Monitoring of temperature effects on animal cell metabolism in a packed bed process

Authors

  • P. Ducommun,

    1. Research and Pharmaceutical Development, Laboratoires Serono S.A., CH-1809 Fenil-sur-Corsier, Switzerland
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  • P.-A. Ruffieux,

    1. Research and Pharmaceutical Development, Laboratoires Serono S.A., CH-1809 Fenil-sur-Corsier, Switzerland
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  • A. Kadouri,

    1. Research and Pharmaceutical Development, Laboratoires Serono S.A., CH-1809 Fenil-sur-Corsier, Switzerland
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  • U. von Stockar,

    1. Laboratory of Chemical and Biochemical Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland; telephone: +4121-6933194; fax: +4121-6933680;
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  • I. W. Marison

    Corresponding author
    1. Laboratory of Chemical and Biochemical Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland; telephone: +4121-6933194; fax: +4121-6933680;
    • Laboratory of Chemical and Biochemical Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland; telephone: +4121-6933194; fax: +4121-6933680;
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Abstract

Animal cell (Chinese Hamster Ovary) concentration was determined on-line in a packed bed process using dielectric spectroscopy. This enabled the evaluation of the effect of temperature on specific metabolic rates during 3 months of continuous culture. The effect of low cultivation temperature on cell growth and metabolism was monitored, and the data were used for process development. At 37°C cells grew exponentially with a specific growth rate of 0.038 d−1 and specific glucose uptake and lactate production rates increased continually. Reduction of the temperature to 33.5°C resulted in a lowering of these metabolic rates while having no effect on cell proliferation. Subsequent reduction of the temperature to 32°C resulted in stabilization of the cell concentration at a high density (3.6 × 107 cell per mL of packed bed). In addition, the specific production rate of the protein of interest increased by a factor of 6 compared to the value at 37°C. During the stationary phase at 32°C, all other specific metabolic rates could be controlled to low and constant levels. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 838–842, 2002; DOI 10.1002/bit.10185

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