Dynamic modelling of cation exchange membrane chromatography for capturing Human Immunoglobulin G (IgG)

Abstract

Membrane chromatography is an emerging technology with great potential for purification of antibodies in the biotechnology industry. To ensure the effective design and development of membrane chromatography, modelling of this system at transient state or dynamic modelling is of great importance. Until this point dynamic modelling studies have mainly focused on anion exchange and affinity membranes. In this study, dynamic modelling of membrane chromatography was performed using two commercial cation exchange membranes (Natrix C and Sartobind S) for purification of the polyclonal antibody Human IgG.

The modelling involved solving three differential equations with eight model parameters and resulted in simulated breakthrough curves for IgG. Three of the model parameters, the overall system volume (Vo), the total porosity of membrane (Ɛ) and the interstitial velocity (U) were determined experimentally using 1% acetone as tracer under two different buffer conditions at pH 5 (phosphate citrate buffer and acetate buffer). The overall range of the porosity estimates for the two membranes was 0.77-0.95, which was in agreement with published porosity values. As no research has used tracer to estimate the porosity of cation exchange membranes so far, this is one of the novel aspects of the study. Further work with an alternative method is required to confirm these porosity estimates.

To obtain experimental breakthrough curves, IgG was purified using both Natrix C and Sartobind S membranes under acetate buffer (pH 5) condition. The model breakthrough curves were fitted to the experimental breakthrough curves with MATLAB. The model fitting using Natrix C membrane was adequate as the sum of squared error (SSE) value was 0.07. However, the model fitting of the breakthrough curve for the Sartobind S membrane was inadequate due to high SSE value of 20.47. From the parameter sensitivity analysis with Natrix C, it was noted that with increasing membrane porosity, the maximum binding capacity of IgG increases.

Overall, this study generated new information regarding the porosity of cation exchange membranes and contributed in expanding research in the area of dynamic modelling of cation exchange membrane chromatography for IgG purification.