Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System
We demonstrate a new micro/nanofluidic system for continuous and automatic monitoring of protein product size and quantity directly from the culture supernatant during a high-cell-concentration CHO cell perfusion culture. A microfluidic device enables clog-free cell retention for a bench-scale (350...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
American Chemical Society (ACS)
2020
|
| Online Access: | https://hdl.handle.net/1721.1/125538 |
| _version_ | 1826212553749954560 |
|---|---|
| author | Kwon, Taehong Ko, Sung Hee Hamel, Jean-Francois P Han, Jongyoon |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Kwon, Taehong Ko, Sung Hee Hamel, Jean-Francois P Han, Jongyoon |
| author_sort | Kwon, Taehong |
| collection | MIT |
| description | We demonstrate a new micro/nanofluidic system for continuous and automatic monitoring of protein product size and quantity directly from the culture supernatant during a high-cell-concentration CHO cell perfusion culture. A microfluidic device enables clog-free cell retention for a bench-scale (350 mL) perfusion bioreactor that continuously produces the culture supernatant containing monoclonal antibodies (IgG1). A nanofluidic device directly monitors the protein size and quantity in the culture supernatant. The continuous-flow and fully automated operation of this nanofluidic protein analytics reduces design complexity and offers more detailed information on protein products than offline and batch-mode conventional analytics. Moreover, chemical and mechanical robustness of the nanofluidic device enables continuous monitoring for several days to a week. This continuous and online protein quality monitoring could be deployed at different steps and scales of biomanufacturing to improve product quality and manufacturing efficiency. |
| first_indexed | 2024-09-23T15:25:02Z |
| format | Article |
| id | mit-1721.1/125538 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:25:02Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1255382022-10-02T02:40:15Z Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System Kwon, Taehong Ko, Sung Hee Hamel, Jean-Francois P Han, Jongyoon Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Research Laboratory of Electronics We demonstrate a new micro/nanofluidic system for continuous and automatic monitoring of protein product size and quantity directly from the culture supernatant during a high-cell-concentration CHO cell perfusion culture. A microfluidic device enables clog-free cell retention for a bench-scale (350 mL) perfusion bioreactor that continuously produces the culture supernatant containing monoclonal antibodies (IgG1). A nanofluidic device directly monitors the protein size and quantity in the culture supernatant. The continuous-flow and fully automated operation of this nanofluidic protein analytics reduces design complexity and offers more detailed information on protein products than offline and batch-mode conventional analytics. Moreover, chemical and mechanical robustness of the nanofluidic device enables continuous monitoring for several days to a week. This continuous and online protein quality monitoring could be deployed at different steps and scales of biomanufacturing to improve product quality and manufacturing efficiency. SMART Innovation Centre (Grant ING137075-BIO) SMART Innovation Centre (Grant ING1510101-BIO) U.S. Food and Drug Administration (Award 1-U01-FD006751-01) 2020-05-28T13:32:25Z 2020-05-28T13:32:25Z 2020-03 2019-12 2020-05-18T15:54:26Z Article http://purl.org/eprint/type/JournalArticle 0003-2700 1520-6882 https://hdl.handle.net/1721.1/125538 Kwon, Taehong et al. "Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System." Analytical Chemistry 92, 7 (April 2020): 5267–5275 © 2020 American Chemical Society en http://dx.doi.org/10.1021/acs.analchem.9b05835 Analytical Chemistry Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Chemical Society (ACS) ACS |
| spellingShingle | Kwon, Taehong Ko, Sung Hee Hamel, Jean-Francois P Han, Jongyoon Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System |
| title | Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System |
| title_full | Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System |
| title_fullStr | Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System |
| title_full_unstemmed | Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System |
| title_short | Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System |
| title_sort | continuous online protein quality monitoring during perfusion culture production using an integrated micro nanofluidic system |
| url | https://hdl.handle.net/1721.1/125538 |
| work_keys_str_mv | AT kwontaehong continuousonlineproteinqualitymonitoringduringperfusioncultureproductionusinganintegratedmicronanofluidicsystem AT kosunghee continuousonlineproteinqualitymonitoringduringperfusioncultureproductionusinganintegratedmicronanofluidicsystem AT hameljeanfrancoisp continuousonlineproteinqualitymonitoringduringperfusioncultureproductionusinganintegratedmicronanofluidicsystem AT hanjongyoon continuousonlineproteinqualitymonitoringduringperfusioncultureproductionusinganintegratedmicronanofluidicsystem |