Combination of the steric mass action and non-ideal surface solution models for overload protein ion-exchange chromatography

A model has been developed for protein ion-exchange equilibria under overloaded chromatographic conditions. This model combines the steric mass action model with the non-ideal surface solution model and accounts for steric hindrance and nearest neighbor interactions between protein-protein, protein-salt and salt-salt in a single formalism. Using the model on protein ion-exchange data, the importance of obtaining ion-exchange heat measurements in addition to adsorption isotherms has been demonstrated. It has been shown that small inaccuracies in the heat of ion-exchange data can lead to large differences in predictions of elution behavior. Additionally, it has also been shown that salt-salt interactions on the surface can strongly influence protein adsorption and that in the presence of these interactions, the shape and orientation of the molecule on the surface are important.