(466f) Small Scale Media Optimization for Continuous Culture – Effect On Cellular Metabolism

Authors: 
Soos, M. - Presenter, ETH Zurich
Karst, D., ETH Zurich
Morbidelli, M., ETH Zurich



The continuous culture of mammalian cells is designed to produce biotherapeutics at high cell density and viability at steady state condition up to months. Thereby, to mimic the physiological cell environment media formulation is one of the most critical process parameters to tune cellular metabolism optimizing growth, viability and productivity. Both the quantitative composition and concentration are known to affect named culture attributes.

In this study various media compositions including primary carbon sources such as glucose and glutamine, as well as supplemental amino acids, trace elements and vitamins are systematically tested in small spinning tube batch cultures. Preselected conditions are transferred to determine their performance in a perfusion culture set up using tangential flow filtration for cell retention. Changing media composition result in distinct steady states of the cell culture, allowing the identification of nutritional needs when facing increased cell densities. Finally, using the experimental data our goal is to characterize the metabolic state of the cell during optimal culture conditions based on a metabolic network applying Flux Balance Analysis (FBA). Information about the activity of certain metabolic pathways, such as glycolysis, TCA cycle or amino acid metabolism is expected to result in better understanding of the cellular requirements during high density perfusion culture.

Gained knowledge will be used to improve the ability of constructing an enhanced culture environment for mammalian cells and will help in tuning their metabolic state with respect to growth and productivity.