Effect of pH Heterogeneity in Large-scale Bioreactor on Fed-batch Culture Process of CHO cells

doi:10.13560/j.cnki.biotech.bull.1985.2015.10.003

Biotechnology Bulletin ›› 2015, Vol. 31 ›› Issue (10): 236-241.doi: 10.13560/j.cnki.biotech.bull.1985.2015.10.003

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Effect of pH Heterogeneity in Large-scale Bioreactor on Fed-batch Culture Process of CHO cells

Liu Jintao¹, Wang Xingyi¹, Fan Li¹, Deng Xiancun^{1, 2}, Liu Xuping¹, Tan Wensong¹

1.State Key Lab of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237; 2. Hisun Pharmaceutical Co.Ltd, Taizhou 318000

Received:2015-01-09 Online:2015-10-28 Published:2015-10-28

Abstract

Abstract: In order to study the effect of pH heterogeneity in large-scale bioreactor on cell culture process of CHO cells, we established a scale down model consistent of stirred tank reactor and plug flow reactor to simulate the pH heterogeneity of large-scale bioreactor based on the mixing characteristic. The results showed that the scale down process with 30 s residence time has no statically difference with the control process. However, significant effect on cell growth, cell metabolism and protein production were found when increased the residence time of PFR. Cell growth rate decreased accompanied by tremendously increase of ammonia and lactate when increased the pH heterogeneity. In addition, the titer, sialic acid content and bioactivity of antibody fusion protein were also decreased when increased the pH heterogeneity.

Key words: CHO cells, scale down, pH heterogeneity, TNFR-Fc, scale up

Liu Jintao, Wang Xingyi, Fan Li, Deng Xiancun, Liu Xuping, Tan Wensong. Effect of pH Heterogeneity in Large-scale Bioreactor on Fed-batch Culture Process of CHO cells[J]. Biotechnology Bulletin, 2015, 31(10): 236-241.

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Effect of pH Heterogeneity in Large-scale Bioreactor on Fed-batch Culture Process of CHO cells

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