Application Note

Real-time Characterization Of Mammalian Cell Culture Bioprocesses By Magnetic Sector MS

By Patrick Floris, a Noemí Dorival-García, Graham Lewis, Graham Josland, Daniel Merrimanb and Jonathan Bones


The complexity of mammalian cell culture processes for biopharmaceutical manufacturing has resulted in the rapid development of Process Analytical Technology (PAT) tools aimed at improving batch-to-batch reproducibility through the implementation of real-time process monitoring techniques. In particular, on-line platforms can provide rapid access to key performance indicators (KPIs) and critical process parameters (CPPs) which can assist the operator's decision-making process and facilitate the timely implementation of required corrective actions.

In this paper 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.

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