? The long-term objective of this project is to develop a complete closed-loop insulin system to keep the glucose level in diabetic patients as close as possible to normal values and prevent complications from the disease. The major component that is needed to realize such a system is a reliable glucose sensor that gives a stable response over a period of months to a year. It is believed that the unstable responses seen in current sensors are due in large part to the body's inflammatory response to the sensor, which causes initial loss of sensor sensitivity, instability over time, signal drift, and uncorrelated signal variations. The main cause of signal instability and drift is the formation of a nonvascular capsule around the sensor that significantly modifies the availability of glucose on the sensor surface. The goal of our R21 proposal is to address the prevention of nonvascular capsule formation on an implanted glucose sensor by controlling the microarchitecture of the sensor. The results of this research will be a glucose sensor that will give a more stable and accurate response. SRI has already shown in collaboration with a commercial client that a passive device with a certain architecture shows a reduced inflammatory response, even when it is implanted for a period of 3 weeks. In the proposed study, we will create 6 different carefully controlled grid structures, two 3-dimensional and four 2-dimensional, in polyimide. We will deposit electrodes on the grid structures, implant them in rats, and monitor the electrochemical signal. Initially, we are using a simplified electrochemical sensor without any analyte-recognition reagents such as enzyme to concentrate our study on the effect of architecture only, not on other issues such as enzyme or other reagents' instability. These issues have been studied by SRI and others, and reasonable solutions are available. The architecture that gives minimum drift in the electrochemical signal will be selected to make a complete glucose sensor that can be implanted for a minimum period of 4 weeks. We have chosen a period of just 4 weeks because we need to optimize the selection and immobilization of the mediator and enzyme to ensure that the implanted sensor will work for a period of 3 months or more, which is our final goal. ? ?
