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Editorial: Sensors and Biosensors
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Editorial: Sensors and Biosensors Robert J. Forster Current Opinion in Electrochemistry 2017, 3:1–3 For a complete overview see the Issue http://dx.doi.org/10.1016/j.coelec.2017.10.002 2451-9103/© 2017 Published by Elsevier B.V.
Robert J. Forster Dublin City University
Robert J. Forster holds the Personal Chair of Physical Chemistry within the School of Chemical Sciences at Dublin City University and is the Director of the National Centre for Sensor research. He received his Ph.D. in metallopolymer electrochemistry from Dublin City University in 1990 and is the author/co-author of more than 230 manuscripts and reviews. Forster’s research focuses on the creation of novel materials that have useful electronic or photonic properties because they are highly ordered on the molecular length scale. These materials are applied to molecule-based electronics, (bio)remediation catalysis and selective sensors for disease biomarkers with attomolar limits of detection.
The performance of electrochemical sensors, i.e., devices that determine the presence, concentration, or quantity of a given analyte using an electrochemical response, continues to improve especially in terms of selectivity, sensitivity and breadth of analytes [1]. The analytical challenge that contemporary sensors address can be extreme in terms of concentration (lower than 10−21 M) and selectivity, e.g., tens of thousands of potentially interfering proteins in the determination of a biomarker in whole blood. Other key performance criteria include long term stability, limit of detection, response time, power consumption, portability, degree of quantitative reliability (precision or accuracy), physical size, as well as cost. This collection of short reviews considers some of the most exciting recent innovations in materials, sensor configurations and applications that illustrate the power of contemporary electrochemical sensing. The global chemical sensors market is enjoying significant growth and is expected to exceed $20 billion by 2018 at a CAGR of 7.60% [2]. Electrochemical sensing shows the greatest rate of growth fuelled, in part, by rising demand for point-of-use testing and monitoring tools in the medical (global epidemic of diabetes), industrial, and environmental sectors. This growth is driven by both economic (lower cost analysis, decentralised testing) and increasing mandated testing. North America leads the market followed by Asia Pacific. As well as this market pull, innovations in (Nano)(Bio)Materials continue to provide a significant technological push towards the development of high performance (bio)chemical sensor systems capable of detecting multiple target analytes sensitively and selectively at low cost. For electrochemical sensing, these materials often feature large surface areas, low dimensions, excellent electron transfer properties and can be processed to build various sensor types. Graphene based materials that exhibit switchable chargecarrier mobility, induced by applying a potential or by target binding, are at the cutting edge of functional and chemically sensitive materials chemistry (Schumann, see pp 14-20). The conducting properties of these materials lends themselves to new sensing concepts and the rebirth of others, including solution-gated field effect transistors that use graphene or related substances as the gate material to sensitively and selectively detect biomolecules. One significant motivation to create new sensing materials is to enable advanced detection or transduction strategies. For example, electrochemiluminescence has particular advantages including high sensitivity due to the dark background and absence of optical excitation, portability and low power that lends itself particularly well to point-of-care testing devices (see
www.sciencedirect.com
Current Opinion in Electrochemistry 2017, 3:1–3
2
Guobao Xu, pp 7-13). One of the key advantages of spectroscopy is that a response can be measured throughout a 3D volume while electrochemical signal generation typically occurs only at the electrode/solution interface or within a relatively thin film. One particularly exciting development is the concept of bipolar or “wireless” electrochemiluminescent devices that allows light to be generated throughout a sample volume by using suspended electronically conducting, particles as “electrodes” whose potential is controlled through an electric field [3]. Systems of this type are likely to significantly influence the design of electrochemical sensor systems in the future. As well as advanced functional materials and detection strategies, the methodologies used to produce electrochemical sensors can significantly influence both their performance, cost, manufacturability and, potentially, overall impact. One of the major technologies for the low cost production of advanced electrochemical sensors is inkjet printing (Del Campo, see pp 32-42). This technique is attractive on the basis of cost and accessible lengthscale, but the inks must meet strict rheological conditions and often requires inkjet printing to be used in conjunction with other manufacturing techniques. A key feature is that photographic desktop printers could lead a future wave in the manufacture of advanced sensors, especially for development and prototyping stages. An important reason for investigating these low cost manufacturing strategies lies in the need for single use, disposable sensors, notably in the medical and food sectors (Killard, see pp 60-65). There is significant effort being invested in making these disposable devices more environmentally sustainable. Disposable devices are key where sterility must be maintained or (cross) contamination avoided. State-of-the-art devices range from dip-pen type sensors to integrated sample-to-answer sensor systems that allow complex measurements to be carried out in a low cost and efficient manner. In the same way that complex hardware, including sensors, and sophisticated software makes the smart phone universally useable, their increasing level of functional integration means that all an operator needs to do is introduce the sample and all reagent additions as well as wash and measurement steps are executed automatically. This integration is vitally important since it minimises the training/qualifications an operator needs to have in order to make the measurement. The combination of advanced materials, flexible low cost mass manufacturing techniques and sophisticated functionality, e.g., rapid, sensitive detection of multiple analytes, is having a profound impact on biomedical analysis in low resource environments (Ozoemena, see pp 54-59). Developing countries face particular challenges in providing effective medical care including highly decentralised delivery systems that often lack suitable high throughput instrumentation, significant additional disease burdens not found elsewhere, coupled to relatively low overall investment per capita. In this context, high-performance, lowCurrent Opinion in Electrochemistry 2017, 3:1–3
cost point-of-care (POC) biomedical electrochemical sensors integrated with digital mobile technologies open up the possibility of rapid and accurate diagnosis of disease and could help prevent additional outbreaks. However, large scale implementation of low-cost POC devices is not just a scientific challenge but requires alignment of government policy and mass manufacture of these low cost (profit) devices. Recently, significant new diversified application domains have emerged for electrochemical sensors. For example, the ability detect illicit substances in street and biological samples, ideally avoiding the need for a centralised lab, could significantly impact the proliferation of drugs of abuse, “drug” driving etc. (Dennany, see pp 26-31). Here, as well as the scientific challenges of delivering a statistically valid result within a physically robust platform and limited operator training, there are the added complications of potentially providing evidence for prosecution, chain of custody issues etc. that need to be considered. However, electrochemical sensors represent a powerful analytical tool for the forensic community. Increased awareness and interest in protecting the environment, minimising human exposure to toxic materials, government policy, e.g., the EU REACH initiative [4], and a desire to avoid animal testing are driving the development of new sensors for toxic chemicals (Hvastkovs, see pp 21-25). These sensors detect changes in cell metabolism or measure DNA damage upon exposure to the target of interest. Significantly, they can enable rapid, massively parallel detection and can effectively screen new organic chemicals, including lead pharmaceuticals, early in their development. Moreover, these electrochemical sensors can provide early indications of naturally occurring environmental threats. Electrochemical sensors are being used in increasingly imaginative ways with their structure being optimised to deliver the required performance under unusual conditions. For example, an important example of “wearable” sensors is the concept of the “smart bandage”. These devices can send early warnings for irregular bleeding, pH changes and markers of inflammation at wound site. Theranostic information is generated allowing optimum therapies and healing conditions to be identified. Particular challenges include the need for repeated, time course measurements without user intervention as well as disposability and the ability to sterilise. Chronic wounds represent a particularly powerful opportunity to use analytical information generated by an electrochemical sensor to reinstate the normal healing processes (Davis, see pp 43-48). This technology could be extended to “smart sutures” that incorporate nanoscale electrochemical sensors(particles) that could be electrochemically addressed wirelessly to collect diagnostic data in real time. www.sciencedirect.com
Editorial: Sensors and Biosensors Forster
While on-body or wearable sensors can provide a wealth of information, going inside the body has distinctive advantages. Simple, robust, and inexpensive implantable sensors could revolutionise the treatment of conditions ranging from diabetes (fully integrated artificial pancreas) to circulating “nanobots” that can detect and treat atherosclerosis or repair nerve damage (Wallace, see pp 7177). The development of implantable sensors is an incredibly challenging area requiring sensors that not only provide analytical information but are completely biocompatible, minimally invasive cost-effective, and have low power demands. Significant success has been achieved through deep collaborations of materials and analytical scientists with clinicians to share new design concepts and technological approaches optimised for real world application. In conclusion, this collection of reviews demonstrates that significant advances in materials, detection methodologies and manufacturing approaches are leading to high performance electrochemical sensors that are playing key roles in the medical, forensic and industrial sectors. Fundamentally, electrochemical sensors are emerging as a key building block in the Internet of Things (IoT) world. Challenges certainly remain to be solved including selectivity and stability especially in the harsh, somewhat unpredictable real world conditions. It is important that these “solved” issues continue to be addressed as significant progress is made in microfluidic devices that separate the components of a complex sample and then detect the individual analytes with sensitive, but nonselective, detectors, i.e., miniaturised, total analytical systems. For example, most of us will reach for an electrode to measure pH and think of it as one of the fields most robust and
www.sciencedirect.com
3
widely applicable sensors. However, the recent Wendy Schmidt Ocean Health XPRIZE, where the task was to provide reliable measurements of pH in the ocean environment, was awarded, not to any (electro)chemical sensor, but to a spectrophotometric device using meta-cresol purple as the indicator! Mass spectrometry is perhaps the most prominent technique that could potentially revolutionise separation-based, miniaturized chemical sensor systems. The low power demands of electrochemical sensors, and the ability of electrochemical fuel cells to generate power in situ, are powerful arguments in favour of electrochemical detection that need to continue to be emphasised. Arrays of electrochemical sensors, the simultaneous measurement of multiple parameters (both Faradaic and nonFaradaic) coupled with mathematical deconvolution of multiple responses from arrays of (imperfectly) selective sensors continues to merit investigation. We hope that you find the contributions that reflect recent advances in the state of the art, identify some challenges and hopefully help signpost future opportunities, interesting and useful! References 1. Mehrotra P: “Biosensors and their applications – A review”. J. Oral Biol. and Craniofac. Res. 2016, 6(2):153–159. 2. Research and Markets, “Global Chemical Sensors Market - Growth, Trends & Forecasts (2014-2020)”. 3. Sequeira CAC, Cardoso DSP, Lurdes M, Gameiro F: “Bipolar Electrochemistry, a Focal Point of Future Research”. Chem.Eng. Commun. 2016, 203:8. 4. https://echa.europa.eu/regulations/reach accessed June 30, 2017.
Current Opinion in Electrochemistry 2017, 3:1–3
Editorial: Sensors and Biosensors Robert J. Forster Current Opinion in Electrochemistry 2017, 3:1–3 For a complete overview see the Issue http://dx.doi.org/10.1016/j.coelec.2017.10.002 2451-9103/© 2017 Published by Elsevier B.V.
Robert J. Forster Dublin City University
Robert J. Forster holds the Personal Chair of Physical Chemistry within the School of Chemical Sciences at Dublin City University and is the Director of the National Centre for Sensor research. He received his Ph.D. in metallopolymer electrochemistry from Dublin City University in 1990 and is the author/co-author of more than 230 manuscripts and reviews. Forster’s research focuses on the creation of novel materials that have useful electronic or photonic properties because they are highly ordered on the molecular length scale. These materials are applied to molecule-based electronics, (bio)remediation catalysis and selective sensors for disease biomarkers with attomolar limits of detection.
The performance of electrochemical sensors, i.e., devices that determine the presence, concentration, or quantity of a given analyte using an electrochemical response, continues to improve especially in terms of selectivity, sensitivity and breadth of analytes [1]. The analytical challenge that contemporary sensors address can be extreme in terms of concentration (lower than 10−21 M) and selectivity, e.g., tens of thousands of potentially interfering proteins in the determination of a biomarker in whole blood. Other key performance criteria include long term stability, limit of detection, response time, power consumption, portability, degree of quantitative reliability (precision or accuracy), physical size, as well as cost. This collection of short reviews considers some of the most exciting recent innovations in materials, sensor configurations and applications that illustrate the power of contemporary electrochemical sensing. The global chemical sensors market is enjoying significant growth and is expected to exceed $20 billion by 2018 at a CAGR of 7.60% [2]. Electrochemical sensing shows the greatest rate of growth fuelled, in part, by rising demand for point-of-use testing and monitoring tools in the medical (global epidemic of diabetes), industrial, and environmental sectors. This growth is driven by both economic (lower cost analysis, decentralised testing) and increasing mandated testing. North America leads the market followed by Asia Pacific. As well as this market pull, innovations in (Nano)(Bio)Materials continue to provide a significant technological push towards the development of high performance (bio)chemical sensor systems capable of detecting multiple target analytes sensitively and selectively at low cost. For electrochemical sensing, these materials often feature large surface areas, low dimensions, excellent electron transfer properties and can be processed to build various sensor types. Graphene based materials that exhibit switchable chargecarrier mobility, induced by applying a potential or by target binding, are at the cutting edge of functional and chemically sensitive materials chemistry (Schumann, see pp 14-20). The conducting properties of these materials lends themselves to new sensing concepts and the rebirth of others, including solution-gated field effect transistors that use graphene or related substances as the gate material to sensitively and selectively detect biomolecules. One significant motivation to create new sensing materials is to enable advanced detection or transduction strategies. For example, electrochemiluminescence has particular advantages including high sensitivity due to the dark background and absence of optical excitation, portability and low power that lends itself particularly well to point-of-care testing devices (see
www.sciencedirect.com
Current Opinion in Electrochemistry 2017, 3:1–3
2
Guobao Xu, pp 7-13). One of the key advantages of spectroscopy is that a response can be measured throughout a 3D volume while electrochemical signal generation typically occurs only at the electrode/solution interface or within a relatively thin film. One particularly exciting development is the concept of bipolar or “wireless” electrochemiluminescent devices that allows light to be generated throughout a sample volume by using suspended electronically conducting, particles as “electrodes” whose potential is controlled through an electric field [3]. Systems of this type are likely to significantly influence the design of electrochemical sensor systems in the future. As well as advanced functional materials and detection strategies, the methodologies used to produce electrochemical sensors can significantly influence both their performance, cost, manufacturability and, potentially, overall impact. One of the major technologies for the low cost production of advanced electrochemical sensors is inkjet printing (Del Campo, see pp 32-42). This technique is attractive on the basis of cost and accessible lengthscale, but the inks must meet strict rheological conditions and often requires inkjet printing to be used in conjunction with other manufacturing techniques. A key feature is that photographic desktop printers could lead a future wave in the manufacture of advanced sensors, especially for development and prototyping stages. An important reason for investigating these low cost manufacturing strategies lies in the need for single use, disposable sensors, notably in the medical and food sectors (Killard, see pp 60-65). There is significant effort being invested in making these disposable devices more environmentally sustainable. Disposable devices are key where sterility must be maintained or (cross) contamination avoided. State-of-the-art devices range from dip-pen type sensors to integrated sample-to-answer sensor systems that allow complex measurements to be carried out in a low cost and efficient manner. In the same way that complex hardware, including sensors, and sophisticated software makes the smart phone universally useable, their increasing level of functional integration means that all an operator needs to do is introduce the sample and all reagent additions as well as wash and measurement steps are executed automatically. This integration is vitally important since it minimises the training/qualifications an operator needs to have in order to make the measurement. The combination of advanced materials, flexible low cost mass manufacturing techniques and sophisticated functionality, e.g., rapid, sensitive detection of multiple analytes, is having a profound impact on biomedical analysis in low resource environments (Ozoemena, see pp 54-59). Developing countries face particular challenges in providing effective medical care including highly decentralised delivery systems that often lack suitable high throughput instrumentation, significant additional disease burdens not found elsewhere, coupled to relatively low overall investment per capita. In this context, high-performance, lowCurrent Opinion in Electrochemistry 2017, 3:1–3
cost point-of-care (POC) biomedical electrochemical sensors integrated with digital mobile technologies open up the possibility of rapid and accurate diagnosis of disease and could help prevent additional outbreaks. However, large scale implementation of low-cost POC devices is not just a scientific challenge but requires alignment of government policy and mass manufacture of these low cost (profit) devices. Recently, significant new diversified application domains have emerged for electrochemical sensors. For example, the ability detect illicit substances in street and biological samples, ideally avoiding the need for a centralised lab, could significantly impact the proliferation of drugs of abuse, “drug” driving etc. (Dennany, see pp 26-31). Here, as well as the scientific challenges of delivering a statistically valid result within a physically robust platform and limited operator training, there are the added complications of potentially providing evidence for prosecution, chain of custody issues etc. that need to be considered. However, electrochemical sensors represent a powerful analytical tool for the forensic community. Increased awareness and interest in protecting the environment, minimising human exposure to toxic materials, government policy, e.g., the EU REACH initiative [4], and a desire to avoid animal testing are driving the development of new sensors for toxic chemicals (Hvastkovs, see pp 21-25). These sensors detect changes in cell metabolism or measure DNA damage upon exposure to the target of interest. Significantly, they can enable rapid, massively parallel detection and can effectively screen new organic chemicals, including lead pharmaceuticals, early in their development. Moreover, these electrochemical sensors can provide early indications of naturally occurring environmental threats. Electrochemical sensors are being used in increasingly imaginative ways with their structure being optimised to deliver the required performance under unusual conditions. For example, an important example of “wearable” sensors is the concept of the “smart bandage”. These devices can send early warnings for irregular bleeding, pH changes and markers of inflammation at wound site. Theranostic information is generated allowing optimum therapies and healing conditions to be identified. Particular challenges include the need for repeated, time course measurements without user intervention as well as disposability and the ability to sterilise. Chronic wounds represent a particularly powerful opportunity to use analytical information generated by an electrochemical sensor to reinstate the normal healing processes (Davis, see pp 43-48). This technology could be extended to “smart sutures” that incorporate nanoscale electrochemical sensors(particles) that could be electrochemically addressed wirelessly to collect diagnostic data in real time. www.sciencedirect.com
Editorial: Sensors and Biosensors Forster
While on-body or wearable sensors can provide a wealth of information, going inside the body has distinctive advantages. Simple, robust, and inexpensive implantable sensors could revolutionise the treatment of conditions ranging from diabetes (fully integrated artificial pancreas) to circulating “nanobots” that can detect and treat atherosclerosis or repair nerve damage (Wallace, see pp 7177). The development of implantable sensors is an incredibly challenging area requiring sensors that not only provide analytical information but are completely biocompatible, minimally invasive cost-effective, and have low power demands. Significant success has been achieved through deep collaborations of materials and analytical scientists with clinicians to share new design concepts and technological approaches optimised for real world application. In conclusion, this collection of reviews demonstrates that significant advances in materials, detection methodologies and manufacturing approaches are leading to high performance electrochemical sensors that are playing key roles in the medical, forensic and industrial sectors. Fundamentally, electrochemical sensors are emerging as a key building block in the Internet of Things (IoT) world. Challenges certainly remain to be solved including selectivity and stability especially in the harsh, somewhat unpredictable real world conditions. It is important that these “solved” issues continue to be addressed as significant progress is made in microfluidic devices that separate the components of a complex sample and then detect the individual analytes with sensitive, but nonselective, detectors, i.e., miniaturised, total analytical systems. For example, most of us will reach for an electrode to measure pH and think of it as one of the fields most robust and
www.sciencedirect.com
3
widely applicable sensors. However, the recent Wendy Schmidt Ocean Health XPRIZE, where the task was to provide reliable measurements of pH in the ocean environment, was awarded, not to any (electro)chemical sensor, but to a spectrophotometric device using meta-cresol purple as the indicator! Mass spectrometry is perhaps the most prominent technique that could potentially revolutionise separation-based, miniaturized chemical sensor systems. The low power demands of electrochemical sensors, and the ability of electrochemical fuel cells to generate power in situ, are powerful arguments in favour of electrochemical detection that need to continue to be emphasised. Arrays of electrochemical sensors, the simultaneous measurement of multiple parameters (both Faradaic and nonFaradaic) coupled with mathematical deconvolution of multiple responses from arrays of (imperfectly) selective sensors continues to merit investigation. We hope that you find the contributions that reflect recent advances in the state of the art, identify some challenges and hopefully help signpost future opportunities, interesting and useful! References 1. Mehrotra P: “Biosensors and their applications – A review”. J. Oral Biol. and Craniofac. Res. 2016, 6(2):153–159. 2. Research and Markets, “Global Chemical Sensors Market - Growth, Trends & Forecasts (2014-2020)”. 3. Sequeira CAC, Cardoso DSP, Lurdes M, Gameiro F: “Bipolar Electrochemistry, a Focal Point of Future Research”. Chem.Eng. Commun. 2016, 203:8. 4. https://echa.europa.eu/regulations/reach accessed June 30, 2017.
Current Opinion in Electrochemistry 2017, 3:1–3