화학공학소재연구정보센터
Journal of Membrane Science, Vol.580, 77-91, 2019
Characterisation of porous anodic alumina membranes for ultrafiltration of protein nanoparticles as a size mimic of virus particles
Viral vectors used in emerging gene therapies face challenges of significant yield loss during downstream processing primarily due to their large size, fragility and mass transfer limitations of the traditional porous chromatography adsorbents. The large size of the vectors in relation to key impurities makes them suitable solutes for ultrafiltration-based separations. Efforts to utilise ultrafiltration for virus purification are often restricted to commercial polymeric membranes with wide pore size distributions and tortuous, interconnected channels. Membranes with narrow pore distributions and straight pore channels such as porous anodic alumina (PAA) may present opportunities for improved virus purification. This paper examines the use of porous anodic alumina membranes for application in virus separation by using model solutes such as thyroglobulin and protein nanoparticles. A systematic approach is used to select a polymeric ultrafiltration membrane rating for comparison with 20 nm rated PAA membrane by comparing hydraulic permeability and dextran sieving characteristics of the membranes. Differences in the filterability of the model solutes were characterised. Finally, a discontinuous diafiltration experiment was employed to fractionate smaller model impurity and protein nanoparticles. Results indicate that PAA membranes have superior fouling resistance with 3-4 folds higher flux recovery ratio and 3-fold higher purification factors compared to the polymeric membranes, but the presence of surface defects make them more susceptible to product loss through leaky transmission.