Through the electrical """"""""wiring"""""""" of glucose oxidase the basis has been formed for subcutaneously implantable, miniature (O.29mm OD) flexible glucose sensors that have no leachable components; are insensitive to variation of partial pressure of oxygen; are insensitive to interferants; operate at 37degreesC for one week with only 4% variation in sensitivity; are not fouled by cell growth; are calibrated, for the first time, in vivo by the long- sought one-point calibration. When the glucose concentration was monitored with pairs of the microwire sensors in rats and the sensors were calibrated at any one point, 99% of the glucose readings were clinically correct. The novel microsensors that are innocuous and comfortable to wear in the abdominal skin, will be developed for enhanced compliance of Type I diabetics with the recommendations of the 1993 Diabetes Control and Compliance Trial (DCCT, 1993). Issues relating to the design and use of reliable innocuous microsensor pairs, weekly replaced by the diabetic, will be answered. Specifically the feasibility of designing electron conducting, enzyme wiring hydrogels to provide sufficient specificity for glucose, for one-point in vivo calibration; the feasibility of further miniaturization, while the reliability, stability and operational life are improved; the feasibility of achieving >99% clinical accuracy through implanting pairs of microsensors and accepting only those readings that pass the probability ratio test applied in nuclear reactors monitored with sensor pairs; and the feasibility of developing algorithms for translating the measured subcutaneous time-concentration profiles to the clinically relevant blood glucose concentrations will be addressed.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZRG7 (06))
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Harmon, Joan T
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University of Texas Austin
Engineering (All Types)
Schools of Engineering
United States
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Chen, T; Friedman, K A; Lei, I et al. (2000) In situ assembled mass-transport controlling micromembranes and their application in implanted amperometric glucose sensors. Anal Chem 72:3757-63
Freeland, A C; Bonnecaze, R T (1999) Inference of blood glucose concentrations from subcutaneous glucose concentrations: applications to glucose biosensors. Ann Biomed Eng 27:525-37
Ishikawa, M; Schmidtke, D W; Raskin, P et al. (1998) Initial evaluation of a 290-microm diameter subcutaneous glucose sensor: glucose monitoring with a biocompatible, flexible-wire, enzyme-based amperometric microsensor in diabetic and nondiabetic humans. J Diabetes Complications 12:295-301
Schmidtke, D W; Freeland, A C; Heller, A et al. (1998) Measurement and modeling of the transient difference between blood and subcutaneous glucose concentrations in the rat after injection of insulin. Proc Natl Acad Sci U S A 95:294-9
Schmidtke, D W; Heller, A (1998) Accuracy of the one-point in vivo calibration of ""wired"" glucose oxidase electrodes implanted in jugular veins of rats in periods of rapid rise and decline of the glucose concentration. Anal Chem 70:2149-55
Wagner, J G; Schmidtke, D W; Quinn, C P et al. (1998) Continuous amperometric monitoring of glucose in a brittle diabetic chimpanzee with a miniature subcutaneous electrode. Proc Natl Acad Sci U S A 95:6379-82
Quinn, C A; Connor, R E; Heller, A (1997) Biocompatible, glucose-permeable hydrogel for in situ coating of implantable biosensors. Biomaterials 18:1665-70
Schmidtke, D W; Pishko, M V; Quinn, C P et al. (1996) Statistics for critical clinical decision making based on readings of pairs of implanted sensors. Anal Chem 68:2845-9
Quinn, C P; Pathak, C P; Heller, A et al. (1995) Photo-crosslinked copolymers of 2-hydroxyethyl methacrylate, poly(ethylene glycol) tetra-acrylate and ethylene dimethacrylate for improving biocompatibility of biosensors. Biomaterials 16:389-96
de Lumley-Woodyear, T; Rocca, P; Lindsay, J et al. (1995) Polyacrylamide-based redox polymer for connecting redox centers of enzymes to electrodes. Anal Chem 67:1332-8

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