Dual sugar and temperature responsive isoporous membranes for protein sieving with improved separation coefficient and decreased denaturation

Abstract

Sugar dissolved in solution is found to stabilize native structure of proteins and notably decrease their denaturation. To better utilization of this unique performance, we herein studied the preparation and application of a novel isoporous membrane with dual sugar and temperature responsiveness that offered both decreased protein denaturation and improved separation efficiency. New block copolymers (BCPs) with poly (N-isopropyl acrylamide-co-acrylamidophenyl boronic acid) P(NIPAM-co-APBA) as pore forming blocks were synthesized and adopted to prepare isoporous membranes via the SNIPS method. The boronic acid moieties in P(NIPAM-co-APBA) were found to endow membranes with adoptive changes of pore size with the variation of sugar concentrations. The microphase separation of BCPs in concentrated solutions and thin film were carefully studied, observing that APBA attached to pore-forming segment greatly increased the phase separation strength for BCPs. Composition analysis indicated that membranes with uniform pore structures showing higher contents of APBA groups on surface, uncovering an interesting structure-composition relationship that segments with higher fractions of APBA moieties segregated much stronger to pores and surface. Sugar dependent permeability and protein sieving were also determined, observing that the separation coefficient increased sharply from 4.2 to 11 for protein mixture of Hemoglobin/Lysozyme, suggesting that prepared isoporous membranes had enabled a faster separation of proteins in the presence of sugars. It was finally found that sugar in solution simultaneously reduced membrane fouling as it decreased protein denaturation during the separation. Our results demonstrate that novel isoporous membranes fabricated from bio-responsive BCPs with specifically designed functionality will enable protein separation with reduced denaturation, decreased membrane fouling and higher separation selectivity, which remain a big challenge for traditional isoporous membranes produced from well-explored BCPs.