A ceramic microsparging aeration system for cell culture reactors

Abstract The supply of oxygen in the cultivation of animal cells in bioreactors still poses a problem. Firstly animal cells must be supplied with the sufficient amount of oxygen, which in turn necessitates the maximum possible oxygen transfer into the liquid phase. Secondly animal cells are very shear stress sensitive. Three different procedures are used as standard in the aeration of cell culture reactors, which are basically bubble aeration, bubble-free aeration and indirect aeration. If the cell damaging impact of gas bubbles is reduced, direct aeration becomes a practical solution with scale up potential and comparatively high oxygen transfer rates. In addition all other aeration methods are technical more complicated and lead to less reliability because of the greater number of connection tubes. Thus in the production of biopharmaceuticals, gas sparging is an efficient and preferred process strategy for oxygen supply to cell cultures. In this paper, a microsparging aeration system made of porous ceramics is presented. The sparging system was used for the cultivation of mammalian cells like suspended CHO cells and adherend MDBK cells immobilized on micro carrier in 2 and 5L standard stirred tank reactors. The system produced bubbles of 100 – 500 μm. Already at a relatively low agitation rate of 50 to 60 rpm in the sparged bioreactor a uniform and constant dissolved oxygen concentration was maintained in the medium. In fact, oxygen transfer measurements revealed that it greatly exceeded the cell requirements. The small bubble diameters and decreased gas flow resulted in a different pattern of foam formation as compared to standard aeration systems.