A Four-Dimensional (4D) Microchip for Proteomics

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Abstract Proposal Title: A Four Dimensional (4D) Microchip for Proteomics, Proposal Number: CTS-0626471, Principal Investigator: Cornelius F. Ivory, Institution: Washington State University Abstract:The project aims at developing an alternative strategy for designing nD separations platforms that emphasizes parallel operation and self-sharpening separation protocols. The proposal is divided into three tasks, first approximately one dozen 1D separations will be adapted to operate on a PDMS platform. The second task is a demonstration of how to move fractionated peaks from one separation dimension to the next, and the third task will involve design of a 4D microchip. This project is an ambitious leap forward in the capabilities of separation science. Reliable separations of tens of thousands of proteins, without overlap and of sufficiently narrow band width, would be the cornerstone of any proteome study. This is because analyzing eluates with overlapping proteins introduce unacceptable uncertainty (and possibly mislead researchers) in the mass spectra. The coupling of micro-fluidics in a massively parallel scheme with a deep knowledge of chromatographic separations is critical. Though admittedly a complete 4-D system would not be fabricated, the PI wisely chose to explore the most significant challenges to the integration using the most cutting edge chromatographic techniques applied to micro-fluidics. The track record of the team is noteworthy. The combination of microfabrication, surface chemistry and chromographic expertise is ideal for the success of this project. The insight in the chemical/transport problems and the strategy for multi-dimensional integration is highly promising. From a broader impacts perspective, success in developing a massively parallel cascade separation system will be a cornerstone for enabling the cataloging of the human proteome. Such success will be a breakthrough for the development of medical treatments for a vast number of illnesses. The scheme can also be applied to medical diagnostics. Insight gained in cascade separations can be applied to higher volume pharmaceutical processes. The proposal will directly support 2 graduate students. Additionally, 3+ undergraduate students per year will also be in the working group. Additional support for teacher participation via the NSF-SWEET program is expected and undergraduates under the NSF-REU program. Overall, the proposal will provide quality educational opportunities to a wide range of individuals._______________________________________Eric S. Peterson, Program Director (1417) Date