In Situ Assembled Mass-Transport Controlling Micromembranes and Their Application in Implanted Amperometric Glucose Sensors

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Abstract
Micromembranes were assembled by sequentially chemisorbing polyanions and polycations on miniature (5 × 10-4 cm2) enzyme electrodes. The sequential chemisorption process allowed the simultaneous tailoring of their sensitivity, dynamic range, drift, and selectivity. When assembled on tips of 250-μm-diameter gold wires coated with redox polymer-“wired” glucose oxidase, they allowed tailoring of the glucose electrodes for >2 nA/mM sensitivity; 0−30 mM dynamic range; drift of ≤5% per 24 h at 37 °C at 15 mM glucose concentration; and ≤5% current increment by the combination of 0.1 mM ascorbate, 0.2 mM acetaminophen, and 0.5 mM urate. The membranes also retained transition metal ions that bound to and damaged the redox polymer “wiring” the enzyme. The electrodes were tested in the jugular veins and in the intrascapular subcutaneous region of anaesthetized and heparinized nondiabetic Sprague−Dawley rats, in which rapid changes of glycemia were forced by intravenous injections of glucose and insulin. After one-point in vivo calibration of the electrodes, all of the 152 data points were clinically accurate when it was assumed that after insulin injection the glycemia in the subcutaneous fluid lags by 9 min behind that of blood withdrawn from the insulin-injected vein.