Monitoring of temperature effects on animal cell metabolism in a packed bed process
Monitoring of temperature effects on animal cell metabolism in a packed bed process
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DOI：
10.1002/bit.10185
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发表时间：
2002-03-30
影响因子：
3.8
通讯作者：
Marison, IW
中科院分区：
文献类型：
--
作者：
Ducommun, P;Rueux, PA;Marison, IW
采用介电谱法在填充床工艺中在线测定动物细胞（中国人卵巢）浓度。这使得能够在3个月的连续培养期间评价温度对特定代谢率的影响。监测了低培养温度对细胞生长和代谢的影响，并将数据用于工艺开发。在37 ℃时，细胞呈指数生长，比生长速率为0.038d（-1），比葡萄糖摄取速率和乳酸产生速率持续增加。将温度降至33.5 ℃导致这些代谢率降低，但对细胞增殖没有影响。随后将温度降至32 ℃，使细胞浓度稳定在高密度（3.6 × 10（7）个细胞/mL填充床）。此外，与37 ℃下的值相比，感兴趣的蛋白质的比生产速率增加了6倍。在32 ℃的稳定期，所有其他特定代谢率都可以控制在较低和恒定的水平。(C)2002年John Wiley Sons，Inc.
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 37degreesC 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 33.5degreesC resulted in a lowering of these metabolic rates while having no effect on cell proliferation. Subsequent reduction of the temperature to 32degreesC 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 37degreesC. During the stationary phase at 32degreesC, all other specific metabolic rates could be controlled to low and constant levels. (C) 2002 John Wiley Sons, Inc.