Highly efficient one-step selective separation of heparin via multi-functional adsorptive membranes

Abstract

Commercial heparin production, a widely applied anticoagulant, requires a series of time-consuming and costly separation units to achieve isolation and purification and the challenging removal of macromolecular impurities, such as proteins. We report a novel separation strategy for the first time that can capture heparin while simultaneously recovering proteins through an efficient one-step separation. Novel adsorptive membranes were prepared by grafting polymer brushes of (3-acrylamidopropyl) trimethylammonium chloride (APTMAC) onto the surface of poly(vinylidene fluoride) (PVDF) membrane via atom transfer radical polymerization (ATRP) by controlling the polymerization time. The prepared membrane exhibited excellent hydrophilicity with water contact angle of 26.57° and adsorption capacity for heparin (598.6 μg/cm2). XPS, FTIR measure and density functional theory (DFT) simulation demonstrated that the adsorptive membrane could effectively adsorb heparin on the surface via the electrostatic interaction between -N(CH3)3+ groups of the grafted APTMAC on the membranes and the reactive functional groups (OSO3−, NHSO3−, COO−) of heparin. Membrane filtration results showed that the adsorptive membranes created one-step separations that could selectively capture heparin via electrostatic interaction while rejecting and concentrating bovine serum albumin (BSA) because of size sieving and hydrated layer repulsion. Besides, the purity of crude heparin increased from 60 % to 93 % through using adsorptive membrane filtration. Moreover, the heparin adsorption capacity remained at 82.3 % of its original capacity after six cycles. This study provides a novel strategy for efficient, economic and selective multi-functional separations for heparin and its similar biomedical medicines.