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Applications of off-gas mass spectrometry in fed-batch mammalian cell culture

Off-gas analysis using a magnetic sector mass spectrometer was performed in mammalian cell cultures in the fed-batch mode at the 5 L bench and 50 L pilot scales. Factors affecting the… Click to show full abstract

Off-gas analysis using a magnetic sector mass spectrometer was performed in mammalian cell cultures in the fed-batch mode at the 5 L bench and 50 L pilot scales. Factors affecting the MS gas traces were identified during the duration of the fed-batch cultures. Correlation between viable cell concentration (VCC) and oxygen concentration of the inlet gas into the bioreactor (O 2 -in) resulted in R 2 ≈ 0.9; O 2 -in could be used as a proxy for VCC. Oxygen mass transfer (kLa) was also quantified throughout the culture period with antifoam addition at different time points which is shown to lower the kLa. Real-time specific oxygen consumption rate ( q O 2 ) of 2–20 pmol/cell/day throughout the bioreactor runs were within the range of values reported in literature for mammalian cell cultures. We also report, to our knowledge, the first instance of a distinct correlation between respiration quotient (RQ) and the metabolic state of the cell culture with regard to lactate production phase (average RQ > 1) and consumption phase (average RQ < 1).

Keywords: mammalian cell; mass; gas; fed batch; cell

Journal Title: Bioprocess and Biosystems Engineering
Year Published: 2019

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