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

The hypothesis of the feasibility of one-point in vivo calibration of intravenously implanted glucose sensors during periods of rapid rise and decline of venous blood glucose concentration was tested. Miniature (5 x 10(-4) cm2 mass transporting area) glucose electrodes with 10-90% response times < 2 min, that did not consume oxygen, were implanted in jugular veins of systemically heparinized rats and used in 4-h experiments, during which the blood glucose concentration was amperometrically monitored. The glucose electrodes were made by electrically connecting ("wiring") reaction centers of glucose oxidase through an electron-conducting redox hydrogel to gold electrode surfaces. The redox polymer and enzyme constituting the electrode sensing layer were immobilized by cross-linking, and thus the electrodes had no diffusional and readily leached redox mediator. One hour after their implantation, the electrodes accurately tracked the blood glucose concentration when calibrated in vivo by a one-point calibration, when the glucose concentration was steady, when rising rapidly, and when declining steeply. For an assumed 2-min lag time, the sensor readings were well correlated with the true blood glucose concentrations, with linear regression analysis yielding a slope of 0.97 +/- 0.07 and an intercept (bias) of 0.3 +/- 0.3 mM. The correlation coefficient, r2, was 0.949 +/- 0.020, and the percent difference through the 2-22 mM range was 1.9 +/- 1.0%. The results suggest that, in combination with understanding and modeling of transient physiological differences between the subcutaneous and the blood glucose concentrations, it will be possible to calibrate by one-point in vivo calibration subcutaneously implanted sensors, even while the glucose concentration changes rapidly.