Biopharmaceutical production processes often use mammalian cells in bioreactors larger than 10,000 L, where gradients of shear stress, substrate, dissolved oxygen and carbon dioxide, and pH are likely to occur. As former tissue cells, producer cell lines such as Chinese hamster ovary (CHO) cells sensitively respond to these mixing heterogeneities, resulting in related scenarios being mimicked in scale-down reactors. However, commonly applied multicompartment approaches comprising multiple reactors impose a biasing shear stress caused by pumping. The latter can be prevented using the single multicompartment bioreactor (SMCB) presented here. The exchange area provided by a disc mounted between the upper and lower compartments in a stirred bioreactor was found to be an essential design parameter. Mimicking the mixing power input at a large scale on a small scale allowed the installation of similar mixing times in the SMCB. The particularities of the disc geometry may also be considered, finally leading to a converged decision tree. The work flow identifies a sharply contoured operational field comprising disc designs and power input to install the same mixing times on a large scale in the SMCB without the additional shear stress caused by pumping. The design principle holds true for both nongassed and gassed systems.

Dedicated to Prof. Dr. Christian Wandrey on the occasion of his 80th birthday A comprehensive experimental characterization of a small-scale bubble column bioreactor (60 mL) is presented. Bubble size distribution (BSD), gas holdup, and k L a were determined for different types of liquids, relevant fermentation conditions and superficial gas velocities u G . The specific interfacial area a and liquid mass transfer coefficient k L have been identified independent of each other to unravel their individual impact on k L a. Results show that increasing u G leads to larger bubbles and higher gas holdup. As both parameters influence a in opposite ways, no increase of a with u G is found. Furthermore, k L increases with increasing bubble size outlining that improved oxygen transfer is not the result of higher a but of risen k L instead. The results build the foundation for further simulative investigations.

Most bubble breakage models have been developed for multiphase simulations using Euler-Euler (EE) approaches. Commonly, they are linked with population balance models (PBM) and are validated by making use of Reynolds-averaged Navier-Stokes (RANS) turbulence models. The latter, however, may be replaced by alternate approaches such as Large Eddy simulations (LES) that play a pivotal role in current developments based on lattice Boltzmann (LBM) technologies. Consequently, this study investigates the possibility of transferring promising bubble breakage models from the EE framework into Euler-Lagrange (EL) settings aiming to perform LES. Using our own model, it was possible to reproduce similar bubble size distributions (BSDs) for EL and EE simulations. Therefore, the critical Weber (Wecrit) number served as a threshold value for the occurrence of bubble breakage events. Wecrit depended on the bubble daughter size distribution (DSD) and a set minimum time between two consecutive bubble breakage events. The commercial frameworks Ansys Fluent and M-Star were applied for EE and EL simulations, respectively. The latter enabled the implementation of LES, i.e., the use of a turbulence model with non-time averaged entities. By properly choosing Wecrit, it was possible to successfully transfer two commonly applied bubble breakage models from EE to EL. Based on the mechanism of bubble breakage, Wecrit values of 7 and 11 were determined, respectively. Optimum Wecrit were identified as fitting the shape of DSDs, as this turned out to be a key criterion for reaching optimum prediction quality. Optimum Wecrit values hold true for commonly applied operational conditions in aerated bioreactors, considering water as the matrix.