Modelling the mass transfer of a polysaccharide-based protein A chromatography membrane with a bimodal porous structure

Abstract

Efficient and scalable purification methods are essential to meet the growing global demand for monoclonal antibodies. Membrane chromatography is a method to intensify antibody purification processes due to its high throughput. In this study, we present the development of a mass transfer model for the protein A affinity membrane Sartobind® Rapid A. Experimental breakthrough curves performed at residence times between 3 and 60 s exhibit dynamic binding capacities at 10 % breakthrough between 30 and 50 g/L. In contrast to conventional media, this material shows n unusual pattern with precise superposition of breakthrough curves above 80 % breakthrough and finally tailing off in a prolonged saturation phase. Confocal laser scanning microscopy images of the membrane material reveal two regimes in the diameter range of ∼5 to 20 µm, one where convective flow occurs and another where diffusive transport is dominant. The chromatographic workstation and the membrane housing were modelled separately using a system of continuously stirred tank reactors and dispersive plug flow reactors. A modified general rate model, taking various diffusive paths inside the stationary phase into account was able to reproduce the experimentally observed trends. The developed model is useful for process design and scale-up of antibody purification on Sartobind® Rapid A membranes.