Scalable Fabrication of Amine‐Functionalized, High‐Throughput Cellulose Acetate Membranes With Controlled Pore Morphology for Bioseparation Applications

ABSTRACT Ion‐exchange membrane chromatography (IEMC) is a promising alternative to conventional resin‐based systems for bioseparation, offering advantages in throughput, pressure drop, and compatibility with continuous processing. However, challenges related to membrane morphology, functional ligand distribution, and scalability remain. In this study, we present a one‐step fabrication approach to prepare cellulose acetate (CA)‐based anion‐exchange membranes by incorporating low‐molecular‐weight poly(ethylene imine) (PEI, M w ~10,000) and epichlorohydrin (ECH) crosslinker into the casting solution, followed by phase separation via a modified NIPS/VIPS method. The influence of PEI molecular weight and crosslinker type on membrane morphology, porosity, permeability, and binding performance was systematically evaluated. SEM analysis revealed that low‐Mw PEI produced a homogeneous sponge‐like structure, favorable for prolonged solute interaction, while high‐Mw PEI ( M w ~750,000) led to dense or irregular morphologies. Among the tested crosslinkers, ECH yielded membranes with the highest flux, high porosity, and strong structural stability. FTIR and EDS analyses confirmed the successful incorporation of amine functional groups. When tested using a single‐pass tangential flow filtration (SPTFF) system, the optimized CA‐PEI‐ECH membrane demonstrated superior BSA retention (up to 85.66%) and a sustained dynamic binding capacity over time compared to a previously studied 2‐(dimethylamino)ethyl methacrylate (DMAEMA) functionalized CA membrane and non‐functionalized supports. Finally, scale‐up was achieved using a pilot‐scale casting system, which produced membranes with consistent structure and performance. This work offers a practical and scalable route to fabricate high‐performance IEMC membranes suitable for modern, continuous bioseparation processes.