Abstract

Membrane chromatography is mainly used for the separation and purification of proteins and biological macromolecules in the downstream processing process, also applications in sewage disposal. Membrane chromatography is recognized as an effective alternative to column chromatography because it significantly improves chromatography from affinity, hydrophobicity, and ion exchange; the development status of membrane chromatography in membrane matrix and membrane equipment is thoroughly discussed, and the applications of protein capture and intermediate purification, virus, monoclonal antibody purification, water treatment, and others are summarized. This review will provide value for the exploration and potential application of membrane chromatography.

Introduction

Traditional column chromatography has high adsorption capacity and separation accuracy for protein [1, 2]; so far, the downstream processing of biological agents has been highly dependent on the use of packed bed resin columns [3, 4]. However, traditional column chromatography generally suffers from a high-pressure drop; the intraparticle diffusion leads to the accumulation of solute molecules, which made the processing time increases, low ligand utilization, and long treatment time, which limits its productivity [5, 6]; meanwhile, column chromatography is expensive; more than 60% of the cost of the biopharmaceutical production process is concentrated in the downstream process of purification and recovery, in which the downstream purification of virus accounts for 70% of the total production cost [7, 8].

Compared with traditional column chromatography, membrane chromatography is more suitable for large proteins of separation and purification (MR > ۲۵۰,۰۰۰); such proteins rarely enter the pores of chromatographic particle matrix [9]. For viruses and macromolecules with obvious diffusion restrictions in conventional chromatographic media, it is particularly important [10]. Although the equilibrium binding capacity is generally low in the membrane, solutes in the membrane pores are mainly transported to the binding sites by convection, reducing the mass transfer resistance of the chromatography process (Fig. 1). Due to the advantage in mass transfer, membrane chromatography is an effective method for extracting trace proteins from large capacity feed, which can maintain their natural conformation by reducing the time in contact with adsorbents, maintaining the biological activity of the required biomolecules while removing impurities [11, 12]. Moenster et al. [13] used the SartobindQ exchange membrane adsorber method to separate and purify penicillin G amidase from cell lysate in one step, compared with previous multiple purification steps, which reduced the operating units and significantly improved the downstream processing efficiency.©

Summary and outlook

As an effective alternative to chromatographic column packing, membrane chromatography has been widely studied in the past to explore the use of virus purification; purified viruses have been used for gene treatment and production of vaccines. Ion-exchange membrane chromatography is currently used for the polishing of monoclonal antibody production processes in the biopharmaceutical industry; hydrophobic interaction chromatography membrane adsorbers are usually in flow mode and are rarely used. At present, the chromatographic process of membrane chromatography combined with column packing or monolithic column has been applied in the field of biological production processes, and has shown good application potential in the treatment of trace harmful matters such as heavy metal ions or dyes in water.

Given the relatively high raw material manufacturing cost of membrane materials, the purification capacity of membrane chromatography must reach a relatively high value, or have a high cycle of reuse to ensure a low commercial cost, to have a relatively high economic value. Predictable and high-precision theoretical models are developing to better clarify the potential mass transfer phenomena and thus improve the separation performance of membranes. Disposable membrane sorbent methods are a small market branch for chromatographic packing at present, from an adoption and evaluation perspective, in the downstream processing technology, which development is more advanced.