The journal, Bioprocess Biosystems Engineering, recently published a research paper, entitled “Applications of off‑gas mass spectrometry in fed‑batch mammalian cell culture.” The journal is an international peer-reviewed forum for discussion between engineering and biological science to find efficient solutions in the development and improvement of bioprocesses. (Note authors below.*)
The paper discussed in detail how the application of off-gas analysis using a magnetic sector mass spectrometer could be successfully implemented in the 5 L and 50 L scales for fed-batch mammalian cell cultures.
Gas Analysis Mass Spectrometers (MS) have been used successfully for over 30 years on bacterial and microbial processes. More recently, there has been increasing interest in mammalian cell culture because they offer the prospect of radical advances in vaccines, monoclonal antibodies and gene therapy. Although the requirements of mammalian cell fermentation processes provide challenges to the off-gas analyzer, some mass spectrometers have already proved invaluable in improving understanding and increasing yields of mammalian cell cultures.
The research paper identified several factors that could affect gas traces from the MS although they would likely change from system to system.
“…The real-time O2-in gas traces in % mol parameter correlated well with the different phases of the cell cultures and especially with the VCC. An inverse relationship was observed between the real-time CO2 gas traces and the lactate profile of the cultures. kLa could be derived throughout the entire culture duration given the necessary known parameters simply from the off-gas data.
Furthermore, specific actions that were known to influence kLa like antifoam additions could be determined from the off-gas analysis. Finally, the observed RQ profiles appeared distinct enough to show a correlation with either the lactate production or consumption phase during the cultures.
It is assumed that the use of an industrial GS-CHO cell line, would have no impact versus the use of a non-GS-CHO line, due to the different metabolisms and the technique would still be applicable….”
For full details, read the research paper, which includes an overview, materials and methods, experimental set-up details, schematic representations, results and discussions, factors affecting MS gas traces, derived parameters from off‑gas data, an explanation of the relationship between RQ and metabolic state of cell culture, and the discussion of potential applications of off‑gas analysis.
- Read the research paper: Applications of off‑gas mass spectrometry in fed‑batch mammalian cell culture.”
- Additional application notes, white papers,webinars, and other free resources are available in the Improved Quality and Productivity for Pharma and Biotech Manufacturing section of our website.
- Authors: Hai‑Yuan Goh1 · Michael Sulu1 · Haneen Alosert1 · Graham L. Lewis2 · Graham D. Josland2 · Daniel E. Merriman2
1 The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London,
2 Thermo Fisher Scientifc, Cheshire, UK