Protein Transport in Charged Gels for Chromatography and Membrane Applications

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AbstractProposal Title: Protein Transport in Charged Gels for Chromatography and Membrane ApplicationsProposal Number: CTS-0414143Principal Investigator: Georgio CartaInstitution: University of VirginiaThe objective of this project is to develop a fundamental understanding of protein partitioning and transport in charged hydrogels. Understanding the transport properties of charged macromolecules in such materials is a key to their development and optimum design. New insights have recently been obtained through microscopic studies, which can provide the basis to develop a mechanistic understanding of transport. This project will expand current efforts in this area with the ultimate goal of developing new adsorbents and membranes for protein separations as well as models to predict their process performance. Protein partitioning and transport in charged dextran gels and agarose-dextran composites will be studied on a microscopic scale focusing on the effects of gel properties and protein molecular weight and charge on equilibrium uptake and mass transfer kinetics. Kinetics of protein ion-exchange in charged poly(acrylamide) gels and charged agarose-dextran composites will be studied using radiotracer techniques to elucidate protein transport under both gradient and tracer diffusion conditions. Modeling single and multicomponent protein transport in ionic gels and application of these models to predict the behavior of column chromatography under processing conditions will be performed. This research will provide a higher level of understanding of transport phenomena in these complex media as well as models to aid the design and optimization of chromatographic processes. The research will have multiple broader impacts. It will guide the development of optimized stationary phases by media manufacturers. It will also provide a basis for the formulation of rate models to predict and optimize chromatographic separations permitting pharmaceutical companies to improve the design and efficiency of bioprocesses. Since separation and purification are often the costliest steps in bioprocessing, there is a critical need for separation scientists and engineers who are trained to develop and implement novel separation media integrating a broad spectrum of experimental and modeling approaches to improve the effectiveness of industrial bioseparations.