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

Animal cell (Chinese Hamster Ovary) concn. was detd. online in a packed bed process using dielec. spectroscopy. This enabled the evaluation of the effect of temp. on specific metabolic rates during 3 mo of continuous culture. The effect of low cultivation temp. on cell growth and metab. was monitored, and the data were used for process development. At 37 DegC cells grew exponentially with a specific growth rate of 0.038 d-1 and specific glucose uptake and lactate prodn. rates increased continually. Redn. of the temp. to 33.5 DegC resulted in a lowering of these metabolic rates while having no effect on cell proliferation. Subsequent redn. of the temp. to 32 DegC resulted in stabilization of the cell concn. at a high d. (3.6 * 107 cell per mL of packed bed). In addn., the specific prodn. rate of the protein of interest increased by a factor of 6 compared to the value at 37 DegC. During the stationary phase at 32 DegC, all other specific metabolic rates could be controlled to low and const. levels. [on SciFinder (R)]