Professor Robert T. Kennedy and his group at the University of Michigan are supported by the Analytical and Surface Chemistry Program in the Division of Chemistry to conceive and implement new methods of measuring proteins and protein reactions based on miniaturized forms of electrophoresis. Work includes development of a high-throughput microfluidic "chip" that can collect aqueous samples as nanoliter volume droplets in a carrier stream of oil and then separate the contents of the droplets by electrophoresis at unusually fast rates of 2-5 per second. As a model system, the group is screening for compounds that can affect certain protein-protein interactions involved in cell signaling. A second thrust involves a microscale Western blot by which proteins are separated by sieving electrophoresis in slabs of gel, transferred to a blotting membrane, and then detected on the membrane by interaction with an antibody. Potential utility of the resulting miniaturized, low-cost and highly automated Western blot method based on microfluidic tools will be demonstrated by measuring proteins secreted from embryos in order to examine their role in embryo development.
Development of this new generation of tools is expected to have impact in fields as diverse as biotechnology, chemical genomics, drug discovery, clinical diagnostics and fundamental biochemistry. The tools will be useful to screen libraries of compounds based on their ability to perturb biochemical interactions, enabling discovery of chemical probes of biological networks or novel drugs. The Western blot method developed will enable high-throughput on microscale samples. If sufficiently low cost, the method may also have application in low-resource environments. The work provides interdisciplinary training opportunities for graduate and post-doctoral students, preparing them to make contributions in a variety of fields, but especially in the areas of biotechnology and bioanalytical chemistry. It is anticipated that students working on this project will take positions in industry or academia thus contributing to national science infrastructure.
