| An implantable and rechargeable glucose biosensor for continuous in vitro and in vivo monitoring of glucose concentrations has been developed and evaluated. The recharging approach makes it possible to extend the sensor's lifetime by in situ sensor refilling--the spent immobilized enzyme can be removed from the sensor body and fresh enzyme suspension can be simultaneously injected via septa, without sensor disassembly or surgical access. The sensor also could be refilled with fresh immobilized enzyme after standard sterilization procedures.; Oxygen detection based amperometric measurement has been utilized due to its linear dependence of signal versus analyte concentration and the elimination of interference from normal physiological substrates. Different glucose/oxygen diffusion membranes (sandwich type membranes, annealed polycarbonate (PC) membranes, and Silastic{dollar}spcircler{dollar} coated polytetrafluoroethylene (PTFE) membranes) have been developed and examined. Various in vitro tests were conducted to evaluate the performance of sensors with different diffusion membranes. These tests include the calibration test (in model buffer solutions and undiluted bovine blood plasma), evaluation of the effect of potential physiological interference, signal reproducibility, and the long-term operational performance. In vitro results suggest that annealed PC membranes have the advantages of good reproducibility, as well as ease of fabrication, and thus were utilized for in vivo application.; An integrated implantable system consisting of a glucose biosensor (with glucose oxidase), an oxygen sensor (without glucose oxidase), a miniature potentiostat, a power supply, and a signal acquiring device was subcutaneously implanted in healthy mongrel dogs. The results of acute subcutaneous implantation of the integrated system showed good agreement between the glucose concentration measured by the biosensor and that obtained using standard glucose determination methods. During chronic implantation the biosensor was successfully refilled in vivo. A rejuvenation of the sensor's response after refilling was observed suggesting the potential of such sensors for long-term implantation.; The studies in this dissertation suggest that the sensors have the good potential for long-term implantation, however, further work are needed to improve the sensor lifetime. More investigations on hysteresis, sensor miniaturization and biocompatibility are suggested for the later studies. |
