We report results of a pilot clinical study of a subcutaneous fluorescence affinity sensor (FAS) for continuous glucose monitoring conducted in people with type 1 and type 2 diabetes. The device was assessed based on performance, safety, and comfort level under acute conditions (4 h). Research Design and Methods:A second-generation FAS (BioTex Inc., Houston, TX) was subcutaneously implanted in the abdomens of 12 people with diabetes, and its acute performance to excursions in blood glucose was monitored over 4 h. After 30-60 min the subjects, who all had fasting blood glucose levels of less than 200 mg/dl, received a glucose bolus of 75 g/liter dextrose by oral administration. Capillary blood glucose samples were obtained from the finger tip. The FAS data were retrospectively evaluated by linear least squares regression analysis and by the Clarke error grid method. Comfort levels during insertion, operation, and sensor removal were scored by the subjects using an analog pain scale. Results:After retrospective calibration of 17 sensors implanted in 12 subjects, error grid analysis showed 97% of the paired values in zones A and B and 1.5% in zones C and D, respectively. The mean absolute relative error between sensor signal and capillary blood glucose was 13% [±15% standard deviation (SD), 100-350 mg/dl] with an average correlation coefficient of 0.84 (±0.24 SD). The actual average "warm-up" time for the FAS readings, at which highest correlation with glucose readings was determined, was 65 (±32 SD) min. Mean time lag was 4 (±5 SD) min during the initial operational hours. Pain levels during insertion and operation were modest. Conclusions:The in vivo performance of the FAS demonstrates feasibility of the fluorescence affinity technology to determine blood glucose excursions accurately and safely under acute dynamic conditions in humans with type 1 and type 2 diabetes. Specific engineering challenges to sensor and instrumentation robustness remain. Further studies will be required to validate its promising performance over longer implantation duration (5-7 days) in people with diabetes.

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Abbreviations: (BG) blood glucose, (FAS) fluorescence affinity sensor, (FRET) fluorescence resonance energy transfer, (MARE) mean absolute relative error, (SD) standard deviation Keywords: concanavalin A, fluorescence affinity sensor, glucose monitoring, hollow fiber Abstract Objective:We assessed and compared the performance levels of a fiber-coupled fluorescence affinity sensor (FAS) for glucose detection in the intradermal tissue and intravascular bed during glucose clamping and insulin administration in a large animal model. Research Design and Methods:The FAS (BioTex Inc., Houston, TX) was implanted in interstitial tissue and in the intravenous space in nondiabetic, anesthetized pigs over 6-7 h. For intradermal assessment, a needle-type FAS was implanted in the upper back using a hypodermic needle. For intravenous assessment, the FAS was inserted through a catheter into the femoral artery and vein. Blood glucose changes were induced by infusion of dextrose and insulin through a catheterized ear or jugular vein. Results:Based on retrospective analysis, the mean absolute relative error (MARE) of the sensor in blood and interstitial tissue was 11.9% [standard deviation (SD) = ±9.6%] and 23.8% (SD = ±19.4%), respectively. When excluding data sets from sensors that were affected by exogenous insulin, the MARE for those sensors tested in interstitial tissue was reduced to 16.3% (SD = ±12.5%). Conclusions:The study demonstrated that the performance level of the FAS device implanted in interstitial tissue and blood can be very high. However, under certain circumstances, exogenous insulin caused the glucose concentration in interstitial tissue to be lower than in blood, which resulted in an overall lower level of accuracy of the FAS device. How significant this physiological effect is in insulin-treated persons with diabetes remains to be seen. In contrast, the level of accuracy of the FAS device in blood was very high because of high mass transfer conditions in blood. While the use of the FAS in both body sites will need further validation, its application in critically ill patients looks particularly promising.