim. Acta, 2005, 50, 3049–3060. G. A. Rivas, M. D. Rubianes, M. C. Rodriguez, N. F. Ferreyra, G. L. Luque, M. L. Pedano, S. A. Miscoria and C. Parrado, Talanta, 2007, 74, 291–307. L. Agui, P. Yanez-Sedeno and J. Pingarron, Anal. Chim. Acta, 2008, 622, 11–47. F. Valentini and G. Palleschi, Anal. Lett., 2008, 41, 479–520. P. Bertoncello, J. P. Edgeworth, J. V. Macpherson and P. R. Unwin, J. Am. Chem. Soc., 2007, 129, 10982–10983. P. Avouris, M. Freitag and V. Perebeinos, Nat. Photonics, 2008, 2, 341–350. V. Sgobba and D. M. Guldi, Chem. Soc. Rev., 2009, 38, 165–184. A. Sun, Q. Qi, X. Wang and P. Bie, Sens. Actuators, 2014, 192, 685–690. C. Chu, M. Li, S. Ge, L. Ge, J. Yu, M. Yan, X. Song, L. Li, B. Han and J. Li, Biosens. Bioelectron., 2013, 47, 68–74.

144 | Electrochemistry, 2019, 15, 96–146

View Online

131 132

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160

Y. Cao, R. Yuan, Y. Chai, H. Liu, Y. Liao and Y. Zhuo, Talanta, 2013, 113, 106–112. Y. Cao, R. Yuan, Y. Chai, L. Mao, H. Niu, H. Liu and Y. Zhuo, Biosens. Bioelectron., 2012, 31, 305–309. J. Yan, M. Yan, L. Ge, S. Ge and J. Yu, Sens. Actuators, B, 2014, 193, 247–254. S. Deng, Z. Hou, J. Lei, D. Lin, Z. Hu, F. Yan and H. Ju, Chem. Commun., 2011, 47, 12107–12109. Y. Li, H. Qi, Q. Gao, J. Yang and C. Zhang, Biosens. Bioelectron., 2010, 26, 754–759. L. R. Hong, J. Zhao, Y. M. Lei, R. Yuan and Y. Zhuo, Electrochim. Acta, 2017, 241, 291–298. B. Wu, C. Hu, X. Hu, H. Cao, C. Huang, H. Shen and N. Jia, Biosens. Bioelectron., 2013, 50, 300–304. A. Venkatanarayanan, K. Crowley, E. Lestini, T. E. Keyes, J. F. Rusling and R. J. Forster, Biosens. Bioelectron., 2012, 31, 233–239. Y. Cheng, R. Yuan, Y. Chai, H. Niu, Y. Cao, H. Liu, L. Bai and Y. Yuan, Anal. Chim. Acta, 2012, 745, 137–142. N. P. Sardesai, J. C. Barron and J. F. Rusling, Anal. Chem., 2011, 83, 6698– 6703. M. Zhang, H. Liu, L. Chen, M. Yan, L. Ge, S. Ge and J. Yu, Biosens. Bioelectron., 2012, 49, 79–85. X. Y. Wang, A. Gao, C. C. Lu, X. W. He and X. B. Yin, Biosens. Bioelectron., 2013, 48, 120–125. L. L. Li, K. P. Liu, G. H. Yang, C. M. Wang, J. R. Zhang and J. J. Zhu, Adv. Funct. Mater., 2011, 21, 869–878. P. Z. Liu, X. W. Hu, C. J. Mao, H. L. Niu, J. M. Song, B. K. Jin and S. Y. Zhang, Electrochim. Acta, 2013, 113, 176–180. G. Jie, L. Li, C. Chen, J. Xuan and J. J. Zhu, Biosens. Bioelectron., 2009, 24, 3352–3358. X. F. Wang, Y. Zhou, J. J. Xu and H. Y. Chen, Adv. Funct. Mater., 2009, 19, 1444–1450. J. Lu, M. Yan, L. Ge, S. Ge, S. Wang and J. Yan, Biosens. Bioelectron., 2013, 47, 271–277. L. Wu, M. Li, M. Zhang, M. Yan, S. Ge and J. Yu, Sens. Actuators, B, 2013, 186, 761–767. N. Liao, Y. Zhuo, Y. Q. Chai, Y. Xiang, J. Han and R. Yuan, Biosens. Bioelectron., 2013, 45, 189–194. G. Jie, Y. Zhao and S. Niu, Biosens. Bioelectron., 2013, 50, 368–372. S. Xu, Y. Liu, T. Wang and J. Li, Anal. Chem., 2011, 83, 3817–3823. Y. Cheng, J. Lei, Y. Chen and H. Ju, Biosens. Bioelectron., 2014, 51, 431–436. N. P. Sardesai, K. Kadimisetty, R. Faria and J. F. Rusling, Anal. Bioanal. Chem., 2013, 405, 3831–3838. P. Bertoncello, L. Dennany, R. J. Forster and P. R. Unwin, Anal. Chem., 2007, 79, 7549–7553. L. Dennany, T. E. Keyes and R. J. Forster, Analyst, 2008, 133, 753–759. B. Leca and L. J. Blum, Analyst, 2000, 125, 789–791. J. S. Littig and T. A. Nieman, Anal. Chem., 1992, 64, 1140–1144. F. R. F. Fan, A. Mau and A. J. Bard, Chem. Phys. Lett., 1985, 116, 400–404. I. Prieto, J. Teetsov, M. A. Fox, D. A. V. Bout and A. J. Bard, J. Phys. Chem. A, 2001, 105, 520–523. M. M. Richter, F. R. F. Fan, F. Klavetter, A. J. Heeger and A. J. Bard, Chem. Phys. Lett., 1994, 226, 115–120. Electrochemistry, 2019, 15, 96–146 | 145

View Online

161 162 163

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00096

164 165 166 167 168 169 170

171 172 173

174

175

176 177

M. M. Sartin, A. J. Boydston, B. L. Pagenkopf and A. J. Bard, J. Am. Chem. Soc., 2006, 128, 10163–10170. K. M. Omer, S. Y. Ku, K. T. Wong and A. J. Bard, Angew. Chem., Int. Ed., 2009, 48, 9300–9303. J. W. Oh, Y. O. Lee, T. H. Kim, K. C. Ko, J. Y. Lee, H. Kim and J. S. Kim, Angew. Chem., Int. Ed., 2009, 48, 2522–2524. M. M. Sartin, C. F. Shu and A. J. Bard, J. Am. Chem. Soc., 2008, 130, 5354– 5360. S. Rashidnadimi, T. H. Hung, K. T. Wong and A. J. Bard, J. Am. Chem. Soc., 2008, 130, 634–639. K. M. Omer, S. Y. Ku, K. T. Wong and A. J. Bard, J. Am. Chem. Soc., 2009, 131, 10733–10741. C. Booker, X. Wang, S. Haroun, J. G. Zhou, M. Jennings, B. L. Pagenkopf and Z. F. Ding, Angew. Chem. Int. Ed., 2008, 47, 7731–7735. D. J. Rosado Jr., W. Miao, Q. Sun and Y. Deng, J. Phys. Chem. B, 2006, 110, 15719–15723. W. I. Lee, Y. Bae and A. J. Bard, J. Am. Chem. Soc., 2004, 126, 8358–8359. Y. L. Chang, R. E. Palacios, J. T. Chen, K. J. Stevenson, S. Guo, W. M. Lackowski and P. F. Barbara, J. Am. Chem. Soc., 2009, 131, 14166– 14167. A. L. Kanibolotsky, R. Berridge, P. J. Skabara, I. F. Perepichka, D. D. C. Bradley and M. Koeberg, J. Am. Chem. Soc., 2004, 126, 13695. M. Moreno Oliva, J. Casado, J. T. Lopez Navarrete, R. Berridge, P. J. Skabara, A. L. Kanibolotsky and I. F. Perepichka, J. Phys. Chem. B, 2007, 111, 4026. G. Tsiminis, Y. Wang, P. E. Shaw, A. L. Kanibolotsky, I. F. Perepichka, M. D. Dawson, P. J. Skabara, G. A. Turnbull and I. D. W. Samuel, Appl. Phys. Lett., 2009, 94, 243304. Y. Wang, G. Tsiminis, Y. Yang, A. Ruseckas, A. L. Kanibolotsky, I. F. Perepichka, P. J. Skabara, G. A. Turnbull and I. D. W. Samuel, Synth. Met., 2010, 160, 1397. N. A. Montgomery, G. J. Hedley, A. Ruseckas, J. C. Denis, S. Schumacher, A. L. Kanibolotsky, P. J. Skabara, I. Galbraith, G. A. Turnbull and I. D. W. Samuel, Phys. Chem. Chem. Phys., 2012, 14, 9176. Z. Mohsan, A. L. Kanibolotsky, A. J. Stewart, A. Regis Inigo, L. Dennany and P. J. Skabara, J. Mater. Chem. C, 2015, 3, 1166–1171. L. Dennany, Z. Mohsan, A. L. Kanibolotsky and P. J. Skabara, Faraday Discuss., 2014, 174, 357.

146 | Electrochemistry, 2019, 15, 96–146

Wearable miniaturized electrochemical sensors: benefits and challenges Mona A. Mohamed Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

DOI: 10.1039/9781788013895-00147

1

Introduction

Chemical sensors and biosensors are advantageous analytical tools which are cost effective, portable and exhibits sensitivity and selectivity towards many target analytes. According to the International Union of Pure and Applied Chemistry, a chemical sensor is defined as: ‘‘a device that transforms chemical information, ranging from the concentration of a specific sample component to total composition analysis, into an analytically useful signal’’,1 Fig. 1. Two basic functional units are involved in the typical chemical sensor: a receptor and a physico-chemical transducer.1 In case the receptor involves a biological component (e.g., antibody, enzyme, DNA etc.), the sensor is called as a biosensor. The analyte concentration was transformed into a chemical or physical output signal by the receptor with a defined sensitivity. The most important role of the receptor is to overcome the potential interference of chemical substances and enhance the selectivity towards the desired analyte (Fig. 1). The transducer is another essential element of the sensor that assists to transform the signal produced by the receptor– analyte interaction to a readable value. Biosensors can be classified according to their receptors, as either catalytic or affinity-based.1 Similarly, they can be classified according to the type of transducer used as electrochemical, optical, piezoelectric, and calorimetric sensors. Various non-invasive sensors were utilized to measure the concentration of biomarkers in readily available body fluids like sweat tears, and saliva are based on miniaturized, planar electrochemical cell technology.2 They typically composed of working (WE), counter (CE), and reference (RE) electrodes.3 Due to redox reactions between the biomarker and the modified working electrode, a current between the working and counter electrode is emerged, while the opposite reaction takes place at the counter electrode.3,4 This causes generation of an electrochemical current which proportional to the concentration of the biomarker/ analyte.5 To increase the existing surface for redox of the biomolecules, the surface of the WE is usually nanotextured, and so enhancing the signal to noise while lowering the limit of detection. The main advantage is that the selectivity can be improved both by coating the nanotexture with highly selective functional groups such as enzymes, antibodies, and carefully engineered peptides, and by choosing the suitable voltage potential for activation of the selected reaction.2 Another kinds of Pharmaceutical Chemistry Dept., National Organization for Drug Control and Research, Pyramids Ave, P.O. Box 29, Giza, Egypt. E-mail: [email protected] Electrochemistry, 2019, 15, 147–185 | 147  c

The Royal Society of Chemistry 2019

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

Fig. 1 Schematic showing the important components of a typical sensor. Reproduced from ref. 1 with permission from Elsevier, Copyright 2014.

solid-state sensors for body fluid analysis involve resistometric and capacitive tools where the detection of the presence and concentration of a biomarker is measured through the variation in resistance6 and capacitance,7 respectively, between a set of functionalized electrodes. Wearable sensors have gained extensive attention over the past decade owing to their massive promise for monitoring the wearer’s health, fitness and his surroundings.8 Wearable electronics are devices that can be worn or mated with human skin to continuously and closely monitor an individual’s activities, without interrupting or limiting the user’s motions.9 Wearable sensors are not restricted to only on-body applications; these devices can also have much wider scope when integrated with other surfaces, such as buildings or vehicles.8 Current wearable sensors usually track the user’s physical activities and vital signs (such as heart rate). The researchers did a lot of efforts on developing different types of wearable sensors that track many targets like alcohol,10 body fluids,9a,11 temperature,12 metabolites,11a,13 toxic gases,14 electrolytes,15 heavy metals,16 saliva,6,17 blood pressure,18 and chemical markers in sweat toward health or fitness applications.1,9a,19 Over the past decade, the interest in the area of Internet-of-Things (IoT) has showed an exponential development over the past decade as markets realize the true potential of real-time data acquisition for numerous entertainment,20 information dissemination,21 healthcare applications,22 defense,23 and environmental.24 The IoT have received the greatest attention due to its massive applications areas such as in the medical field for saving lives or improving the quality of life e.g., monitoring of physiologically relevant parameters,25 monitoring activities, support for independent living, and monitoring medicines intake.26 By providing such important information, the user can continuous monitor health abnormalities towards taking precautionary steps and circumventing severe medical situations.26b 148 | Electrochemistry, 2019, 15, 147–185

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

Wearable sensors can show an essential part in IoT in healthcare as these devices offer new ways for continuous monitoring of individuals. So, these types of sensors afford the wearer with important physiological information about his health in a personalized fashion.1,15b,15d,27 The ideal diabetes management for regular glucose monitoring and measuring the electrolytes for athletes during their training are examples of continuous health care monitoring. Also, real-time for biofluids to detect the pathogens is an additional way in which continuous measurements of great benefits.1 The rising interest in wearable sensors shows main changes from centralized hospital-based patient care to home-based personal management, which ongoing lowers health-care costs.1 Unlike wearable physical sensors that are used for monitoring importantsigns, non-invasive chemical sensors and biosensors, which are based on the transduction of chemical information, are still in their infancy.28 Wearable chemical sensors faces many challenges that imitate further progress towards application in health care monitoring. Some of the main challenges like very low response due low concentration of the target analyte, martials, data acquisition, low volumes of biofluid sample, mechanical flexibility, processing, security, biofouling, biocompatibility of the sensors.8 Lithographic30–33 and printing34–38 methods have been the primary technologies utilized for fabricating wearable electrochemical devices. The primary techniques were utilized for fabrication of wearable sensors are lithographic29 and printing30 technologies. Lithographic methodologies have many limitations like the need for clean-room facilities and expensive chemicals.31 While Screen printing technology can display a wide range advantages like low cost mass production of electrochemical and stretchable devices.32 Extensive works have been dedicated towards progress of stretchable screen-printed electrochemical devices like using synthesized stretch-enduring inks.33 There are many challenges that facing and make limitation for the propagation of non-invasive chemical sensors towards the personal continuous health care monitoring. Mechanical resiliency, low analyte concentrations, small sampling volumes of the biofluid, biocompatibility and biofouling of the sensors are the main key challenges for widespread of electrochemical wearable sensors.1 Herein, we discuss some challenges and defects towards the understanding and successful applications of the e wearable chemical sensor platforms. Like to their in vitro symmetric, wearable non-invasive electrochemical sensors can target analytes in sweat, saliva, tears, and skin interstitial fluid. Scientists have lately made extensive efforts to improve wearable chemical sensors that can conveniently monitor these biofluids. The present chapter discusses different types of wearable electrochemical sensors and challenges facing the progress of such technology.

2

Sweat-based sensors

Human sweat is a biofluid which contains massive physiological information that enable the non-invasive continuous monitoring of health.34 For example, electrolytes (such as sodium and potassium ions), Electrochemistry, 2019, 15, 147–185 | 149

Published on 15 October 2018 on https://pubs.rsc.org | d

150 | Electrochemistry, 2019, 15, 147–185 Fig. 2 (A): Schematic illustration of a three-electrode ‘‘NE’’ tattoo biosensor for electrochemical epidermal monitoring of lactate with representation of a working electrode for an electrochemical sensor and constituents of the reagent layer of the working electrode;11a (B) Photographs of wireless transceiver worn by a subject along with the Na-tattoo (inset: a zoomed image of the entire device);15c (C) On-body ammonium measurements: Sensing tattoo platform located on the shoulder; and final design of the tattoo in order to facilitate a path where sweat can flow;44; (D) Graphic illustration of the construction platform utilized in the manufacture of temporary transfer tattoo-based solid-contact ion-selective electrode (ISE) sensors and photograph of the tattoo ISE sensor.45 Figure A reproduced from ref. 11a with permission from American Chemical Society, Copyright 2013. Figure B reproduced from ref. 15c with permission from Elsevier, Copyright 2014. Figure C reproduced from ref. 44 with permission from the Royal Society of Chemistry. Figure D reproduced from ref. 45 with permission from the Royal Society of Chemistry.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

ammonium, calcium and lactate levels in sweat are indicators for cystic fibrosis (CF),35 imbalance of electrolyte,9a,36 bone mineral loss,37 and osteoporosis,38 respectively. Another useful applications of sweat analysis include the monitoring of signs of drug abuse39 and intoxication level.40 Continuous monitoring and detection of the previous mentioned analytes are highly recommended for ideal physiological balance. Referring to the above mentioned vital uses for sweat monitoring, wearable noninvasive sensors become highly demanded. Recently, the screen printing technology was utilized for mass production of stretchable devices. These device has been fabricated to have 2D serpentine interconnects with turns of 1801 between the electrode areas and contact pads. Such interconnect designs can endure high levels of strain without failure.41 One of the best substrates for wearable sensors are the fabrics due to their stable contact with the skin. Also, the high surface area of textiles enable the incorporating the associated electronics. Due these attributes, Wang research group developed low-cost textile-based electrochemical sensors that were screen-printed onto various fabrics.42 The same group developed a textile-based dual potentiometric sensor was used for simultaneously detecting sodium and potassium in the human sweat.15d Another examples are bandage-based printed pH sensor was developed for wound monitoring,43 optical monitoring of sweat pH by a textile fabric wearable sensor.11b Many core demands of epidermal sensing were raised in the rapid growing field of wearable technologies like low weight, intimate skin conformance, and durability,11a Fig. 2A. Flexible printed temporarytransfer tattoos are another excellent new platforms of wearable electrochemical biosensors that were utilized for the continuous physiological monitoring for maintaining an optimal health status. Ramı´rez et al.11a developed an electrochemical tattoo biosensors for continuous monitoring of sweat lactate dynamics during cycling where lactate oxidase was immobilized as a biomarker of physical stress. Latter, tattoo sensors were combined with solid-state potentiometry to develop epidermal sensors for monitoring ammonium44 (Fig. 2B) and acidity45 (Fig. 2C) in sweat. Another sensors were coupled with wearable transceiver, for continuous wireless monitoring of sodium levels in human perspiration,15c Fig. 3D. Different researches were led to skin patch-based sensors for sweat lactate13 or alcohol.10,46 Power source is one of the main challenges in wearable ocular sensoring. Falk et al. have established biofuel cells that are capable of producing usable energy from lycramal ascorbate47 and glucose.48

3

Breath monitoring using miniaturized gas sensing

Among the least instinctive and invasive tools of medical diagnostics are the analysis of volatile organic compounds. Breath analysis shows solitary advantages for the continuous monitoring and measuring important, because the needless to in direct contact with any body organ or dipped in a body fluid.2 Electrochemistry, 2019, 15, 147–185 | 151

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

Fig. 3 (A) The facemask with the implanted paper-based sensor; (B) Picture of the data acquisition electronics; (C) Picture of displaying device (tablet computer running the Android app). Reproduced from ref. 53a with permission from John Wiley & Sons, Copyright r 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The preventive medicine depends on the early stage diagnostics which enhance the chances of treating with promising manner the widespread diseases like melanoma and lung cancer, while lowering the average costs of therapy.2 The corrective actions that could be taken via continuous monitoring of vital biomarkers would help the deny of chronic diseases development like asthma and circulatory system disorders. So, the regular scan for health of individuals to help fighting against such diseases becomes not available due to high cost of several medical analysis.2 The exhaled air from during the respiration contain immense information about the individual health state. Beside the main gases that the exhaled air contained, about 2000 different compounds were detected including some important volatile biomarkers (VOCs).49 The breath makes the non-invasive detection of many analytes including VOCs considerable with high demand. 152 | Electrochemistry, 2019, 15, 147–185

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

In spite of this, VOC analysis does not play a main role in clinical diagnostics due to many challenges. The main challenges are associated with the accurate measurements of very low concentrations of gas molecules in complex gas matrix of breath. So, this has led to postponement of the progress of a robust set of VOCs and levels associated with specific diseases and metabolic states. As exceptional cases the determination of ammonia for diagnosis of helicobacter pylori infections of the stomach50 and exhaled NO (eNO) concentrations for diagnosis of asthma.51 Currently, the analysis of VOCs are becoming more and more attractive because of the immense development in the field of analytical techniques for the analysis of ultra-low VOCs concentrations in the biological body fluids which include blood, breath, skin and urine. Volatile organic compounds (VOCs) that exist in breath can originate at the cellular level (endogenous) or from environ-mental sources (exogenous).52 Volatomics is the analysis of VOCs in the body, which needs a theoretical framework for the origin of endogenous VOCs to predict potential correlations between diseases and volatile biomarkers. The Haick research group explained excellently the theory behind the origin of VOCs in breath,53 Fig. 3. Firat et al.82 developed a sensor that is capable of measuring the rate of respiration of a person by detecting the transient difference in moisture adsorbed on paper from inhaled and exhaled air. The developed sensor is composed of a piece paper with digitally printed graphite electrodes, and is attached inside a flexible textile procedure mask with a battery-powered unit that can interface with an internet-enabled tablet computer/smartphone. To epitomize the theoretical base, VOCs are products or byproducts of cellular metabolism or oxidative stress caused by reactive oxidative species (ROS).53b Abnormal gene expression may cause deviation in cellular metabolism, which in turn affects the concentration of these compounds in blood serum, and consequently in other excreted fluids, such as breath. Farhi mathematically modeled the proportional relationship between VOC concentration in alveolar air (CA) and VOC concentration in mixed venous blood (CV).54 The relationship of CA to CV depends on the blood/air partition coefficient (lblood/air), the respiratory transport of alveolar air (VA), and the cardiac output (QC) controlling the rate at which VOC-rich blood is delivered to the lungs [eqn (1)].   VA CA ¼ CV lblood = air þ QC

(1)

The human breath contains predominant endogenous VOCs which involve aldehydes, ketones, and hydrocarbons. Hydrocarbons, such as ethane and pentane, as well as aldehydes, can result from the peroxidation of lipids by ROS.55 During high levels of fat metabolism, Ketone concentrations rise which resulting in detectable levels of acetone in the breath. Starvation, low-carbohydrate diets, and low levels of insulin resulting from type 1 diabetes can cause ketosis, which is a metabolic state wherein ketones rather than glucose are the body’s predominant energy currency. A correlation between breath acetone concentration and Electrochemistry, 2019, 15, 147–185 | 153

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

ketosis level provides potential for anoninvasive method to monitor fat metabolism in certain dieters and patient groups.56 Volatile sulfuric compounds (VSCs) are another subclass of VOC compounds present in breath owing to exogenous sources. Even though low quantities of VSCs can rise endogenously, most VSCs present in exhaled breath originate from metabolism of oral bacteria.57 Patients who suffer from chronic halitosis exhale higher concentrations of hydrogen sulfide, and dimethyl sulfide, methyl mercaptan.58 These compounds are known to be the source of malodor in breath. Also, dimethyl sulfide can also be found in breath at high concentrations because of liver disease. These compounds are known to be the source of malodor in breath. Also, dimethyl sulfide can also be found in breath at high concentrations because of liver disease.59 Inorganic gases, such as carbon monoxide (CO), hydrogen (H2), nitrogen oxides (NOx), ammonia (NH3), and, carbon dioxide (CO2) are present in breath at various ranges of concentrations. CO2 exists in breath in the percentage range; H2 and CO exist in the ppm range, whereas ammonia and nitric oxide exist in the ppb range. Table 1 summarized some breath biomarkers for various diseases and conditions. Determining CO2 in expired breath is an excellent practice, known as capnography, that permits clinicians to monitor respiratory patterns and examine the quantity of CO2 elimination for cases of pulmonary obstruction (Table 1). Nitric oxide found in the breath above 50 ppb can be symptomatic of respiratory inflammation, such as asthma attacks, whereas CO concentrations above 5ppm are related to chronic obstructive pulmonary disease (COPD). H2 gas in breath found as a result of gut bacteria activity, which allows a correlation to be drawn between H2 gas concentration and malabsorption of certain sugars.60 Malabsorption can be caused by a diversity of cases, involving celiac disease, parasites, and lactose intolerance. Actually, the release of VOCs from fat storage to the circulatory system61 can be detected directly from the headspace of cells62 and blood.63 There are several pathways for secretion involving skin/sweat,64 saliva,17b,17c,65 urine,66 feces,67 and breast milk.68 The main challenge facing volatolomic methods for personalized and preventive medicine is the development of miniaturized low-power chemical sensors capable of selective sensing of a few particles per Table 1 Breath biomarkers for various diseases and conditions. Reproduced from ref. 56 with permission from John Wiley & Sons, Copyright r 2016 WileyVCH Verlag GmbH & Co. KGaA, Weinheim. Breath biomarker

Condition

Ref.

VOCs VSCs CO2 NOx CO NH3 H2

Cancer (lung, colorectal), ketoacidosis Liver failure, halitosis Pulmonary inflammation (e.g., COPD) ulmonary inflammation Pulmonary inflammation Renal failure Malabsorption

55, 78 59, 79 80 81 82 83 84

154 | Electrochemistry, 2019, 15, 147–185

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

billion concentrations of VOCs in the presence of high concentrations of water vapor and other gases.69 Significative VOCs analysis needs reproducible and stable responses and removal of additional issues such as gender, age, and smoking status.70 Groups of nanomaterial-based sensors, often termed as nano-arrays,71 have high potency to meet these clinical challenges and become powerful diagnostic techniques due to the inherently non-invasive nature of volatolomics. The large surface-to-volume ratio of the nanomaterials offers high sensitivity and quick response and recovery times. The wide range of well-designed nanomaterials can help to rise the selectivity and sensitivity to the target VOC.69 Their small size also allows on-chip application of several arrays.72 Improvement of novel solid-state sensors for selective detection of ultra-low concentrations of certain gas molecules is becoming more and more feasible due to the recent development in nanofabrication methods, which are capable of providing atomic-level control of the surface composition of high-surface-area detectors.73 Common VOC sensing devices for wearable and miniaturized sensors involve chemo-resistive semiconductors,69,74 surface acoustic wave resonators,75 and capacitive polymers.7a,76 Semiconductor chemo-resistive sensing mechanism has been summarized by Antonio et al.69 Briefly, nanostructured sensor film the conductivity changes considerably as a function of the concentration of reducing and oxidizing gases and their reactivity with the semiconductor surface. This technology enables ppb detection of important VOCs such as acetone69 and ethanol77 by a simple and highly miniaturizable resistance measurement. Surface acoustic wave (SAW) resonators are based on the modulation of acoustic waves traveling between reference points in a medium.75 The existence of analytes in the medium effects factors of the wave like its speed and amplitude. The substrate used in a SAW resonator has piezoelectric properties that permit transversal waves to spread through the surface.85 The reception of the wave will be modified when a receptor is adhered to the surface (whether through adsorption or some other kind of reaction) due to changes in the wave characteristics.86 SAW resonators have been used as an immunoassay format,85 for the detection of VOCs such as ethanol, acetone, and propanol,87 and as part of gas chromatography for the early screening of lung cancer.2 Capacitive polymer sensors are basically depend on dielectric layers with imprinted polymers on the surfaces. A surface insulated with a polymer coating will change in thickness or dielectric constant when definite analytes are in the medium.7a This change can be detected by changes in the capacitance or impedance of the capacitor itself, and the degree of this change is proportional to the concentration of the analyte. Ultra-thin polymer layers are used in capacitive polymer sensors, which are fabricated by electro-polymerization.88 Another main challenges are the humidity degree and insufficient accuracy of breath measurement methods. Due to the function groups presented in graphene oxide (GO) which will allow the interaction with water vapour, GO is considered as one of the promising martials that can used as a solution for humidity issue. Promising results were attained Electrochemistry, 2019, 15, 147–185 | 155

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

using 15 nm GO layers deposited by spray-coating on top of Ag screen printed interdigitated electrodes which allow changes through the range 10–90%, with fast response.89 A self-healable polymer substrate was integrated with 5 kinds of ligands-functionalized gold nanoparticles (GNP) films to develop a sensor array gives a fast self-healing rate (o3h) for sensing pressure and 11 kinds of VOCs,90 Fig. 4A.

Fig. 4 (A) Graphical representation of the self-healable GNP-based sensor sensor array with different ligands functionalized GNPs; (B) The measurement system for monitoring human respiration the demonstration of monitoring human respiration by the NC-based humidity sensor. Figure A reproduced from ref. 90 with permission from American Chemical Society, Copyright 2016. Figure B reproduced from ref. 91 with permission from American Chemical Society, Copyright 2017. 156 | Electrochemistry, 2019, 15, 147–185

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

91

Shinya et al. employed a flexible humidity sensor on a polymer substrate by using the all-inorganic colloidal Si NCs. An all-inorganic Si NC film was used as a humidity-sensitive material. The current readout of the sensor changed by five orders of magnitude in the relative humidity range between 8 and 83%, Fig. 4B. The work by Azam Gholizadeh et al.92 described a portable noninvasive tool for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in Exhaled Breath Condensate (EBC) via fabrication of a miniaturized screen-printed electrodes that were modified with electrochemically reduced graphene oxide for detecting nitrite content in EBC using reduced graphene oxide. Firat Gıˆder et al.53a developed a paper-based moisture sensor that uses the hygroscopic character of paper to measure patterns and rate of respiration by converting the changes in humidity caused by cycles of inhalation and exhalation to electrical signals. The study of NO level and its related substances (NO2 and NO3) are very essential for understanding many of important biological activities and health cases.19b In asthmatic patients, events are signaled by release of NO from inflammatory cells. NO in breath ranges between low ppb to around 100 ppb. Most NO sensors are based on electrochemical techniques, and while these can cover the range of interest,93 in general they are not yet integrated into point of care systems for breath analysis. Optical fibers is another promising inexpensive material that can be utilized in wearable devices. Organically Modified SILicate (ORMOSIL) sol–gel was integrated with embedded ruthenium O2 sensitive luminophores [Ru(III)-tris(4,7-diphenyl-1,10-phenanthroline] ([Ru(ddp)3]21)94 or the cyclometalated iridium complexes bis(1-phenylisoquinoline)(acetylacetonate)iridium(III) ([Ir(piq)2(acac)]) O2 sensitive fluorophores for the analysis of O2 in breath.95

4 Saliva-based sensors Saliva is considered as a great diagnostic fluid which supplying substitutional to direct blood analysis through the penetration of blood compositions.17b The early work of Graf in the 1960s was constructed by electrochemical salivary sensors for the determination of fluoride ion levels and pH on a partial denture.96 Several substances in the saliva are strongly associated with the systemic and oral diseases, as a result of the high rate of interactions between these pathways and the mouth.2 The main benefit of saliva analysis is the great quantity of fluid available and the pointedly larger space usable for the localization of the devices. Moreover, in contrast to tear analysis, the mouth is also a less delicate environment for the integration of implants and can benefit from the extensive research in biocompatible materials pursued for dentistry. Saliva sampling is relatively simple and the existence of numerous disease-signalling biomarkers in saliva has meant that it can precisely reveal normal and disease statuses in individuals. Although saliva collection and determination present some disadvantages, it has been Electrochemistry, 2019, 15, 147–185 | 157

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

familiar as an attractive diagnostic fluid with an increasing amount of assay developments and technological advancements for the detection of various salivary biomarkers.97 So far, an extensive spectrum of substances existing in saliva has emerged as highly useful and discriminatory. However, the understanding of wearable biosensors for real-time monitoring of chemical markers has been restricted by the low number of demonstrated measurable analytes and the lack of integrated wireless data transmission.15c,97 Numerous efforts have more recently developed salivary sensors based on screen-printing tools that take advantage of scalable low-cost fabrication. The work of Mannoor et al.6 described a graphene-based wire-less resistometric sensor for continuous monitoring of bacteria on a silk dental tattoo platform (Fig. 5a–d). Graphene is considered as an interesting material for flexible electronic applications due to its significant electrical conductivity and mechanical properties having an intrinsic strength of 42 N m1 and Young’s modulus of E1 TPa.98 Mannoor et al.6 work reported the self-assembly of antimicrobial peptide (AMP), consisting of dodecapeptide graphene binding peptide, a triglycine linker and the AMP odorranin-HP, onto graphene was utilized to achieve bioselective detection of bacteria at single-cell levels,6 Fig. 5A. A mouth guard sensor which integrated with a Bluetooth low energy communication system-on-chip for continuous real-time amperometric monitoring of non-invasively monitoring salivary uric acid (SUA) levels was developed by Kim et al.17b (Fig. 5B). A uricase enzyme-modified surface was screen-printed on the mouth guard with a three-electrode layout. SUA levels were monitored in a hyperuricemia patient and a healthy individual to assess the validity of this approach for in vivo measurements. For wireless transmission, a 2.45 GHz chip antenna and impedance-matched balun were employed (Fig. 6c). For a power source, two watch batteries of 1.55 V and 33 mA h each were utilized in series. SUA concentrations of the hyperuricemia patient and control volunteer was determined which determined the difference between the SUA levels in the healthy control (178.5 mm  20.7 mm) and hyperuricemia patient (822.6 mm  26.25 mm), indicating that this approach can be utilized for diagnostics of hyperuricemia. A sensitivity of 2.45 mA per m mof uric acid was observed for concentration of uric acid from 100 to 600 mm with a R2 correlation coefficient of 0.998. Uric acid (UA) is the product of purine metabolism in the human body. The abnormal concentration of UA is a biomarker for many diseases, involving renal syndrome, gout, Lesch–Nyhan syndrome, and hyperuricemia.99 In addition, higher UA concentrations imply a higher future danger of type 2 diabetes.100 UA can also be an pointer of physical-stressinvolve reactive oxygen species (ROS), acting as a free radical scavenger.101 While blood UA measurements require invasive blood collection, salivary uric acid (SUA) measurements could be carried out non-invasively and in a continuous real-time manner. The work of Shibasaki et al.102 and Soukup et al.103 have found a good correlation of UA blood and saliva levels, indicating that this metabolite 158 | Electrochemistry, 2019, 15, 147–185

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

Fig. 5 (A) Schematic and real image of a wireless tattoo-based resistive sensor for Staphylococcus aureus; (B) Illustration of an electrochemical SUA sensor incorporated on a mouthguard and a selective working electrode was achieved with uricase enzymemodified surface with a Bluetooth low-energy communication system on-chip. Figure A reproduced from ref. 6 with permission from Springer Nature, Copyright 2012. Figure B reproduced from ref. 17b with permission from Elsevier, Copyright 2015.

can be examined in saliva in a noninvasive way without need for blood sampling. The presence of cell cycle regulatory proteins such as Cyclin D1 and ki67 have been found to correlated with oral cancer,76 cortisol, and metastatic breast cancer.104 Although the expression of certain miRNAs can help to distinguish between acute lymphoid and acute myeloid leukemia.105

5

Tears-based sensors

Tears unique body fluid that is mainly consisted of thousands of molecules involving proteins/peptides, lipids, electrolytes, and small Electrochemistry, 2019, 15, 147–185 | 159

Published on 15 October 2018 on https://pubs.rsc.org | d

160 | Electrochemistry, 2019, 15, 147–185 Fig. 6 Tear-based electrochemical sensors. (A) A screen-printed electrochemical sensor for continuous glucose and neurotransmitters sensing; (B) Fabrication processes and imaging of hardwired sensor; (C) A soft contact lens-based wireless glucose sensor. Figure A reproduced from ref. 113 with permission from John Wiley and Sons, Copyright r 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Figure B reproduced from ref. 136 with permission from Elsevier, Copyright 2011. Figure C reproduced from ref. 114e with permission from IOP Publishing, Copyright 1991.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

molecule metabolites secreted from the main and accessory lacrimal glands, Meibomian glands, goblet cells and ocular surface epithelial cells.106 Also, it assists many roles in order to preserve the health of the eye.107 As blood is one of the sources of these components, tears can be used as an attractive fluid for non-invasive monitoring. This is especially true for continuous diabetes management because a good correlation between glucose levels in tears and blood,108 Table 2. Table 2 lists some common biomarkers measured in readily available

Table 2 List of some common biomarkers measured in readily available body fluids. Reproduced from ref. 2 with permission from John Wiley & Sons, Copyright r 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Fluid

Saliva

Sweat

Tears

Biomarker

Purpose

Sensing technology

Ref.

Caffeine

Potentiometric

116

CD59 CYFRA-21-1

Metabolizing activity in hepatocytes Oral cancer diagnosis Oral cancer diagnosis

117 118

Chloride

Kidney disease

Electrochemical Differential pulse voltammetry Chronoamperometry Electrochemical

Glucose

Diabetes

Electrochemiluminescence

Lactate Lead

Physical exertion Exposure complication

Thiocyanate, nitrite, and nitrate

Detection of inorganic metabolites

Chemiluminescence Anodic stripping voltammetry Capillary electrophoresis Artificial neural networks Dual-enzyme biosensor composed of glucose oxidase (GOx) and pistol-like DNAzyme (PLDz) Electrochemical

Glucose

Diabetes

H2O2

Physical exertion

Lactate Lactate/pyruvate MDMA Plasma L-dopa

Physical exertion Physical exertion Drug testing Parkinson’s disease

Glucose

Diabetes

Interleukin-1a

Detecting pathogenic attack ¨gren’s syndrome Sjo

Lactoferrin a

119 120 121 122 123 124 125 126 127

128

Chemiluminescence LCa GCa–MSa LCa þ Electrochemical Ratiometric sensing with near-infrared photonic crystal Amperometry

123 129 130 131 132

Theranostic lens

133

Microfluidic immunoassay

134

108

LC ¼ liquid chromatography; GC ¼ gas chromatography; MS ¼ mass spectrometry.

Electrochemistry, 2019, 15, 147–185 | 161

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

body fluids. Traditional instruments have been usually used for detecting antioxidants,109 metabolites,110 and amino acids111 in human tears. However, in vitro tear analysis has several limitations. Main limitation of tear analysis is the evaporation of collected tears (commonly 5–10 mL) during transportation to laboratories. Taking into account the delicate nature of the human eye, extreme care must be taken during the collection of sample. Moreover, the measured analyte concentration often depends on the of collection applied.110 Wearable sensors that detect analytes directly on the human retina may overcome the previously mentioned limitations. The first prototypes of optical sensors were fabricated on strip-based flexible substrates. Bare electrodes were fabricated first by using standard lithographic techniques on flexible or stretchable substrates.112 Functionalization of the electrode transducers with receptors to construct high-fidelity ocular sensors have been done using low cost printing technology via different methods like drop casting and polymer entrapment,112b and direct mixing of biomolecules within inks.113 Strip-based ocular sensors have been developed for monitoring keratoconjunctivitis sicca,112a glucose,47,113,114 and transcutaneous oxygen.115 These selective and fast devices were evaluated with bench-top analyzers. Due to the little effort to integrate the electronics directly on the sensor platform for data processing and readout, these sensors were less attractive for on-body operations.1 Moreover, most of the sensors are partially flexible that may cause eye irritation, which stimulates tear glands and leads to formation of reflex tears. Thus, in turns alter the analyte concentration and lead to false readings.1 Tear sensors are usually incorporated on the inner side of a flexible contact lens. The position of the electrodes and associated circuitry is on the perimeter of the iris and adequately distant from the pupil to eschew covering the vision field.2 Transparent substrates are mostly flat MPC, PDMS, and PET, which enable the deposition of electrodes and circuitry by sputtering,114b and CVD/PVD deposition114d or e-beam.114c Then, this may followed by lithography and wet-etching methods.135 Most electrode materials involve Pt/Ag/AgCl,114b Au/Ag/AgCl,47 and Ti/Pd/Pt114c-e with a curved or rectangular layout. An appropriate structural shape is imparted to the flat substrates by moulding with heat and pressure,114c-e Fig. 6. Parviz’s research reported the design, construction, and testing of a contact lens with an integrated amperometric glucose sensor, proposing the possibility of in situ human health monitoring simply by wearing a contact lens with in-built wireless electronics for continuous data transmission.114d,114e,136 Recently, Google has developed this device. Parviz’s group demonstrated the biofunctionalization of a PET-based contact-lens with glucose oxidase enzyme (GOx) within a Titania sol–gel matrix.136 During this initial study the sensor was hardwired, but the group later developed a contact-lens sensor with integrated wireless electronics for data recording and charging.114d The same group later modified their wireless device to include a dual sensor consisting of activated and deactivated GOx for minimizing 162 | Electrochemistry, 2019, 15, 147–185

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

114e

interference effect, Fig. 6C. They studied the effects of ageing, temperature, and biofouling on the sensor response and demonstrated excellent sensitivity, detection limit, and linear range using a polymer eye model. Another main challenge for these types of devices is the integration of an appropriate power source and readout system.47 Implementation of inductive links and radio frequency (RF) circuits has been successful in reducing the needed wiring and device size.114e,137 In addition to the miniaturized RF sensor system, this method needs a reader antenna coil system of adequate size and power being close proximity (5–10 cm) to the device. Another solution, incorporation of biofuel cells (BFC) into these bionic contact lens has been proposed.47 Enzyme catalysts were employed to change the chemical energy from existing biofuel (glucose) and biooxidant (oxygen) into electrical energy.47,48 In case of using as a power source for sensing of glucose, application of glucose from the same tear fluid may interfere with the precision of the measurements. Falk et al.47 developed a microscale membrane-less biofuel cell, capable of generating electrical energy from human lachrymal liquid by utilizing the ascorbate and oxygen naturally present in tears as fuel and oxidant, Fig. 7A. This device was constructed on three-dimensional nanostructured gold electrodes covered with abiotic (conductive organic complex) and biological (redox enzyme) materials functioning as efficient anodic and cathodic catalysts, respectively. Chronopotentiometry was utilized for the measurements using a three-electrode rotating disk with Ag–AgCl3 and a platinum wire mesh as reference and counter electrodes, respectively. Although the device showed no sensor response to pure glucose solutions, a strong electrochemical sensor response was achieved with the addition of ascorbate (broken line) and ascorbate-dopamine fuels (dotted line). An open-circuit voltage of 0.54 V and a maximal power density of 3.1 mW cm2 at 0.25 V were achieved with human basal tears (Fig. 4c). This device was able to keep a stable current density output of 0.55 mA cm2 at 0.4 V over 6 h of continuous operation. Thomas et al.114c developed an electronic enzymatic L-lactate sensor on a polymer substrate molded into contact lens shape for potential in situ monitoring of L-lactate levels in tear fluid. The platinum sensing structures were functionalized by cross-linkage of lactate oxidase with glutaraldehyde and bovine serum albumin, and coated with medical grade polyurethane. The platform composed of an amperometric sensor based on a Pt working and reference electrode, and an auxiliary Pt counter electrode as a current drain. This three-electrode platform permits for a stable reference voltage between WE and RE. Flavoenzyme LOx was utilized as a selective sensing element for L-lactate. The electrodes were deposited on 100-mm-thick PET substrates,114c Fig. 7B.

6

Skin fluid-based sensors

Like sweat analysis, skin perspiration analysis is getting increasing attention and research efforts because of its ability of placing relatively Electrochemistry, 2019, 15, 147–185 | 163

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

large devices on the body surface without causing major discomfort. This enables the development of fully automated sensor systems for continuous monitoring of key biomarkers. Also, in contrast to breath analysis, perspiration from the skin is relatively clean from exogenous gas molecules, and thus does not need, per se, careful selection of the exhalation phase to be analyzed.2 Biomarkers move to the dermal layer through the interstitial fluid between blood vessels. During this transport, there is an amount of leakage and osmosis from a blood capillary to the interstitial fluid, which arrives the dermal layer.138 One of the main challenges facing skin sensors that the concentration of VOCs is lower than in the breath, which need lower limit of detections in the low ppb–ppt level. Many protocols are being suggested to overcome this severe constraint, including chemical stimulation of the release of specific compounds10 and innovative concentrator approaches.139 A recent study described highly stretchable, transparent gas sensor based on silver nanowire–graphene hybrid nanostructures.140 The hybrid parts serve as electrodes in the sensor, such as source, drain, interconnects, and antenna coil. In addition, chemical vapor deposition (CVD)-synthesized graphene, which has a 2D structure and high surface area, is used to monolithically form channels and electrodes. DMMP is used as a simulant of the nerve agent, sarin gas (isopropyl methyl phosphono fluoridate) and its sensing by miniaturized sensor has immediate applications in workplace safety and defense. For electrodes and an RF antenna, hybrid nanostructures made of silver nanowires and graphene were used. This sensor was able to detect as little as 5 ppm of DMMP and sustained this ability to up to 20% strain. Although this device platform has not been applied for VOC monitoring, its wireless, compactness, and powerless capabilities makes it mainly remarkable for skin perspiration analysis,140 Fig. 8A. Guo et al.141 developed an e-skin compatible humidity sensor based on a large-area polycrystalline few layer WS2 film synthesized by metal sulfurization, Fig. 8B. The as-fabricated humidity sensor on the SiO2 substrate with an unoptimized device structure already shows a room temperature water moisture sensing behavior with a sensitivity up to 2357 (for 90% humidity) and fast response time in a few seconds. The flexible humidity sensor built on a polydimethylsiloxane (PDMS) membrane (thickness, 200 mm) with a bent curvature down to 5 mm shows repeatable water moisture sensing properties. Also, applying patterned graphene as electrodes and a thinner PDMS membrane (thickness, 55 mm) as a substrate, a transparent, flexible, and stretchable sensor was obtained. A vast amount of of vital information can be obtained from skin interstitial fluid (ISF) in a continuous and completely non-invasive manner. Over the past years, scientists have used the ISF for noninvasive detection of organ failure,142 drug efficacy,143 and inherited metabolic diseases.144 Most of the studies in this field have focused on non-invasive glucose sensors in connection to efficient diabetes monitoring.145 The correlation between ISF and blood glucose has encouraged many industrial and academic researchers to improve optical-, ultrasound-, heat-, and 164 | Electrochemistry, 2019, 15, 147–185

Published on 15 October 2018 on https://pubs.rsc.org | d Electrochemistry, 2019, 15, 147–185 | 165

Fig. 7 (A) Schematic layout of an electrochemical sensor with an integrated biofuel cell (BFC) on a contact lens for tear glucose analysis; (B) Schematic of the fabrication process for L-lactate sensor contact lens on the transparent PET substrate and completed contact lens sensor held on a finger. Figure A reproduced from ref. 47 with permission from American Chemical Society, Copyright 2013. Figure B reproduced from ref. 114c with permission from Elsevier, Copyright 2011.

Published on 15 October 2018 on https://pubs.rsc.org | d

166 | Electrochemistry, 2019, 15, 147–185 Fig. 8 (A) Schematic and demonstration of a flexible and transparent dimethyl methylphosphonate (DMMP) gas sensor based on PPy coated graphene field effect transistor sensors. (B) Humidity sensing properties of a transparent and flexible WS2 humidity sensor and transmittance spectra of the graphene IDE/WS2/PDMS on a glass substrate holder and the PDMS on the glass for comparison with the inset shows the scanning electron microscopy image of the sample. Figure A reproduced from ref. 140 with permission from the Royal Society of Chemistry. Figure B reproduced from ref. 141 with permission from the Royal Society of Chemistry.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

Fig. 9 Skin interstitial fluid-based electrochemical sensor. An exploded schematic revealing various components of the GlucoWatch. Reproduced from ref. 146 with permission from Elsevier, Copyright 2001.

electrochemical-based devices for continuous, non-invasive glucose monitoring.145 For example, reverse iontophoresis-based electrochemical glucose sensing is extensively familiar technique.146 This technique led to the development of the commercial wearable glucose watch (GlucoWatch1 Automatic Glucose Biographer Manufacturer; Cygnus, Inc., Fig. 9). Due to concern of patients reporting skin irritation led to subsequent retrieval of the device from the market.145 Another wearable non-invasive glucose sensors utilized different transducers which depend on impedance spectroscopy (Pendra, Pendragon Medical Ltd.) or optical (C8 MediSensors, C8 MediSensors, Inc.) have face the same issues or have not well commercialized. Such developments emphasize the technical challenges related to continuous non-invasive glucose sensors and the need to find sustainable solutions to these serious problems.

7 Implemented materials for printed wearable electrochemical devices Printing technology offers a novel field of wearable technology due to its widespread, vast-area, and high production abilities. Printing technology is considered as interesting technique due to miniaturization, costeffective, and omitting several production steps. According to the modern printing technologies which have been applied in printed electronic devices—including electrochemical ones—can be mostly classified into template and non-template based approaches31 (Fig. 10). Further classification of template-based printing processes includes screen printing, gravure printing, flexography, and imprinting. Screen Electrochemistry, 2019, 15, 147–185 | 167

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

Fig. 10 Schematic illustration of widely utilized printing methods for fabricating printed electrochemical devices. Reproduced from ref. 31 with permission from John Wiley & Sons, Copyright r 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

printing process includes printing inks at a low pressure where a screen mesh containing a designed pattern of uniform thickness was used. For squeezing the thixotropic fluidic ink through the patterned mesh/stencil and onto the substrate, a metal or rubber squeegee can be used.31 Further printing process were fully discussed in lectures.31,147 The printing ink composes of fillers, binders, additives and solvents,31 Fig. 11. The followed printing methodology controls the selection of these components. Controlling the characteristic features required for specific applications take place via choosing the fillers. According to the applications, the fillers could be organic,148 metallic,149 and ceramic.150 Due to the rapid improvements in nanotechnology, scientists have been able to manufacture inks involving tailor-made nano-materials, like nanoparticles,151 nanowires,152 and nanosheets.153 New areas of costly effective electronics have been emerged as a result of combining printing technology with nanoscience.31 Another key constituent of an ink is the binder-a polymeric material, which supports in homogeneous dispersion of the fillers into the ink.31 Regarding the printing process, the binders have important role of holding the ink constituents jointly after evaporation of solvent and assist bind the printed trace onto the substrate. A diversity of binders with fluoroelastomers,154 styrene,155 acryclic,156 silicone33,156 or 168 | Electrochemistry, 2019, 15, 147–185

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

Fig. 11 Key components (conductive fillers, additives, solvents, and binders) of printable inks for electrochemical devices. Reproduced from ref. 31 with permission from John Wiley & Sons, Copyright r 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

urethane157 backbones have been designed as ink binders for printing self-healing, flexible, stretchable devices. The choice of the binder ultimately depends on the properties of the fillers. Through recognizing the properties of surface chemistry for the fillers, the selection of an appropriate binder makes their homogeneous dispersion within the ink. The propose for printing is another factor which affecting binder choice.31 To meet a wide range of applications, different types of heat158 and UV159 curing binders have been developed to meet the needs of a wide range of applications. Another essential constituent of the ink is the solvent, which allows the ink to flow. The solvent should offer good solubility to the polymeric binder and impart surface tension, homogeneity and viscosity. Hillenbrand and Hansen solubility parameters which determine the energy of cohesive between the molecule solvent and other constituents of the ink can be used to choose the optimal solvent for certain fillers and binder. This is serious for gaining homogeneous ink preparations and best printing properties. Through printing multi-layer devices, the choice of solvent becomes highly challenging. For example, after printing an ink layer on a printed surface and due to the presence of solvent as a constituent of the ink, potential damage can be occurred to the underlying printed film.160 This challenge can be controlled through adjusting the composition of the ink, like fillers, solvent and binder. In this situation every layer is Electrochemistry, 2019, 15, 147–185 | 169

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

printed with a different group of binder and solvent so that each binder is soluble only in its corresponding solvent.31 Because of difference in the solubility factors, the used inks will affect in lower way on each other through the fabrication of multi-layer tools. Due to the difference in the solubility parameters, the inks will have minimal effect on each other while fabricating multi-layer devices. Separately from binder, filler and solvent, additives are also involved to impart desired healing,31,161 stretching,33,162 rheological,163 or wetting164 properties to the inks. To tailor the ink properties for certain uses, the additives have been used in the form of stabilizers,149b surfactants,162 humectants,165 adhesion improvers,33,166 and penetration promoters.167 Over the past decade, a plethora of different ink formulations has been developed for getting printed devices that support sized for constructing printed tools that have the desired level of flexibility without compromising their performance.31 The main two ink constituents are binders156 and adhesion promoters/ surfactants,168 which do a significant role in making the ink highly flexible. To obtain optimal binder, it should be has the ability to uniformly disperse the strain generated during flexing with minimal effect on the filler component. Moreover, appropriate adhesion agents help improve the shear stress experienced between the printed ink and the underlying substrate when subject to mechanical deformation.31 Many research groups have developed carbon based nanomaterials for printable inks to tap in the notable electronic and mechanical characteristics of carbon nanotubes162,169 and graphene.170 The recently developed printable flexible inks consist of metallic,151b,171 graphene,153,172 carbon nanotubes,173 and semiconductor174 have been utilized for a wide range of applications. These newly fabricated inks can be further classified into aqueous and organic solvent-based inks. Carbon-based inks have received particular attention due to numerous attractive properties of carbonaceous nanomaterials. CNT (carbon nanotube) and graphene inks offers high quality for the printed devices. These interactions of CNT/graphene due to their high surface area affect the printability, print morphology and conductive properties of the printed films.175 So, several surfactants,176 polymers,177 functional group generation techniques178 have thus been utilized that alleviate aggregation and help attain homogeneously dispersed CNTs/graphene inks.

8 Key challenges for wearable sensors implementations Many key challenges are facing the field of wearable chemical sensors like security, power, data processing, materials, data acquisition, communication and analytical requirements (Fig. 12). For obtaining complete monitoring about the wearer, many factors should be determined simultaneously. For instance, detection a whole wearer of chemical179 and physical180 parameters in the same time to get comprehensive description of person’s well-being. 170 | Electrochemistry, 2019, 15, 147–185

Published on 15 October 2018 on https://pubs.rsc.org | d Electrochemistry, 2019, 15, 147–185 | 171

Fig. 12 Current status and challenges in wearable chemical sensors. Reproduced from ref. 8 with permission from American Chemical Society, Copyright 2016.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

Many works were reported a multi-analyte flexible device which can simultaneously detect the lactate and glucose metabolites along with potassium and sodium electrolytes.9a Currently, nanotechnology has implies the importance for constructing miniaturized multi-analyte chemical sensors that have very low detection limits.181 By decreasing the device size, scientists should apply their attention towards incorporating multiple sensor modalities for inquiring multi-parameter sensing. Recently, nearly all the wearable chemical sensors have single transduction mechanism optical,182 electrochemical,19b,183 and electrical.14c,184 Gao et al.9a developed a multi-analyte flexible and fully integrated sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (glucose and lactate) and electrolytes (sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). A flexible and wearable microsensor array was described for simultaneous multiplexed monitoring of heavy metals in human body fluids. Zn, Cd, Pb, Cu, and Hg ions are chosen as target analytes for detection via electrochemical square wave anodic stripping voltammetry (SWASV) on Au and Bi microelectrodes.29a The Javey group recently developed a wearable electrochemical device for continuous monitoring of ionized calcium and pH of body fluids using a disposable and flexible array of Ca21 and pH sensors, which interfaces with a flexible printed circuit board.185 The developed platform allows real-time quantitative analysis of these sensing elements in body fluids such as sweat, urine, and tears. The growing of chemical sensors that have huge importance in the wearable’s market mandates bio-affinity assays.8 The detection of a large number of physiologically significant biomarkers depends on bio-affinity based sensors.186 Also, sensors used for environmental applications for the detection of toxic chemicals187 and agents of chemical warfare187b need bio-affinity receptors. By developing reliable wearable formats of such bio-affinity sensors has the potential to completely change the overview of the wearable chemical sensors field.8 These sensors will guide in an innovative and significant phase in the field of IoT for critical security, healthcare, and environmental monitoring. Understanding bio-affinity based wearable chemical sensors is challenging (owing to their slow response, limited re-usability, and analytical requirements), and so such devices have not yet been established.8 The bio-affinity receptors such as aptamers,182b,188 PNA,189 RNA,190 antibodies,187,191 and DNA192 are quite labile and denature rather quickly when subjected for long durations to environments common for wearable applications.8 The bio-receptors depend on ‘‘lock-and-key’’ mechanism for the detection of the analyte and any small deviations in the receptor’s structure significantly affect its capability to identify the target analyte,193 which leads to the decreasing in the device’s sensing ability. The flexibility is another critical challenge facing the electrochemical wearable technologies. The traditional chemical sensors are heavy194 and 172 | Electrochemistry, 2019, 15, 147–185

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

bulky, and therefore cannot be utilized for wearable uses. So, the need for light, small, and flexible devices to integrate with human body is raised. The concern associated to conformal contact between the human body and wearable chemical sensors can be fixed by simulate the device mechanical properties with that of the human body tissues. Soft, stretchable and curvilinear with unique mechanical properties are the characterization of the human tissue. In order to associate the mechanical characteristics of the sensor with that of the body tissues, scientists have developed highly flexible textile11b,14b,15d and plastic195 based wearable chemical sensors, which can be utilized for different applications like the detect of volatile organic compounds,14a,14b,196 electrolytes,11b,15d,196 or metabolites.9a,11a,195a The previously mentioned advances are laudable when considering the high rigidity of traditional chemical sensors. By comparing the flexible plastics to human tissues, still have mismatch between them, which can cause irritation of the skin and even to device peel off during body-motion induced mechanical deformations.8 Otherwise, textile-based sensors have mechanical characteristics more comparable to that of the human skin, giving conformal contact between the body and the sensor. However, textile-based sensors can be in close contact with the skin only at limited locations. This limits the use of textile-based sensors for wide-ranging applications that mandate sensors to be located at places that are not covered with clothing.8 Addressing the previous mentioned issues are via using stretchable and soft elastomers. Roger’s group introduced an ultrathin, soft, skin-conforming sensor technology that offers advanced capabilities in continuous and precise blood flow mapping.197 Another platforms were utilized for determination of instantaneous UV exposure levels and skin temperature,198 and an ultrathin, leakage-free, biocompatible dielectric layer can completely seal an underlying array of flexible electronics while allowing for electrophysiological measurements through capacitive coupling between tissue and the electronics, without the need for direct metal contact.199 Wang group has been developed a flexible glove-based electrochemical biosensor with highly stretchable printed electrode system as a wearable point-of-use screening tool for defense and food security applications. The biosensor based on organophosphorus hydrolase (OPH)- index finger allows rapid on-site detection of organophosphate (OP) nerve-agent compounds on suspicious surfaces and agricultural products following their swipe collection on the thumb finger.200 Another work of the same group described materials, designs, and integration strategies for thin, stretchable ion sensors that mount on cellular substrates with well-defined geometries.201 The device comprises chemical sensors incorporates an ion selective membrane based on poly(vinyl chloride) (PVC) coated on a layer of electrodeposited poly(3,4ethylenedioxythiophene)/polystyrene sulfonate (PEDOT/PSS) conducting polymer. Innovative studies by Bao202 and Someya203 have explained tissue like, stretchable, and soft electronic devices. Bandodkar et al.162 developed a highly stretchable CNT-based, allprinted electrochemical device through utilizing specially tailored Electrochemistry, 2019, 15, 147–185 | 173

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

screen printable stretchable inks that combine the attractive electrical and mechanical properties of CNTs with the elastomeric properties of polyurethane as a binder along with a judiciously designed free-standing serpentine pattern enables the printed device to possess two degrees of stretchability. The printed device was able to endure strains as high as 500% with minimal effect on its electrochemical response. Powering wearable sensors is another challenge that emerged as those devices are becoming ‘‘energy-hungry’’ in order to follow the growing needs of monitoring and detecting multiple factors simultaneously, doing complex data analysis, interactive with other devices, sensors and data transmission.8 Many studies have concerned with addressing this issue has mostly depended on three approaches-construct lowpower energy effective devices,204 thin, energy dense wearable power sources205 and adaptive algorithms for intelligent, low-power consuming electronics.206 Scientists are trying to solve the problem associated to batteries’ bulkiness and rigidity by constructing stretchable207 and flexible,208 batteries on different substrates like textile,209 paper,210 and elastomeric.211 But still there is a need for compact, solid state flexible batteries cannot meet the conventional, state-of-the-art battery system.8 The progress in the martial science make a great solutions regarding this issue. Rogers’ research group introduced a set of materials and design concepts for a rechargeable lithium ion battery technology that exploits thin, low modulus silicone elastomers as substrates, with a segmented design in the active materials, and unusual ‘self-similar’ interconnect structures between them.211 Lin et al.212 constructed a rechargeable aluminium battery with high-rate capability that uses an aluminium metal anode and a three-dimensional graphitic-foam cathode, which considered as a critical improvement that can have huge effect in the field of wearables. As the fast growing of wearable sensors, the demand to improve quick, multi-functional, compacted, smart wearable sensors will raise with time. The continuous flowing of data from different sensor nodes to the wearer is one of the most attractive aspects of the wearable sensor field. These devices are expected to relate with a close smart device like iPad or mobile phone, which will automatically translates the target effect to offer timely intervention. So far, near-field communication (NFC)17a,213 and Bluetooth low energy (BLE)11b,15c,17b technologies have been applied the most for wearable sensors applications. The Wang group have exploited RF and BLE technologies for constructing wearable chemical sensors for detecting analytes on the skin,11b,15c,17a in tears,214 and saliva.17b The extensive widespread of wearable sensors led to rise the demand of developing devices with big data analytics and data security.8 By sending massive amounts of this unprocessed sensor data will only confuse the wearer, thus causing underuse of the wearable device.8 Due to the widespread adoption of wearable sensor technology, rising the most relevant and applicable analytical data in an easy-to-understand way is thus essential.8 This will include big data processing to reveal significant 174 | Electrochemistry, 2019, 15, 147–185

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

View Online

information before offer it to the wearer. Scientists are developing different ways to offer efficient plans to solve these issues. Several data analytical methods such as data-mining techniques or stream processing and continuous event processing techniques are appropriate in this regard.215 But the current data mining algorithms will not be able to process the vast volumes of data that wearable sensor networks are expected to generate.216 Data miners are working on new algorithms to address many issues like data cleaning and filtering217 and expanding data mining protocols for handling heterogeneous information.218

9

Conclusion

Clearly, the features of electrochemical wearable sensors are vast and can be successfully applied in different fields. This chapter has reviewed some latest studies in the field of miniaturized electrochemical sensors technologies for the non-invasive detection of some important biomarkers for medical diagnostics, and healthcare monitoring. The new non-invasive electrochemical sensors for continuous personalized health monitoring are expected to provide low-cost, fast, and reliable prospects for self-management of chronic diseases, and remote monitoring of healthcare for as example old people at home or in hospitals. Such health-monitoring tools would thus result in main developments in public health with low cost, accurate, and in field technology. Highly discriminating body fluid electrochemical sensors for sweat, saliva, and tears have been established leveraging on existing biosensor electrochemical devices, which can advantage from a wide variety of enzymes for detection of biomolecule. However, the area of electrochemical wearable sensors has numerous key challenges to solve. Addressing such challenges will facilitate the commercial feasibility of wearable chemical sensors, which supposed to be low-power and easily incorporated with the human body offering valued data in a user-friendly and safe way to the wearer in a continuous fashion. Pioneering cross-disciplinary research can address and solve the main challenges facing the area of wearable electrochemical sensors. This could happen by integration of scientists from different fields like materials science, engineering, chemistry and biology.

References 1 2 3 4 5 6

A. J. Bandodkar and J. Wang, Trends Biotechnol., 2014, 32, 363. A. Tricoli, N. Nasiri and S. De, Adv. Funct. Mater., 2017, 27, 1605271. W.-S. Wang, W.-T. Kuo, H.-Y. Huang and C.-H. Luo, Sensors, 2010, 10, 1782. S. Azzouzi, L. Rotariu, A. M. Benito, W. K. Maser, M. B. Ali and C. Bala, Biosens. Bioelectron., 2015, 69, 280. `, G. Favero, L. Gorton and P. Bollella, G. Fusco, C. Tortolini, G. Sanzo R. Antiochia, Biosens. Bioelectron., 2017, 89, 152. M. S. Mannoor, H. Tao, J. D. Clayton, A. Sengupta, D. L. Kaplan, R. R. Naik, N. Verma, F. G. Omenetto and M. C. McAlpine, Nat. Commun., 2012, 3, 763. Electrochemistry, 2019, 15, 147–185 | 175

View Online

7

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

8 9

10 11

12 13

14

15

16

17

18

(a) M. J. Whitcombe, I. Chianella, L. Larcombe, S. A. Piletsky, J. Noble, R. Porter and A. Horgan, Chem. Soc. Rev., 2011, 40, 1547; (b) G.-Z. Chen, I.-S. Chan and D. C. Lam, Sens. Actuators, A, 2013, 203, 112. A. J. Bandodkar, I. Jeerapan and J. Wang, ACS Sens., 2016, 1, 464. (a) W. Gao, S. Emaminejad, H. Y. Y. Nyein, S. Challa, K. Chen, A. Peck, H. M. Fahad, H. Ota, H. Shiraki and D. Kiriya, Nature, 2016, 529, 509; (b) D. J. Lipomi, M. Vosgueritchian, B. C. Tee, S. L. Hellstrom, J. A. Lee, C. H. Fox and Z. Bao, Nat. Nanotechnol., 2011, 6, 788; (c) K. Takei, T. Takahashi, J. C. Ho, H. Ko, A. G. Gillies, P. W. Leu, R. S. Fearing and A. Javey, Nat. Mater., 2010, 9, 821; (d) W. Wu, L. Wang, Y. Li, F. Zhang, L. Lin, S. Niu, D. Chenet, X. Zhang, Y. Hao and T. F. Heinz, Nature, 2014, 514, 470; (e) M. Kaltenbrunner, T. Sekitani, J. Reeder, T. Yokota, ¨diauer, I. Graz and K. Kuribara, T. Tokuhara, M. Drack, R. Schwo S. Bauer-Gogonea, Nature, 2013, 499, 458; (f) S. Xu, Y. Zhang, L. Jia, K. E. Mathewson, K.-I. Jang, J. Kim, H. Fu, X. Huang, P. Chava and R. Wang, Science, 2014, 344, 70. J. Kim, I. Jeerapan, S. Imani, T. N. Cho, A. Bandodkar, S. Cinti, P. P. Mercier and J. Wang, ACS Sens., 2016, 1, 1011. ´s-Ramı´rez, J. R. Windmiller, Z. Yang, (a) W. Jia, A. J. Bandodkar, G. Valde J. Ramı´rez, G. Chan and J. Wang, Anal. Chem., 2013, 85, 6553; (b) M. Caldara, C. Colleoni, E. Guido, V. Re and G. Rosace, Sens. Actuators, B, 2016, 222, 213; (c) A. P. Selvam, S. Muthukumar, V. Kamakoti and S. Prasad, Sci. Rep., 2016, 6, 23111. T. Q. Trung, S. Ramasundaram, B. U. Hwang and N. E. Lee, Adv. Mater., 2016, 28, 502. D. Khodagholy, V. F. Curto, K. J. Fraser, M. Gurfinkel, R. Byrne, D. Diamond, G. G. Malliaras, F. Benito-Lopez and R. M. Owens, J. Mater. Chem., 2012, 22, 4440. (a) P. Lorwongtragool, E. Sowade, N. Watthanawisuth, R. R. Baumann and T. Kerdcharoen, Sensors, 2014, 14, 19700; (b) T. Seesaard, P. Lorwongtragool and T. Kerdcharoen, Sensors, 2015, 15, 1885; (c) Y. H. Kim, S. J. Kim, Y.-J. Kim, Y.-S. Shim, S. Y. Kim, B. H. Hong and H. W. Jang, ACS Nano, 2015, 9, 10453; (d) C. Ataman, T. Kinkeldei, G. Mattana, A. V. Quintero, ¨ster and F. Molina-Lopez, J. Courbat, K. Cherenack, D. Briand, G. Tro N. de Rooij, Sens. Actuators, B, 2013, 177, 1053. (a) Y. C. Du, W. T. Chen, C. H. Chuang and M. J. Wu, IEEE Sensors, 2016, 1–3; (b) S. R. Steinhubl, E. D. Muse and E. J. Topol, Sci. Transl. Med., 2015, 7, 283rv3; (c) A. J. Bandodkar, D. Molinnus, O. Mirza, T. Guinovart, ´s-Ramı´rez, F. J. Andrade, M. J. Scho ¨ning and J. R. Windmiller, G. Valde ´novas, J. Wang, Biosens. Bioelectron., 2014, 54, 603; (d) M. Parrilla, R. Ca I. Jeerapan, F. J. Andrade and J. Wang, Adv. Healthcare Mater., 2016, 5, 996. (a) G. Lisak, T. Arnebrant, T. Ruzgas and J. Bobacka, Anal. Chim. Acta, 2015, 877, 71; (b) J. Kim, W. R. de Araujo, I. A. Samek, A. J. Bandodkar, W. Jia, ˜o and J. Wang, Electrochem. Commun., 2015, 51, 41. B. Brunetti, T. R. Paixa (a) P. Kassal, J. Kim, R. Kumar, W. R. de Araujo, I. M. Steinberg, M. D. Steinberg and J. Wang, Electrochem. Commun., 2015, 56, 6; (b) J. Kim, ´s-Ramı´rez, T. R. Paixa ˜o, S. Imani, W. R. de Araujo, J. Warchall, G. Valde P. P. Mercier and J. Wang, Biosens. Bioelectron., 2015, 74, 1061; (c) J. Kim, ´s-Ramı´rez, A. J. Bandodkar, W. Jia, A. G. Martinez, J. Ramı´rez, G. Valde P. Mercier and J. Wang, Analyst, 2014, 139, 1632. (a) M. Ramuz, B. C.-K. Tee, J. B.-H. Tok, Z. Bao, Adv. Mater., 2012, 24, 3223; (b) H.-H. Chou, A. Nguyen, A. Chortos, J. W. To, C. Lu, J. Mei, T. Kurosawa, W.-G. Bae, J. B.-H. Tok and Z. Bao, Nat. Commun., 2015, 6, 8011.

176 | Electrochemistry, 2019, 15, 147–185

View Online

19

20

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

21 22

23

24

25

26

27 28 29

30

31 32 33 34

35 36 37 38 39

(a) M. D. Steinberg, P. Kassal and I. M. Steinberg, Electroanalysis, 2016, 28, 1149; (b) G. Matzeu, L. Florea and D. Diamond, Sens. Actuators, B, 2015, 211, 403; (c) J. Gonzalo-Ruiz, R. Mas, C. de Haro, E. Cabruja, R. Camero, ˜ oz, Biosens. Bioelectron., 2009, 24, 1788. M. A. Alonso-Lomillo and F. J. Mun L. Atzori, A. Iera, G. Morabito and M. Nitti, Comput. Networks, 2012, 56, 3594. ´mez, J. F. Huete, O. Hoyos, L. Perez and D. Grigori, Procedia Comput. J. Go Sci., 2013, 21, 132. (a) K. Lorincz, D. J. Malan, T. R. Fulford-Jones, A. Nawoj, A. Clavel, V. Shnayder, G. Mainland, M. Welsh and S. Moulton, IEEE Pervasive Comput., 2004, 3, 16; (b) M. Canale, D. Bacco, S. Calimani, F. Renna, N. Laurenti, G. Vallone and P. Villoresi, ISABEL ’11 Proceedings of the 4th International Symposium on Applied Sciences in Biomedical and Communication Technologies, n. 186, 2011; (c) Z. Pang, L. Zheng, J. Tian, S. Kao-Walter, E. Dubrova and Q. Chen, Enterp. Inf. Syst., 2015, 9, 86. M. Darianian and M. P. Michael, in Advanced Computer Theory and Engineering, 2008. ICACTE’08. International Conference on, IEEE, 2008, pp. 116–120. (a) C. Chen, F. Tsow, X. Xian, E. Forzani, N. Tao and R. Tsui, Mobile Health Technol.: Methods Protoc., 2015, 201; (b) J. K. Hart and K. Martinez, EarthSpace Sci., 2015, 2, 194. B. J. Drew, R. M. Califf, M. Funk, E. S. Kaufman, M. W. Krucoff, M. M. Laks, P. W. Macfarlane, C. Sommargren, S. Swiryn and G. F. Van Hare, Circulation, 2004, 110, 2721. (a) M. C. Domingo, J. Network Comput. Appl., 2012, 35, 584; (b) N. Bui and M. Zorzi, Proceedings of the 4th International Symposium on Applied Sciences in Biomedical and Communication Technologies, ACM, 2011, p. 131; (c) R. Khan, S. U. Khan, R. Zaheer and S. Khan, in Frontiers of Information Technology (FIT), 2012 10th International Conference on, IEEE, 2012, pp. 257–260. Z. Zhu, T. Liu, G. Li, T. Li and Y. Inoue, Sensors, 2015, 15, 3721. J. R. Windmiller and J. Wang, Electroanalysis, 2013, 25, 29. (a) W. Gao, H. Y. Nyein, Z. Shahpar, H. M. Fahad, K. Chen, S. Emaminejad, Y. Gao, L.-C. Tai, H. Ota and E. Wu, ACS Sens., 2016, 1, 866; (b) M. Berggren, D. Nilsson and N. D. Robinson, Nat. Mater., 2007, 6, 3. ´s-Ramı´rez, M. J. Scho ¨ning and (a) K. Malzahn, J. R. Windmiller, G. Valde J. Wang, Analyst, 2011, 136, 2912; (b) S. Imani, A. J. Bandodkar, A. V. Mohan, R. Kumar, S. Yu, J. Wang and P. P. Mercier, Nat. Commun., 2016, 7, ncomms11650. J. Kim, R. Kumar, A. J. Bandodkar and J. Wang, Adv. Electron. Mater., 2017, 3, 1. J. P. Metters, R. O. Kadara and C. E. Banks, Analyst, 2011, 136, 1067. ˜ez-Flores, W. Jia and J. Wang, Adv. Mater., 2015, A. J. Bandodkar, R. Nun 27, 3060. Z. Sonner, E. Wilder, J. Heikenfeld, G. Kasting, F. Beyette, D. Swaile, F. Sherman, J. Joyce, J. Hagen and N. Kelley-Loughnane, Biomicrofluidics, 2015, 9, 031301. R. C. Stern, N. Engl. J. Med., 1997, 336, 487. M. F. Bergeron, J. Sci. Med. Sport, 2003, 6, 19. R. C. Klesges, K. D. Ward, M. L. Shelton, W. B. Applegate, E. D. Cantler, G. M. Palmieri, K. Harmon and J. Davis, JAMA, 1996, 276, 226. R. P. Heaney, J. Intern. Med., 1992, 231, 169. M. Burns and R. C. Baselt, J. Anal. Toxicol., 1995, 19, 41. Electrochemistry, 2019, 15, 147–185 | 177

View Online

40 41

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

42

43 44 45

46 47 48 49 50 51 52 53

54 55 56 57 58 59 60 61

62

63

64

´pez-Colino, M. Gamella, S. Campuzano, J. Manso, G. G. de Rivera, F. Lo ´n, Anal. Chim. Acta, 2014, 806, 1. A. Reviejo and J. Pingarro M. Gonzalez, F. Axisa, M. V. Bulcke, D. Brosteaux, B. Vandevelde and J. Vanfleteren, Microelectron. Reliab., 2008, 48, 825. (a) N. J. Ronkainen, H. B. Halsall and W. R. Heineman, Chem. Soc. Rev., 2010, 39, 1747; (b) Y.-L. Yang, M.-C. Chuang, S.-L. Lou and J. Wang, Analyst, 2010, 135, 1230. ´s-Ramı´rez, J. R. Windmiller, F. J. Andrade and T. Guinovart, G. Valde J. Wang, Electroanalysis, 2014, 26, 1345. T. Guinovart, A. J. Bandodkar, J. R. Windmiller, F. J. Andrade and J. Wang, Analyst, 2013, 138, 7031. ´s-Ramı´rez, J. R. Windmiller, A. J. Bandodkar, V. W. Hung, W. Jia, G. Valde A. G. Martinez, J. Ramı´rez, G. Chan, K. Kerman and J. Wang, Analyst, 2013, 138, 123. R. M. Swift, C. S. Martin, L. Swette, A. LaConti and N. Kackley, Alcohol.: Clin. Exp. Res., 1992, 16, 721. M. Falk, V. Andoralov, M. Silow, M. D. Toscano and S. Shleev, Anal. Chem., 2013, 85, 6342. M. Falk, V. Andoralov, Z. Blum, J. Sotres, D. B. Suyatin, T. Ruzgas, T. Arnebrant and S. Shleev, Biosens. Bioelectron., 2012, 37, 38. A. Ulanowska, T. Ligor, M. Michel and B. Buszewski, Ecol. Chem. Eng, 2010, 17, 9. D. J. Kearney, T. Hubbard and D. Putnam, Dig. Dis. Sci., 2002, 47, 2523. A. D. Smith, J. O. Cowan, K. P. Brassett, G. P. Herbison and D. R. Taylor, N. Engl. J. Med., 2005, 352, 2163. J. D. Pleil, M. A. Stiegel and T. H. Risby, J. Breath Res., 2013, 7, 017107. ¨der, A. Ainla, J. Redston, B. Mosadegh, A. Glavan, T. Martin and (a) F. Gu G. M. Whitesides, Angew. Chem., 2016, 128, 5821; (b) M. Hakim, Y. Y. Broza, O. Barash, N. Peled, M. Phillips, A. Amann and H. Haick, Chem. Rev., 2012, 112, 5949. L. Farhi, Respir. Physiol., 1967, 3, 1. W. Miekisch, J. K. Schubert and G. F. Noeldge-Schomburg, Clin. Chim. Acta, 2004, 347, 25. J. E. Ellis and A. Star, ChemPlusChem, 2016, 81, 1248–1265. N. Takahashi, J. Dent. Res., 2015, 94, 1628. S. Van den Velde, D. van Steenberghe, P. Van Hee and M. Quirynen, J. Dent. Res., 2009, 88, 285. A. Tangerman, M. Meuwese-Arends and J. M. Jansen, Lancet, 1994, 343, 1569. A. Newman, Gut, 1974, 15, 308. (a) H. Haick, Y. Y. Broza, P. Mochalski, V. Ruzsanyi and A. Amann, Chem. Soc. Rev., 2014, 43, 1423; (b) J. H. Heo, H. H. Cho, J. W. Lee and J. H. Lee, Analyst, 2014, 139, 6486; (c) Y. Y. Broza and H. Haick, Nanomedicine, 2013, 8, 785. (a) O. Barash, W. Zhang, J. M. Halpern, Q.-L. Hua, Y.-Y. Pan, H. Kayal, K. Khoury, H. Liu, M. P. Davies and H. Haick, Oncotarget, 2015, 6, 44864; ¨llriegl, S. Mo ¨rtl, H. Oelmez, A. Bergner, (b) C. Brunner, W. Szymczak, V. Ho R. Huber, C. Hoeschen and U. Oeh, Anal. Bioanal. hem., 2010, 397, 2315; (c) P. Mochalski, A. Sponring, J. King, K. Unterkofler, J. Troppmair and A. Amann, Cancer Cell Int., 2013, 13, 72. (a) C. Deng, X. Zhang and N. Li, J. Chromatogr. B, 2004, 808, 269; (b) R. Xue, L. Dong, S. Zhang, C. Deng, T. Liu, J. Wang and X. Shen, Rapid Commun. Mass Spectrom., 2008, 22, 1181. (a) A. D’amico, R. Bono, G. Pennazza, M. Santonico, G. Mantini, M. Bernabei, M. Zarlenga, C. Roscioni, E. Martinelli and R. Paolesse, Skin

178 | Electrochemistry, 2019, 15, 147–185

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

65

66

67

68

69 70

71 72 73

74

75

76 77 78

79 80

Res. Technol., 2008, 14, 226; (b) G. Pennazza, M. Santonico, E. Martinelli, R. Paolesse, V. Tamburrelli, S. Cristina, A. D’Amico, C. Di Natale and A. Bartolazzi, Sens. Actuators,, 2011, 154, 288; (c) A. N. Thomas, S. Riazanskaia, W. Cheung, Y. Xu, R. Goodacre, C. Thomas, M. S. Baguneid and A. Bayat, Wound Repair Regen., 2010, 18, 391. (a) C. Zuliani, G. Matzeu and D. Diamond, Electrochim. Acta, 2014, 132, 292; (b) T. Pfaffe, J. Cooper-White, P. Beyerlein, K. Kostner and C. Punyadeera, Clin. Chem., 2011, 57, 675. (a) Y. Hanai, K. Shimono, K. Matsumura, A. Vachani, S. Albelda, K. Yamazaki, G. K. Beauchamp and H. Oka, Biosci., Biotechnol., Biochem., 2012, 76, 679; (b) K. M. Banday, K. K. Pasikanti, E. C. Y. Chan, R. Singla, K. V. S. Rao, V. S. Chauhan and R. K. Nanda, Anal. Chem., 2011, 83, 5526; (c) K. U. Alwis, B. C. Blount, A. S. Britt, D. Patel and D. L. Ashley, Anal. Chim. Acta, 2012, 750, 152. (a) B. D. L. Costello, R. Ewen, A. Ewer, C. Garner, C. Probert, N. M. Ratcliffe and S. Smith, J. Breath Res., 2008, 2, 037023; (b) T. G. Meij, I. B. Larbi, M. P. Schee, Y. E. Lentferink, T. Paff, J. S. Terhaar sive Droste, C. J. Mulder, A. A. Bodegraven and N. K. Boer, Int. J. Cancer, 2014, 134, 1132; (c) M. K. Bomers, F. P. Menke, R. S. Savage, C. M. Vandenbroucke-Grauls, M. A. Van Agtmael, J. A. Covington and Y. M. Smulders, Am. J. Gastroenterol., 2015, 110, 588. (a) S. R. Kim, R. U. Halden and T. J. Buckley, Environ. sci. technol., 2007, 41, 1662; (b) J. Fisher, D. Mahle, L. Bankston, R. Greene and J. Gearhart, Am. Indus. Hyg. Assoc., 1997, 58, 425. A. Tricoli, M. Righettoni and A. Teleki, Angew. Chem., Int. Ed., 2010, 49, 7632. ´, S. ˇ (a) I. Kushch, B. Arendacka Stolc, P. Mochalski, W. Filipiak, K. Schwarz, L. Schwentner, A. Schmid, A. Dzien and M. Lechleitner, Clin. Chem. Lab. Med., 2008, 46, 1011; (b) M. Basanta, R. M. Jarvis, Y. Xu, G. Blackburn, R. Tal-Singer, A. Woodcock, D. Singh, R. Goodacre, C. P. Thomas and S. J. Fowler, Analyst, 2010, 135, 315. Y.-H. Yun, E. Eteshola, A. Bhattacharya, Z. Dong, J.-S. Shim, L. Conforti, D. Kim, M. J. Schulz, C. H. Ahn and N. Watts, Sensors, 2009, 9, 9275. R. M. Gelfand, D. Dey, J. Kohoutek, A. Bonakdar, S. C. Hur, D. Di Carlo and H. Mohseni, Opt. Photonics News, 2011, 22, 32. ¨ntner, V. Koren, K. Chikkadi, M. Righettoni and S. E. Pratsinis, (a) A. T. Gu ACS Sens., 2016, 1, 528; (b) M. Righettoni, A. Tricoli and S. E. Pratsinis, Anal. Chem., 2010, 82, 3581. H. G. Moon, Y.-S. Shim, H. Y. J. Do Hong Kim, M. Jeong, J. Y. Jung, S. M. Han, J. K. Kim, J.-S. Kim, H.-H. Park and J.-H. Lee, Sci. Rep., 2012, 2. (a) R. Arsat, M. Breedon, M. Shafiei, P. Spizziri, S. Gilje, R. Kaner, K. Kalantar-zadeh and W. Wlodarski, Chem. Phys. Lett., 2009, 467, 344; (b) M. K. Kurosawa, Ultrasonics, 2000, 38, 15. F. D. Shah, R. Begum, B. N. Vajaria, K. R. Patel, J. B. Patel, S. N. Shukla and P. S. Patel, Indian J. Clin. Biochem., 2011, 26, 326. A. Tricoli and S. E. Pratsinis, Nat. Nanotechnol., 2010, 5, 54. (a) M. Phillips, R. N. Cataneo, A. R. Cummin, A. J. Gagliardi, K. Gleeson, J. Greenberg, R. A. Maxfield and W. N. Rom, Chest J., 2003, 123, 2115; (b) P. J. Mazzone, J. Thorac. Oncol., 2008, 3, 774. S. Van den Velde, F. Nevens, D. van Steenberghe and M. Quirynen, J. Chromatogr. B, 2008, 875, 344. S.-Y. Liu, T.-S. Lee and F. Bongard, Chest, 1992, 102, 1512. Electrochemistry, 2019, 15, 147–185 | 179

View Online

¨gman, T. Holmkvist, T. Wegener, M. Emtner, M. Andersson, (a) M. Ho ¨m and P. Merila ¨inen, Respir. Med., 2002, 96, 24; H. Hedenstro (b) M. R. McCurdy, A. Sharafkhaneh, H. Abdel-Monem, J. Rojo and F. K. Tittel, J. Breath Res., 2011, 5, 016003. 82 K. Zayasu, K. Sekizawa, S. Okinaga, M. Yamaya, T. Ohrui and H. Sasaki, Am. J. Respir. Crit. Care Med., 1997, 156, 1140. 83 C. Popa, D. Dutu, R. Cernat, C. Matei, A. Bratu, S. Banita and D. C. Dumitras, Appl. Phys B, 2011, 105, 669. 84 (a) D. A. Lindberg, Gastroenterol. Nurs., 2010, 33, 8; (b) A. Hryniuk and B. M. Ross, J. Gastrointest. Liver Dis., 2010, 19. 85 M. Puiu, A.-M. Gurban, L. Rotariu, S. Brajnicov, C. Viespe and C. Bala, Sensors, 2015, 15, 10511. 86 D. D. Deobagkar, V. Limaye, S. Sinha and R. Yadava, Sens. Actuators, B, 2005, 104, 85. 87 Y. Chang, N. Tang, H. Qu, J. Liu, D. Zhang, H. Zhang, W. Pang and X. Duan, Sci. Rep., 2016, 6, 23970. 88 T. L. Panasyuk, V. M. Mirsky, S. A. Piletsky and O. S. Wolfbeis, Anal. Chem., 1999, 71, 4609. 89 S. Borini, R. White, D. Wei, M. Astley, S. Haque, E. Spigone, N. Harris, J. Kivioja and T. Ryhanen, ACS Nano, 2013, 7, 11166. 90 H. Jin, T.-P. Huynh and H. Haick, Nano Lett., 2016, 16, 4194. 91 S. Kano, K. Kim and M. Fujii, ACS Sens., 2017, 2, 828–833. 92 A. Gholizadeh, D. Voiry, C. Weisel, A. Gow, R. Laumbach, H. Kipen, M. Chhowalla and M. Javanmard, Microsyst. Nanoeng., 2017, 3, 17022. 93 (a) A. Haynes and P. Gouma, IEEE Sens. J., 2008, 8, 701; (b) G. W. Hunter, J. C. Xu, A. Biaggi-Labiosa, D. Laskowski, P. Dutta, S. Mondal, B. Ward, D. Makel, C. Liu and C. Chang, J. Breath Res., 2011, 5, 037111; (c) S. Pantalei, E. Zampetti, A. Bearzotti, F. De Cesare and A. Macagnano, Sens. Actuators,, 2013, 179, 87. 94 C. Higgins, D. Wencel, C. S. Burke, B. D. MacCraith and C. McDonagh, Analyst, 2008, 133, 241. 95 Y. Xiong, Z. Ye, J. Xu, Y. Zhu, C. Chen and Y. Guan, Analyst, 2013, 138, 1819. ¨hlemann, Helv. Odontol. Acta, 1966, 10, 94. 96 H. Graf and H. Mu ´rcoles, BioMed Res. Int., 97 R. S. Malon, S. Sadir, M. Balakrishnan and E. P. Co 2014, 2014, 20. 98 C. Lee, X. Wei, J. W. Kysar and J. Hone, Science, 2008, 321, 385. 99 (a) T. Nakagawa, H. Hu, S. Zharikov, K. R. Tuttle, R. A. Short, O. Glushakova, X. Ouyang, D. I. Feig, E. R. Block and J. Herrera-Acosta, Am. J. Physiol.Renal Physiol., 2006, 290, F625; (b) G. F. Falasca, Clin. Dermatol., 2006, 24, 498; (c) W. Nyhan, J. Inherited Metab. Dis., 1997, 20, 171; (d) T. R. Merriman and N. Dalbeth, Joint Bone Spine, 2011, 78, 35. 100 (a) A. Dehghan, M. Van Hoek, E. J. Sijbrands, A. Hofman and J. C. Witteman, Diabetes Care, 2008, 31, 361; (b) M. Zloczower, A. Z. Reznick, R. O. Zouby and R. M. Nagler, Antioxid. Redox Signaling, 2007, 9, 765; (c) A. Costa, I. Igual, J. Bedini, L. Quint and I. Conget, Metab., Clin. Exp., 2002, 51, 372; (d) V. Bhole, J. W. J. Choi, S. W. Kim, M. De Vera and H. Choi, Am. J. Med., 2010, 123, 957. 101 Y. Hellsten, P. C. Tullson, E. A. Richter and J. Bangsbo, Free Radicals Biol. Med., 1997, 22, 169. 102 K. Shibasaki, M. Kimura, R. Ikarashi, A. Yamaguchi and T. Watanabe, Metabolomics, 2012, 8, 484.

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

81

180 | Electrochemistry, 2019, 15, 147–185

View Online

103

104

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

105 106 107

108 109 110 111 112

113 114

115 116 117 118 119 120 121 122 123 124 125

M. Soukup, I. Biesiada, A. Henderson, B. Idowu, D. Rodeback, L. Ridpath, E. G. Bridges, A. M. Nazar and K. G. Bridges, Diabetol. Metab. Syndr., 2012, 4, 14. J. M. Turner-Cobb, S. E. Sephton, C. Koopman, J. Blake-Mortimer and D. Spiegel, Psychosom. Med., 2000, 62, 337. S. Mi, J. Lu, M. Sun, Z. Li, H. Zhang, M. B. Neilly, Y. Wang, Z. Qian, J. Jin and Y. Zhang, Proc. Natl. Acad. Sci., 2007, 104, 19971. L. Zhou and R. W. Beuerman, Prog. Retinal Eye Res., 2012, 31, 527. J. You, M. Willcox, A. Fitzgerald, B. Schiller, P. J. Cozzi, P. J. Russell, B. J. Walsh, V. C. Wasinger, P. H. Graham and Y. Li, Anal. Biochem., 2016, 496, 30. Q. Yan, B. Peng, G. Su, B. E. Cohan, T. C. Major and M. E. Meyerhoff, Anal. Chem., 2011, 83, 8341. C. K. M. Choy, P. Cho, W.-Y. Chung and I. F. Benzie, Invest Ophthalmol. Visual Sci., 2001, 42, 3130. ¨r klinische N. Van Haeringen and E. Glasius, Albrecht von Graefes Archiv fu und Exp. Ophthalmol., 1977, 202, 1. M. Nakatsukasa, C. Sotozono, K. Shimbo, N. Ono, H. Miyano, A. Okano, J. Hamuro and S. Kinoshita, Am. J. Ophthalmol., 2011, 151, 799. (a) K. Ogasawara, T. Tsuru, K. Mitsubayashi and I. Karube, Graefe’s Arch. Clin. Exp. Ophthalmol., 1996, 234, 542; (b) H. Kudo, T. Sawada, E. Kazawa, H. Yoshida, Y. Iwasaki and K. Mitsubayashi, Biosens. Bioelectron., 2006, 22, 558. A. Kagie, D. K. Bishop, J. Burdick, J. T. La Belle, R. Dymond, R. Felder and J. Wang, Electroanalysis, 2008, 20, 1610. (a) M. Chu, T. Shirai, D. Takahashi, T. Arakawa, H. Kudo, K. Sano, S.-I. Sawada, K. Yano, Y. Iwasaki and K. Akiyoshi, Biomed. Microdevices, 2011, 13, 603; (b) M. X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S.-I. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi and M. Mochizuki, ¨hdesma ¨ki and B. A. Parviz, Sens. Talanta, 2011, 83, 960; (c) N. Thomas, I. La Actuators, B, 2012, 162, 128; (d) Y.-T. Liao, H. Yao, A. Lingley, B. Parviz and B. P. Otis, IEEE J. Solid-State Circuits, 2012, 47, 335; (e) H. Yao, Y. Liao, ¨hdesma ¨ki, B. Otis and B. Parviz, J. Micromech. A. Lingley, A. Afanasiev, I. La Microeng., 2012, 22, 075007. S. Iguchi, K. Mitsubayashi, T. Uehara and M. Ogawa, Sens. Actuators, B, 2005, 108, 733. I. Timofeeva, K. Medinskaia, L. Nikolaeva, D. Kirsanov and A. Bulatov, Talanta, 2016, 150, 655. M. Choudhary, P. Yadav, A. Singh, S. Kaur, J. Ramirez-Vick, P. Chandra, K. Arora and S. P. Singh, Electroanalysis, 2016, 28, 2565. S. Kumar, J. G. Sharma, S. Maji and B. D. Malhotra, Biosens. Bioelectron., 2016, 78, 497. B. I. Freedman, S. C. Smith, B. M. Bagwell, J. Xu, D. W. Bowden and J. Divers, Am. J. Nephrol., 2015, 41, 438. J. Liu, S. Sun, H. Shang, J. Lai and L. Zhang, Electroanalysis, 2016, 28. Y. Du, W. Zhang and M. L. Wang, Biosensors, 2016, 6, 10. L. Yu, X. Wei, C. Fang and Y. Tu, Electrochim. Acta, 2016, 211, 27. A. Roda, M. Guardigli, D. Calabria, M. M. Calabretta, L. Cevenini and E. Michelini, Analyst, 2014, 139, 6494. C. Timchalk, T. S. Poet, A. A. Kousba, J. A. Campbell and Y. Lin, J. Toxicol. Environ. Health, Part A, 2004, 67, 635. L. Guo, Y. Wang, Y. Zheng, Z. Huang, Y. Cheng, J. Ye, Q. Chu and D. Huang, J. Chromatogr. B, 2016, 1014, 70. Electrochemistry, 2019, 15, 147–185 | 181

View Online

126 127 128

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150

151

152 153

˘lu and M. Koçan, Expert Syst., 2010, 27, 156. H. M. Saraog C. Liu, Y. Sheng, Y. Sun, J. Feng, S. Wang, J. Zhang, J. Xu and D. Jiang, Biosens. Bioelectron., 2015, 70, 455. M. M. Pribil, G. U. Laptev, E. E. Karyakina and A. A. Karyakin, Anal. Chem., 2014, 86, 5215. S. Biagi, S. Ghimenti, M. Onor and E. Bramanti, Biomed. Chromatogr., 2012, 26, 1408. ˜ o, M. Farre ´, S. Pichini, M. Navarro, R. Pacifici, P. Zuccaro, J. Ortun P. N. Roset, J. Segura and R. de la Torre, J. Anal. Toxicol., 2003, 27, 294. M. Tsunoda, M. Hirayama, T. Tsuda and K. Ohno, Clin. Chim. Acta, 2015, 442, 52. Y. Hu, X. Jiang, L. Zhang, J. Fan and W. Wu, Biosens. Bioelectron., 2013, 48, 94. W. C. Mak, K. Y. Cheung, J. Orban, C.-J. Lee, A. P. Turner and M. Griffith, ACS Appl. Mater. Interfaces, 2015, 7, 25487. K. Karns and A. E. Herr, Anal. Chem., 2011, 83, 8115. N. M. Farandos, A. K. Yetisen, M. J. Monteiro, C. R. Lowe and S. H. Yun, Adv. Healthcare Mater., 2015, 4, 792. ¨hdesma ¨ki and B. A. Parviz, Biosens. H. Yao, A. J. Shum, M. Cowan, I. La Bioelectron., 2011, 26, 3290. Y. Yan, M. Zhang, K. Gong, L. Su, Z. Guo and L. Mao, Chem. Mater., 2005, 17, 3457. T. Shi, D. Li, Y. Ji, G. Li and K. Xu, Proc. of SPIE Vol, 2012, 82150U–82151U. Y. Yamada, S. Hiyama, T. Toyooka, S. Takeuchi, K. Itabashi, T. Okubo and H. Tabata, Anal. Chem., 2015, 87, 7588. ´Cheong, J. Hyeba ´Song and J. Joona ´Kim, Nanoscale, 2016, 8, 10591. W. Hyunga H. Guo, C. Lan, Z. Zhou, P. Sun, D. Wei and C. Li, Nanoscale, 2017, 9, 6246. I. T. Degim, S. Ilbasmis, R. Dundaroz and Y. Oguz, Pediatr. Nephrol., 2003, 18, 1032. B. T. Leboulanger, R. H. Guy and M. B. Delgado-Charro, Eur. J. Pharm. Sci., 2004, 22, 427. A. Sieg, F. Jeanneret, M. Fathi, D. Hochstrasser, S. Rudaz, J.-L. Veuthey, R. H. Guy and M. B. Delgado-Charro, Eur. J. Pharm. Biopharm., 2009, 72, 226. S. K. Vashist, Anal. Chim. Acta, 2012, 750, 16. M. J. Tierney, J. A. Tamada, R. O. Potts, L. Jovanovic, S. Garg and C. R. Team, Biosens. Bioelectron., 2001, 16, 621. A. P. R. de Souza, C. W. Foster, A. V. Kolliopoulos, M. Bertotti and C. E. Banks, Analyst, 2015, 140, 4130. S. H. Eom, S. Senthilarasu, P. Uthirakumar, S. C. Yoon, J. Lim, C. Lee, H. S. Lim, J. Lee and S.-H. Lee, Org. Electron., 2009, 10, 536. (a) B. Tay and M. Edirisinghe, J. Mater. Sci., 2002, 37, 4653; (b) A. Kamyshny, J. Steinke and S. Magdassi, Open Appl. Phys. J., 2011, 4. (a) Z. Pan, Y. Wang, H. Huang, Z. Ling, Y. Dai and S. Ke, Ceram. Int., 2015, 41, 12515; (b) J. A. Lewis, J. E. Smay, J. Stuecker and J. Cesarano, J. Am. Ceram. Soc., 2006, 89, 3599. (a) B. Y. Ahn, D. J. Lorang and J. A. Lewis, Nanoscale, 2011, 3, 2700; (b) B. Y. Ahn, E. B. Duoss, M. J. Motala, X. Guo, S.-I. Park, Y. Xiong, J. Yoon, R. G. Nuzzo, J. A. Rogers and J. A. Lewis, Science, 2009, 323, 1590. G. A. dos Reis Benatto, B. Roth, M. Corazza, R. R. Søndergaard, S. A. Gevorgyan, M. Jørgensen and F. C. Krebs, Nanoscale, 2016, 8, 318. (a) E. B. Secor, P. L. Prabhumirashi, K. Puntambekar, M. L. Geier and M. C. Hersam, J. Phys. Lett., 2013, 4, 1347; (b) D. J. Finn, M. Lotya, G. Cunningham, R. J. Smith, D. McCloskey, J. F. Donegan and J. N. Coleman, J. Mater. Chem. C, 2014, 2, 925.

182 | Electrochemistry, 2019, 15, 147–185

View Online

154 155

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

156 157 158 159

160 161 162 163 164 165 166 167 168 169 170

171 172 173

174 175 176 177 178

179 180 181

N. Matsuhisa, M. Kaltenbrunner, T. Yokota, H. Jinno, K. Kuribara, T. Sekitani and T. Someya, Nat. Commun., 2015, 6. M. Hu, X. Cai, Q. Guo, B. Bian, T. Zhang and J. Yang, ACS Nano, 2015, 10, 396. D. R. Kumar, M. R. Reddy, V. Mulay and N. Krishnamurti, Eur. Polym. J., 2000, 36, 1503. R. Ma, B. Kang, S. Cho, M. Choi and S. Baik, ACS Nano, 2015, 9, 10876. C. A. Zuniga, J. Abdallah, W. Haske, Y. Zhang, I. Coropceanu, S. Barlow, B. Kippelen and S. R. Marder, Adv. Mater., 2013, 25, 1739. (a) G. H. Kwon, J. Y. Park, J. Y. Kim, M. L. Frisk, D. J. Beebe and S. H. Lee, Small, 2008, 4, 2148; (b) W. Zhu, J. Li, Y. J. Leong, I. Rozen, X. Qu, R. Dong, Z. Wu, W. Gao, P. H. Chung and J. Wang, Adv. Mater., 2015, 27, 4411. K. Suganuma, Introduction to Printed Electronics, Springer, 2014, pp. 1–22. S. A. Odom, S. Chayanupatkul, B. J. Blaiszik, O. Zhao, A. C. Jackson, P. V. Braun, N. R. Sottos, S. R. White and J. S. Moore, Adv. Mater., 2012, 24, 2578. ˜ez-Flores and J. Wang, Nano A. J. Bandodkar, I. Jeerapan, J.-M. You, R. Nun Lett., 2015, 16, 721. W. S. Mardis, J. Am. Oil Chem. Soc., 1984, 61, 382. S. Azoubel, S. Shemesh and S. Magdassi, Nanotechnology, 2012, 23, 344003. S. B. Walker and J. A. Lewis, J. Am. Chem. Soc., 2012, 134, 1419. D. Jang, D. Kim, B. Lee, S. Kim, M. Kang, D. Min and J. Moon, Adv. Funct. Mater., 2008, 18, 2862. J. K. Fink, The Chemistry of Printing Inks and Their Electronics and Medical Applications, John Wiley & Sons, 2014. M. Vosgueritchian, D. J. Lipomi and Z. Bao, Adv. Funct. Mater., 2012, 22, 421. K. Takei, Z. Yu, M. Zheng, H. Ota, T. Takahashi and A. Javey, Proceedings of the National Academy of Sciences, 2014, 111, 1703. (a) C.-L. Lee, C.-H. Chen and C.-W. Chen, Chem. Eng. J., 2013, 230, 296; (b) D. Wei, P. Andrew, H. Yang, Y. Jiang, F. Li, C. Shan, W. Ruan, D. Han, L. Niu and C. Bower, J. Mater. Chem., 2011, 21, 9762. Y. Hu, T. Zhao, P. Zhu, Y. Zhu, X. Shuai, X. Liang, R. Sun, D. D. Lu and C.-P. Wong, J. Mater. Chem. C, 2016, 4, 5839. F. Torrisi, T. Hasan, W. Wu, Z. Sun, A. Lombardo, T. S. Kulmala, G.-W. Hsieh, S. Jung, F. Bonaccorso and P. J. Paul, ACS Nano, 2012, 6, 2992. (a) E. B. Secor, S. Lim, H. Zhang, C. D. Frisbie, L. F. Francis and M. C. Hersam, Adv. Mater., 2014, 26, 4533; (b) P. H. Lau, K. Takei, C. Wang, Y. Ju, J. Kim, Z. Yu, T. Takahashi, G. Cho and A. Javey, Nano Lett., 2013, 13, 3864. A. Pierre, M. Sadeghi, M. M. Payne, A. Facchetti, J. E. Anthony and A. C. Arias, Adv. Mater., 2014, 26, 5722. A. Kamyshny and S. Magdassi, Small, 2014, 10, 3515. M. Lotya, Y. Hernandez, P. J. King, R. J. Smith, V. Nicolosi, L. S. Karlsson, F. M. Blighe, S. De, Z. Wang and I. McGovern, J. Am. Chem. Soc., 2009, 131, 3611. C.-X. Liu and J.-W. Choi, Nanomaterials, 2012, 2, 329. (a) P. Ma, N. Siddiqui, G. Marom and J. Kim, Sci. Manufact., 2010, 41, 1345; (b) D. S. Hecht, L. Hu and G. Irvin, Adv. Mater., 2011, 23, 1482; (c) L. Hu, D. S. Hecht and G. Gruner, Chem. Rev., 2010, 110, 5790. R. Lu, W.-W. Li, B. Mizaikoff, A. Katzir, Y. Raichlin, G.-P. Sheng and H.-Q. Yu, Nat. Protoc., 2016, 11, 377. D. H. Ho, Q. Sun, S. Y. Kim, J. T. Han, D. H. Kim and J. H. Cho, Adv. Mater., 2016, 28, 2601. G. Zheng, F. Patolsky, Y. Cui, W. U. Wang and C. M. Lieber, Nat. Biotechnol., 2005, 23, 1294. Electrochemistry, 2019, 15, 147–185 | 183

View Online

182

183

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

184 185

186 187

188 189

190

191 192

193

194

195

196 197 198 199

(a) Y. Wang, A. La, Y. Ding, Y. Liu and Y. Lei, Adv. Funct. Mater., 2012, 22, 3547; (b) A. S. Emrani, N. M. Danesh, M. Ramezani, S. M. Taghdisi and K. Abnous, Biosensors Bioelectron., 2016, 79, 288. T. Choudhary, G. Rajamanickam and D. Dendukuri, Lab Chip, 2015, 15, 2064. S. Mubeen, M. Lai, T. Zhang, J.-H. Lim, A. Mulchandani, M. A. Deshusses and N. V. Myung, Electrochim. Acta, 2013, 92, 484. H. Y. Y. Nyein, W. Gao, Z. Shahpar, S. Emaminejad, S. Challa, K. Chen, H. M. Fahad, L.-C. Tai, H. Ota and R. W. Davis, ACS Nano, 2016, 10, 7216. Y. Takatsuji, R. Wakabayashi, T. Sakakura and T. Haruyama, Electrochim. Acta, 2015, 180, 202. (a) S. T. Gaylord, T. L. Dinh, E. R. Goldman, G. P. Anderson, K. C. Ngan and ¨m, D. R. Walt, Anal. Chem., 2015, 87, 6570; (b) S. Loyprasert, M. Hedstro P. Thavarungkul, P. Kanatharana and B. Mattiasson, Biosens. Bioelectron., 2010, 25, 1977. P. Jolly, V. Tamboli, R. L. Harniman, P. Estrela, C. J. Allender and J. L. Bowen, Biosens. Bioelectron., 2016, 75, 188. (a) J. Lee, I.-S. Park, H. Kim, J.-S. Woo, B.-S. Choi and D.-H. Min, Biosens. Bioelectron., 2015, 69, 167; (b) W. Knoll, H. Park, E.-K. Sinner, D. Yao and F. Yu, Surf. Sci., 2004, 570, 30. (a) H. Yin, Y. Zhou, Z. Yang, Y. Guo, X. Wang, S. Ai and X. Zhang, Sens. Actuators, B, 2015, 221, 1; (b) H. Tran, B. Piro, S. Reisberg, L. H. Nguyen, T. D. Nguyen, H. Duc and M. Pham, Biosens. Bioelectron., 2014, 62, 25. K. Kadimisetty, S. Malla, N. P. Sardesai, A. A. Joshi, R. C. Faria, N. H. Lee and J. F. Rusling, Anal. Chem., 2015, 87, 4472. (a) S. Mariani, S. Scarano, J. Spadavecchia and M. Minunni, Biosensors ´n ˜ez-Seden ˜o and Bioelectron., 2015, 74, 981; (b) S. Campuzano, P. Ya ´n, Sensors, 2017, 17, 866. J. M. Pingarro (a) T. Vo-Dinh, Nanotechnology in Biology and Medicine: Methods, Devices, ´ndez and A. L. and Applications, CRC Press, 2007; (b) J. Rodrı´guez-Herna Cortajarena, Design of Polymeric Platforms for Selective Biorecognition, Springer, 2015, pp. 1–9. (a) T. Goda, E. Yamada, Y. Katayama, M. Tabata, A. Matsumoto and Y. Miyahara, Biosens. Bioelectron., 2016, 77, 208; (b) L. B. Baker, C. T. Ungaro, K. A. Barnes, R. P. Nuccio, A. J. Reimel and J. R. Stofan, Physiol. Rep., 2014, 2, e12007; (c) J. Musso, W. Buchmann, F. Gonnet, N. Jarroux, S. Bellon, C. Frydman, D.-L. Brunet and R. Daniel, Anal. Bioanal. Chem., 2015, 407, 1285; (d) E. Leickly, M. G. McDonell, R. Vilardaga, F. A. Angelo, J. M. Lowe, S. McPherson, D. Srebnik, J. M. Roll and R. K. Ries, Am. J. Drug Alcohol Abuse, 2015, 41, 246. (a) A. P. Selvam, S. Muthukumar, V. Kamakoti and S. Prasad, Sci. Rep., 2016, 6, 23111; (b) M. C. McAlpine, H. Ahmad, D. Wang and J. R. Heath, Nat. Mater., 2007, 6, 379; (c) Z. Zheng, J. Yao, B. Wang and G. Yang, Sci. Rep., 2015, 5, 11070. G. Liu, C. Ho, N. Slappey, Z. Zhou, S. Snelgrove, M. Brown, A. Grabinski, X. Guo, Y. Chen and K. Miller, Sens. Actuators, B, 2016, 227, 35. R. C. Webb, Y. Ma, S. Krishnan, Y. Li, S. Yoon, X. Guo, X. Feng, Y. Shi, M. Seidel and N. H. Cho, Sci. Adv., 2015, 1, e1500701. H. Araki, J. Kim, S. Zhang, A. Banks, K. E. Crawford, X. Sheng, P. Gutruf, Y. Shi, R. M. Pielak and J. A. Rogers, Adv. Funct. Mater., 2017, 27. H. Fang, K. J. Yu, C. Gloschat, Z. Yang, E. Song, C.-H. Chiang, J. Zhao, S. M. Won, S. Xu and M. Trumpis, Nat. Biomed. Eng., 2017, 1, 0038.

184 | Electrochemistry, 2019, 15, 147–185

View Online

200 201

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00147

202

203

204

205

206

207

208 209 210 211 212 213

214

215

216

217 218

R. K. Mishra, L. J. Hubble, A. Martı´n, R. Kumar, A. Barfidokht, J. Kim, M. M. Musameh, I. L. Kyratzis and J. Wang, ACS Sens., 2017, 2, 553. Y. K. Lee, K. I. Jang, Y. Ma, A. Koh, H. Chen, H. N. Jung, Y. Kim, J. W. Kwak, L. Wang and Y. Xue, Adv. Funct. Mater., 2017, 27. (a) H.-H. Chou, A. Nguyen, A. Chortos, J. W. To, C. Lu, J. Mei, T. Kurosawa, W.-G. Bae, J. B.-H. Tok and Z. Bao, Nat. Commun., 2015, 6, 8011; (b) D. J. Lipomi, B. C. K. Tee, M. Vosgueritchian and Z. Bao, Adv. Mater., 2011, 23, 1770; (c) M. Ramuz, B. C. K. Tee, J. B. H. Tok and Z. Bao, Adv. Mater., 2012, 24, 3223. (a) S. Lee, A. Reuveny, J. Reeder, S. Lee, H. Jin, Q. Liu, T. Yokota, T. Sekitani, T. Isoyama and Y. Abe, Nat. Nanotechnol., 2016, 11, 472; (b) R. A. Nawrocki, N. Matsuhisa, T. Yokota and T. Someya, Adv. Electron. Mater., 2016, 2; (c) T. Sekitani, Y. Noguchi, K. Hata, T. Fukushima, T. Aida and T. Someya, Science, 2008, 321, 1468. (a) P. Kassal, I. M. Steinberg and M. D. Steinberg, Sens. Actuators, B, 2013, 184, 254; (b) G. Orecchini, L. Yang, M. Tentzeris and L. Roselli, Microwave Symposium Digest (MTT), 2011 IEEE MTT-S International, IEEE, 2011, pp. 1–4. (a) Y. Zi, L. Lin, J. Wang, S. Wang, J. Chen, X. Fan, P. K. Yang, F. Yi and Z. L. Wang, Adv. Mater., 2015, 27, 2340; (b) L. Dong, C. Xu, Y. Li, C. Wu, B. Jiang, Q. Yang, E. Zhou, F. Kang and Q. H. Yang, Adv. Mater., 2016, 28, 1675. (a) R. Sarpeshkar, IEEE Transactions on Circuits and Systems II: Express Briefs, 2012, vol. 59, 193; (b) R. Kannan and A. Garg, SENSORS, 2015 IEEE, IEEE, 2015, pp. 1–4. (a) M. Mirasoli, M. Guardigli, E. Michelini and A. Roda, J. Pharm. Biomed. Anal., 2014, 87, 36; (b) C. Yan, X. Wang, M. Cui, J. Wang, W. Kang, C. Y. Foo and P. S. Lee, Adv. Energy Mater., 2014, 4. S. Berchmans, A. J. Bandodkar, W. Jia, J. Ramı´rez, Y. S. Meng and J. Wang, J. Mater. Chem. A, 2014, 2, 15788. Y.-H. Lee, J.-S. Kim, J. Noh, I. Lee, H. J. Kim, S. Choi, J. Seo, S. Jeon, T.-S. Kim and J.-Y. Lee, Nano Lett., 2013, 13, 5753. (a) T. H. Nguyen, A. Fraiwan and S. Choi, Biosens. Bioelectron., 2014, 54, 640; (b) L. David, R. Bhandavat and G. Singh, ACS Nano, 2014, 8, 1759. S. Xu, Y. Zhang, J. Cho, J. Lee, X. Huang, L. Jia, J. A. Fan, Y. Su, J. Su and H. Zhang, Nat. Commun., 2013, 4, 1543. M.-C. Lin, M. Gong, B. Lu, Y. Wu, D.-Y. Wang, M. Guan, M. Angell, C. Chen, J. Yang and B.-J. Hwang, Nature, 2015, 520, 325. (a) M. S. Mannoor, H. Tao, J. D. Clayton, A. Sengupta, D. L. Kaplan, R. R. Naik, N. Verma, F. G. Omenetto and M. C. McAlpine, Nat. Commun., 2013, 4, 1900; (b) J. F. Oudenhoven, L. Baggetto and P. H. Notten, Adv. Energy Mater., 2011, 1, 10. (a) L. Kong, C. Zhang, J. Wang, W. Qiao, L. Ling and D. Long, ACS Nano, ´lez-Arribas, Z. Blum and S. Shleev, 2015, 9, 11200; (b) D. Pankratov, E. Gonza Electroanalysis, 2016, 28, 1250. A. Mukherjee, A. Pal and P. Misra, in Next generation mobile applications, services and technologies (NGMAST), 2012 6th international conference on, IEEE, 2012, pp. 193–198. (a) J. Andreu-Perez, D. R. Leff, H. M. Ip and G.-Z. Yang, IEEE Trans. Biomed. Eng., 2015, 62, 2750; (b) F. Chen, P. Deng, J. Wan, D. Zhang, A. V. Vasilakos and X. Rong, Int. J. Distrib. Sens. Networks, 2015, 11, 1. M. Chen, V. C. Leung and S. Mao, Mobile Networks Appl., 2009, 14, 220. X. Wu, X. Zhu, G.-Q. Wu and W. Ding, IEEE Trans. Knowl. Data Eng., 2014, 26, 97. Electrochemistry, 2019, 15, 147–185 | 185

The application of electrochemical impedance spectroscopy to electrochemical sensor devices Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

Edward Randviir DOI: 10.1039/9781788013895-00186

1

Electrochemical impedance spectroscopy

The study of electrode–electrolyte interfaces are commonplace in academic research in the 21st century. Countless person hours of work have been coordinated towards the fundamental understanding of the way chemical species behave at surfaces at equilibrium through potentiometry, through to the case of dynamic experiments where perturbations are applied at an electrode–electrolyte interface to drive an electrode away from its equilibrium, promoting electrochemical reactions to occur. The resulting currents observed between the working and counter electrodes provide information on the nature of charge transfer reactions at the electrode and are exploited in a number of ways. The evidence obtained from such experiments hold several applications ranging from fuel cell design to solar cell efficiency, through to medical diagnostics. Electrochemical Impedance Spectroscopy (EIS) is an alternative technique where a small alternating perturbation is applied to an electrochemical cell, while measuring the current responses at steady state over a long period. The advantages of this technique, as described by Bard and Faulkner, are: an ability to make high-precision measurements due to the indefinite steady-state current responses; an ability to treat the response as pseudolinear (i.e. current is directly proportional to the applied ac perturbation); and that measurements are conducted in the frequency domain, allowing rigorous examination of the time-dependent components of an electrochemical cell.1 Faradaic impedance measurements, such as those in EIS, are focused on an electrochemical cell with an electrochemically active species. Traditionally one would probe a mixture of the oxidised and reduced species in question, so that the potential of the working electrode is effectively fixed. However, in the case of electroanalytical applications, where the interest is of one species that is not necessarily a reversible electrochemical system, a DC potential is superimposed upon the cell at the target analyte’s half wave potential. This replicates the condition of equal concentrations of oxidised and reduced species at the electrode surface in a given environment. This modus operandi intuitively creates a diffusion layer due to the applied potential, but since the applied potential is steady (i.e. it is held for a long time frame and remains unchanged during the experiment), the layer quickly becomes large enough in size to Manchester Metropolitan University, Manchester M1 5GD, UK E-mail: [email protected] 186 | Electrochemistry, 2019, 15, 186–205  c

The Royal Society of Chemistry 2019

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

exceed the changes observed by the rapid ac fluctuations. Furthermore, in practice it is common to condition the electrode at the applied halfwave potential before making changes to the frequency of the ac perturbation, to aid in the development of the diffusion layer and to allow the electrode to reach an equilibrium with its surroundings prior to EIS measurements. When the equilibrium is reached, the ac perturbation is applied to the cell. The application of the ac perturbation allows current flows of varying magnitudes dependent upon the point in time. The ratio of the current to the applied voltage (via an Ohm’s law relationship) at each point in time is calculated by the computer software, and through Fourier Transformation over several current measurements along the wave profile, a total impedance value is configured at a given frequency. This impedance value is only valid when the applied ac perturbation is so small that the current–voltage relationship is effectively pseudo-linear. Larger perturbations than 20 mV would introduce significant errors into the technique since current–voltage relationships in relative terms are non-linear. In EIS, this process is repeated over several frequencies: a small perturbation is applied at a given frequency and the impedance value is configured by the system. The data is the presented in several ways, each holding their own advantages and disadvantages. A plot of frequency (and phase angle shift) versus the total impedance of the system is known as a Bode plot. These plots are common in applications such as corrosion science, since the total impedance is an indicator of corrosion formation upon a metallic surface, and thus more complex de-convolution of individual impedance components are not necessary. While Bode plots carry the advantage of being able to identify the total impedance behaviour as a function of frequency, they are limited in terms of their impedance contributions, making this method of data presentation far less common for electrochemical sensors, which are the focus of this Chapter. The more common data presentation method for EIS, a Nyquist plot, shows the variation of the real and imaginary impedance components with respect to one another. Fig. 1 depicts a Nyquist plot for EIS, revealing the real (Z 0 ) and imaginary (Z00 ) components, termed such because the de-convolution of the latter component requires manipulation using complex numbers. To think of this in another way, the total impedance of a cell is constituted from two components: the resistance (Z 0 ); and the reactance (Z00 ). The resistance is defined as the opposition to electrical current of the materials or devices that electrons travel through. This quantity is frequency independent; it does not change as a result of alterations to the time domain. The reactance of a circuit therefore is the imaginary component and is frequency dependent, meaning that the impedance due to the reactance changes with respect to the applied frequency. This must be considered because components in circuits, such as capacitors or inductors, give rise to differing impedances within different time domains. The total impedance is a summation of these two components. An electrochemical cell is constituted from several components that contribute towards the total cell impedance. The total impedance of the Electrochemistry, 2019, 15, 186–205 | 187

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

Fig. 1 Nyquist plot depicting the real (Z 0 ) and imaginary (Z00 ) components of the total cell impedance. The image demonstrates that while exact frequencies are not part of a Nyquist plot, the high frequency domain is on the left hand side, while the low frequency domain is on the right. Inset is the theoretical model for the components of the electrochemical cell. These components are: the resistance of the solution (Rs), the double layer charging (Cd), the charge transfer resistance (Rct), and the Warburg (ZW) component, which is the impedance due to diffusion. The diameter of the semicircle in a Nyquist plot is known as the charge transfer resistance and is the quantity often reported in the literature to provide evidence of desired phenomena. Reproduced from ref. 10 with permission from the Royal Society of Chemistry.

cell is the sum of all these contributions. The most dominating components to the total impedance observed in EIS are known as the solution resistance (Rs), the charge transfer resistance (Rct), the doublelayer capacitance (Cd), and the Warburg element (ZW). Note these terminologies are consistent within this Chapter, but many other terms are utilised especially for charge transfer resistance. The first three parameters are self-explanatory; the latter is the impedance observed due to diffusive flux and is dominant in the low frequency domain where the rate of diffusion is faster than the response of the electroactive species to the ac perturbation. A final component that is rarely seen within EIS for electrochemical sensors is the inductor component, termed L. This appears in the high frequency range (above 105 Hz) and is normally þ901 out of phase with the applied perturbation. In EIS, the Rct component becomes informative to the electrode processes and is often 188 | Electrochemistry, 2019, 15, 186–205

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

measured to predict behaviours at the electrode. More fittingly, in electroanalytical applications the Rct value changes with respect to the concentration of the target analyte, according to eqn (1) (where R is the molar gas constant, T is the absolute temperature, n is the number of electrons transferred, F is the Faraday constant, k0 is the standard electron transfer rate constant, and C is the concentration of the electroactive species). Note the concentration element of the equation is actually the product of the concentrations of the oxidised and reduced species (e.g. Zna  Zn21(1a)); in EIS, where the experiment is operated at the half wave potential, the concentrations of these species are assumed to be equal, therefore the bulk concentration is an adequate approximation for eqn (1).2 Rct ¼

RT n2 F 2 Ak0 C

(1)

The practical use of this equation comes with some limitations; for example rigorous assessment of the electron transfer rate constant is required before electroanalytical measurements can be made. Without a known value for the electron transfer rate constant, the equation cannot be solved analytically, making this equation potentially limited in its use. This information can be deciphered using voltammetric or amperometric methods. An assumption is also made that the half wave potential of a charge transfer reaction remains the same across all measured frequencies. It is well-known that the scan rate (or frequency!) of a voltammetric experiment has significant impacts on the half-wave potentials in quasi- and irreversible electrochemical systems where broadening of the peak-to-peak separation is often observed as the scan rate of an experiment is altered. In EIS an assumption therefore has to be made that the half wave potential remains the same across the entire frequency range, which is logically flawed. For example, at what scan rate do you assign a half wave potential for adequate testing within EIS experiments? In a quasi- or irreversible electrochemical process the half wave potential will change within the upper and lower limits of voltammetric scan rate. Indeed previous work (see Fig. 2 described later) a scan rate of 100 mV s1 has been used to assign the half-wave potential, yet an argument could be made for the half wave potential of any scan rate from 1–1000 mV s1 is appropriate in this case. Aside from this, EIS is a technique that tends to require longer data acquisition times, and the electroanalytical application of eqn (1) is presently not well understood; ˇevc´ik therefore, most electoanalytical chemists prefer using the Randles–S equation for diffusional electrode processes in their experimental design. That being said, eqn (1) is often applied for assessment of electron transfer rate constants, and thus is used as a qualitative technique in many applications. Despite such limitations, eqn (1) can be utilised for electroanalytical purposes provided the limitations are understood and efforts are made to account for the limitations. One such example is the case of hydroquinone (see Fig. 2), where a decrease in Rct value represents an increase Electrochemistry, 2019, 15, 186–205 | 189

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

Fig. 2 EIS profiles of hydroquinone in the concentration range 0.1–0.7 mM, where a decrease in semicircle diameter is indicative of a higher concentration of hydroquinone (parameters: 10 000–0.2 Hz; 10 mV ac amplitude; E1/2 ¼ þ 0.12 V).

in the concentration, since more electroactive species at the electrode will intuitively present less resistance to charge transfer (i.e. there are less water molecules as nearest neighbours to the electrode surface). The linearity of the calibration curve inset of Fig. 2 demonstrates the analytical power of EIS. The linear range of 0.1–0.7 mM is realised with a regression coefficient of 0.9981, predicting a k0 value for hydroquinone of 3.38104 cm s1. Comparing this to the voltammetric determination, where the regression coefficient was 0.9742 and the k0 (determined using the Nichiolson method) was 2.90103 cm s1, it is clear that there is a disparity between the two methods. The EIS profile demonstrates that the mechanism for hydroquinone is not diffusional in its nature; this is evidenced by the lack of straight line in the diffusionally-controlled low frequency region as seen in Fig. 1. Therefore, we can immediately conclude that systems such as hydroquinone are unsuitable for analysis using the Randles–Sevcik equation, since hydroquinone appears to be a non-diffusionally controlled process. For further information regarding recent advances using EIS (up to 2013), the reader is referred to Bandarenka’s review.3

2

Information from Nyquist plots

The previous section highlighted the Nyquist plot as a common method to present EIS data, where the shape of the Nyquist plot gives information to the user regarding the Faradaic and non-Faradaic processes occurring. In a normal experiment, data points are gathered at several frequencies, then an equivalent circuit model is applied to the experimental dataset in order to estimate the resistive, capacitive, diffusional, and inductive impedance components within a proposed model. This section highlights the aspects of circuit models that EIS users often look for and how they relate to interfacial behaviour. Fig. 3 depicts the common circuit models implemented in EIS, and an example Nyquist plot that is indicative of the circuit model. The first case 190 | Electrochemistry, 2019, 15, 186–205

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

Fig. 3 A summary of the relevant equivalent circuit models in electrode design, and the ideal Nyquist plots to accompany the circuit models. Top: simple Randles cell, pertaining to a diffusionless electrochemical system with kinetic control only. Middle: modified Randles cell incorporating the Warburg element (ZW) for diffusional impedance, combining kinetic and diffusional control. Bottom: coated porous electrode, with a coating capacitance (Cc), and pore resistance (Rpo) contribution.

is that of an electrochemical cell where the kinetics of the process only contribute to the impedance spectrum within the prescribed frequency range. The typical feature of the Nyquist plot is a semicircle that starts and ends at zero on the imaginary axis, thus bisecting the Z 0 abscissa twice. In this case, the only impedance effects observed are due to double-layer charging, charge transfer, and the resistance of the solution. The double layer charging (Cd) component is calculated from the semicircle peak maximum (the highest point of the parabola) with eqn (2). This quantity is complex and the waveform appears out of phase with the applied voltage by 901. Z 00 ¼

1 2pfC

(2)

Electrochemistry, 2019, 15, 186–205 | 191

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

The charge transfer resistance (Rct) is calculated as the difference between the first high frequency data point that intersects the real axis and zero (or in other words, the diameter of the semicircle, measured in ohms – see Fig. 1). Note in practice, equivalent circuit modelling software will automatically calculate an effective value for each component so manual intervention is not necessary. One applied example of this type of circuit model by Franceschini et al. used a rotating disk electrode to monitor the behaviour of the Hydrogen Evolution Reaction (HER) using a bimetallic nickel/ruthenium electrode surface.4 Their work highlights a single time constant process for the HER at 0.3 V overpotential to the onset potential, indicating that the mechanism of hydrogen evolution is likely to be a single step process. In their modelling, they erroneously use a circuit model for a failed coating, though this does not appear to affect their simulations to a great extent. Filipe and Brett also use the simple Randles model to estimate the interaction between carbon thin film electrodes and several buffer solutions, confirming that even at low frequencies, the interfacial behaviour was dominated by charge transfer behaviour, with a notable absence of diffusional impedance.5 The second case in Fig. 3 is the case of mixed kinetic and diffusional control, where in the low frequency domain the overall impedance begins to increase due to the diffusional flux at the electrode surface. This only happens in the low frequency domain since the diffusion characteristics of a reversible redox system are much slower than the kinetic contributions, therefore the diffusional impedance only becomes dominant when the timescale of the experiment is slowed to a point where the time taken for data measurement is slower than the diffusion itself. The resultant Nyquist plot takes the form of a merged semicircle and straight line with a 45-degree angle, indicating that the resistance and reactance components of impedance increase linearly with respect to the frequency. There are countless examples of the mixed kinetic and diffusional regime. Examples of note include Pei et al. who use impedance to monitor antibody/antigen binding, observing increases in charge transfer resistance towards the Fe(CN)63/4 couple as layers of an electrode are sequentially added.6 The mechanism for the redox probe is well-known to contain a mixed diffusional and charge transfer component at many electrode surfaces. The third case in Fig. 3 is the case of a porous electrode and is particularly useful when looking at electrode designs because this model can predict both the pore resistance and the charge transfer resistance of a porous electrode. This appears in the Nyquist plot as two concurrent semicircles with different diameters and heights, indicating two separate electrode processes giving rise to changes in impedance, in two different timescales. One such example of this is the work by Hitz and Lasia, who utilise EIS to examine porous nickel electrodes to identify the effects of porosity on the cell behaviour. They note a reduction in cell impedance due to charge transfer at high overpotentials, while the pore resistance remains independent of the overpotential, indicating that the movement of ions in and out of the pores creates an impedance that may not be circumvented, but nevertheless may not limit the application of the 192 | Electrochemistry, 2019, 15, 186–205

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

7

material since the contribution is so small. Indeed recent reports have suggested that, although the user can select several methods for fundamental understanding of electron transfer processes at porous electrodes, EIS is a favourable approach compared to methods such as chronoamperometry since the ohmic drop in porous electrodes can lead to potential dispersions under high current conditions.8 EIS on the other hand uses small potential perturbations and thus small current fluctuations are measured, which limits the effect of ohmic drop within porous substrates. This is especially pertinent in the case of electrode composite materials in coating and sensing applications, since the coatings are normally multi-faceted and contain porous networks where the electron transfer processes dominate. These three examples typify ideal behaviour. In practice, the capacitance elements are often replaced by the constant phase element, which represents a capacitor that deviates from ideal behaviour. There are several possible reasons for the capacitive component deviating from linearity, including different rate constants across the same material, surface deformations or undulations, or passivation of the electrode surface during experimentation. The profiles discussed within this section will form the basis of the literature reports that follow within this Chapter, which will now move on towards how EIS is implemented in electrode design for electrochemical sensors.

3

EIS in the design of electrochemical sensors

In the design of electrochemical sensors, EIS is utilised for both qualitative and quantitative purposes, although authors often preferentially report qualitative changes in the impedance profile resulting from certain electrode events, such as self-assembly or biorecognition. In the field of electrochemical sensors, where electrode designs comprise of several different features, the use of impedance emerges as a powerful tool to demonstrate the success of the construction of the electrode. For example, electrodes are often modified with carbon nanomaterials through methods such as self-assembly or drop-casting. Comparison of EIS spectra before and after immobilisation provides evidence of the ‘success’ of the immobilisation, since changes in impedance provide evidence of the surface change, and thus an argument to say that the immobilisation of the material is successful. This is equally true when adding a more complex component to an electrode surface, such as DNA, Nafion, or bovine serum albumin, where the introduction affects the interaction of the composite with its environment. Researchers routinely design electrodes such that they can target specific species through the use of agents such as ionophores, single stranded DNA, and antibodies/ antigens, where the success of the binding with the target species can be identified using EIS before and after the binding event through monitoring of the charge transfer resistances. EIS may also be utilised to assess the degradation of an electrode over time, since the charge transfer characteristics can perturb or augment as electrode constructs degrade. EIS therefore becomes a useful tool for understanding the Electrochemistry, 2019, 15, 186–205 | 193

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

changes in kinetics at electrode surfaces as a result of a variety of phenomena. The remainder of this section will focus on how researchers have used EIS in the design of electrochemical sensors, where it is often utilised as a way to prove successful electrode construction. Further information can be found in the review by Xu and Davis.9 Ferreira et al. used EIS to demonstrate the changes in electrode resistance resulting from several phases of electrode construction during the design of a sensor for b-nicotinamide adenine dinucleotide (NADH), while serving as an appropriate way to ensure adequate control of the electrode surface. Their sensor was constructed using a Glassy Carbon (GC) electrode, with a Graphene Oxide (GO) modification to efficiently link DNA to the electrode. In the production process, the graphene oxide and DNA strands are sonicated together in the presence of Methylene Blue (MB), which acts as a redox mediator for NADH. Interestingly, the proposed design utilises DNA not for its hybridisation ability, which is often seen with bioanalytical application of EIS,10 but as a biological matrix that improves the compatibility of the GO with the aqueous environment, while preventing the dissolution of MB, which is hydrophilic and thus difficult to anchor to the electrode. This creates a synergistic effect between the GO and the MB, where the electrical wiring ability of GO can be exploited using DNA as a ‘molecular wire casing’, the ends of which are tethered to the MB that acts as the redox mediator. The successful construction of the sensor was demonstrated using EIS.11 Fig. 4 depicts the Nyquist plots for the bare GC electrode, a graphenemodified GC electrode, a DNA and GO modified GC electrode, and finally

Fig. 4 EIS profiles for each sequential step of the electrode design process. The bare GC and graphene-modified electrodes do not significantly prevent the charge transfer process from occurring, although the diffusional impedance contribution is high at low frequency. The introduction of DNA intuitively increases the charge transfer resistance, while intercalation of methylene blue circumvents the resistive effects of the DNA, such that the overall charge transfer resistance of the electrode is very low. Parameters: ac amplitude ¼ 5 mV; frequency range ¼ 100 000–0.53 Hz; probe ¼ 1 mM Fe(CN)63/4 in 1 M KCl. Reproduced from ref. 11 with permission from Elsevier, Copyright 2013. 194 | Electrochemistry, 2019, 15, 186–205

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

a DNA, MB, and GO modified GC electrode. It is demonstrated that the incorporation of GO reduces the charge transfer resistance of the Fe(CN)63/4 redox couple, indicating a favourable interaction between oxygen-terminating species of GO and Fe(CN)63/4, while the addition of DNA significantly enhances the resistance, demonstrating the insulating nature of the DNA backbone. However, intercalation of the MB redox mediator allows a current signal to flow through the DNA/GO composite, as demonstrated in Fig. 4 by a significant reduction in the charge transfer resistance. The resultant electrode design is capable of observing charge transfer reactions within complex environments without the worry of electrode dissolution (degradation) into the aqueous environment, something that is commonly observed for a range of electrode constructs. The work also demonstrates that the addition of several layers of complexity doesn’t affect the electrochemical mechanism in any tangible way, since the shape of the Nyquist plot remains the same from the bare GC electrode through to the GO/DNA/MB composite electrode. This allows the electrodes to be comparable to one another, whereas a change in mechanism may limit the ability to compare the electrodes. Moving towards more recent applications, EIS has found some use in the understanding of the behaviour of metal/organic dyes such as iron phthalocyanine (FePc), which is a useful material for host–guest chemistry. Phthalocyanines have several applications (solar cells etc.), but recently they have been employed for the selective determination of drugs such as isoniazid, which is used as a treatment for tuberculosis despite concerns over its long-term carcinogenicity. Indeed, the amperometric measurements obtained in the paper by Spindola et al. demonstrate good analytical performance of FePc towards the drug, however it requires multi-walled carbon nanotubes (MWCNTs) to be grafted to the underlying electrode surface to connect the FePc to the electrode, and a covering of Nafions for electrode preservation purposes.12 The voltammetry in acetate buffer for the as-prepared sensor was thought to exhibit diffusionless voltammetry due to the surface confinement offered by Nafions, and thus the voltammetric repsonses were typical of the FePc complex itself. However, when the EIS assay was completed, the Nyquist plots indicated a mixed diffusional and kinetic regime towards Fe(CN)63/4. This demonstrates the ability of an inner-sphere redox probe to undergo charge transfer across a membrane such as Nafions, since a linear increase in total impedance in the low frequency zone was observed in the case of MWCNTs/FePc. Further, an approximate 50% decrease in the charge transfer resistance of the electrode was observed through EIS after electrode modification, which is beneficial for electrochemical sensors since it is important that the material can undergo charge transfer efficiently. This section has highlighted to utility of EIS for the purpose of building electrode materials. It is most certainly a powerful tool to demonstrate evidence of immobilisation of electrode layers, all of which contribute to electrochemical sensors in their own unique way. Conducting elements such as carbon nanomaterials often reduce the total impedance observed at an electrode surface, while elements like DNA that are incorporated for Electrochemistry, 2019, 15, 186–205 | 195

View Online Table 1 List of examples of research using EIS as a method to monitor the effectiveness of electrode construction and the corresponding sensory application. Electrode design

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

GC/MWCNT/PANI/MSA

a

Target molecule

Comments

Reference

Ascorbic acid

EIS evidence presented demonstrates no added benefit of using MWCNTs Both GO and MB offer demonstrable advantages to the sensor construction The work presents an optimal level of copolymer in a hydrogel to enhance electrode conductivity characteristics EIS used but explanation of the reasons why is lacking Demonstrates connective ability of MWCNTs and purported BR9 selectivity towards epinephrine Detection of acetaminophen and theophylline simultaneously Equivalent circuit fitting looks erroneous

35

GC/GO/DNA/MBb

NADH

GC/LAP/VBT/LOxc

Lactate

GC/PDPA/Ptd

Nitrite

GC/MWCNT/BR9e

Epinephrine

GC/EGR/ZnOf

Acetaminophen

GCE/Pan-LB/DNAg

Salbutamol

11

36

37 38

39

40

a

Glassy carbon, multi-walled carbon nanotubes, polyaniline, mercaptosuccinic acid. Glassy carbon, graphene oxide, deoxyribosenucleic acid, methylene blue. Glassy carbon, laponite, 4-vinylbenzene thymine, lactate oxidase. d Glassy carbon, polydiphenylamine, platinum nanoparticles. e Glassy carbon, multi-walled carbon nanotubes, basic red 9. f Glassy carbon, electropolymerised graphene, zinc oxide. g Glassy carbon, polyaniline, DNA. b c

their amphiphilic qualities are more resistive and provide increased impedances. The importance of the technique in a qualitative sense is therefore to observe a change, when compared to the bare electrode. There are countless examples of EIS as a tool to prove the stability of newly built electrodes; some recent examples are provided in Table 1. The next section will focus upon how EIS is used within electrochemical sensor assays, which is a EIS methodology that holds a plethora of different applications in medicinal, environmental, and food security applications.

4 The use of EIS in electrochemical sensor assays The pursuit of new point-of-care detection devices has sprung open several avenues of research for proponents of EIS. Point-of-care testing in a clinical setting is becoming more sought after, since savings are continually pursued to improve the operation of healthcare systems. However, healthcare applications are just one area that point-of-care devices may be useful. As will be seen in this section, certain antibody/antigen, DNA hybridisation, and aptamer sensor methods hold applications within environmental and food security issues as well as in clinical 196 | Electrochemistry, 2019, 15, 186–205

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

diagnostics. As a result, research is tailored towards designing point-ofcare tests for a range of simple chemical species, to more complex molecules and even proteins and microbes. In the case of clinical diagnostics, the overall purpose is to triage patients more quickly and limit the requirement for skilled personnel in laboratories. The latter is true for the case of environmental contamination and food security, where regulatory compliance issues bring a need for complex chemical detection techniques. Electrochemical methods, including EIS, may hold an advantage to take the lab to the scene of an environmental release, or contaminated foodstuffs. The difficulties faced with developing these ideas are tailoring the electrode surfaces towards the individual needs of the user. This section will discover some different methods of designing electrodes for EIS for the purpose of electrochemical sensors, most of which utilise an electrochemical assay as its general detection principle, which is a method where an electrode is immersed for a known period of time in a solution containing a target species before being removed and scanned using an electrochemical method (such as EIS) to identify surfaces changes. This section will discuss three different EIS methodologies and discuss some recent examples of each. The aforementioned methodologies incorporating EIS are generally split into categories ranging between immunosensors, oligonucleotide sensors and aptamer sensors, though this is not exhaustive.9 Each one of these types of sensors rely upon a specific biorecognition event unique to the target species, which otherwise would not occur in the presence of other interfering species. Immunosensors are a common detection strategy applicable to EIS that rely upon the specific interactions between antibodies and antigens. In a typical immunosensor, an electrode material is constructed such that the antibody is the outward facing component of the electrode/ electrolyte interface, and is achieved through methods such as dropcasting upon an electrode, through to more replicable methods such as self-assembly. Often nanomaterials are used as part of electrode composites since they can increase the number of surface sites available for antibody immobilisation, while providing larger surface areas to improve the transduction of current signals, improving the sensitivity of the sensors. The impedance data in the case of immunosensors is obtained as a result of exposure to the electrode to a matrix containing the corresponding antigen, which selectively binds to the antibody, creating an impedance effect at the electrode surface due to the selective binding that generally increases the impedance of charge transfer. Palomar et al. recently researched a EIS sensor for the determination of cholera in water samples, since it is still a prevalent disease in third world countries.13 Their sensor uses the filtration/disintegration method, where a nanomaterial (in this case MWCNTs), employed for its signal amplification properties, is filtered through a cellulose membrane highlighted in Fig. 5. The process of filtration through the membrane leaves the MWCNTs deposited upon the membrane, creating a replicable MWCNT network. The membrane is then shaped and inserted onto a Electrochemistry, 2019, 15, 186–205 | 197

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

Fig. 5 Top: electrode fabrication procedure for the impedimetric cholera detection platform reported by Palomar et al.13 Bottom: (A) normalised charge transfer resistance versus the logarithm of cholera antibody concentration using 1.6 mm (squares), 2.8 mm (triangles), and 4.0 mm (circles) thicknesses of MWCNTs. (B) Nyquist plots of the working electrode hybridised with increasing concentrations of cholera antibody (a ¼ bare; b–f ¼ 1013 to 105 g mL1). Reproduced from ref. 13 with permission from Elsevier, Copyright 2017.

working electrode before disintegration of the cellulose with a solvent. The MWCNT network offers a larger surface area for electropolymerisation of pyrrole on the working electrode, which is key for the chelation of copper ions at the electrode that provide anchor points for the detection unit, which is a form of cholera toxin that selectively binds to cholera antibodies. Upon incubating the electrode for 30 minutes with the target antibody, an electroanalytical method using impedance was realised (Fig. 5), since the hybridisation of the antibody/antigen complex provided a surface blocking mechanism that prevents the oxidation of the redox probe Fe(CN)63/4. It is immediately apparent from Fig. 5B that there are two electrochemical processes occurring within the 50 kHz to 0.2 Hz region, evidenced by the double humped Nyquist plots. However, the authors attribute the shape to a modified Randles circuit (see Fig. 3) with a charge transfer resistance and Warburg element in parallel with a double layer charging effect, which is an interpretation that is possibly incorrect. The plot more likely represents a mechanism combining 198 | Electrochemistry, 2019, 15, 186–205

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

diffusionless charge transfer combined with a resistance due to the porous nature of the MWCNT network, where the redox probe becomes trapped at the surface but is unable to provide a diffusional impedance within the low-frequency time domain. Instead, the redox probe becomes trapped at the surface such as in a thin-layer electrode effect. Returning to Fig. 5, it is apparent that the normalised charge transfer resistances increase with respect to hybridisation concentration, allowing the relative amounts of cholera to be identified in a water sample and therefore be used as an aid for water safety technology in the developing world. Similar detection philosophies are witnessed in abundance for a range of diseases including cardiovascular disorders,14 prostate cancer,15 Alzheimer’s disease,16 hepatitis C,17 and diabetes.18 Further authoritative commentary on immunosensors is provided in reviews by Ricci et al.19 and Byrne et al.20 Oligonucleotide sensors differ significantly from immunosensors since the sensory component of oligonucleotide sensors requires a specific DNA binding interaction to influence the transduction of the biorecognition event into an observable current. In order to achieve this, an electrode must be designed that can successfully harbour single-stranded DNA (ssDNA) in combination with some form of charge transfer element. Impedance is often the technique of choice for such sensors, since upon performing an assay with complimentary target DNA, the hybridisation event prevents charge transfer from occurring with the underlying surface. This phenomenon is monitored by observing changes in the charge transfer resistances at the electrode surface, which increase as a function of target DNA concentration in the assay. The oligonucleotide approach carried some drawbacks preventing large-scale manufacture of sensors, mainly surrounding the immobilisation of oligonucleotides onto the electrode surface. Affinity interactions or covalent bonding between oligonucleotides and electrodes were promising but issues of probe sequences to targets and leaching of probe molecules prevented mass producibility. Therefore, recent developments have focussed upon sequential construction of sensors using conducting polymers pregrafted to oligonucleotides to circumvent issues identified with previous sensor development technologies.21 Kerr-Phillips et al. use an oligonucleotide approach in their work that investigates the detection of the non-Hodgkin lymphoma gene for diagnosis of immune disorders.22 In their work, nitrile rubber spun-coated with a conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), is the working electrode base utilised to specifically target the gene. This construct was chosen due to the ability to spin-coat a fibre mat of this material into a workable, flexible, and conductive platform that can be exploited in electrochemical sensing applications with a good level of repeatability. The fibre mat must, however, be tailored specifically for the target species, and in this case the specificity is achieved through further electropolymerisation with a second conducting polymer, and subsequent immobilisation of oligonucleotides onto the active sites remaining using a conducting monomer-functionalised ssDNA oligonucleotide; the procedure is outlined in Fig. 6. Upon hybridisation for Electrochemistry, 2019, 15, 186–205 | 199

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

Fig. 6 Top: scheme of the fabrication of the oligonucleotide sensor described by KerrPhillips et al. Bottom: normalised charge transfer relationship as a function of electrochemical assay concentration. Reproduced from ref. 22 with permission from Elsevier, Copyright 2017.

1 hour at 42 1C in a solution containing the complimentary target ssDNA sequence for non-Hodgkins lymphoma, a 400-fold increase in detection limit is observed, to 1 aM (see Fig. 6), compared with previous reports. The attomolar concentration detection limit is observed in Fig. 6, where there is approximately double the change in charge transfer resistance observed for the oligonucleotide sensor compared to control experiments using phosphate buffer incubation rather than complimentary target ssDNA. The selectivity of the sensor is also reported to be enhanced beyond previous literature reports, with claims that the negatively charged carboxylic acid species used in the electrode design efficiently repel non-complimentary and mismatch ssDNA strands, which exhibit a maximum of 4.6% of the signal of the complimentary ssDNA. Oligonucleotide sensors coupled with EIS are not only applied in disease 200 | Electrochemistry, 2019, 15, 186–205

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

diagnosis, but in several areas of analytical sciences, for example within environmental monitoring of mercury,23 detection of radioactive compounds,24 and identification of inherited genetic disorders.25 Aptamer sensors utilise a sensing vehicle that is more complex in its nature than an immunosensor or an oligonucleotide sensor. Aptamers are complex networks of peptides or oligonucleotides that form a distinct shape that allows specific interactions with target molecules based upon the molecular configuration of the target species. They are suited to detecting larger molecules and bacteria, since the modus operandi of an aptamer sensor is that of shape recognition inducing a conformational change, thus creating a ‘‘barrier’’ effect at the electrode surface upon interaction with its target that can be observed as an increase in the electrochemical impedance.9 Aptamers are considered advantageous because they have a longer lifetime than antibodies and antigens, offer improved selectivity over many oligonucleotide sensors, and can be synthesized easily in the lab. Aptamer sensors are researched to detect E. Coli strains in fields such as water research, but often utilise indirect detection methods where the sensing element is not directly responsible for the signal output. However, one particular example of direct detection utilised an impedimetric aptamer sensor for the detection of E. coli O157:H7 in water samples, where immobilisation of the aptamer was achieved covalently through linkage using 3-mercaptopropyl-trimethoxysilane (known as a ‘‘molecular adhesive’’26) to TaSi2 electrodes (Fig. 7).27 The aptamers utilised, which contained a DNA probe for E. coli O157:H7 with a terminating disulfide bond, were self-assembled upon the exposed thiol group. Fig. 7 demonstrates a linear response to the bacterium in the range of 101– 105 cfu mL1, a linear range that could offer some diagnostic utility since the infection dose of E. coli O157:H7 is around 100 colony forming units. Fig. 7 also demonstrates that the aptamer sensor in this case could be argued to be selective towards the E. coli O157:H7 strain, since the observed charge transfer resistances (denoted as Rs) are overwhelmingly larger when the electrode is assayed with the target strain compared to non-target species. Another potential advantage of aptamer sensors is the ability to recycle the sensor and reuse multiple times. Indeed, in the previously quoted example, the authors show evidence that the sensor can be regenerated by immersing the ‘‘hybridised’’ sensors (i.e. sensor combined with target strain) in distilled water for 30 minutes at 80 1C. The process transfers the E. coli from the electrode to the water without denaturing the aptamer, which can then be reused, with no significant losses in impedance reported after two regenerations, though the %RSD increases. This work demonstrates that aptamer sensors can detect larger molecules with results within a suitable diagnostic range, though the next challenge for such work would be to mass produce the electrodes. Metal–organic frameworks are also utilised as anchorage units for aptamer sensors due to their high thermal and chemical stabilities, in addition to the ability of MOFs to interact with a range of small targeted molecules. Shi et al. reported a metal–organic framework synthesized Electrochemistry, 2019, 15, 186–205 | 201

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

Fig. 7 Top: aptamer sensor design procedure in the work reported by Brosel-Oliu et al.27 Bottom left: charge transfer resistance versus E. coli O157:H7 concentration in the electrochemical assay. Bottom right: demonstration of the aptamer sensor’s selectivity towards E. coli O157:H7. Reproduced from ref. 27 with permission from Elsevier, Copyright 2017.

from cerium ions and 2-aminoterephthalic acid that was used successfully as a base to harbour an aptamer for adenosine triphosphate (ATP).28 Their method found a linear range spanning five orders of magnitude (108–103 M) and a detection limit of 5.6 nM. The sensor was unusually simple for one of its kind since the synthesis was performed in one step, followed by hybridisation with ATP. MOFs have also been utilised for the detection of cocaine for drug enforcement applications with detection limits as low as 0.437 pg mL1. Interestingly in the case reported by Su et al., use of the MOF framework to harbour aptamers resulted in no change in the Nyquist profile over a 3 orders of magnitude concentration range. Furthermore, comparative experiments with the more commonly utilised differential pulse voltammetry approach showed that EIS returned a detection limit nearly 50% less than the case of DPV. Several other recent works on aptamer sensors focus on targets in a range of applications such as aldicarb for environmental monitoring purposes,29 Salmonella typhimurium for food security issues,30 determination of microplastic contamination,31 and clinical diagnostics.32 202 | Electrochemistry, 2019, 15, 186–205

View Online

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

5

Challenges facing EIS sensors

The previous sections of this work have discussed the utility of EIS and given some very recent examples and applications of the technique to several societal challenges. It is intuitive that such a technique, that can yield a vast amount of both qualitative and quantitative information, would have some applications in areas outside of academic research, following examples such as cyclic voltammetry, a technique much younger than EIS, which is utilised in clinical applications for the detection of glucose in blood. Yet EIS is not a technique that is used extensively in an applied sense, nor are its disadvantages fully understood at the present time. As MacDonald correctly points out in the abstract of their review on impedance in corrosion analysis: ‘‘The principal pitfall of the method is the tendency of many workers to analyze their data in terms of simple equivalent electrical circuits. . .’’33 which has been evident (and subsequently contested) in some of the recent works displayed within this chapter. While the utility of simple equivalent circuits itself is fine, there has to be a full philosophical process to support the reasoning for the use of an equivalent circuit, less a researcher could simply insert random equivalent circuit models through trial and error until one is stumbled upon that fits experimental data. This might not be considered entirely reasonable, logical, or academic, and is therefore a major drawback of EIS. One could then extend this argument to question why equivalent circuit models are needed at all, but experience suggests that it is both difficult and time-consuming to return quantitative data from EIS measurements without the use of equivalent circuit models. This is possibly one reason why voltammetric methods are consistently favoured for electrochemical sensors, but in cases where voltammetric methods see increased peak potentials with respect to concentration (as is the case in many host-guest interactions, MIPs, aptamers, etc.), EIS may find its niche. Another drawback to EIS is that the impedance profiles returned to the user are a summation of both the specific and non-specific binding that occurs at an electrode surface. Obviously, the aim of tailoring electrode surfaces is to allow the specificity of the electrode to a desired target species to increase to the point where the non-specific binding interactions are little or nil. Unfortunately, guaranteeing this phenomenon is not always simple. Aside from using immunosensors/oligonucleotides/ aptamers etc. other elements are often added to improve specificity to electrode materials, especially elements that prevent larger molecules from passivating electrode surfaces. Molecules such as bovine serum albumin or salmon sperm DNA are normally utilised as blocking agents for non-specific binding sites at electrode materials, which prevents false positive readings from occurring during data acquisition. Anti-fouling agents such as poly(ethylene glycol) are another route for preventing passivation.34 In the case of self-assembled oligonucleotide sensor design, where sulphur/gold chemistry is frequently utilised as a route for self-assembly, non-specific adsorption of ssDNA strands can occur at gold surfaces that create extra blocking of the surface; such molecules Electrochemistry, 2019, 15, 186–205 | 203

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online

can be chemically removed by incubating with 6-mercapto-1-hexanol after ssDNA assembly. Data acquisition time is one aspect of EIS that is unlikely to challenge voltammetric methods. While data acquisition can be speeded up if the low-frequency scan is truncated, this is limited to systems where the charge transfer occurs well within the medium to high frequency domain (over 1 Hz). One can always truncate the scan and predict charge transfer resistances using equivalent circuit modelling, but limiting the number of data points obtained severely limits the sensitivity and reliability of the presented data. In terms of the electrode designs themselves, there has been some shifts towards to use of MOFs to enhance durability, reliability, and selectivity of electrodes for both simple and more complex target species. The field needs to continue the good work in this area and continue to report sensors that can operate within complex matrices. Clinical diagnostics is a frequently researched area for EIS sensors but the technology requires to be reliable not just within ideal environments, but within biological samples too. Several methods have been witnessed within this Chapter to obviate complex molecules from affecting EIS traces, such as the use of filtration/disintegration, MIPs, and MOFs. Incorporating nanomaterials such as MWCNTs or graphene is now commonplace, but the technology hasn’t progressed beyond academia and into a workable solution due to selectivity issues within complex matrices. This is a challenge that EIS sensors must overcome in order for the technique to be truly viable on a grand scale.

References 1 2 3 4 5 6 7 8 9 10 11

12 13 14

A. J. Bard and L. R. Faulkner, Electrochemical Methods: Fundamentals and Applications, John Wiley & Sons Inc., USA, 2nd edn, 2001. J. H. Sluyters and J. J. C. Oomen, Recl. Trav. Chim. Pays-Bas, 1960, 79, 1101–1110. A. S. Bandarenka, Analyst, 2013, 138, 5540–5554. E. A. Franceschini, G. I. Lacconi and H. R. Corti, Int. J. Hydrogen Energy, 2016, 41, 3326–3338. O. M. S. Filipe and C. M. A. Brett, Electroanalysis, 2004, 16, 994–1001. R. Pei, Z. Cheng, E. Wang and X. Yang, Biosens. Bioelectron., 2001, 16, 355–361. C. Hitz and A. Lasia, J. Electroanal. Chem., 2001, 500, 213–222. J. Friedl and U. Stimming, Electrochim. Acta, 2017, 227, 235–245. Q. Xu and J. J. Davis, Electroanalysis, 2014, 26, 1249–1258. E. P. Randviir and C. E. Banks, Anal. Methods, 2013, 5, 1098–1115. G. M. M. Ferreira, F. M. de Oliveira, F. R. F. Leite, C. M. Maroneze, L. T. Kubota, F. S. Damos and R. D. C. S. Luz, Electrochim. Acta, 2013, 111, 543–551. R. F. Spindola, H. Zanin, C. S. Macena, A. Contin, R. D. C. S. Luz and F. S. Damos, J. Solid State Electrochem., 2017, 21, 1089–1099. Q. Palomar, C. Gondran, M. Holzinger, R. Marks and S. Cosnier, Biosens. Bioelectron., 2017, 97, 177–183. R. Pruna, F. Palacio, A. Baraket, N. Zine, A. Streklas, J. Bausells, A. Errachid ´pez, Biosens. Bioelectron., 2018, 100, 533–540. and M. Lo

204 | Electrochemistry, 2019, 15, 186–205

View Online

15 16

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

T. Vural, Y. T. Yaman, S. Ozturk, S. Abaci and E. B. Denkbas, J. Colloid Interface Sci., 2018, 510, 318–326. G.-Z. Garyfallou, O. Ketebu, S. -Sahin, B. E. Mukaetova-Ladinska, M. Catt and H. E. Yu, Sensors, 2017, 17. A. Valipour and M. Roushani, Microchim. Acta, 2017, 184, 2015–2022. F. Shao, L. Jiao, Q. Wei and H. Li, Microchim. Acta, 2017, 184, 2031–2038. F. Ricci, G. Volpe, L. Micheli and G. Palleschi, Anal. Chim. Acta, 2007, 605, 111–129. B. Byrne, E. Stack, N. Gilmartin and R. O’Kennedy, Sensors, 2009, 9. N. Aydemir, E. Chan, P. Baek, D. Barker, D. E. Williams and J. Travas-Sejdic, Biosens. Bioelectron., 2017, 97, 128–135. ¨m, T. E. Kerr-Phillips, N. Aydemir, E. W. C. Chan, D. Barker, J. Malmstro C. Plesse and J. Travas-Sejdic, Biosens. Bioelectron., 2018, 100, 549–555. A. Kamal, Z. She, R. Sharma and H.-B. Kraatz, Electrochim. Acta, 2017, 243, 44–52. ´rski, J. Electrochem. Soc., 2017, 164, B470–B475. A. Bala, J. Re ˛bis´ and Ł. Go S. Tripathy, S. R. Krishna Vanjari, V. Singh, S. Swaminathan and S. G. Singh, Biosens. Bioelectron., 2017, 90, 378–387. C. A. Goss, D. H. Charych and M. Majda, Anal. Chem., 1991, 63, 85–88. S. Brosel-Oliu, R. Ferreira, N. Uria, N. Abramova, R. Gargallo, ˜ oz-Pascual and A. Bratov, Sens. Actuators, B, 2018, 255, 2988–2995. F.-X. Mun P. Shi, Y. Zhang, Z. Yu and S. Zhang, Sci. Rep., 2017, 7, 6500. S. Li, C. Liu, B. Han, J. Luo and G. Yin, Microchim. Acta, 2017, 184, 1669–1675. S. Ranjbar, S. Shahrokhian and F. Nurmohammadi, Sens. Actuators, B, 2018, 255, 1536–1544. Y. Ma, J. Liu and H. Li, Biosens. Bioelectron., 2017, 92, 21–25. Z. A. Carter and R. Kataky, Sens. Actuators, B, 2017, 243, 904–909. D. D. Macdonald, Corrosion, 1990, 46, 229–242. J. S. Daniels and N. Pourmand, Electroanalysis, 2007, 19, 1239–1257. Y. Liu, Z. Su, Y. Zhang, L. Chen, T. Gu, S. Huang, Y. Liu, L. Sun, Q. Xie and S. Yao, J. Electroanal. Chem., 2013, 709, 19–25. ´pez, de Mishima and V. I. Paz Zanini, F. Tulli, D. M. Martino, B. Lo C. D. Borsarelli, Sens. Actuators, B, 2013, 181, 251–258. B. Unnikrishnan, P.-L. Ru, S.-M. Chen and V. Mani, Sens. Actuators, B, 2013, 177, 887–892. Y. Li, M. A. Ali, S.-M. Chen, S.-Y. Yang, B.-S. Lou and F. M. A. Al-Hemaid, Colloids Surf. B: Biointerfaces, 2014, 118, 133–139. L. Jiang, S. Gu, Y. Ding, F. Jiang and Z. Zhang, Nanoscale, 2014, 6, 207–214. L. Zou, Y. Li, S. Cao and B. Ye, Electroanalysis, 2014, 26, 1051–1058.

Electrochemistry, 2019, 15, 186–205 | 205

Published on 15 October 2018 on https://pubs.rsc.org | doi:10.1039/9781788013895-00186

View Online