Affinity Chromatography for Cell Separation: Mathematical Model and Experimental Analysis

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Abstract
A model for cell affinity chromatography, a separation technique that exploits the differential adhesion of cells to ligand‐coated surfaces, is presented. This adhesion is mediated by specific, noncovalent binding between cell surface macromolecules and ligand. Our model predicts how bound cell levels and selectivity depend on rates of deposition and reen trainment, as well as on the degree of adhesive interactions between the cell and surface, which is characterized by an adhesion efficiency, P. Both transport rates and adhesion efficiencies critically affect the degree of cell retention and separation. Two modes of column operation are considered: cell enrichment, in which we wish to retain a large pure fraction of cells in the column, and cell depletion, in which we wish to remove a large fraction of a particular subpopulation from a cell mixture. Our analysis indicates that each method should work satisfactorily only under restricted parameter conditions, and the requirements are different in the two modes.We also use our model to analyze several sets of experiments. The results of this analysis indicate how adhesion efficiencies vary as a function of flow rate and temperature.This work provides the first quantitative engineering studies of proper operating conditions for successful cell separation using affinity chromatographic methods.

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