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Monitoring of temperature effects on animal cell metabolism in a packed bed process
Author(s) -
Ducommun P.,
Ruffieux P.A.,
Kadouri A.,
von Stockar U.,
Marison I. W.
Publication year - 2002
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.10185
Subject(s) - chinese hamster ovary cell , metabolism , cell growth , growth rate , chemistry , cell culture , biochemistry , cell , biophysics , chromatography , analytical chemistry (journal) , biology , geometry , mathematics , receptor , genetics
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 × 10 7 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