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In addition to its annual lectures, ChBE hosts a weekly seminar throughout the year with invited lecturers who are prominent in their fields. Unless otherwise noted, all seminars are held on Wednesdays in the Molecular Science and Engineering Building ("M" Building) in G011 (Cherry Logan Emerson Lecture Theater) at 4:00 p.m. Refreshments are served at 3:30 p.m. in the Emerson-Lewis Reception Salon.
Transport Phenomena in New and Improved Stationary Phases for Downstream Processing of Biopharmaceuticals
Downstream processing of pharmaceutical proteins such as monoclonal antibodies (mAbs) is currently limited by capacity and rate bottlenecks. Binding capacity is limited by the large size of these biomolecules while their slow diffusion requires long processing times. The key to removing these bottlenecks is thus to devise new and improved stationary phases for protein chromatography where both capacity and mass transfer rates are increased without sacrificing mechanical strength so that more can be adsorbed faster. Composite materials, incorporating soft, charged polymers supported by a rigid structure have been introduced for this purpose in recent years and appear to be a significant step in the desired direction. But how do these materials achieve faster transport without comprising capacity? The combined use of macroscopic measurements, microscopic measurements using confocal laser scanning microscopy to track the movement of proteins within the chromatographic particles, and transport modeling provides mechanistic insight. We show that protein capacity is increased by multilayer binding while transport is enhanced by close-range biomolecular interactions within the charged polymers giving rise to a large diffusional driving force. We also address the large effects that subtle charge variants arising from post-translational modifications have on chromatography and transport in these materials. Mechanistic models and conditions under which these composite matrices show promise for various applications are illustrated and an outlook for the future is provided.