Mass transfer, mixing, Chinese hamster ovary cell growth and antibody production characterization using Rushton turbine and marine impellers

Large scale production of monoclonal antibodies has been carried out over the years using bioreactors with different length to diameter ratios, and diverse impeller and sparger designs. The differences in these physical attributes often result in dissimilar mass transfer, shear dynamics and mixing inside the bioreactor, that lead to disparities in cell growth and antibody production. A rational analysis of impeller design parameters on cell growth, protein expression levels and subsequent antibody production is needed to understand such differences and has not been investigated in depth before. The purpose of this study was to examine the impact of Rushton turbine and marine impeller designs on Chinese hamster ovary (CHO) cell growth and metabolism, and antibody production and quality. Experiments to evaluate the mass transfer and mixing characteristics were conducted to determine if the nutrient requirements of the culture would be met. The analysis of mixing times indicated significant differences between marine and Rushton turbine impellers at the same power input per unit volume of liquid (P/V). However, no significant differences were observed between the two impellers at constant P/V with respect to oxygen and carbon dioxide mass transfer properties. Experiments were conducted with CHO cells to determine the impact of different flow patterns arising from the use of different impellers on cell growth, metabolism and antibody production. The analysis of cell culture data did not indicate any significant differences in any of the measured or calculated variables between marine and Rushton turbine impellers. A deterministic model was constructed to describe culture behavior under the different flow patterns and the parameters were solved for both marine and Rushton turbine impellers. This work was intended to bridge the gap in understanding the relationship between impellers with different flow patterns and their effect on CHO cells and productivity. Literature in this area has been inadequate and therefore this work is a significant advancement in this area. More importantly, this study was able to demonstrate that the quality of the antibody was not altered with a change in the impeller geometry, which is of critical importance to the biopharmaceutical industry today.