  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.
