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Many virus particles, however, are not stable and either lose their infectivity or physically degrade resulting in significant product losses if not harvested continuously. Even hollow fiber membranes with a nominal pore size of 0.2\u2009\u00b5m can retain much smaller virions within a bioreactor. Here, we report on a systematic study to characterize structural and physicochemical membrane properties with respect to filter fouling and harvesting of yellow fever virus (YFV; ~50\u2009nm). In tangential flow filtration perfusion experiments, we observed that YFV retention was only marginally determined by nominal but by effective pore sizes depending on filter fouling. Evaluation of scanning electron microscope images indicated that filter fouling can be reduced significantly by choosing membranes with (<jats:italic>i<\/jats:italic>) a flat inner surface (low boundary layer thickness), (<jats:italic>ii<\/jats:italic>) a smooth material structure (reduced deposition), (<jats:italic>iii<\/jats:italic>) a high porosity (high transmembrane flux), (<jats:italic>iv<\/jats:italic>) a distinct pore size distribution (well\u2010defined pore selectivity), and (<jats:italic>v<\/jats:italic>) an increased fiber wall thickness (larger effective surface area). Lowest filter fouling was observed with polysulfone (PS) membranes. While the use of a small\u2010pore PS membrane (0.08\u2009\u00b5m) allowed to fully retain YFV within the bioreactor, continuous product harvesting was achieved with the large\u2010pore PS membrane (0.34\u2009\u00b5m). Due to the low protein rejection of the latter, this membrane type could also be of interest for other applications, that is, recombinant protein production in perfusion cultures.<\/jats:p>","DOI":"10.1002\/bit.27470","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T09:22:12Z","timestamp":1592817732000},"page":"3040-3052","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Virus harvesting in perfusion culture: Choosing the right type of hollow fiber membrane"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4475-9556","authenticated-orcid":false,"given":"Alexander","family":"Nikolay","sequence":"first","affiliation":[{"name":"Bioprocess Engineering Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-768X","authenticated-orcid":false,"given":"Joris","family":"de Grooth","sequence":"additional","affiliation":[{"name":"Films in Fluids University of Twente Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-5943","authenticated-orcid":false,"given":"Yvonne","family":"Genzel","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9438-1048","authenticated-orcid":false,"given":"Jeffery A.","family":"Wood","sequence":"additional","affiliation":[{"name":"Soft Matter, Fluidics and Interfaces, Faculty of Science and Technology, MESA+ Institute for Nanotechnology University of Twente Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6538-1332","authenticated-orcid":false,"given":"Udo","family":"Reichl","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg Germany"},{"name":"Chair for Bioprocess Engineering Otto\u2010von\u2010Guericke\u2010University Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2018.04.011"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2514"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA19239D"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2015.11.044"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-45736-4_7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-7388(99)00176-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.memsci.2004.08.027"},{"key":"e_1_2_9_9_1","unstructured":"Cornelissen E. 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