Mechanistic role of hydrophobic interactions in biofouling and viral retention of poly(isoprene-b-styrene-b-4-vinylpyridine) membranes

We investigate the biofouling and viral retention mechanisms of poly (isoprene-b-styrene-b-4-vinylpyridine) (ISV) membranes designed for viral clearance in downstream bioprocessing. Analysis of flux decay across 14 monoclonal antibody (mAb) feeds (1–2 g/L) confirms that protein adsorption is the main cause of fouling. We present evidence that mAb hydrophobicity, not charge, strongly correlates with fouling propensity, demonstrating the dominance of a non-DLVO hydrophobic interaction between the mAb and the membrane surface. Crucially, rendering the membrane surface chemistry more hydrophilic effectively suppresses the biofouling. Building on this insight, we explored viral retention using bacteriophages PP7 and ΦX-174, which possess similar size but distinct hydrophobicity, revealing dual retention mechanisms: adsorption and size exclusion. Similar to mAb behavior, a highly hydrophilic membrane surface minimizes adsorptive fouling, driving viral retention predominantly toward a reliable size exclusion mechanism. Our results provide a detailed mechanistic understanding of ISV membrane performance, underscoring the critical role of hydrophobic interactions in both fouling and viral clearance, with significant implications for processing complex biologicals under various solution conditions.