Real-time characterization of mammalian cell culture bioprocesses by magnetic sector MS.

Mammalian cell culture processes were characterized upon the analysis of the exhaust-gas composition achieved through the on-line integration of a magnetic sector MS analyser with benchtop bioreactors. The non-invasive configuration of the magnetic sector MS provided continuous evaluation of the bioreactor's exhaust gas filter integrity and facilitated the accurate quantification of O2 and CO2 levels in the off-gas stream which ensured preserved bioreactor sterility prior to cell inoculation and provided evidence of the ongoing cellular respiratory activity throughout the cultures. Real-time determination of process parameters such as the Respiratory Quotient (RQ) allowed for precise pin-pointing of the occurrence of shifts in cellular metabolism which were correlated to depletion of key nutrients in the growth medium, demonstrating the suitability of this technology for tracking cell culture process performance.

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 (O-in) resulted in R ≈ 0.