Nutrient Optimization for the Production of Biologicals from Animal Cells Cultured at High Density
The formulation components necessary to maintain animal cells in vitro at high density for biological production may differ quantitatively and qualitatively from the nutrient requirements for routine cell cultivation at low densities. Elimination of serum to facilitate downstream processing and regulatory approval necessitates compensation for the nutritional and biophysical roles of serum in the cell culture environment. Biochemical analysis of spent culture effluents from high density bioreactors offers a helpful insight to the unique nutrient requirements of that specialized system and permits iterative optimization of serum-free, synthetic medium composition to sustain bioreactor productivity. This information may be exploited, either by enhancing the nutrient levels of the basal medium or by providing nutritional supplementation of exhausted metabolites via batch or perfusion feeding of liquid concentrates. This paper focuses upon techniques utilized in this laboratory to assess bioreactor depletion of amino acids, carbohydrates and lipids. These data are applied to the design of serum-free media for biopharmaceutical and biotechnological applications of hybridomas, recombinant CHO cells, and invertebrate cells.
KeywordsChinese Hamster Ovary Cell Maximal Cell Density Culture Expansion Monoclonal Antibody Production BACULOVIRUS Expression Vector System
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