Our goal is to develop an implantable, enzyme electrode-type glucose sensor that can operate reliably in the body for a period of at least one year. The sensor will continuously measure blood or tissue fluid glucose concentration and provide information that may enable the diabetic to effect an improved metabolic control, either by means or by employing the sensor as a component of an implantable artificial beta cell being developed by others that automatically dispenses insulin as needed. This may ameliorate some of the vascular consequences of the disease. Our past efforts have centered on obtaining a basic understanding of sensor operation. We have developed a comprehensive model of the reaction and diffusion process within the enzymatic membrane of the sensor that allows prediction o the glucose-dependent different current under conditions that are useful for glucose monitoring in the body. This model has clarified thinking about the problem and has led to the design of novel membranes. In conjunction, we have developed a unique rotated disc experimental apparatus for characterizing membranes and have developed new insights on the stability of the oxygen electrode. We will expand our fundamental developmental efforts to include: (1) Analysis of the sensor response time; (2) Determination of the factors that stabilize the enzymes and extension of the catalytic lifetime; (3) Incorporation of novel membranes; (4) Determination of the factors that contribute to the stability of the oxygen electrode and use this information to develop an acceptable, long-term oxygen electrode; (5) Fabrication and testing of complete sensors in vitro; (6) Initiation of physiologic and biocompatibility studies with sensors implanted in guinea pigs and dogs; and (7) Modeling of glucose distribution in the body. This program will build on our previous progress and take maximal advantage of a unique group of talented investigators.