Tailoring stimuli-responsive PVDF-based copolymer membrane with engineered pore structure for efficient antibody purification

Membrane chromatography is considered as a sustainable alternative for downstream purification to overcome the production bottleneck of biopharmaceuticals. However, two of the major factors impeding its industrial adoption are the lack of controllable functionalization and competitive binding capacity. This work aimed to develop a one-pot synthesis strategy for fabricating a new class of pH-responsive poly(vinylidene fluoride)-graft-poly(dimethylaminoethyl methacrylate) (PVDF-g-PDMAEMA) membranes with anion exchangers, to achieve fast and accurate removal of albumin impurities from antibody streams. By utilizing a pre-functionalized copolymer with controlled ligand density, PVDF-g-PDMAEMA membranes with advantageous bicontinuous pore network structure were obtained via an unconventional nonsolvent thermally induced phase separation method. The membrane showed a competitive water permeance of > 6000 L m-2h−1 bar−1. Combining with dedicated static binding and isotherm studies, the membranes demonstrated distinct pH-responsive binding behaviour to model impurity bovine serum albumin (BSA) with maximal binding of 318.0 mg/g at pH 5.5. The dynamic flow-through binding experiments indicated that the membrane could effectively capture BSA from immunoglobulin G (IgG) (model antibody)/BSA mixed solution with a competitive binding capacity of 210.5 mg/g, producing IgG with purity > 90 % and nearly full recovery. Also, comprehensive analysis demonstrated the robustness of the membrane performance through five consecutive operation cycles, with or without harsh alkaline regeneration. The biocompatibility analysis further proved the membranes' suitability in biopharmaceutical applications. This study provided a new route for designing future chromatographic membranes to promote its industrial uptake, pushing for energy-saving and effective downstream bioprocessing.