Sharma, A;
Bracewell, DG;
(2019)
Characterisation of porous anodic alumina membranes for ultrafiltration of protein nanoparticles as a size mimic of virus particles.
Journal of Membrane Science
, 580
pp. 77-91.
10.1016/j.memsci.2019.02.071.
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Anshul Sharma Manuscript Accepted.pdf - Accepted Version Download (3MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | Characterisation of porous anodic alumina membranes for ultrafiltration of protein nanoparticles as a size mimic of virus particles |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.memsci.2019.02.071 |
| Publisher version: | http://doi.org/10.1016/j.memsci.2019.02.071 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Ultrafiltration, viral vectors, protein nanoparticles, porous anodic alumina, membranes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10071387 |
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