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

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