SBIR Phase I: Gas-Phase Two-Dimensional Electrophoresis

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This Small Business Innovation Research (SBIR) Phase I project will develop a prototype gas-phase two-dimensional electrophoresis (GP2DE) instrument for analyzing protein structures in mixtures with less sample and higher throughput compared to traditional two-dimensional gel electrophoresis (2DGE). The instrument leverages the previously developed multi-dimensional ion mobility spectrometry (MDIMS) method for separating gas-phase protein ions based on molecular size and shape in both time and space with high-performance IMS. Understanding proteins' functions will be crucial to achieving the advances required for personalized medicine, which will be a strong driver of the proteomics field both scientifically and economically. Consequently, designing specialized therapies requires intricate knowledge of the complete protein structure. GP2DE will provide a rapid tool for detecting differences in protein structures using coupled ion mobility spectrometry analyses to give 2D gel electrophoresis-type separations in seconds to minutes. Increasing the throughput for analyses of protein structures addresses the inefficiencies in the labor intensive 2DGE process to build the structure knowledge base more rapidly. In particular, tools that can detect post-translational modifications of proteins, such as glycosylation or phosphorylation, will be valuable to proteomics. GP2DE can detect these structural changes easily because the structural differences will result in different ion mobilities. The broader impact/commercial potential of this project, if successful, will provide a flexible, general purpose biomolecule analysis tool for researchers with limited budgets and/or facility space. This would be particularly useful for undergraduate laboratories where the shortened learning curve would allow for more productive research under typical time and resource constraints. The proposed gas-phase two-dimensional electrophoresis (G2DPE) evolves from advanced IMS technologies for structural size and shape analyses that are geared to be user-friendly. The market for proteomics research products has been projected to be several billion dollars in the next five years. GP2DE reduces the need to perform many more time consuming 2DGE analyses that have higher operating costs from labor and supplies, decreasing research costs and adding to laboratory productivity. Therefore, having another powerful tool for elucidating protein structural information will propel the rate of development of the next-generation of biotherapies better tailored to individual physiologies. The research conducted will be disseminated in peer-reviewed scientific journals and at scientific conferences to foster the adoption and advancement of multi-dimensional IMS methods for proteomics.