The objective of the proposed research is to develop a new class of nitric oxide (NO)-releasing bioanalytical sensors and evaluate their utility for in vivo subcutaneous sensor applications. The concept of using local NO release to enhance the performance of in vivo subcutaneous sensors represents a novel approach to overcoming the difficulties that have thus far prevented the development of reliable in vivo biosensors. Current scientific knowledge regarding the role of NO in angiogenesis, phagocytosis, thrombosis, and wound healing suggests that controlled in situ NO release may effectively help reduce biofouling and increase blood flow to the sensor, thus minimizing physiological responses that tend to diminish the in vivo performance of subcutaneous sensors. Specifically, it is envisioned that slow release of NO locally at the implant site will both a) reduce bacterial adhesion and associated biofouling problems, and b) enhance overall wound healing and the formation of capillaries near the implant site such that analyte diffusion from blood to the sensor electrode is enhanced. The fundamental question to be answered by the proposed research is whether electrochemical bioanalytical sensors that continuously release NO can be prepared with improved biocompatibility without compromising the sensor's analytical response. Thus, we seek to determine if the chemistries required for sustained NO release can be made compatible with the chemistries required for selective and sensitive detection of glucose. In addition, we aim to employ micropatterning methods to create unique sensor architectures that support NO release while retaining superior analytical sensitivity. The versatility of the sol-gel process in terms of tuning NO release properties by varying the amount of aminosilane, combined with the variety of pattern geometries that may be created using micropatterning techniques, will allow for the development of numerous types of heterogeneous NO-releasing surfaces with a broad range of possible applications.
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