title: A sensitive monitoring system for mammalian cell cultivation processes: a PAT approach.
abstract: 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 × 10(5) 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.
authors.affiliation: Institute of Nano and Biotechnologies (INB), FH Aachen University of Applied Sciences, Campus Jülich, Heinrich-Mubmann-Str.1, 52428, Jülich, Germany, Winckler@fh-aachen.de.
authors.forename: Silvia
authors.initials: S
authors.lastname: Winckler
authors.forename: Rolf
authors.initials: R
authors.lastname: Krueger
authors.forename: Thomas
authors.initials: T
authors.lastname: Schnitzler
authors.forename: Werner
authors.initials: W
authors.lastname: Zang
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.forename: Manfred
authors.initials: M
authors.lastname: Biselli
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000096:biosynthesis*; D019149:Bioreactors; D016466:CHO Cells; D002245:Carbon Dioxide / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006825:Hybridomas / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010101:Oxygen Consumption
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D002245:Carbon Dioxide