Continuous amperometric monitoring of glucose in a brittle diabetic chimpanzee with a miniature subcutaneous electrode

Abstract

The performance of an amperometric biosensor, consisting of a subcutaneously implanted miniature (0.29 mm diameter, 5 x 10(-4) cm2 mass transporting area), 90 s 10-90% rise/decay time glucose electrode, and an on-the-skin electrocardiogram Ag/AgCl electrode was tested in an unconstrained, naturally diabetic, brittle, type I, insulin-dependent chimpanzee. The chimpanzee was trained to wear on her wrist a small electronic package and to present her heel for capillary blood samples. In five sets of measurements, averaging 5 h each, 82 capillary blood samples were assayed, their concentrations ranging from 35 to 400 mg/dl. The current readings were translated to blood glucose concentration by assaying, at t = 1 h, one blood sample for each implanted sensor. The rms error in the correlation between the sensor-measured glucose concentration and that in capillary blood was 17.2%, 4.9% above the intrinsic 12.3% rms error of the Accu-Chek II reference, through which the illness of the chimpanzee was routinely managed. Linear regression analysis of the data points taken at t>1 h yielded the relationship (Accu-Chek) = 0. 98 x (implanted sensor) + 4.2 mg/dl, r2 = 0.94. The capillary blood and the subcutaneous glucose concentrations were statistically indistinguishable when the rate of change was less than 1 mg/(dl. min). However, when the rate of decline exceeded 1.8 mg/(dl.min) after insulin injection, the subcutaneous glucose concentration was transiently higher.

Figure 1

Schematic drawing of the sensor. 1: “Wired” enzyme sensing layer. 2: Mass transport controlling membrane. 3: Biocompatible polyethylene oxide film. [Reproduced with permission from ref. (Copyright 1998, American Chemical Society)].

Figure 2

Comparison of the Accu-Chek (•) and sensor estimated (○) glucose readings for the five individual experiments. The implanted subcutaneous glucose sensors were calibrated at t = 1 h by a one-point in vivo calibration.

Figure 3

Overall correlation of the Accu-Chek-measured capillary blood and the sensor-measured subcutaneous glucose concentrations.