The goal of this research is to design, fabricate, and conduct pilot studies on microfluidic systems with integrated mitochondria-based biosensors. To realize a working device based on the release and electrochemical detection of adsorbed cytochrome c (cyt. c) secreted by mitochondria. Three aspects will be explored. 1-Self-assembled monolayer surface (SAM) chemistries for binding mitochondria and cyt. c will be identified. 2-Electrochemical studies will be carried out on the redox properties of cyt. c adsorbed onto SAMs. 3-Microfluidic channels incorporating patterned SAMs for binding mitochondria and cyt. c, and patterned microelectrodes, will be fabricated. With a working microfluidic device in-hand, mitochondria induced apoptosis will be studied using known inducers and inhibitors of apoptosis. The misregulation of apoptosis by mitochondria has been implicated in a number of human diseases: immunodeficiencies, Parkinson's disease, Alzheimer's disease, and carcinogenesis. The proposed research will not only provide a sensitive analytical tool for studying events in mitochondria induced cellular apoptosis, but will also produce a device for the high-throughput screening of small molecules that initiate and inhibit apoptotic signals secreted by mitochondria.
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