Abstract
Batch-to-batch reproducibility of animal cell cultures can significantly be enhanced using process control procedures. Most informative signals for advanced process control can be derived from the volume fractions of oxygen and carbon dioxide in the vent line of the reactors. Here we employed simple low-cost sensors, previously not considered for off-gas analysis at a laboratory-scale cell cultures, and compared them with a simultaneously used quadrupole mass spectrometer, i.e., the standard equipment. A decisive advantage is that the sensors did not need any calibration and are easy to use. We show that monitoring and advanced control of cell cultures can significantly be simplified using the devices tested here and that the same batch-to-batch reproducibility can be obtained with much less effort than before.
Similar content being viewed by others
References
Aehle M, Kuprijanov A, Schaepe S, Simutis R, Lübbert A (2011a) Increasing batch-to-batch reproducibility of CHO cultures by robust open-loop control. Cytotechnology 63(1):41–47
Aehle M, Schaepe S, Kuprijanov A, Simutis R, Lübbert A (2011b) Simple and efficient control of CHO cultures. J Biotechnol 153:56–61
Aström K, Hägglund T (2006) Advanced PID control. ISA, Research Triangle Park, NC 27709
Eyer K, Oeggerli A, Heinzle E (1995) On-line gas analysis in animal cell cultivation: II. Methods for oxygen uptake rate estimation and its application to controlled feeding of glutamine. Biotechnol Bioeng 45:54–62
Fiechter A, von Meyenburg K (1968) Automatic analysis of gas exchange in microbial systems. Biotechnol Bioeng 10:535–549
Frahm B, Blank H-C, Cornand P, Oelßner W, Guth U, Lane P, Munack A, Johannsen K, Pörtner R (2002) Determination of dissolved CO2 concentration and CO2 production rate of mammalian cell suspension culture based on off-gas measurement. J Biotechnol 99:133–148
Gnoth S, Kuprijanov A, Simutis R, Lübbert A (2010) Simple adaptive pH control in bioreactors using gain-scheduling methods. Appl Microbiol Biotechnol 85:955–964
Jenzsch M, Gnoth S, Kleinschmidt M, Simutis R, Lübbert A (2007) Improving the batch-to-batch reproducibility of microbial cultures during recombinant protein production by regulation of total carbon dioxide production. J Biotechnol 128:858–867
Kuprijanov A, Schaepe S, Aehle M, Simutis R, Lübbert A (2011) Improving cultivation processes for recombinant protein production. Submitted to Bioproc Biosyst Eng
Oeggerli A, Eyer K, Heinzle E (1995) On-line gas analysis in animal cell cultivation: I. Control of dissolved oxygen and pH. Biotechnol Bioeng 45:42–53
Royce PN (1992) Effect of changes in the pH and carbon dioxide evolution rate on the measured respiratory quotient of fermentations. Biotechnol Bioeng 40:1129–1138
Acknowledgments
The authors thank Dr. Holger Müller (BlueSens GmbH, Herten, Germany) for supplying the gas analyzers and for technical discussions. The financial support of the German State of Sachsen-Anhalt is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Aehle, M., Kuprijanov, A., Schaepe, S. et al. Simplified off-gas analyses in animal cell cultures for process monitoring and control purposes. Biotechnol Lett 33, 2103–2110 (2011). https://doi.org/10.1007/s10529-011-0686-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-011-0686-5