Mechanistic insights into the membrane fouling mechanism during ultrafiltration of high-concentration proteins via in-situ electrical impedance spectroscopy (EIS)

Membrane fouling by the high protein concentrations used in the biopharmaceutical industry remains poorly understood. In this study, feed concentrations of up to 10,000 ppm of bovine serum albumin (BSA) were investigated with three polymeric membranes, two of which had the same molecular weight cut-off (namely, PES100 and PSF100), and two were of the same membrane material (namely, PES100 and PES10). A crossflow ultrafiltration (UF) setup equipped with electrical impedance spectroscopy (EIS) was used. Results indicate that fouling was predominantly external for all cases, except for the PES100 membrane (i.e., most porous) at 10,000 ppm of BSA, whereby fouling was internal which led to the greatest flux decline. For 10,000 ppm of BSA, (i) for the PES100 and PSF100 membranes, the Nyquist plots shifted to the left initially, then to the right as the BSA deposition started, but (ii) for the tighter PES10 membrane, the shifts kept going leftwards due to NaCl accumulation out-pacing BSA build-up. The main takeaway for filtering feeds with high BSA concentrations is that higher steady-state flux could be achieved by averting internal fouling, either through using membranes with dense internal structures or lower MWCO.