Experimental and theoretical considerations on oxygen supply for animal cell growth in fixed-bed reactors

The supply of oxygen is a crucial parameter when cultivating animal cells i n fixed-bed reactors because of the reaction-diffusion limitation within th e porous carriers. To reduce limitation and increase productivity, the diss olved oxygen concentration was raised to above air saturation (hyperoxia) i n long-term experiments using hybridoma cultures. This resulted in a threef old increase of the steady-state antibody production at high dilution rates compared to air saturated medium. A reaction-diffusion model was developed as a tool to describe the oxygen distribution in fixed-bed systems. The mo del corresponded well to the experimental data. It was also used to study t he influence of several parameters on the performance of the fixed-bed syst em, such as the carrier size, the dissolved oxygen concentration, or the su perficial flow velocity. By adapting the model it was shown that reaction-d iffusion limitation is generally not a problem for other substrates such as glucose or glutamine. (C) 1999 Elsevier Science B.V. All rights reserved.