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

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.