Multifunctional membranes for lipidic nanovesicle capture

Tangential flow filtration membrane systems are employed for the isolation and concentration of extracellular vesicles. However, interfacial interactions between the membrane surface and species influence the flux and membrane performance. Here we propose a strategy aimed at introducing functional ligands over the membrane surface to improve the separation process through combined size-exclusion and affinity-based mechanisms, avoiding the binding of contaminants and other non-target molecules. Polysulfone membranes were modified by a nanometric coating of differently functionalized copolymers with the dual purpose of limiting non-specific interactions while promoting the chemoselective conjugation of a membrane-sensing peptide ligand (BPt) for lipid nanovesicles capture. Copoly azide polymer coating positively affects the physico-chemical properties of the membrane, improving filtration performance and antifouling capacity. A decrease of the flux decline ratio from 38.7 ± 3.9% to 21.2 ± 2.4% and an increase of the ratio of protein permeate concentration (Cp) to the respective feed concentration (Cf) to values of 0.97 was measured after coating the membrane with c-(DMA-N3-BP-MAPS) highlighting its capability to reduce protein adsorption. In addition, the BPt-functionalized membrane displayed a high capturing efficiency towards synthetic liposomes which, notably, can be promptly released upon mild treatment with a divalent cation solution. Overall, our work integrates conventional TFF principles with affinity-based isolation, broadening TFF perspective applications.