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Electrochemical Glucose Sensors and Their Applications in Diabetes Management Adam Heller*,† and Ben Feldman‡ Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, and Abbott Diabetes Care, 1360 South Loop Road, Alameda, California 94502 Received September 17, 2007 Contents 1. Scope B 1.1. Coverage B 1.2. Exclusion of Studies on Glucose Electrooxidizing Anodes of Cardiac Assist Devices, Pacemakers, Waste-Utilizing Electrical Power Generators, and Bioelectronic Devices B 2. Roots and Fundamentals C 2.1. Direct, Nonenzymatic, Electrooxidation and Electroreduction of Glucose C 2.2. The Enzymes of Glucose Electrooxidizing Anodes C 2.3. Enzyme-Catalyzed O2-Oxidation of Glucose C 2.4. Enzyme-Catalyzed Redox Couple-Mediated Electrooxidation of Glucose D 2.4.1. Organic Mediators D 2.4.2. Inorganic Mediators D 2.4.3. Metal-Organic Mediators E 2.5. Electrical Wiring of GOx by Electron-Conducting Redox Hydrogels E 2.5.1. Mechanism of Electron-Conduction in Redox Hydrogels E 2.5.2. Mechanism of Direct Glucose Electrooxidation F 2.5.3. Organic and Metal-Organic Redox Centers in Electron-Conducting Hydrogels F 2.5.4. Mechanical Properties: Balancing the Strength against the Electronic Conductivity F 2.5.5. Electrodeposition of Glucose Electrooxidation- Catalyzing Electron-Conducting Hydrogels by Ligand Exchange F 2.5.6. Redox Potentials of the Electron Conducting Hydrogels G 2.5.7. Charge of the Polymer Backbones of the Electron Conducting Hydrogels G 2.5.8. Applications of Glucose Oxidation Electrocatalysts Based on Electron Conducting Redox Hydrogels G 2.6. Metal-Particle GOx-Plug Relay Based Glucose-Electrooxidation Catalysts G 3. Electrochemical Monitoring of the Glucose Concentration by Its GOx-Catalyzed O2-Oxidation H 3.1. O2-Depletion Monitoring upon GOx-Catalyzed O2-Oxidation of Glucose H 3.2. Electrooxidation of the H2O2 Produced upon Enzyme-Catalyzed O2-Oxidation of Glucose H 3.3. Electroreduction of H2O2 Produced upon Enzyme Catalyzed O2-Oxidation of Glucose H 3.3.1. Peroxidase-Catalyzed H2O2 Electroreduction H 3.4. Monitoring the Drop in pH upon Enzyme Catalyzed O2-Oxidation of Glucose with Field Effect Transistors H 4. Central Laboratory and Desktop Glucose-Analyzers I 4.1. The First Central Laboratory Glucose-Analyzers I 4.2. Contemporary Central Laboratory Electrochemical Glucose Analyzers I 4.3. Hand-Held Electrochemical Glucose- Analyzers for Hospital Wards, Emergency Rooms, and Physician¡¯s Offices I 5. Home Blood-Glucose Monitors Used by Self-Monitoring Diabetic People J 5.1. The Need for Glucose Monitoring in Diabetes Management J 5.2. Roots of the Electrochemical Glucose Assays Performed by Self-Monitoring Diabetic People J 5.3. Gradual Shift from Photonic to Electrochemical Monitoring of Blood-Glucose by Self-Monitoring Diabetic People J 5.4. Practical Considerations in Home Glucose Test Strip Design K 5.4.1. Plastic Substrates for Home Glucose Test-Strips L 5.4.2. Working Electrodes for Home Glucose Test-Strips L 5.4.3. Counter/Reference Electrodes for Home Glucose Test-Strips L 5.4.4. Capillary Chamber for Home Glucose Test-Strips L 5.4.5. Reagents for Home Glucose Test-Strips M 5.4.6. Fill Detection in Home Glucose Test-Strips M 5.5. Calibration and Characterization of Home Blood-Glucose Test-Strips M 5.5.1. Calibration of Home Blood-Glucose Test-Strips M 5.5.2. Linearity and Coefficient of Variation (CV) of Home Blood-Glucose Test-Strips M 5.5.3. Hematocrit Dependence of Home Blood-Glucose Test-Strips N 5.5.4. Electrochemical Interferents in Home Blood-Glucose Test-Strips N 5.5.5. Additional Testing of Home Blood-Glucose Test-Strips N 5.6. Variables Affecting the Outcome of the Glucose Assays Performed by Self-Monitoring Diabetic People N 6. Diabetes Management Based on Frequent or Continuous Amperometric Monitoring of Glucose O 6.1. Bedside Glucose-Monitors Measuring the Blood-Glucose Concentration in a By-Stream of Venous Blood O 6.2. Surgeon-Implanted Long-Term Glucose Monitors O 6.3. Systems with Subcutaneous Ultrafiltration and Microdialysis Fibers and Externally-Worn Sensors O 6.4. Reverse-Iontophoretic Systems P 6.5. Subcutaneously Inserted User-Replaced Miniature Amperometric Sensors P 6.5.1. Subcutaneously Inserted User-Replaced Miniature Sensors Based on GOx Catalyzed Generation of H2O2 and Its Electrooxidation P 6.5.2. Implanted Amperometric Glucose Sensors Built on the Wiring of Glucose Oxidase Q 6.5.3. Flux-Limiting Membranes for Transcutaneous Amperometric Sensors Q 6.5.4. Calibration of Transcutaneous Amperometric Sensors Q 6.5.5. The Relationship between the Glucose Concentrations in Blood and in the Subcutaneous Interstitial Fluid R 6.6. Research Aimed at Integrating a Miniature Power-Source in a 5-Day Patient-Replaced Subcutaneously Implanted Glycemic Status Monitoring and Transmitting Package S 6.6.1. The Potentially Implantable Miniature Zn/AgCl Cell S 6.6.2. The Potentially Implantable Miniature Zn-O2 Cell S 6.6.3. The Potentially Implantable Miniature Glucose-O2 Biofuel Cell S 7. Concluding Remarks T 8. Acknowledgments T 9. References T |
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