Regular monitoring of blood glucose is essential for diabetics and may minimize the long term health consequences of fluctuations and/or high levels of blood glucose. Present methods to monitor blood glucose are inconvenient, and require taking a blood sample followed by enzymatic determination of the glucose level. Our goal is to develop the technology needed for a low cost and portable optical glucose sensor. We propose a primarily non-invasive method for monitoring blood glucose, based on trans-dermal optical fluorescence measurement of an implantable glucose sensing element. While this sensor would reveal tissue glucose, it is known that tissue glucose follows blood glucose with only a modest time delay. The proposed method takes advantage of recent developments in fluorescence lifetime-based sensing, which enables quantitative measurements in scattering and/or absorbing media. In order to transduce the glucose level to a change in lifetime, we propose to use the phenomenon of fluorescence resonance energy transfer, which can detect changes in proximity between a fluorescent donor-labeled glucose binding protein and an acceptor-labeled glucose analog such as a dextran polymer. This permits glucose sensing without requiring any consumable reagents. In order to provide practical monitoring of the glucose level, it is necessary that the fluorescence he excited and detected with a simple instrumentation. Toward this end, we propose to develop the glucose assay with donor-acceptor pairs which enable simple instrumentation. We will use osmium-ligand complexes which not only display long-lived luminescence, but also can be excited at longer wavelengths in the red region of the spectrum. The advantage of this approach is that human skin is translucent to red light. With this approach, these probes can he excited with an inexpensive red-emitting diode laser. Preliminary data have demonstrated the possibility and practicality of measuring fluorescence decay times through reasonable thicknesses of skin. An additional component of this project will include judicious selection and testing of glucose permeable implant materials and their biocompatibility. We will use BB/Wistar rats which develop diabetes as test systems for our sensors. Preliminary tests will be conducted in bioreactors to minimize maximal use. The demands of this project are complex and interdisciplinary. Therefore, our team includes specialists in Bio, Chemical and Electrical Engineering, Chemistry and Veterinary Medicine.