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Power input is an important engineering and scale-up/down criterion in stirred bioreactors. However, reliably measuring power input in laboratory-scale systems is still challenging. Even though torque measurements have proven to be suitable in pilot scale systems, sensor accuracy, resolution, and errors from relatively high levels of friction inside bearings can become limiting factors at smaller scales. An experimental setup for power input measurements was developed in this study by focusing on stainless steel and single-use bioreactors in the single-digit volume range. The friction losses inside the air bearings were effectively reduced to less than 0.5% of the measurement range of the torque meter. A comparison of dimensionless power numbers determined for a reference Rushton turbine stirrer (NP = 4.17 ± 0.14 for fully turbulent conditions) revealed good agreement with literature data. Hence, the power numbers of several reusable and single-use bioreactors could be determined over a wide range of Reynolds numbers between 100 and >104. Power numbers of between 0.3 and 4.5 (for Re = 104) were determined for the different systems. The rigid plastic vessels showed similar power characteristics to their reusable counterparts. Thus, it was demonstrated that the torque-based technique can be used to reliably measure power input in stirred reusable and single-use bioreactors at the laboratory scale.

Suspension cultures, in which human mesenchymal stem cells (hMSCs) are cultivated on microcarriers in scalable single-use stirred bioreactor types, have been shown to be a promising alternative to planar flask cultures. However, stirred single-use bioreactors were originally developed for production processes with robust, permanent cell lines. hMSCs are adherent primary cells and thus expanding them in such bioreactor systems imposes more stringent requirements on bioreactor systems. For low-serum conditions (5%) and different types of stirred single-use bioreactors, a suspension criteria-based approach for expanding human adipose tissue-derived mesenchymal stem cells (hASCs) from mL- to pilot scale was successfully developed. For process scale-up, experimental and numerical investigations were performed to (1) predict optimum impeller speeds, (2) determine the main engineering parameters (local shear stress, turbulent dissipation rate, Kolmogorov microscale), and (3) verify suspension criteria NS1 and NS1u for rapid process transfer from 100 mL to 2 L and 35 L cultures. Using optimized mediummicrocarrier combinations as well as NS1 and NS1u as scale-up factors, total hASC quantities between 3 •107 (100 mL scale) and 1 • 1010 (35 L scale) were obtained. The cell quantities obtained are the highest reported to date for scalable single-use bioreactors under low-serum conditions.

Mechanical stress caused to transfected Chinese hamster ovary (CHO) suspension cells by reusable and single-use magnetically levitated, bearingless centrifugal pumps was investigated. Cell death rates were determined for different pump speeds and compared with data from a peristaltic and a 4-piston diaphragm pump. Furthermore, the fluid distribution inside the PuraLev® 200 pump was modeled using computational fluid dynamics. The results reveal considerably lower mechanical stress to CHO cells caused by the magnetically levitated bearingless centrifugal pumps than by the peristaltic and diaphragm pump.