DESIGN, CHARACTERIZATION, AND ONE-POINT IN-VIVO CALIBRATION OF A SUBCUTANEOUSLY IMPLANTED GLUCOSE ELECTRODE

A 0.29-mm-diameter flexible electrode designed for subcutaneous in viv o amperometric monitoring of glucose is described. The electrode was d esigned to allow ''one-point'' in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. A valid zero point, along with a measurement of the glucose concentration in a withdrawn s ample of blood at which the current is known, defined the sensitivity in the linear response range. The electrode was four-layered, with the layers serially deposited within a 0.125-mm recess upon the tip of a polyimide-insulated 0.25-mm gold wire. The recessed structure reduced the sensitivity to movement and allowed, through control of the depth of the recess, control of the transport of glucose and thus the range of linearity. The recess contained the four polymeric layers, with a t otal mass less than 5 mu g and no leachable components. The bottom glu cose concentration-to-current transducing layer consisted of the enzym e ''wiring'' redox polymer poly-[(vinylimidazole)Os(bipyridine)(2)Cl]( +/2+), complexed with recombinant glucose oxidase and cross-linked wit h poly(ethylene glycol) diglycidyl ether, to form an electron-conducti ng hydrogel. The layer was overcoated with an electrically insulating layer of polyaziridine-cross-linked poly(allylamine), on which an immo bilized interference-eliminating horseradish peroxidase based film was deposited. An outer biocompatible layer was formed by photo-cross-lin king derivatized poly(ethylene oxide). The current output of a typical electrode at 10 mM glucose and at 37 degrees C was 35 nA, the apparen t K-m was 20 mM, and the 10-90% response time was similar to 1 min. Th e sensitivity varied only by +/-5% over a 72-h test period. The electr ode tracked the blood glucose concentration in a rat model before, dur ing, and following intraperitoneal glucose infusion. Two failure modes were observed. The first, deactivation of hydrogen peroxide-producing lactate oxidase in the interference-eliminating layer, resulted in in adequate preoxidation of interferants. The second was an abrupt drop i n the sensitivity of implanted electrodes, similar to 7 h after implan tation. The failed electrodes promptly regained their sensitivity in b uffer.