Slip flow in protein chromatography
Abstract
Protein and antibody based drugs are significant growth areas for the pharmaceutical industry. Formulation, quality control and screening all require very rapid, high resolution chemical separations to eliminate heterogeneity in post-translational modifications as well as assess the aggregation state. In this work, capillary columns packed with sub-micrometer diameter colloidal silica have been shown to significantly increase separation efficiency for reverse phase protein separations. The universal metric for efficiency, plate height, is improved by a factor of 500 over the best previous reports. Columns are shown to separate a monoclonal antibody from its aggregates in less than a minute at room temperature, a ten-fold improvement in speed. This dramatic increase in efficiency can be attributed to the nanoscale flow phenomenon of slip flow. Slip flow has been demonstrated to drastically increase volumetric flow rates and reduce deleterious parabolic flow profiles over traditional separation materials. It is shown that the magnitude of the effect can be tuned easily by reducing the particle size, allowing for even faster and more efficient separations.
Degree
Ph.D.
Advisors
Wirth, Purdue University.
Subject Area
Analytical chemistry
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