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Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System

Author(s)
Kwon, Taehong; Ko, Sung Hee; Hamel, Jean-Francois P; Han, Jongyoon
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Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/
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Abstract
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.
Date issued
2020-03
URI
https://hdl.handle.net/1721.1/125538
Department
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
Journal
Analytical Chemistry
Publisher
American Chemical Society (ACS)
Citation
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
Version: Final published version
ISSN
0003-2700
1520-6882

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