Towards next generation high throughput ion exchange membranes for downstream bioprocessing: A review

Membrane chromatography is recognised as a potential solution to streamline downstream processing for protein purification, where ion exchange membrane chromatography (IEMC) as a polishing step to remove impurities has been successfully demonstrated in small scales. Despite limited commercial adoption in large-scale production, the concept of IEMC attracts many interests and tremendous progress is made. To fill the review gap for advancements in the last decade, this article provides a timely analysis on key performance-determining aspects in IEMC systems. Modern laboratory-made membranes with polymeric chains of tuneable surface area and charge allow for high binding capacity (up to 10-fold higher than that of traditional resins) while simultaneously mitigating the loss of permeance due to the introduction of grafted layers up to 40%. Nevertheless, robust evaluation are yet to be conducted. Despite making equal contribution to binding, the review on process-related work was supported by only <1/3 of the cited articles, where a transition of empirical to mechanistic models was identified, enabling rationale system design and upscaling. The use of molecular simulation into binding studies reveals the roles of membrane properties but limited work was found. While highlighting disconnection between academic and commercial efforts, research gaps for future work were identified.