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Keywords:

  • monoclonal antibody charge variants;
  • ion exchange;
  • multicomponent adsorption kinetics;
  • mass transfer modeling;
  • diffusion

Abstract

Transport models are developed for the adsorption of monoclonal antibody charge variants in cation exchange columns for two different matrices: UNOsphere S, which has a macroporous architecture, and Capto S, which contains charged dextran polymers grafted to an agarose matrix. The UNOsphere S protein adsorption kinetics is described by a macropore diffusion model with effective pore diffusivity De = 8.3 × 10−8 cm2/s, which successfully predicts resolution of charge variants by frontal analysis at residence times, L/u, between 0.9 and 5.4 min. The Capto S adsorption kinetics is very fast for individual charge variants and for coadsorption of their mixtures, but is dramatically slower for sequential adsorption, when a more strongly bound variant displaces a more weakly bound one. A Maxwell-Stefan model assuming single-file diffusion predicts, in agreement with experiments, poor resolution of charge variants by frontal analysis even at long residence times as a result of highly hindered counterdiffusion. © 2011 American Institute of Chemical Engineers AIChE J, 58: 2503–2511, 2012