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Adaptive Control at Low Glucose Concentration of HEK‐293 Cell Serum‐Free Cultures
Author(s) -
Siegwart Pascal,
Côté Johanne,
Male Keith,
Luong John H. T.,
Perrier Michel,
Kamen Amine
Publication year - 1999
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp990077v
Subject(s) - glutamine , metabolism , glycolysis , chemistry , carbohydrate metabolism , cell culture , biochemistry , fed batch culture , respiration , glucose uptake , growth rate , chromatography , biology , endocrinology , amino acid , insulin , fermentation , botany , geometry , mathematics , genetics
Fed‐batch cultures were implemented to study the metabolism of HEK‐293 cells. Glucose, measured every 30 min by a FIA biosensor system, was maintained at 1 mM throughout the culture using an adaptive nonlinear controller based on minimal process modeling. The controller performed satisfactorily at both low and high cell concentrations without the need for retuning between different culture phases. Overall, lactate production was significantly reduced by maintaining a low glucose concentration, thus decreasing the rate of glycolysis. The rates of glucose and glutamine uptake as well as the lactate and ammonia production were compared to those obtained in batch mode with an initial glucose concentration of 21 mM. Basically, three phases were observed in both culture modes. The metabolic shift from the first to the second phase was characterized by a significant reduction in glucose consumption and lactate production while maximum growth rate was maintained. The specific respiration rate appeared unchanged during the first two phases, suggesting that no change occurred in the oxidative pathway capacity. In the third phase, cell growth became slower very likely due to glutamine limitation.