POL Scientific / JBM / Volume 12 / Issue 1 / DOI: 10.14440/jbm.2025.0046
RESEARCH ARTICLE

Integration of an automated cell culture analyzer with a closed-system hollow-fiber bioreactor for online metabolite detection and cell monitoring

Nathan Schwab1 Nathan Frank1 Tonya Acker1 Kelly Richardson2 Mindy Miller1*
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1 Department of Research and Development, Terumo Blood and Cell Technologies, Lakewood, Colorado 80215, United States
2 Department of Nova BioProfile Applications, Nova Biomedical, Waltham, Massachusetts 02454, United States
JBM 2025 , 12(1), e99010043; https://doi.org/10.14440/jbm.2025.0046
Submitted: 31 July 2024 | Revised: 7 September 2024 | Accepted: 21 November 2024 | Published: 4 March 2025
© 2025 by the Journal of Biological Methods published by POL Scientific. Licensee POL Scientific, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Background: On-line sensing technologies for expanding cell cultures are becoming essential tools for understanding metabolic activity during critical stages of expansion. These tools generate data that indicate when user interventions are required, such as harvesting cells or cell products, inducing cell differentiation, or altering growth medium inputs. The platform must reliably measure the biochemical and physiochemical properties of interest in a dependable, aseptic, and non-invasive manner to benefit users. Objective: In this proof-of-concept study, we used the Nova Biomedical BioProfile FLEX2 as a platform for metabolic and cellular measurements due to its ability to detect a range of metabolically relevant compounds, measure cell counts and viability, and acquire samples automatically. Methods: Here, we demonstrated the straightforward integration of the analyzer with the Quantum Flex™ Cell Expansion System (Quantum Flex) using an available sampling port. While this approach can accommodate both suspension and adherent cell types, this study focused on suspension cells only. In addition, we developed a simple method to integrate the sampling adapter into a Quantum cell expansion set, allowing sample collection at precise intervals. Results: In both cases, the samples were acquired automatically using the analyzer’s timing function, facilitating an automated expansion process with increased data collection frequency – previously impractical with manual sampling. Conclusion: This model provides Quantum Flex users with an option for online sensing to monitor cell expansion at scheduled intervals without requiring additional user input.

Keywords
Hollow-fiber bioreactor
On-line sensing
Metabolic monitoring
Nova Biomedical BioProfile FLEX2
Quantum Flex
Funding
This study was funded by Terumo Blood and Cell Technologies and Nova Biomedical.
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Conflict of interest
Nathan Schwab, Nathan Frank, Tonya Acker, and Mindy Miller are employed by Terumo Blood and Cell Technologies, and Kelly Richardson is employed by Nova Biomedical.
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Journal of Biological Methods, Electronic ISSN: 2326-9901 Print ISSN: TBA, Published by POL Scientific