Selective Separation of Similarly Sized Proteins with Tunable Nanoporous Block Copolymer Membranes

Abstract

An integral asymmetric membrane was fabricated in a fast and one-step process by combining the self-assembly of an amphiphilic block copolymer (PS-b-P4VP) with nonsolvent-induced phase separation. The structure was found to be composed of a thin layer of densely packed highly ordered cylindrical channels with uniform pore sizes perpendicular to the surface on top of a nonordered sponge-like layer. The as-assembled membrane obtained a water flux of more than 3200 L m–2 h–1 bar–1, which was at least an order of magnitude higher than the water fluxes of commercially available membranes with comparable pore sizes, making this membrane particularly well suited to size-selective and charge-based separation of biomolecules. To test the performance of the membrane, we conducted diffusion experiments at the physiological pH of 7.4 using bovine serum albumin (BSA) and globulin-γ, two proteins with different diameters but too close in size (2-fold difference in molecular mass) to be efficiently separated via conventional dialysis membrane processes. The diffusion rate differed by a factor of 87, the highest value reported to date. We also analyzed charge-based diffusive transport and separation of two proteins of similar molecular weight (BSA and bovine hemoglobin (BHb)) through the membrane as a function of external pH. The membrane achieved a selectivity of about 10 at pH 4.7, the isoelectric point (pI) of BSA. We then positively charged the membrane to improve the separation selectivity. With the modified membrane BSA was completely blocked when the pH was 7.0, the pI of BHb, while BHb was completely blocked at pH 4.7. Our results demonstrate the potential of our asymmetric membrane to efficiently separate biological substances/pharmaceuticals in bioscience, biotechnology, and biomedicine applications.

Block Copolymer‐Derived Monolithic Polymer Films and Membranes Comprising Self‐Organized Cylindrical Nanopores for Chemical Sensing and Separations

“…For electrochemical sensing and chemical separations, BCPderived nanoporous monoliths have been prepared as thin films immobilized on electrodes (Figure 2 a) and as flowthrough membranes (Figure 2 b and c), [45,46] respectively.…”

“…The detachment issue could be overcome by preparing asymmetric membrane structures from a single BCP (Figure 2 c) through SNIPS. [46,[97][98][99][100] SNIPS gives a bicontinuous microporous membrane covered with a skin layer (ca. 100 nm thick) comprising vertically aligned cylindrical nanopores (7-70 nm in diameter) without any transfer and etching processes.…”

“…The membranes exhibited high water permeability owing to continuous connection from the nanoporous layer to the microporous support [46] and also sharp MWCO owing to the nanoporous skin layer. [46,[98][99][100] It should be noted that the water permeability of many amphiphilic BCP-derived membranes could be controlled by solution pH on the basis of electrostatic swelling/deswelling of charged polymer chains on the nanopores. [46,61,90,98] …”

Topology and Shape Control for Assemblies of Block Copolymer Blends in Solution

“…A variety of morphologies have been extensively reported, [1][2][3][4] including, small spherical micelles, rods, large compound micelles, vesicles as well as bicontinous structures. The local segregation of the AB blocks induces the characteristic shape and topology of the different morphologies.…”

Polymer sieving matrices in microanalytical electrophoresis

“…69 BSA and globulin-g (IgG) were effectively resolved in the system. Furthermore the membrane allowed the selective separation of similarly sized proteins based on charge effects.…”