期刊
METABOLIC ENGINEERING
卷 19, 期 -, 页码 1-9出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2013.04.005
关键词
Industrial cell culture engineering; GC-MS metabolomics; Perfusion cultures; Multivariate statistical analysis; Metabolic network reconstruction
Metabolic profiling was used to characterize the time course of cell physiology both in laboratory- and manufacturing-scale mammalian cell perfusion cultures. Two independent experiments were performed involving three vials from the same BHK cell bank, used to inoculate three laboratory-scale bioreactors, horn which four manufacturing-scale cultures were initiated It was shown that metabolomic analysis can indeed enhance the prime variable dataset for the monitoring of perfusion cultures by providing a higher resolution view of the metabolic state. Metabolic profiles could capture physiological state shifts over the course of the perfusion cultures and indicated a metabolic signature of the phase transitions, which was not observable from prime variable data. Specifically, the vast majority of metabolites had lower concentrations in the middle compared to the other two phases. Notably, metabolomics provided orthogonal (to prime variables) evidence that all cultures followed this same metabolic state shift with cell age, independently of bioreactor scale. (C) 2013 Elsevier Inc. All rights reserved.
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