Methods development in multimodal chromatography with mobile phase modifiers using the steric mass action model

•Provides industrial scientists a simple tool for development of multimodal chromatography.•Demonstrates the high selectivity of multimodal chromatography.•Shows the importance of using appropriate mobile phase modifiers.•Illustrates the use of the SMA isotherm in multimodal chromatography.•Provides an experimental protocol for how to estimate model parameters. The ability to predict downstream protein purification processes is of great value in the biopharmaceutical industry; saving time, cost and resources. While many complex models exist, the appropriate use of simple models can be a useful tool for rapidly designing and optimizing processes as well as for risk analysis and establishing parameter ranges. In this study, the steric mass action isotherm is successfully employed to predict the chromatographic behavior of a multimodal anionic Capto adhere system in the presence of various mobile phase modifiers. An experimental protocol consisting of only a few column experiments is shown to be sufficient to establish the model. Proof of concept is carried out using human insulin and bovine serum albumin which have varying degrees of hydrophobicity, charge and size. Finally, the model predictions are verified under various experimental conditions and the unique selectivity of this multimodal system is explored and compared with traditional anion exchange resins. The simple model approach described here represents a rapid and useful method for model based process development of multimodal chromatography.