Characterization of Pilot Scale Single-Use Bioreactors

Traditional stainless steel bioreactors are relatively well characterized in terms of mixing efficiency and oxygen mass transfer. Disposable bioreactors, however, are relatively new, and understanding of key operational parameters is constantly evolving. These insights are also critical for determining optimal sparging configurations and impeller speeds, since single-use units cannot be scaled up using the traditional power per unit volume criterion. Mixing times were determined for a 200 L disposable bioreactor based on pH shift following acid addition. In general, high volume, high agitation rate sub-surface additions were found to produce the shortest mixing times. Oxygen mass transfer rates (kLa) were determined for 200 L and 1000 L units, based on different sparging configurations and air flow rates. The 2 μm and 20 μm spargers were generally found to be superior to 2 mm T-spargers in terms of overall oxygen mass transfer. Future work can build upon these insights by examining how operational parameters affect the viability of cell culture, elucidating the influence that various agitation and sparging strategies have on cell shear rate, antifoam requirements, and CO2 stripping in single-use bioreactors.