Surface charge-regulated nanofiltration membrane for precise separation cordycepin from salts

Precise control over the pore size of polyamide nanofiltration membranes is critical for achieving efficient separation between small-molecule biological substances and inorganic salts. However, general polyamide membranes of negatively charged exhibit limited pore-size tunability due to the rapid kinetics of interfacial polymerization, which severely compromises the separation efficiency between small molecules and inorganic salt ions. Herein, a pore-size engineering strategy for interfacial polymerization was proposed by introducing a zwitterionic triamine monomer, tris(2-aminoethyl)amine N-oxide (TRENO) into the piperazine (PIP) aqueous phase to react with trimesoyl chloride (TMC). The strong hydrophilicity of TRENO retards the diffusion of monomers to organic phase, thereby yielding a thinner polyamide layer. Meanwhile, its triamine structure renders the polyamide layer denser and decreases pore radius from 0.35 nm to 0.28 nm. Furthermore, the multi-amine structure of TRENO increases the crosslinking density of the polyamide layer by consuming more acyl chloride groups, thereby reducing the formation of hydrolyzed carboxyl groups on membrane surface. It lowers the surface negative charge and weakens Donnan exclusion effects, allowing small charged solutes such as inorganic salts and amino acids to permeate more readily. As a result, the optimal membrane achieves a pure water flux of 86.0 L m −2  h −1 (nearly three times that of the pristine membrane), and when tested with a ternary mixture of cordycepin, KH 2 PO 4 and FeCl 2 , it exhibits a high cordycepin rejection of 83.6%, low salt rejection, and a cordycepin/KH 2 PO 4 selectivity of 5.65. It also exhibits excellent stability and high flux recovery ratio (FRR) of 93%. This work proves that zwitterion-modulated interfacial polymerization offers a viable route to address the trade-off between selectivity and permeability in biomolecule purification.