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.
| Krishnamurthy, Vijay M; Kaufman, George K; Urbach, Adam R et al. (2008) Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding. Chem Rev 108:946-1051 |
| Siegel, Adam C; Shevkoplyas, Sergey S; Weibel, Douglas B et al. (2006) Cofabrication of electromagnets and microfluidic systems in poly(dimethylsiloxane). Angew Chem Int Ed Engl 45:6877-82 |
| Xu, Shengqing; Nie, Zhihong; Seo, Minseok et al. (2005) Generation of monodisperse particles by using microfluidics: control over size, shape, and composition. Angew Chem Int Ed Engl 44:724-8 |
| Weibel, Douglas B; Garstecki, Piotr; Ryan, Declan et al. (2005) Microoxen: microorganisms to move microscale loads. Proc Natl Acad Sci U S A 102:11963-7 |
| Weibel, Douglas B; Kruithof, Maarten; Potenta, Scott et al. (2005) Torque-actuated valves for microfluidics. Anal Chem 77:4726-33 |
| Weibel, Douglas B; Lee, Andrew; Mayer, Michael et al. (2005) Bacterial printing press that regenerates its ink: contact-printing bacteria using hydrogel stamps. Langmuir 21:6436-42 |
| Stevens, Molly M; Mayer, Michael; Anderson, Daniel G et al. (2005) Direct patterning of mammalian cells onto porous tissue engineering substrates using agarose stamps. Biomaterials 26:7636-41 |
| Weibel, Douglas B; Boulatov, Roman; Lee, Andrew et al. (2005) Modeling the anodic half-cell of a low-temperature coal fuel cell. Angew Chem Int Ed Engl 44:5682-6 |
