Characteristics Of Liquid Mixing And Gas-Liquid Mass Transfer For Animal Cell Culture Processes In Large-Scale Bioreactors

High-density cell culture in large-scale bioreactors becomes critical with the rapid development of animal cell culture technology and the growth of therapeutic protein demand. Liquid mixing and mass transfer are two important issues for animal cell high-density culture processes in large-scale bioreactors, in which the contradiction between oxygen supply and carbon dioxide stripping has become a key problem to be studied.This study focused on characteristics of fluid mixing and gas-liquid mass transfer in animal cell culture bioreactors. Firstly, the influence of operating parameters on fluid mixing characteristics was investigated. The results indicated that liquid mixing improved with the increasing stirring speed. On the contrary, it became worse when the scale of bioreactors were increased. Based on above results, we established the mixing time model and predicted the mixing time well in different scale bioreactors, in which Reynolds number, the reactor volume and the diameter of impellers were taken as argument.Secondly, study on the characteristics of mass transfer of oxygen and carbon dioxide in large scale bioreactors found that the transfer rate of carbon dixode was24times more than that of oxygen in the same option. As a result it was easier to reach gas-liquid equilibrium for carbon dioxide than oxygen, and the smaller the bubble diameter was, the shorter the time required for gas-liquid equilibrium was. Aeration rate had great impacts on oxygen and carbon dioxide transfer rate. Higher agitation speed improved the transfer rate of oxygen while showed little effect on that of carbon dioxide. The transfer coefficients of oxygen and carbon dioxide increased when diameters of the bubble became smaller, but on the same transfer coefficients of oxygen smaller bubbles made carbon dioxide stripping worse.Finally, we established the mass transfer models for oxygen supply and carbon dioxide stripping based on our reaseach, and the study predicted the transfer coefficients well in200L bioreactors. Besides, we optimized operating parameters and strategies of oxygen supply and carbon dioxide stripping for animal cell high-density culture processes in200L bioreactors, which avoided carbon dioxide from overaccumulation. The average relative deviations between the experimental data and predictive value was15%, showed that mass transfer models play an important role in forecast of accumulation of carbon dioxide well for cell culture process in200L bioreactors. Based on the study of the characteristics of liquid mixing and mass transfer in bioreactors, laid the foundation for scale-up and optimization of animal cell culture processes in large-scale bioreactors, and provide a scientific basis for the design of large-scale bioreactors.