Development of a predictive model for cell growth in shaken bioreactors as a function of the effects of temperature, oxygen transfer rate and seeding cell concentration

The objective of this study was to develop a model for the growth of Chinese Hamster Ovary (CHO) cells in shaken bioreactors. For this purpose a modified three parameters Gompertz equation was used to fit lag, exponential and stationary growth phases. Using a statistically based experimental design, second order polynomial equations with interactions between factors were built in order to describe the maximum slope in exponential phase, the lag duration and the maximal capacity of the cell culture environment. Doehlert design was employed to generate response surfaces with 3 factors: the seeding cell density, the temperature and the oxygen transfer rate (OTR). The physical model of bioreactor was a 50 ml cylindrical vessel with a filter cap (TubeSpin50®) with 10 ml working volume. Some complementary analysis of the glucose and glutamine consumption, lactate and ammonium production and pH correlation with the metabolism were also performed