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A sensitive monitoring system for mammalian cell cultivation processes: a PAT approach

  • Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells, which must be monitored to comply with good manufacturing practice. We, therefore, developed a fully automated system comprising a specific exhaust gas analyzer, inline analytics and a corresponding algorithm to precisely determine the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer rate, transfer quotient and respiratory quotient without interrupting the ongoing cultivation, in order to assess its reproducibility. The system was verified using chemical simulation experiments and was able to measure the respiratory activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary cells) with satisfactory results at a minimum viable cell density of ~2.0 × 10⁵ cells ml⁻¹. The system was suitable for both batch and fed-batch cultivations in bubble-aerated and membrane-aerated reactors, with and without the control of pH and dissolved oxygen.

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Metadaten
Author:Silvia Winckler, Rolf Krueger, Thomas Schnitzler, Werner Zang, Rainer Fischer, Manfred Biselli
DOI:https://doi.org/10.1007/s00449-013-1062-8
ISSN:1615-7591 (Print) 1615-7605 (Online)
Parent Title (English):Bioprocess and biosystems engineering
Publisher:Springer
Place of publication:Berlin, Heidelberg
Document Type:Article
Language:English
Year of Completion:2014
Volume:37
Issue:5
First Page:901
Last Page:912
Link:https://doi.org/10.1007/s00449-013-1062-8
Zugriffsart:campus
Institutes:FH Aachen / Fachbereich Chemie und Biotechnologie
collections:Verlag / Springer