Localized Sampling Enables Monitoring of Cell State via Inline Electrospray Ionization Mass Spectrometry
Mason A Chilmonczyk1,2, Gilad Doron2, Peter A Kottke1,2
1The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Biotechnology Journal
|September 25, 2020
Summary
A new Dynamic Sampling Platform (DSP) monitors cell bioreactors, providing real-time data on critical quality attributes (CQAs) to improve advanced therapy manufacturing and reduce costs.
Area of Science:
- Biotechnology
- Process Analytical Technology
- Regenerative Medicine
Background:
- Advanced therapies like cell and gene therapies face manufacturing challenges.
- Unreliable processes lead to batch variability and high costs, limiting patient access.
- A lack of Process Analytical Technologies (PATs) hinders characterization of critical quality attributes (CQAs).
Purpose of the Study:
- To introduce a novel PAT for real-time monitoring of cell bioreactors.
- To assess the capability of the Dynamic Sampling Platform (DSP) for spatial and temporal CQA analysis.
- To demonstrate the utility of DSP for improving biomanufacturing feedback control.
Main Methods:
- Coupling the Dynamic Sampling Platform (DSP) with electrospray ionization mass spectrometry.
- Direct-from-culture sampling for in situ CQA measurement in bulk media and microenvironment.
- Continuous monitoring throughout a 3-week cell culture process.
Main Results:
- Real-time spatial and temporal CQA data was obtained from cell bioreactors.
- Microenvironment sampling enabled effective monitoring of cell states like confluence and differentiation.
- The DSP provided critical data for understanding cell culture dynamics.
Conclusions:
- The Dynamic Sampling Platform (DSP) is a viable PAT for bioreactor monitoring.
- Incorporating spatial and temporal resolution is crucial for effective PATs in biomanufacturing.
- DSP data can serve as essential input for feedback control, enhancing process reliability and reducing costs.
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