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

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.

Bovine Serum Albumin and Myoglobin Separation by Ion-Exchange SMB

“…The maximum percentage (% max ) is represented by the following equation, and it depends on the salt concentration. This equation was obtained from the desorption experimental data at different salt concentrations (8) Initial conditions for each column (9) The following equations describe the boundary conditions (10) (11) where L is the column length and C F is the feed concentration (12) (13) Mass balances at the SMB nodes for proteins • Desorbent node (14) • Extract node (15) • Feed node (16) • Raffinate node (17) • Nodes between other columns (18) (19) where C̅ ps is the average salt concentration in the pores in the solid mass base.…”

“…14,15 There are also a few studies regarding ion-exchange SMB separations, such as separating a ternary mixture of proteins in a cation-exchanger SP Sepharose FF. 16 The separation of bovine serum albumin and myoglobin by salt gradient ion exchange was studied by Li et al using a computer-based approach. 17,18 The selected proteins for this study are bovine serum albumin (BSA) and myoglobin (Mb).…”

“…The binding model is described based on the SMA model, previously described (eq 1). 16 The adsorption equilibrium, when only a variation of protein concentration occurs, and the salt concentration is kept constant, was considered since it represents a stage of the procedure in the breakthrough experiments, where a buffer solution with the same salt concentration without protein is fed to the system after an adsorption step. This way, it was necessary to study the existence of hysteresis in desorption using these operating conditions.…”

Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

“…Model reliability plays a crucial role in enhancing the dependability of model-assisted decisionmaking. Model-assisted decision-making has found widespread applications in the field of IEC, such as process optimization, [37] process characterization, [38] process scale-up, [25,39,40] and process control. [41] It is essential to consider the normativity and standardization of model development in IEC processes.…”

Using a machine learning model for the optimal design of simulated moving bed processes and its application to separate rebaudioside A and stevioside

“…Simulated moving bed (SMB) is an important unit operation in chemical engineering to separate chemically similar compounds 14‐16 . Taking advantage of a continuous multicolumn chromatographic process, SMB obtains products with high productivity, good purity, and higher product yield while reducing the consumption of solvent and solid‐phase greatly compared to that consumed using the traditional preparative chromatography 17‐19 . SMB has been widely used in various fields, including fine petrol‐chemicals, pharmaceuticals, and biotechnology industries 20‐22 .…”