Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper
This study is dedicated to the rapid removal of protein aggregates and viruses from plasma-derived human serum albumin (HSA) product to reduce the risk of viral contamination and increase biosafety. A two-step filtration approach was implemented to first remove HSA aggregates and then achieve high m...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/7/209 |
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| author | Lulu Wu Athanasios Mantas Simon Gustafsson Levon Manukyan Albert Mihranyan |
| author_facet | Lulu Wu Athanasios Mantas Simon Gustafsson Levon Manukyan Albert Mihranyan |
| author_sort | Lulu Wu |
| collection | DOAJ |
| description | This study is dedicated to the rapid removal of protein aggregates and viruses from plasma-derived human serum albumin (HSA) product to reduce the risk of viral contamination and increase biosafety. A two-step filtration approach was implemented to first remove HSA aggregates and then achieve high model virus clearance using a nanocellulose-based filter paper of different thicknesses, i.e., 11 μm (prefilter) and 22 μm (virus filter) at pH 7.4 and room temperature. The pore size distribution of these filters was characterized by nitrogen gas sorption analysis. Dynamic light scattering (DLS) and size-exclusion high performance liquid chromatography (SE-HPLC) were performed to analyze the presence of HSA aggregates in process intermediates. The virus filter showed high clearance of a small-size model virus, i.e., log<sub>10</sub> reduction value (LRV) > 5, when operated at 3 and 5 bar, but a distinct decrease in LRV was detected at 1 bar, i.e., LRV 2.65–3.75. The throughput of HSA was also dependent on applied transmembrane pressure as was seen by Vmax values of 110 ± 2.5 L m<sup>−2</sup> and 63.6 ± 5.8 L m<sup>−2</sup> at 3 bar and 5 bar, respectively. Protein loss was low, i.e., recovery > 90%. A distribution of pore sizes between 40 nm and 60 nm, which was present in the prefilter and absent in the virus filter, played a crucial part in removing the HSA aggregates and minimizing the risk of virus filter fouling. The presented results enable the application of virus removal nanofiltration of HSA in bioprocessing as an alternative to virus inactivation methods based, e.g., on heat treatment. |
| first_indexed | 2024-03-10T18:31:00Z |
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| language | English |
| last_indexed | 2024-03-10T18:31:00Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d297357634424a84a7a20a9fa50d0f732023-11-20T06:39:35ZengMDPI AGBiomedicines2227-90592020-07-018720910.3390/biomedicines8070209Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter PaperLulu Wu0Athanasios Mantas1Simon Gustafsson2Levon Manukyan3Albert Mihranyan4Nanotechnology and Functional Materials, Department of Materials Science and Engineering, Box 35, Uppsala University, 751 03 Uppsala, SwedenNanotechnology and Functional Materials, Department of Materials Science and Engineering, Box 35, Uppsala University, 751 03 Uppsala, SwedenNanotechnology and Functional Materials, Department of Materials Science and Engineering, Box 35, Uppsala University, 751 03 Uppsala, SwedenNanotechnology and Functional Materials, Department of Materials Science and Engineering, Box 35, Uppsala University, 751 03 Uppsala, SwedenNanotechnology and Functional Materials, Department of Materials Science and Engineering, Box 35, Uppsala University, 751 03 Uppsala, SwedenThis study is dedicated to the rapid removal of protein aggregates and viruses from plasma-derived human serum albumin (HSA) product to reduce the risk of viral contamination and increase biosafety. A two-step filtration approach was implemented to first remove HSA aggregates and then achieve high model virus clearance using a nanocellulose-based filter paper of different thicknesses, i.e., 11 μm (prefilter) and 22 μm (virus filter) at pH 7.4 and room temperature. The pore size distribution of these filters was characterized by nitrogen gas sorption analysis. Dynamic light scattering (DLS) and size-exclusion high performance liquid chromatography (SE-HPLC) were performed to analyze the presence of HSA aggregates in process intermediates. The virus filter showed high clearance of a small-size model virus, i.e., log<sub>10</sub> reduction value (LRV) > 5, when operated at 3 and 5 bar, but a distinct decrease in LRV was detected at 1 bar, i.e., LRV 2.65–3.75. The throughput of HSA was also dependent on applied transmembrane pressure as was seen by Vmax values of 110 ± 2.5 L m<sup>−2</sup> and 63.6 ± 5.8 L m<sup>−2</sup> at 3 bar and 5 bar, respectively. Protein loss was low, i.e., recovery > 90%. A distribution of pore sizes between 40 nm and 60 nm, which was present in the prefilter and absent in the virus filter, played a crucial part in removing the HSA aggregates and minimizing the risk of virus filter fouling. The presented results enable the application of virus removal nanofiltration of HSA in bioprocessing as an alternative to virus inactivation methods based, e.g., on heat treatment.https://www.mdpi.com/2227-9059/8/7/209virus removal filtration<i>Cladophora</i> celluloseplasma-derived biologicscell culturecell therapies |
| spellingShingle | Lulu Wu Athanasios Mantas Simon Gustafsson Levon Manukyan Albert Mihranyan Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper Biomedicines virus removal filtration <i>Cladophora</i> cellulose plasma-derived biologics cell culture cell therapies |
| title | Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper |
| title_full | Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper |
| title_fullStr | Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper |
| title_full_unstemmed | Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper |
| title_short | Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper |
| title_sort | aggregate removal nanofiltration of human serum albumin solution using nanocellulose based filter paper |
| topic | virus removal filtration <i>Cladophora</i> cellulose plasma-derived biologics cell culture cell therapies |
| url | https://www.mdpi.com/2227-9059/8/7/209 |
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