Scale-up of Oxygen Transfer in Animal Cell Cultures

Abstract

Animal cells are beginning to be considered for the production of recombinant proteins. The growth of animal cells can be achieved using either suspension or anchoragedependent cells. One common feature using either system is the medium component, serum. The presence of serum introduces a foaming problem specific to animal cell cultures. Due to the fragility of animal cells, antifoams can not be readily used. Furthermore, direct sparging in animal cell cultures can have additional adverse effects due to the presence of the gas-liquid interfaces. Therefore the problem of oxygen transfer during scale-up of animal cell cultures must be addressed if the commercial development of this technology is to be realized. One method to oxygenate animal cell bioreactors without direct sparging is through the use of highly oxygen permeable membranes made of silicon. Furthermore the use of surface aeration can also be explored in combination. In this paper our research on the scale-up of oxygen transfer will be presented. The relationship of the operating parameters on the mass transfer coefficients using silicon tubing in combination with surface aeration will be presented for 0.5 liter and 10 liter fermentors. The studies were performed using anchorage-dependent, recombinant Chinese Hamster Ovary cells for the production of human plasminogen activator.