Protein Adsorption and Transport in Chromatographic Bioprocessing

University Of Delaware, Newark DE

Investigators

Abstract

CBET-0828590 Lenhoff This NSF award by the Chemical and Biological Separations program supports work by Professor Abraham Lenhoff at the University of Delaware to characterize quantitatively the structure-performance relationship in ion-exchange chromatography of proteins. The results of such analyses will then be used to develop systematic approaches for predicting chromatographic behavior on the basis of a small number of relevant experimental measurements. Ion-exchange chromatography is a major unit operation in industrial bioprocessing, and the prevalence of empirical screening methods can make efficient methods for reducing the scope of trial-and-error methods of optimization particularly valuable. The proposed research will distinguish between traditional adsorbents on consolidated polymeric or gel-like base matrices, and polymer-modified phases in which additional flexible inclusions of various kinds have been shown to offer some performance improvements. For the traditional adsorbents, prior work has produced approaches to predict adsorption isotherms and transport properties to a degree that should allow effective prediction of overall chromatographic behavior. Such capabilities are still lacking for the polymer-modified adsorbents, however. We will therefore measure retention and transport properties for the polymer-modified adsorbents and seek to correlate them with structural characteristics of the materials. In addition, starting with traditional media and moving on to polymer-modified ones, mechanistic methods will be used to develop predictive models of protein loading and elution in packed columns. The proposed research should have an impact in several areas. First, it should contribute significantly to improving the efficiency of conceptual and detailed design of chromatographic steps in bioprocessing. A complementary contribution will be to stationary-phase design, where suitable use of our results can allow desirable characteristics to be designed into such materials. Second, the research will be an effective educational vehicle for training of graduate and undergraduate students; numerous such students who have worked on previous projects of this kind are employed in the biotech and pharma industries. Finally, the proposed research will include a component to disseminate the findings to the larger community interested in chromatographic research and practice by making computational packages for column modeling available as both Matlab routines and as applets that can be run in any web browser.