This is a revised application. The broad, long-term objectives of this Phase I STTR proposal is to demonstrate feasibility in developing a novel optical-electronic biosensor for microscopic applications to permit simultaneous integration of photonic and electronic signals for comprehensive time-lapsed microscopy applications. Optical microscopy has limitations in sensitivity to evaluate the impact of signal transduction on cell-membrane function. Light microscopy is unable to detect cell-membrane displacement at the low nanometer level, and its specificity is limited by the potential over-interpretation of observed microscopic changes at the micron level. Thus, optical signals need to be properly interpreted within the contexts of an independent method. In contrast, electronic sensors have the resolution to measure cell surface cell membrane function at the low nanometer level but have limited intracellular spatial resolution. In collaboration with Iowa State University, CET Inc. will develop a novel, optical-electronic biosensor that will measure several functional parameters in cultured cells in a nondestructive fashion with a resolution of transmission electron microscopy. This sensor will combine the complementary strengths of electronic and optical signals. The outcome of this research is to demonstrate feasibility that will leverage a Phase II proposal that leads to further developments in sensor design, software and hardware development and image analysis and signal processing to provide comprehensive information on signal transduction in cultured living cells. The commercial product will provide a comprehensive platform for cell microscopists. The specific objectives for Phase I of this STTR are: (1) fabricate an optical-electronic sensor that can quantitatively and dynamically measure cell adhesion and motility without electrode signal degradation; (2) experimentally validate that the sensor is not inherently toxic to cells over both short and long time periods; (3) validate that the sensor does not impede the photonic signals from phase, DIC, and fluorescent microscopy. ? ? ?
