Process-oriented strategies for mitigating protein fouling in ultrafiltration: in-situ growth of microspheres on membrane surfaces

Protein-based therapeutics, including monoclonal antibodies, enzymes, and cytokines, often require concentration to achieve clinical efficacy, improve stability and administration efficiency. Ultrafiltration (UF) is the mainstream technique for protein concentration, but its efficiency remains limited by severe flux decline and protein loss. This study demonstrates that, during the re-concentration process, fouling resistance arising from severe concentration polarization and cake layer formation, rather than the intrinsic membrane resistance, is the primary determinant of filtration flux. To alleviate this resistance, nano-protrusion arrays are patterned on the UF membrane via co-assembly of glutaraldehyde (GA) and hydroxypropyl cellulose (HPC), which act as a turbulence promoter to enhance localized shear forces while minimizing mechanical damage to proteins in the bulk solution. This approach effectively inhibits the formation of the cake layer and alleviated concentration polarization during protein concentration. Compared to the pristine membrane, the as-prepared membrane exhibits great anti-fouling performance with a 40.5 % increase in average permeate flux and a 57.0 % reduction in permeability decline after protein concentration. This work proposes an insightful approach to protein concentration and designing an anti-fouling UF membrane with a gentler filtration process, which holds promise for reducing protein denaturation and minimizing energy consumption by mitigating bulk turbulence.