Development of Methodology to Determine in Vivo Metabolic Rates in Mammalian Cells as a Tool to Evaluate and Improve Bioreactor Performance

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To date, the optimization of mammalian cell bioreactor performance has been implemented via the application of empirical correlations relating easily observable cellular kinetics to medium composition and bioreactor operation. While moderately successful, there is a limit to the success that may be achieved with such an empirical approach. A greater degree of success maybe obtained by selectively altering the activity of the metabolic pathways of the cells in a manner that increases bioreactor performance. However, it is difficult to alter pathway activities in a rational fashion if the regulatory characteristics of these pathways are not known, or, more importantly, if they can not even be accurately measured. The development of a method to measure in vivo metabolic activities, as presented in this proposal, addresses this limitation. This method will provide a tool for mammalian cell technologists to approach process optimization from a different and more knowledgeable direction.