Protein adsorption on ion exchange adsorbers: A comparison of a stoichiometric and non-stoichiometric modeling approach.

For mechanistic modeling of ion exchange (IEX) processes, a profound understanding of the adsorption mechanism is important. While the description of protein adsorption in IEX processes has been dominated by stoichiometric models like the steric mass action (SMA) model, discrepancies between experimental data and model results suggest that the conceptually simple stoichiometric description of protein adsorption provides not always an accurate representation of nonlinear adsorption behavior. In this work an alternative colloidal particle adsorption (CPA) model is introduced. Based on the colloidal nature of proteins, the CPA model provides a non-stoichiometric description of electrostatic interactions within IEX columns. Steric hindrance at the adsorber surface is considered by hard-body interactions between proteins using the scaled-particle theory. The model's capability of describing nonlinear protein adsorption is demonstrated by simulating adsorption isotherms of a monoclonal antibody (mAb) over a wide range of ionic strength and pH. A comparison of the CPA model with the SMA model shows comparable model results in the linear adsorption range, but significant differences in the nonlinear adsorption range due to the different mechanistic interpretation of steric hindrance in both models. The results suggest that nonlinear adsorption effects can be overestimated by the stoichiometric formalism of the SMA model and are generally better reproduced by the CPA model.