Separation of Macromolecules Based on Conformation Pathways

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CBET-0756588TripathiThis NSF award by the Chemical and Biological Separations program supports work by Professor Anubhav Tripathi at Brown University to explore a novel approach for separation and/or quantification of such ?similar? macromolecules by performing separation under conditions in which conformations differences arise between two isoforms that have similar mobilities in completely folded or unfolded states. The research work determines the dependence of conformation changes of macromolecules on solvent quality to identify the optimal buffer using a microfluidic screening platform. The research program also develops a new microfluidic system for separation of the isoforms in the optimal buffers with high salts. Lastly, the research work develops numerical and analytical tools to analyze separation of close mobility macromolecules with altered conformations. The results of this work is likely to result in a new research direction in separation and purification science, capable of separating and/or quantifying isoforms by utilizing minute amounts of sample, and can lead to a mechanistic understanding of the proposed approach separation. Quantification of macromolecules with similar mobilities has become important in light of their central role in pathological states of mutations, improper expression or function (e.g. prion and cancer diseases). In addition to its clinical utility, this research work can assist in development of a ?library? of conformational signatures of various proteins, which could help researchers that are exploring the complex problem of protein folding. Finally, the educational program couples core skills of thermodynamics, kinetics and transport phenomenon to separation and purification science. The program supports development of new courses in transport processes. The program offers excellent opportunities to new undergraduate laboratories exploring microfluidics. Strong ties are promoted between the fundamental engineering research and assay development in biotechnology and nanotechnology industries.