Fundamentals of Protein Transport in Charged Gels for Chromatography and Membrane Applications

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CTS-0079334Giorgio CartaUniversity of Virginia Fundamentals of Protein Transport in Charged Gels for Chromatography and Membrane ApplicationsAbstractThis project examines protein transport in charged hydrogels prepared for chromatography and membrane applications. The focus is placed on supported gels made by synthesizing them in situ within porous matrices and other rigid structures. The following properties are being investigated: (i) Size exclusion, hydrodynamic permeability, and electrical properties of supported ionic gels; (ii) Protein and electrolyte partitioning and mobility in ionic gels measured through isotope exchange and autoradiography methods; and (iii) Interdiffusion rates for single-protein adsorption and for multicomponent systems in ionic gels stabilized in capillaries and in porous particles using both direct microscopic visualization methods and macroscopic measurements. The experimental data are being used to develop rate models to describe transport of proteins in ionic gels, and the rate theories are incorporated in models for column chromatography to predict and optimize separation performance with practical media. An additional goal is to develop novel membranes based on supported ionic gels to effect protein separations.The overall goal of this research is a fundamental understanding of protein transport in oppositely charged ionic polymeric hydrogels to serve as a basis for the rational development of effective media for biotechnological applications. Polymeric hydrogels have many current and potential uses in this field. While neutral hydrogels serve as size-exclusion media, incorporation of a fixed charge, bound to the polymer backbone introduces the ability to accumulate macromolecules reversibly from dilute solutions. Ionic hydrogels can thus be used in chromatographic and membrane processes for protein separations, for the transdermal delivery of drugs, as implantable vehicles for the long-term delivery of therapeutic agents, and as elements in diagnostic instruments. Understanding the transport properties of charged macromolecules is a key to the optimum design of these materials. The research will also have significant impact on education and development of human resources through the involvement of students and will enhance the development of biotechnology. Separation and purification are generally thought to be the costliest steps in industrial bioprocessing. Hence, the development of improved chromatographic stationary phases and membranes for separations and the education of scientists and engineers in this field are crucial.