(531a) Evaluation of the Impact of Viable Cell Density on kLa for Oxygen Transfer in Perfusion Bioreactors
AIChE Annual Meeting
2017
2017 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Cell Culture Engineering & Process Design II: Reactor Engineering
Wednesday, November 1, 2017 - 12:30pm to 12:48pm
In this study, we implemented an indirect but convenient strategy to evaluate the impact of cells on kLa for oxygen transfer. As part of this study the effect of operating with and without Alternating Tangential Flow (ATF), a widely adopted perfusion technology used in industry, was evaluated. CHO cells expressing a recombinant protein were cultured in two bench-scale perfusion bioreactors at a fixed DO set point. During exponential growth phase (when cell specific oxygen consumption rate is assumed constant), DO controller output required to maintain the DO set point were tracked for a series of conditions of increasing VCDs. After the cell culture finished, kLa was measured at these DO outputs using a standard test media with or without ATF. The predicted oxygen transfer rates at different VCD levels were calculated using kLa measured in test media. By plotting the predicted oxygen transfer rates against VCD, the impact of VCD on actual kLa for oxygen transfer can be inferred by the shape of the curve. Our results indicate that increasing VCD of CHO cells from 10e5 to 350e5 cells/mL results minimal impact on kLa for oxygen transfer. The results also showed that the impact of ATF on kLa is also not significant. In summary, our study presented a useful strategy to understand the role of cells and ATF on kLa for oxygen transfer. The data generated provides justification for using kLa measured in test media without ATF for the study of bioreactors at different scales in industrial settings.