Probing lactate metabolism variations in large-scale bioreactors

Biotechnology Progress
Sen XuHao Chen

Abstract

Lactate metabolism variations are frequently encountered in mammalian cell culture processes, especially during process scale-up. In this study, we took a multipronged approach to investigate the impact of pH, pCO2 , osmolality, base addition, and mixing conditions on the observed lactate variations in a Chinese Hamster Ovary (CHO) fed-batch process at 2,000 L scale. Two cultivating methods, CO2 -controlled and pH-controlled, were used to decouple the individual and synergistic effects from those factors. The individual effects from pH, pCO2 , and osmolality on lactate consumption/reproduction in the stationary phase were insignificant in the ranges studied though the initial lactate production rates varied. In contrast, lactate metabolism was found to be impacted by an interaction between mixing conditions and CO2 accumulation. High CO2 accumulation and poor mixing led to lactate reproduction, whereas either low CO2 or improved mixing were sufficient to result in lactate consumption. Base addition was not required for pH control in the low CO2 conditions, and therefore lactate reproduction was correlated with base addition under poor mixing conditions. Under good mixing conditions, CO2 -triggered base addition did not signific...Continue Reading

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Citations

Nov 11, 2018·Biotechnology Progress·Kahina MellahiOlivier Henry
Nov 14, 2018·Biotechnology Progress·Linda HoshanSen Xu
Aug 9, 2018·Bioprocess and Biosystems Engineering·Rubin JiangSen Xu
Sep 19, 2020·Engineering in Life Sciences·Katrin PaulChristoph Herwig
Apr 5, 2021·Metabolic Engineering·Conor M O'BrienWei-Shou Hu

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