- Email: [email protected]
Japan — Polymers for biosensors
Biosensors & Bioelectronics Vol. 11 No. 6/7 (1996)
U S A - M i c r o c h i p glucose sensor
In ASAIO J. (41/3 (M409-M413) 1995) J.F. Patzer lI, S.J. Yao, W. Xu, T.-L Day, S.K. Wolfson Jr. & C.-C. Liu of University of Pittsburgh report on 'A microchip glucose sensor'. A major problem in development of a glucose sensor for use in an implantable artificial pancreas is the lack of reproducibility in signals from sensor to sensor. Each glucose sensor fabricated with currently used methods has a unique response to varying levels of glucose concentration and thus needs to be individually calibrated before use. We have adapted microchip manufacturing techniques for the fabrication of electrochemically based glucose sensors with standardized and reproducible function. Scanning electron microscopic study of the resulting electrode surfaces shows them to be smooth and featureless at all levels of magnification. X-ray diffraction analysis of the electrodes indicates preferential exposure of the [1,1,1] crystal interface. Cyclic voltammetry evaluation of initial sensor response to varying glucose concentrations shows excellent sensor to sensor reproducibility for all sensors made with the same underlayment. Sensors made with titanium underlayment appear to be more differentiated and thus more sensitive to variations in glucose concentration than are sensors with chromium underlayment. Although the initial response of microchip glucose sensors appears to be standardized and reproducible, additional development of an appropriate electrical insulation material is required before long-term study of signal stability is feasible.
Contact: Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA. USA
- Nitric oxide sensor
In ASAIO J. (41/3 (M413-M418) 1995) W. Xu, S.J. Yao & S.K. Wolfson Jr. of the University of Pittsburgh report on 'A nitricoxide sensor using reduction current'. Nitric oxide (NO) has a wide range of biologic activity. Methods commonly used for the detection of biologically derived NO are indirect and measure only the amount of NO released during an
interval of time. An electrochemical method available is capable of being direct and continuous but is subject to interference. The recent explosion of scientific research into NO activity requires better methods of NO detection. This article reports a new NO electrochemical sensing method and sensor design. The tip of the sensor is covered with a hydrophobic membrane and contains an internal electrolyte. Platinum is used for the working and counter electrodes and silver/silver bromide (Ag/AgBr) for the reference electrode. The components of the internal electrolyte are potassium bromide and sulfuric acid. The NO that diffuses to the working electrode is In'st oxidized to NO+; the NO + is reduced to NO; and the reduction current is determined. An integrated pulsed amperometric method is used to achieve the redox of NO and the measurement and integration of the reduction current. The results show that the NO sensor is sensitive and has a rapid response and less interference.
Contact: Center for Bwtechnol./Bioengineering, University of Pittsburgh, 300 Technology Drive, Pittsburgh, PA 15219, USA. J a p a n - Polymers for biosensors
In ASAIO J. (41/3 (M418-M421) 1995) Y. Nakayama, Q. Zheng, J. Nishimura & T. Matsuda of Nat. Cardiovasc. Center Res. Inst. report on 'Design and properties of photocurable electroconductivepolymers for use in bioseusors'. The authors report preparation of a new hydrophilic photocurable electroconductive polymer to be used as a matrix for an enzyme based biosensor. Polymers, prepared by radical terpolymerization, consisted of N,N-dimethylacrylarnide (DMAA) as the water soluble part, m-azidostyrene (AzSt) as the photochemically active center to entrap an enzyme and to fix it on an electrode, and vinylferrocene (VFe) as the charge transfer mediator between an enzyme and an electrode. Ultraviolet light (UV) irradiation to the terpolymer coated on a carbon electrode produced a water swellable cross-linked polymer that was chemically fixed on a carbon electrode. Cyclic voltammetry on a hydrogelated
V
Biosensors & Bioelectronics Vol. 11 No. 6/7 (1996)
eleetrode in a phosphate buffered solution exhibited single oxidation/reduction reproducibly, indicating that the formed conducting hydrogel was stable. An increase in VFe content and a decrease in AzSt content of a terpolymer resulted in larger electrochemical responses on normal pulse voltammetry. When glucose oxidase was immobilized in a hydrogel, a dose dependent electrochemicalresponse to glucose was observed. Contact: Department of Bioengineering, Nat. Cardiovasc. Center Res. Inst., 5- 7-1 Fufishirodai, Suita, Osaka 565, Japan.
USA Clinical application of disposable heparin sensors In ASAIO J. (41/3 (M661-M664) 1995) J.-H. Yun, L.-M. Lee, J.A. Wahr, B. Fu, M.E. Meyerhoff & V.C. Yang of the University of Michigan report on 'Clinical application of disposable heparin sensors. Blood heparin measurements during open heart surgery'. The authors previously reported the development of an ion selective electrode type heparin sensor consisting of a specially formulated polymer membrane doped with tridodeeylmethylammoniumchloride as the heparin complexing agent. They also demonstrated the feasibility of measuring blood heparin levels by protamine titration, using a disposable copper wire sensor coated with the heparin sensing membrane to probe the titration end point. In this article, the results of further titration studies conducted on 44 clinical whole blood specimens obtained from 8 patients undergoing open heart surgery were reviewed. Samples were taken from patients at four different stages during the bypass surgery: 1) before heparin administration; 2) immediately after heparin administration; 3) within 30 min to 3 hr after heparin administration; and 4) within 30 min after protamine administration. Heparin anticoagulant activity in these samples was monitored by the activated clotting time assay, whereas heparin concentrations were measured by protamine titration using either the Hepcon HMS Titrator (Medtronic HemoTec Inc., Englewood, CO) or the coated wire heparin sensor to determine titration end points. Results indicate that heparin
vi
levels determined by the sensor method were in good agreement with those determined by the Hepcon HMS Titrator. When the heparin concentrationsestimated by the two methods show significant discrepancy (> 1.0 unit/ml), the sensor method seems to provide more precise values, as verified by an additional chromogenic heparin assay. The overall time required to complete the titration process and heparin measurement with a pre made heparin sensor was less than 3 min. Clinically, the heparin sensor could be used as a safeguard to precisely monitor heparin levels during surgical procedures. Alternatively, the sensor could be used to assess the accurate protamine dose required for full heparin reversal. Contact: College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USA.
Singapore monitoring
On-line system for glucose
In ANAL. CHIM. ACTA (317/1-3 (223-232) 1995) Y.L. Huang, T.J. Foellmer, K.C. Ang, S.B. Khoo & M.G.S. Yap of the National University of Singapore report on 'Characterization and application of an on-line flow injection analysis/wall-jet electrode system for glucose monitoring during fermentation'. An on-line system for glucose monitoring during fermentation was developed. The system employed now-injection analysis coupled with a wall-jet electrode. Glucose was converted enzymatically in a tubular reactor packed with controlledpore glass beads containing immobilized glucose oxidase. The hydrogen peroxide produced was detected amperometrically. A filtration/samplingmodule operated by a peristaltic pump enabled sample withdrawal from the fermenter. The system was interfaced to a programmable language controller which was in turn linked to a microcomputer. The dual injection valve of the new system was operated in a novel configuration to achieve sample dilution, by dispersion, and standardization simultaneously. The developed system was characterized for dilution factor, stability and linearity of response. After conditioning of the reactor, sample peak
U S A - M i c r o c h i p glucose sensor
In ASAIO J. (41/3 (M409-M413) 1995) J.F. Patzer lI, S.J. Yao, W. Xu, T.-L Day, S.K. Wolfson Jr. & C.-C. Liu of University of Pittsburgh report on 'A microchip glucose sensor'. A major problem in development of a glucose sensor for use in an implantable artificial pancreas is the lack of reproducibility in signals from sensor to sensor. Each glucose sensor fabricated with currently used methods has a unique response to varying levels of glucose concentration and thus needs to be individually calibrated before use. We have adapted microchip manufacturing techniques for the fabrication of electrochemically based glucose sensors with standardized and reproducible function. Scanning electron microscopic study of the resulting electrode surfaces shows them to be smooth and featureless at all levels of magnification. X-ray diffraction analysis of the electrodes indicates preferential exposure of the [1,1,1] crystal interface. Cyclic voltammetry evaluation of initial sensor response to varying glucose concentrations shows excellent sensor to sensor reproducibility for all sensors made with the same underlayment. Sensors made with titanium underlayment appear to be more differentiated and thus more sensitive to variations in glucose concentration than are sensors with chromium underlayment. Although the initial response of microchip glucose sensors appears to be standardized and reproducible, additional development of an appropriate electrical insulation material is required before long-term study of signal stability is feasible.
Contact: Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA. USA
- Nitric oxide sensor
In ASAIO J. (41/3 (M413-M418) 1995) W. Xu, S.J. Yao & S.K. Wolfson Jr. of the University of Pittsburgh report on 'A nitricoxide sensor using reduction current'. Nitric oxide (NO) has a wide range of biologic activity. Methods commonly used for the detection of biologically derived NO are indirect and measure only the amount of NO released during an
interval of time. An electrochemical method available is capable of being direct and continuous but is subject to interference. The recent explosion of scientific research into NO activity requires better methods of NO detection. This article reports a new NO electrochemical sensing method and sensor design. The tip of the sensor is covered with a hydrophobic membrane and contains an internal electrolyte. Platinum is used for the working and counter electrodes and silver/silver bromide (Ag/AgBr) for the reference electrode. The components of the internal electrolyte are potassium bromide and sulfuric acid. The NO that diffuses to the working electrode is In'st oxidized to NO+; the NO + is reduced to NO; and the reduction current is determined. An integrated pulsed amperometric method is used to achieve the redox of NO and the measurement and integration of the reduction current. The results show that the NO sensor is sensitive and has a rapid response and less interference.
Contact: Center for Bwtechnol./Bioengineering, University of Pittsburgh, 300 Technology Drive, Pittsburgh, PA 15219, USA. J a p a n - Polymers for biosensors
In ASAIO J. (41/3 (M418-M421) 1995) Y. Nakayama, Q. Zheng, J. Nishimura & T. Matsuda of Nat. Cardiovasc. Center Res. Inst. report on 'Design and properties of photocurable electroconductivepolymers for use in bioseusors'. The authors report preparation of a new hydrophilic photocurable electroconductive polymer to be used as a matrix for an enzyme based biosensor. Polymers, prepared by radical terpolymerization, consisted of N,N-dimethylacrylarnide (DMAA) as the water soluble part, m-azidostyrene (AzSt) as the photochemically active center to entrap an enzyme and to fix it on an electrode, and vinylferrocene (VFe) as the charge transfer mediator between an enzyme and an electrode. Ultraviolet light (UV) irradiation to the terpolymer coated on a carbon electrode produced a water swellable cross-linked polymer that was chemically fixed on a carbon electrode. Cyclic voltammetry on a hydrogelated
V
Biosensors & Bioelectronics Vol. 11 No. 6/7 (1996)
eleetrode in a phosphate buffered solution exhibited single oxidation/reduction reproducibly, indicating that the formed conducting hydrogel was stable. An increase in VFe content and a decrease in AzSt content of a terpolymer resulted in larger electrochemical responses on normal pulse voltammetry. When glucose oxidase was immobilized in a hydrogel, a dose dependent electrochemicalresponse to glucose was observed. Contact: Department of Bioengineering, Nat. Cardiovasc. Center Res. Inst., 5- 7-1 Fufishirodai, Suita, Osaka 565, Japan.
USA Clinical application of disposable heparin sensors In ASAIO J. (41/3 (M661-M664) 1995) J.-H. Yun, L.-M. Lee, J.A. Wahr, B. Fu, M.E. Meyerhoff & V.C. Yang of the University of Michigan report on 'Clinical application of disposable heparin sensors. Blood heparin measurements during open heart surgery'. The authors previously reported the development of an ion selective electrode type heparin sensor consisting of a specially formulated polymer membrane doped with tridodeeylmethylammoniumchloride as the heparin complexing agent. They also demonstrated the feasibility of measuring blood heparin levels by protamine titration, using a disposable copper wire sensor coated with the heparin sensing membrane to probe the titration end point. In this article, the results of further titration studies conducted on 44 clinical whole blood specimens obtained from 8 patients undergoing open heart surgery were reviewed. Samples were taken from patients at four different stages during the bypass surgery: 1) before heparin administration; 2) immediately after heparin administration; 3) within 30 min to 3 hr after heparin administration; and 4) within 30 min after protamine administration. Heparin anticoagulant activity in these samples was monitored by the activated clotting time assay, whereas heparin concentrations were measured by protamine titration using either the Hepcon HMS Titrator (Medtronic HemoTec Inc., Englewood, CO) or the coated wire heparin sensor to determine titration end points. Results indicate that heparin
vi
levels determined by the sensor method were in good agreement with those determined by the Hepcon HMS Titrator. When the heparin concentrationsestimated by the two methods show significant discrepancy (> 1.0 unit/ml), the sensor method seems to provide more precise values, as verified by an additional chromogenic heparin assay. The overall time required to complete the titration process and heparin measurement with a pre made heparin sensor was less than 3 min. Clinically, the heparin sensor could be used as a safeguard to precisely monitor heparin levels during surgical procedures. Alternatively, the sensor could be used to assess the accurate protamine dose required for full heparin reversal. Contact: College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USA.
Singapore monitoring
On-line system for glucose
In ANAL. CHIM. ACTA (317/1-3 (223-232) 1995) Y.L. Huang, T.J. Foellmer, K.C. Ang, S.B. Khoo & M.G.S. Yap of the National University of Singapore report on 'Characterization and application of an on-line flow injection analysis/wall-jet electrode system for glucose monitoring during fermentation'. An on-line system for glucose monitoring during fermentation was developed. The system employed now-injection analysis coupled with a wall-jet electrode. Glucose was converted enzymatically in a tubular reactor packed with controlledpore glass beads containing immobilized glucose oxidase. The hydrogen peroxide produced was detected amperometrically. A filtration/samplingmodule operated by a peristaltic pump enabled sample withdrawal from the fermenter. The system was interfaced to a programmable language controller which was in turn linked to a microcomputer. The dual injection valve of the new system was operated in a novel configuration to achieve sample dilution, by dispersion, and standardization simultaneously. The developed system was characterized for dilution factor, stability and linearity of response. After conditioning of the reactor, sample peak