Model-based process design of a ternary protein separation using multi-step gradient ion-exchange SMB chromatography

TL;DR

This study develops a model-based design approach for multi-step gradient ion-exchange SMB chromatography to optimize protein separation, outperforming traditional batch systems in purity, yield, and productivity.

Contribution

It introduces a nonlinear binding model and a multi-objective sampling algorithm to design and evaluate complex SMB schemes for protein separation.

Findings

Cascade and eight-zone SMB schemes outperform batch systems.

Pareto fronts reveal trade-offs between purity and yield.

Model-based design improves process performance.

Abstract

Model-based process design of ion-exchange simulated moving bed (IEX-SMB) chromatography for center-cut separation of proteins is studied. Use of nonlinear binding models that describe more accurate adsorption behaviours of macro-molecules could make it impossible to utilize triangle theory to obtain operating parameters. Moreover, triangle theory provides no rules to design salt profiles in IEX-SMB. In the modelling study here, proteins (i.e., ribonuclease, cytochrome and lysozyme) on the chromatographic columns packed with strong cation-exchanger SP Sepharose FF is used as an example system. The general rate model with steric mass-action kinetics was used; two closed-loop IEX-SMB network schemes were investigated (i.e., cascade and eight-zone schemes). Performance of the IEX-SMB schemes was examined with respect to multi-objective indicators (i.e., purity and yield) and productivity, and compared to a single column batch system with the same amount of resin utilized. A multi-objective sampling algorithm, Markov Chain Monte Carlo (MCMC), was used to generate samples for constructing the Pareto optimal fronts. MCMC serves on the sampling purpose, which is interested in sampling the Pareto optimal points as well as those near Pareto optimal. Pareto fronts of the three schemes provide the full information of trade-off between the conflicting indicators of purity and yield. The results indicate the cascade IEX-SMB scheme and the integrated eight-zone IEX-SMB scheme have the similar performance that both outperforms the single column batch system.