Development of a glucose sensor with on/off control of enzyme activity without the effects of protein adsorption

The main factor mitigating against the realization of a hypodermically inserted glucose sensor for an artificial pancreas is the change in response current due to fibroblast adhesion and protein adsorption to the sensor surface. To overcome this problem, we have developed a method whereby the activity of glucose oxidase (GOD) fixed on the membrane of the sensor surface is switched on and off, and measurements are made during a transient state in which the glucose concentration gradient within the GOD membrane is small. Measuring in a transient state while GOD activity is being controlled, a correlation was observed between glucose concentration and response current in a phosphate buffer solution. Calibration curves of response current against glucose concentration in aqueous solutions of human serum albumin and in phosphate buffer solution were then compared using the transient method and a steady state method without control of GOD activity. In addition, glucose concentration was measured in bovine plasma for 480 min, and the time courses of the response currents for the transient and steady state measurements were compared. It was found that in both experiments the response current decreased greatly under steady state measurement as a result of protein adsorption, but during the transient measurement, response current was virtually unchanged. By measuring glucose concentration in the transient state while controlling GOD activity, it is possible to inhibit the effects of protein adsorption.