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 degrees 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 degrees C resulted in a lowering of these metabolic rates while having no effect on cell proliferation. Subsequent reduction of the temperature to 32 degrees C resulted in stabilization of the cell concentration at a high density (3.6 x 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 degrees C. During the stationary phase at 32 degrees C, all other specific metabolic rates could be controlled to low and constant levels.
Ducommun
P
P
Ruffieux
P -A
P-
Kadouri
A
A
von Stockar
U
U
Marison
I W
IW
D000818:Animals; D019149:Bioreactors; D016466:CHO Cells / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D006224:Cricetinae; D025802:Electric Capacitance; D004563:Electrochemistry / Q000379:methods; D013696:Temperature