- Email: [email protected]
Portable electrochemical systems
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trends in analytical chemistry, vol. 21, no. 4, 2002
Portable electrochemical systems Joseph Wang* Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USA
Electroanalysis offers tremendous promise for scaling down analytical systems, with features that include high sensitivity, inherent miniaturization, low cost, low-power requirements, and high compatibility with advanced micromachining and microfabrication technologies. This article reviews the development of portable electrochemical analyzers for near-patient clinical testing, for on-site environmental monitoring, and for decentralized genetic testing. There is discussion of the challenges of creating a true ‘Lab-on-a-Chip’ and of integrating multiple electrochemical techniques and sensing schemes into a compact hand-held meter. Such microscale electrochemical systems hold great promise for meeting the needs and challenges of analytical chemistry in the twenty-first century. # 2002 Published by Elsevier Science B.V. All rights reserved.
chemical analyzers offer tremendous potential for obtaining the desired analytical information in a faster, simpler (‘user-friendly’) and cheaper manner than do traditional laboratory-based assays. This article highlights recent advances, trends, and applications of miniaturized electrochemical systems. There is discussion of several representative examples that illustrate the scope, power, and versatility of microscale electrochemical devices and systems. Readers are referred to books for a comprehensive information on electrochemical systems [1,2].
Keywords: Electrochemistry; Miniaturization; Portable systems; DNA chips; Lab-on-a-Chip
Hand-held glucose meters, widely used for home (personal) diabetes testing, represent the best example of a (commercially) successful miniaturized electrochemical device. The majority of personal blood-glucose meters are based on disposable enzyme electrode test strips. Such single-use electrode strips are mass produced by the thick-film (screen-printing) microfabrication technology. Each strip contains the printed working and reference electrodes, with the former coated with the necessary reagents (enzyme, mediator, stabilizer and linking agent). These reagents are commonly dispensed by inkjet printing. A counter and an additional (‘baseline’) working electrode may also be included. Such single-use devices get round problems of carry over, contamination, or drift. The control meter is typically light, small (pocket-sized) and battery-operated, and relies on a potential-step (chronoamperometric) operation. Such devices offer great promise for obtaining the desired clinical information in a
1. Introduction Miniaturization is a growing trend in the field of analytical chemistry. Electrochemistry is particularly attractive for microscale analysis, as it can be miniaturized and multiplexed without compromising its capabilities. The portable nature and low power demands of electrochemical analyzers [1,2] satisfy many of the requirements for on-site and in-situ measurements. Modern microfabrication technologies allow us to replace the traditional bulky electrodes and cumbersome cells with easy-touse miniaturized electrochemical systems. Such portable (hand-held), battery-powered, electro*Tel.: +1 (505) 646-2505; fax: +1 (505) 646-2649. E-mail: [email protected]
0165-9936/02/$ - see front matter PII: S0165-9936(02)00402-8
2. Decentralized clinical diagnostics 2.1. In-vitro glucose testing
# 2002 Published by Elsevier Science B.V. All rights reserved.
227
trends in analytical chemistry, vol. 21, no. 4, 2002
fast, simple manner. The first product was a pen-style device (ExacTech), launched by MediSense, Inc. in 1987; it used a ferrocene-derivative mediator. Various commercial strips and pocket-sized test meters, for self-monitoring of blood glucose – based on the use of ferricyanide or ferrocene mediators – have since been introduced [3,4]. In all cases, the diabetic patient pricks the finger, places the small blood droplet on the sensor strip, and obtains the blood-glucose concentration (on a liquid-crystal display) in 15–30 s. In addition to their small size and fast response, such modern personal glucose meters have other features, such as extended memory and computer downloading. Non-invasive approaches for continuous glucose monitoring represent a promising route for getting round the challenges of implantable devices or the inconvenience of finger-stick sampling. In particular, Cygnus, Inc. has developed an attractive, wearable glucose monitor, based on the coupling of reverse iontophoretic collection of glucose and biosensor functions [5]. The new GlucoWatch Biographer (Fig. 1) provides three glucose readings per hour for up to 12 h (36 readings in a 12 h period). The system can measure the electroosmotically extracted glucose and track bloodglucose changes with good clinical accuracy. An alarm capability is included to alert the individual to very low or high glucose levels. The complete electronics, including the iontophore-
tic galvanostat, the dual-sensor bipotentiostat, the control circuitry, microprocessor, and LCD display, are packaged in wristwatch format, which is powered by a single AAA battery.
2.2. Miniaturized multi-analyte devices The success of pocket-sized blood-glucose monitors has stimulated tremendous interest in new devices offering a panel of blood tests at the patient’s side or valuable real-time information on key metabolites or drugs. One successful example is the i-STAT Portable Clinical Analyzer that performs simultaneously eight common clinical tests on a 60 ml patient blood in about 90 s [6]. These tests are based on various enzyme electrodes, gas sensors, or ionselective electrodes, connected to both amperometric and potentiometric detection schemes. Fig. 2 displays a cross-sectional view of the iSTAT electrolyte/gas sensor cartridge. The disposable cartridge contains a series of thin-film electrodes microfabricated on a silicon chip. Once the cartridge is inserted into the hand-held meter, the analytical procedure is carried out under automatic control. Upon completion of the assay, the results are displayed on a liquid-crystal screen, along with the patient-identification number and the time. The unit has been adopted by over 1000 hospitals, and has been utilized in remote locations, including the microgravity environment of space
Fig. 1. Various components of the GlucoWatch Biographer (Courtesy of Cygnus, Inc).
228
Fig. 2. Design of the disposable sensor-array cartridge used in the I-STAT Portable Clinical Analyzer. (Courtesy of i-STAT Corporation).
flight [7]. Extension of the unit to further critical blood chemistries is anticipated.
3. Instant electrical detection of DNA Wide-scale genetic testing requires the development of easy-to-use, fast, compact DNA analyzers. Electrochemical devices are ideally suited to shrinking DNA diagnostics and meeting future requirements of large-scale genetic testing. In addition to meeting the size and
trends in analytical chemistry, vol. 21, no. 4, 2002
power requirements of decentralized DNA testing, they offer elegant routes for interfacing (at the molecular level) nucleic acid systems and electrical devices. Recent efforts have led to the development of portable electrochemical analyzers for electrical detection of DNA hybridization [8,9]. Such devices rely on the conversion of the DNA base-pair recognition event into a useful electrical signal in connection with various label and label-free electrochemical transduction schemes. Elegant strategies for such direct electrical reading of DNA hybridization and for amplifying the hybridization signal have been developed in a number of laboratories [8,9]. Several innovative ideas have already reached the marketplace. One example is the compact gene-expression electrical system of Xanthon, which uses electrocatalytic detection of the DNA hybridization, based on oxidation of the target guanine nucleobase by a soluble metal mediator. This assay employs a 96-well microtiter-plate format, with each well containing seven separate probe-coated indium-tin-oxide electrodes (two of which are used as controls). A single microtiter plate thus allows 672 measurements (480 tests and 192 controls). Another example is Motorola Inc.’s CMS eSensor DNA chip platform that can detect up to 48 different sequences in connection with elegant surface chemistry (combining self-assembly of thiolated probes, phenylacetylene ‘molecular wires’ and the use of a ferrocene label) [10]. Coupling of mass-producible thick-film DNA biosensors with hand-held, battery-operated chronopotentiometric analyzers has also been reported [11]. Advances in micromachining technology will lead to the integration of electrochemical sensor gene arrays with sample clean-up, DNA extraction and amplification, and separation on a microchip platform (as discussed in the next section). On-going fundamental studies on nucleic-acid electrochemistry and on new signal transduction/amplification strategies, coupled to extensive commercialization, should have a tremendous impact on decentralized genetic testing.
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trends in analytical chemistry, vol. 21, no. 4, 2002
4. Lab-on-a-Chip based on electrochemical detection The development of microscale (chip-based) separation devices, particularly micromachined capillary electrophoresis (CE) systems, has experienced explosive growth in recent years. Such miniaturized devices represent the ability to shrink conventional ‘bench-top’ analytical systems to yield major advantages in speed, cost, portability, and solvent and sample consumption. As the field of chip-based separation microsystems continues its rapid growth, there is an urgent need to develop compatible detection modes. Much of the work on CE microchips uses laser-induced fluorescence (LIF) detection. Yet, LIF detection requires a large, expensive off-chip supporting optical system that greatly compromises the benefits of miniaturization and portability. Electrochemical detection has recently attracted considerable interest for miniaturized analytical systems [12,13]. Electrochemistry (EC) holds great promise for such microsystems, as it offers: high sensitivity (approaching that of fluorescence); inherent miniaturization of both the detector and control instrumentation; independence of optical path length or sample turbidity; low cost; low-power requirements; and, high compatibility with advanced micromachining and microfabrication technologies. Various detector configurations, based on different capillary/working-electrode arrangements and the position of the electrode relative to the flow direction, have been proposed to meet these requirements (Fig. 3). Placing the working electrode just outside the exit of the separation channel results in self isolation from the high separation potential, owing to the dramatic drop of the potential across the capillary. The practical utility of such CE-EC microfluidic systems has been demonstrated for the on-chip separation and detection of nucleic acids, catecholamine neurotransmitters, nitroaromatic explosives, organophosphate pesticides, or chlorophenol compounds. The complete selfcontained microsystem (a true ‘Lab-on-a-Chip’) will be realized through an on-chip integration
of the potentiostatic (control) circuitry and additional functional elements (performing steps such as clean-up, preconcentration, or derivatization reactions). For example, fast-responding, field-deployable explosive or nerve-agent analyzers, providing a timely warning and alarm (in case of sudden concentration change), are being developed in our laboratory. It is expected that electrochemical detection will become a powerful tool for microscale analytical systems and will facilitate the creation of truly portable (and possibly disposable) devices.
5. Portable metal analyzers A major incentive for the introduction of disposable stripping-based metal sensors has been
Fig. 3. Common configurations of electrochemical detectors for capillary-electrophoresis microchips, based on different capillary/working-electrode arrangements and the position of the electrode (W) relative to the flow direction: (A) flow by (using two plates); (B) flow onto (with the surface normal to the flow direction); (C) flow through (with the detector placed directly on the channel exit).
230
the initiative of the US Centers for Disease Control (CDC) aimed at large-scale screening of lead in children’s blood. Such an extensive screening program requires portable, yet highly reliable blood-lead-measurement systems. Atomic spectroscopic techniques, commonly used for measuring trace metals in the central laboratory, are not suitable for use in on-site assays. Electrochemical stripping analysis has always been recognized as a powerful tool for measuring trace metals [1]. Its remarkable sensitivity is attributed to the ‘built-in’ preconcentration step, during which the target metals are accumulated onto the working electrode. The portable instrumentation and the low-power demands of stripping analysis satisfy many of the requirements for on-site and in-situ measurements of trace metals. Portable (hand-held), battery-powered, easy-to-use stripping analyzers have thus been developed [14]. These hand-held stripping meters have incorporated disposable screenprinted electrodes [15]. Micromachined metal analyzers, integrating fluid-handling silicon microstructures and an on-chip three-electrode system, represent a significant departure from existing (laboratorybased) flow stripping systems in that they are extremely small, mass produced and require minimal amounts of sample and reagent. Such miniaturized stripping flow analyzers thus allow testing for trace metals to be performed more reliably, easily and inexpensively in a field setting. One such microsystem consists of vertically-aligned functional modules (each 1 inch square), stacked on top of each other, including the sample and reagent reservoirs, two micropumps, mixer, reaction coil, and a flow detector (Fig. 4) [14]. As required for adsorptive stripping measurements (based on the formation and detection of metal chelates), the sample and reagent are thus brought together, mixed, and allowed to react in a reproducible manner.
6. ‘Lab-on-a-Cable’ Environmental chemists are still limited by having to arrange for samples to be collected in
trends in analytical chemistry, vol. 21, no. 4, 2002
Fig. 4. View of a stacked micromachined flow system for adsorptive stripping monitoring of trace metals, based on vertically aligned functional modules (reproduced from [14]).
the field and then transported to a centralized laboratory for analysis. An attractive route that circumvents the cost, delays, and contamination risks of such centralized environmental analysis involves moving the laboratory to the field. In particular, the ability to perform in-situ various steps of an analytical protocol should have an enormous impact on pollution control and prevention. Automated shipboard electrochemical flow analyzers were developed during the 1970s [16]. Our recent activity has led to the development of submersible electrochemical analyzers [17]. As opposed to current in-situ sensors (that lack the sample-preparation steps essential for optimal analytical performance), the new on-cable automated microanalyzer incorporates several functions into a single, sealed, submersible package. The first generation of this submersible microlaboratory integrates microdialysis sampling, with reservoirs for the reagent, waste, and calibration/standard solution, along with the
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trends in analytical chemistry, vol. 21, no. 4, 2002
micropump and necessary fluidic network on a cable platform (Fig. 5). The sample and reagent are thus brought together, mixed, and allowed to react in a reproducible manner. Future generations will accommodate additional functions (such as preconcentration, filtration and extraction) to address the needs of complex environmental samples as well as compact, low-powered, automated instrumentation for unattended operation, ‘smart’
data processing, and signal transmission (via satellite links). Such a stand-alone ‘microlaboratory’ can be submersed directly in the environmental sample, to provide real-time continuous information on a wide range of priority pollutants. The utility of such a ‘Lab-ona-Cable’ has been demonstrated for stripping monitoring of trace metals or in-situ biosensing of phenols and various enzyme inhibitors.
7. Conclusions and prospects Electrochemical devices are receiving a major share of attention in the development of portable analytical systems. The above examples illustrate the scope, power, and versatility of such miniaturized analyzers. As we enter the twenty-first century, we no longer rely on cumbersome electrochemical cells and bulky electrodes, but rather fast, small, easy-to-use electrochemical systems. In the near future, we can expect even smaller and more sophisticated portable analyzers that integrate many steps of the analytical protocol with the electrical detection on credit-card-sized platforms. Given the impressive progress in portable electrochemical systems, there is no doubt that they will have major impact on point-of-care clinical diagnostics, decentralized genetic testing, and on-site environmental and industrial monitoring. Acknowledgements Financial support from the National Institutes of Health and the Office of Naval Research is gratefully acknowledged.
References Fig. 5. Schematic diagram of the electrochemical ‘Lab-ona-Cable’ system. (A) Cable connection; (B) micropump; (C) reservoirs for reagent and waste solutions; (D) microdialysis sampling tube and an (E,F) electrochemical flow detector, with working and reference electrodes, respectively. (Reproduced with permission from [17]).
[1] J. Wang, Analytical Electrochemistry, Wiley-VCH, New York, 2000. [2] P.T. Kissinger, W.R. Heineman, Laboratory Techniques in Electroanalytical Chemistry, Dekker, New York, 1996. [3] M. Green, P. Hilditch, Anal. Proc. 28 (1991) 374. [4] M. Shichiri, Y. Yamasaki, N. Hakui, H. Abe, Lancet 2 (1982) 1129.
232
[5] M. Tierney, H. Kim, M. Burns, J. Tamada, R. Potts, Electroanalysis 12 (2000) 666. [6] K. Erickson, P. Wilding, Clin. Chem. 39 (1993) 283. [7] S.M. Smith, J. Davis-Street, T. Fontenot, H. Lane, Clin. Chem. 43 (1997) 1056. [8] E. Palecek, M. Fojta, Anal. Chem. 3 (2001) 75A. [9] J. Wang, Chem. Eur. J. 5 (1999) 1681. [10] R. Umek, S. Lin, Y. Chen, B. Irvine, C. Paulluconi, V. Chan, Y. Chong, L. Cheung, J. Vielmetter, D. Farkas, Molecular Diagnosis 5 (2000) 321. [11] J. Wang, X. Cai, B. Tian, H. Shiraishi, Analyst 121 (1996) 965.
trends in analytical chemistry, vol. 21, no. 4, 2002
[12] A. Woolley, K. Lao, A. Glazer, R. Mathies, Anal. Chem. 70 (1998) 684. [13] J. Wang, B. Tian, E. Sahlin, Anal. Chem. 71 (1999) 5436. [14] J. Wang, B. Tian, J. Lu, C. Olsen, C. Yarnitsky, K. Olsen, D. Hammerstrom, W. Bennett, Anal. Chim. Acta 385 (1999) 429. [15] J. Wang, B. Tian, Anal. Chem. 64 (1992) 1706. [16] A. Zirino, S. Lieberman, C. Clavell, Env. Sci. Tech. 12 (1978) 73. [17] J. Wang, J. Lu, B. Tian, S. Ly, M. Vuki, W. Adeniyi, R. Armennderiz, Anal. Chem. 72 (2000) 2659.
trends in analytical chemistry, vol. 21, no. 4, 2002
Portable electrochemical systems Joseph Wang* Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USA
Electroanalysis offers tremendous promise for scaling down analytical systems, with features that include high sensitivity, inherent miniaturization, low cost, low-power requirements, and high compatibility with advanced micromachining and microfabrication technologies. This article reviews the development of portable electrochemical analyzers for near-patient clinical testing, for on-site environmental monitoring, and for decentralized genetic testing. There is discussion of the challenges of creating a true ‘Lab-on-a-Chip’ and of integrating multiple electrochemical techniques and sensing schemes into a compact hand-held meter. Such microscale electrochemical systems hold great promise for meeting the needs and challenges of analytical chemistry in the twenty-first century. # 2002 Published by Elsevier Science B.V. All rights reserved.
chemical analyzers offer tremendous potential for obtaining the desired analytical information in a faster, simpler (‘user-friendly’) and cheaper manner than do traditional laboratory-based assays. This article highlights recent advances, trends, and applications of miniaturized electrochemical systems. There is discussion of several representative examples that illustrate the scope, power, and versatility of microscale electrochemical devices and systems. Readers are referred to books for a comprehensive information on electrochemical systems [1,2].
Keywords: Electrochemistry; Miniaturization; Portable systems; DNA chips; Lab-on-a-Chip
Hand-held glucose meters, widely used for home (personal) diabetes testing, represent the best example of a (commercially) successful miniaturized electrochemical device. The majority of personal blood-glucose meters are based on disposable enzyme electrode test strips. Such single-use electrode strips are mass produced by the thick-film (screen-printing) microfabrication technology. Each strip contains the printed working and reference electrodes, with the former coated with the necessary reagents (enzyme, mediator, stabilizer and linking agent). These reagents are commonly dispensed by inkjet printing. A counter and an additional (‘baseline’) working electrode may also be included. Such single-use devices get round problems of carry over, contamination, or drift. The control meter is typically light, small (pocket-sized) and battery-operated, and relies on a potential-step (chronoamperometric) operation. Such devices offer great promise for obtaining the desired clinical information in a
1. Introduction Miniaturization is a growing trend in the field of analytical chemistry. Electrochemistry is particularly attractive for microscale analysis, as it can be miniaturized and multiplexed without compromising its capabilities. The portable nature and low power demands of electrochemical analyzers [1,2] satisfy many of the requirements for on-site and in-situ measurements. Modern microfabrication technologies allow us to replace the traditional bulky electrodes and cumbersome cells with easy-touse miniaturized electrochemical systems. Such portable (hand-held), battery-powered, electro*Tel.: +1 (505) 646-2505; fax: +1 (505) 646-2649. E-mail: [email protected]
0165-9936/02/$ - see front matter PII: S0165-9936(02)00402-8
2. Decentralized clinical diagnostics 2.1. In-vitro glucose testing
# 2002 Published by Elsevier Science B.V. All rights reserved.
227
trends in analytical chemistry, vol. 21, no. 4, 2002
fast, simple manner. The first product was a pen-style device (ExacTech), launched by MediSense, Inc. in 1987; it used a ferrocene-derivative mediator. Various commercial strips and pocket-sized test meters, for self-monitoring of blood glucose – based on the use of ferricyanide or ferrocene mediators – have since been introduced [3,4]. In all cases, the diabetic patient pricks the finger, places the small blood droplet on the sensor strip, and obtains the blood-glucose concentration (on a liquid-crystal display) in 15–30 s. In addition to their small size and fast response, such modern personal glucose meters have other features, such as extended memory and computer downloading. Non-invasive approaches for continuous glucose monitoring represent a promising route for getting round the challenges of implantable devices or the inconvenience of finger-stick sampling. In particular, Cygnus, Inc. has developed an attractive, wearable glucose monitor, based on the coupling of reverse iontophoretic collection of glucose and biosensor functions [5]. The new GlucoWatch Biographer (Fig. 1) provides three glucose readings per hour for up to 12 h (36 readings in a 12 h period). The system can measure the electroosmotically extracted glucose and track bloodglucose changes with good clinical accuracy. An alarm capability is included to alert the individual to very low or high glucose levels. The complete electronics, including the iontophore-
tic galvanostat, the dual-sensor bipotentiostat, the control circuitry, microprocessor, and LCD display, are packaged in wristwatch format, which is powered by a single AAA battery.
2.2. Miniaturized multi-analyte devices The success of pocket-sized blood-glucose monitors has stimulated tremendous interest in new devices offering a panel of blood tests at the patient’s side or valuable real-time information on key metabolites or drugs. One successful example is the i-STAT Portable Clinical Analyzer that performs simultaneously eight common clinical tests on a 60 ml patient blood in about 90 s [6]. These tests are based on various enzyme electrodes, gas sensors, or ionselective electrodes, connected to both amperometric and potentiometric detection schemes. Fig. 2 displays a cross-sectional view of the iSTAT electrolyte/gas sensor cartridge. The disposable cartridge contains a series of thin-film electrodes microfabricated on a silicon chip. Once the cartridge is inserted into the hand-held meter, the analytical procedure is carried out under automatic control. Upon completion of the assay, the results are displayed on a liquid-crystal screen, along with the patient-identification number and the time. The unit has been adopted by over 1000 hospitals, and has been utilized in remote locations, including the microgravity environment of space
Fig. 1. Various components of the GlucoWatch Biographer (Courtesy of Cygnus, Inc).
228
Fig. 2. Design of the disposable sensor-array cartridge used in the I-STAT Portable Clinical Analyzer. (Courtesy of i-STAT Corporation).
flight [7]. Extension of the unit to further critical blood chemistries is anticipated.
3. Instant electrical detection of DNA Wide-scale genetic testing requires the development of easy-to-use, fast, compact DNA analyzers. Electrochemical devices are ideally suited to shrinking DNA diagnostics and meeting future requirements of large-scale genetic testing. In addition to meeting the size and
trends in analytical chemistry, vol. 21, no. 4, 2002
power requirements of decentralized DNA testing, they offer elegant routes for interfacing (at the molecular level) nucleic acid systems and electrical devices. Recent efforts have led to the development of portable electrochemical analyzers for electrical detection of DNA hybridization [8,9]. Such devices rely on the conversion of the DNA base-pair recognition event into a useful electrical signal in connection with various label and label-free electrochemical transduction schemes. Elegant strategies for such direct electrical reading of DNA hybridization and for amplifying the hybridization signal have been developed in a number of laboratories [8,9]. Several innovative ideas have already reached the marketplace. One example is the compact gene-expression electrical system of Xanthon, which uses electrocatalytic detection of the DNA hybridization, based on oxidation of the target guanine nucleobase by a soluble metal mediator. This assay employs a 96-well microtiter-plate format, with each well containing seven separate probe-coated indium-tin-oxide electrodes (two of which are used as controls). A single microtiter plate thus allows 672 measurements (480 tests and 192 controls). Another example is Motorola Inc.’s CMS eSensor DNA chip platform that can detect up to 48 different sequences in connection with elegant surface chemistry (combining self-assembly of thiolated probes, phenylacetylene ‘molecular wires’ and the use of a ferrocene label) [10]. Coupling of mass-producible thick-film DNA biosensors with hand-held, battery-operated chronopotentiometric analyzers has also been reported [11]. Advances in micromachining technology will lead to the integration of electrochemical sensor gene arrays with sample clean-up, DNA extraction and amplification, and separation on a microchip platform (as discussed in the next section). On-going fundamental studies on nucleic-acid electrochemistry and on new signal transduction/amplification strategies, coupled to extensive commercialization, should have a tremendous impact on decentralized genetic testing.
229
trends in analytical chemistry, vol. 21, no. 4, 2002
4. Lab-on-a-Chip based on electrochemical detection The development of microscale (chip-based) separation devices, particularly micromachined capillary electrophoresis (CE) systems, has experienced explosive growth in recent years. Such miniaturized devices represent the ability to shrink conventional ‘bench-top’ analytical systems to yield major advantages in speed, cost, portability, and solvent and sample consumption. As the field of chip-based separation microsystems continues its rapid growth, there is an urgent need to develop compatible detection modes. Much of the work on CE microchips uses laser-induced fluorescence (LIF) detection. Yet, LIF detection requires a large, expensive off-chip supporting optical system that greatly compromises the benefits of miniaturization and portability. Electrochemical detection has recently attracted considerable interest for miniaturized analytical systems [12,13]. Electrochemistry (EC) holds great promise for such microsystems, as it offers: high sensitivity (approaching that of fluorescence); inherent miniaturization of both the detector and control instrumentation; independence of optical path length or sample turbidity; low cost; low-power requirements; and, high compatibility with advanced micromachining and microfabrication technologies. Various detector configurations, based on different capillary/working-electrode arrangements and the position of the electrode relative to the flow direction, have been proposed to meet these requirements (Fig. 3). Placing the working electrode just outside the exit of the separation channel results in self isolation from the high separation potential, owing to the dramatic drop of the potential across the capillary. The practical utility of such CE-EC microfluidic systems has been demonstrated for the on-chip separation and detection of nucleic acids, catecholamine neurotransmitters, nitroaromatic explosives, organophosphate pesticides, or chlorophenol compounds. The complete selfcontained microsystem (a true ‘Lab-on-a-Chip’) will be realized through an on-chip integration
of the potentiostatic (control) circuitry and additional functional elements (performing steps such as clean-up, preconcentration, or derivatization reactions). For example, fast-responding, field-deployable explosive or nerve-agent analyzers, providing a timely warning and alarm (in case of sudden concentration change), are being developed in our laboratory. It is expected that electrochemical detection will become a powerful tool for microscale analytical systems and will facilitate the creation of truly portable (and possibly disposable) devices.
5. Portable metal analyzers A major incentive for the introduction of disposable stripping-based metal sensors has been
Fig. 3. Common configurations of electrochemical detectors for capillary-electrophoresis microchips, based on different capillary/working-electrode arrangements and the position of the electrode (W) relative to the flow direction: (A) flow by (using two plates); (B) flow onto (with the surface normal to the flow direction); (C) flow through (with the detector placed directly on the channel exit).
230
the initiative of the US Centers for Disease Control (CDC) aimed at large-scale screening of lead in children’s blood. Such an extensive screening program requires portable, yet highly reliable blood-lead-measurement systems. Atomic spectroscopic techniques, commonly used for measuring trace metals in the central laboratory, are not suitable for use in on-site assays. Electrochemical stripping analysis has always been recognized as a powerful tool for measuring trace metals [1]. Its remarkable sensitivity is attributed to the ‘built-in’ preconcentration step, during which the target metals are accumulated onto the working electrode. The portable instrumentation and the low-power demands of stripping analysis satisfy many of the requirements for on-site and in-situ measurements of trace metals. Portable (hand-held), battery-powered, easy-to-use stripping analyzers have thus been developed [14]. These hand-held stripping meters have incorporated disposable screenprinted electrodes [15]. Micromachined metal analyzers, integrating fluid-handling silicon microstructures and an on-chip three-electrode system, represent a significant departure from existing (laboratorybased) flow stripping systems in that they are extremely small, mass produced and require minimal amounts of sample and reagent. Such miniaturized stripping flow analyzers thus allow testing for trace metals to be performed more reliably, easily and inexpensively in a field setting. One such microsystem consists of vertically-aligned functional modules (each 1 inch square), stacked on top of each other, including the sample and reagent reservoirs, two micropumps, mixer, reaction coil, and a flow detector (Fig. 4) [14]. As required for adsorptive stripping measurements (based on the formation and detection of metal chelates), the sample and reagent are thus brought together, mixed, and allowed to react in a reproducible manner.
6. ‘Lab-on-a-Cable’ Environmental chemists are still limited by having to arrange for samples to be collected in
trends in analytical chemistry, vol. 21, no. 4, 2002
Fig. 4. View of a stacked micromachined flow system for adsorptive stripping monitoring of trace metals, based on vertically aligned functional modules (reproduced from [14]).
the field and then transported to a centralized laboratory for analysis. An attractive route that circumvents the cost, delays, and contamination risks of such centralized environmental analysis involves moving the laboratory to the field. In particular, the ability to perform in-situ various steps of an analytical protocol should have an enormous impact on pollution control and prevention. Automated shipboard electrochemical flow analyzers were developed during the 1970s [16]. Our recent activity has led to the development of submersible electrochemical analyzers [17]. As opposed to current in-situ sensors (that lack the sample-preparation steps essential for optimal analytical performance), the new on-cable automated microanalyzer incorporates several functions into a single, sealed, submersible package. The first generation of this submersible microlaboratory integrates microdialysis sampling, with reservoirs for the reagent, waste, and calibration/standard solution, along with the
231
trends in analytical chemistry, vol. 21, no. 4, 2002
micropump and necessary fluidic network on a cable platform (Fig. 5). The sample and reagent are thus brought together, mixed, and allowed to react in a reproducible manner. Future generations will accommodate additional functions (such as preconcentration, filtration and extraction) to address the needs of complex environmental samples as well as compact, low-powered, automated instrumentation for unattended operation, ‘smart’
data processing, and signal transmission (via satellite links). Such a stand-alone ‘microlaboratory’ can be submersed directly in the environmental sample, to provide real-time continuous information on a wide range of priority pollutants. The utility of such a ‘Lab-ona-Cable’ has been demonstrated for stripping monitoring of trace metals or in-situ biosensing of phenols and various enzyme inhibitors.
7. Conclusions and prospects Electrochemical devices are receiving a major share of attention in the development of portable analytical systems. The above examples illustrate the scope, power, and versatility of such miniaturized analyzers. As we enter the twenty-first century, we no longer rely on cumbersome electrochemical cells and bulky electrodes, but rather fast, small, easy-to-use electrochemical systems. In the near future, we can expect even smaller and more sophisticated portable analyzers that integrate many steps of the analytical protocol with the electrical detection on credit-card-sized platforms. Given the impressive progress in portable electrochemical systems, there is no doubt that they will have major impact on point-of-care clinical diagnostics, decentralized genetic testing, and on-site environmental and industrial monitoring. Acknowledgements Financial support from the National Institutes of Health and the Office of Naval Research is gratefully acknowledged.
References Fig. 5. Schematic diagram of the electrochemical ‘Lab-ona-Cable’ system. (A) Cable connection; (B) micropump; (C) reservoirs for reagent and waste solutions; (D) microdialysis sampling tube and an (E,F) electrochemical flow detector, with working and reference electrodes, respectively. (Reproduced with permission from [17]).
[1] J. Wang, Analytical Electrochemistry, Wiley-VCH, New York, 2000. [2] P.T. Kissinger, W.R. Heineman, Laboratory Techniques in Electroanalytical Chemistry, Dekker, New York, 1996. [3] M. Green, P. Hilditch, Anal. Proc. 28 (1991) 374. [4] M. Shichiri, Y. Yamasaki, N. Hakui, H. Abe, Lancet 2 (1982) 1129.
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