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 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 (O₂-in) resulted in R² ≈ 0.9; O₂-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 (qO₂) 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).