Optimization of Fed-Batch Mammalian Cell Culture Processes

Abstract

Fed-batch cultures of hybridoma cells in a serum free medium were carried out in a computer controlled bioreactor. Oxygen uptake rate (OUR) and base addition for controlling pH were employed to calculate key physiologically related variables. Using established stoichiometric relationships between measured variables and the physiological demand we were able to sustain optimal cell growth by feeding salt free concentrated medium while also maintaining glucose at a prescribed range. A reduced lactic acid production and glucose consumption were observed A high cell concentration with a very high viability was achieved through the prolongation of exponential growth stage. The results demonstrate the potential benefit of on-line instrumentation and control in mammalian cell culture.