Bioreactors are essential tools in biotechnological processes, especially for cell culture and microbial fermentation. Among the different bioreactor systems available, this chapter provides a comparison of Orbital Shaken Bioreactors (OSBs) and Stirred Tank Bioreactors (STRs), highlighting their respective strengths and limitations.
OSBs use an orbital shaking motion to induce liquid circulation and promote surface aeration. This design eliminates the need for internal mechanical components such as impellers or spargers. As a result, OSBs provide a low-shear environment, making them particularly well-suited for cultivating shear-sensitive cells, including mammalian, insect, and plant cells. (Klöckner et al., 2014; Klöckner & Büchs, 2012; Raval et al., 2006) They are commonly available in cylindrical or bag-based single-use formats, and their oxygen transfer performance can be accurately modeled using computational fluid dynamics (CFD) or empirical methods (Klöckner et al., 2014; Zhang et al., 2009). Additionally, the scalability of OSBs has improved in recent years, supporting volumes from milliliters to several hundred liters. (Eibl et al., 2010)
In contrast, STRs employ mechanical agitation via impellers, often combined with gas sparging, to achieve efficient mixing and high oxygen transfer rates (k L a) (Eibl et al., 2010). While highly effective for dense microbial cultures, the combination of shear forces from impellers and bubble-induced stress from sparging can compromise the viability of sensitive cell lines. (Hu et al., 2011) Therefore, STR operation requires precise control of agitation speed, impeller type, and gas flow rates to balance oxygen supply with mechanical stress. (Garcia-Ochoa & Gomez, 2009)
Single-use OSBs offer scalability from microliter volumes, such as those used in microtiter plates, up to 2500 liters. Thanks to their consistent hydrodynamic behavior and low shear forces, OSBs are particularly well-suited for early-stage development, high-throughput screening, and GMP-compliant processes involving sensitive cell types. (Eibl et al., 2010; Klöckner et al., 2014; Kuhner – SB2500-Z, 2025) STRs typically start at the milliliter scale and can be scaled up to 100 m³ in stainless-steel configurations. Modern single-use STRs are commercially available in volumes of up to 6000 liters. (‘ABEC CSR® Single-Use Fermenters’, n.d.; Ambr® 250, 2025; OGI3 BioReactor System, n.d.; Eibl et al., 2010)
In summary, OSBs offer a gentle, predictable environment optimal for shear-sensitive applications, while STRs provide robust mixing and oxygen transfer capabilities suitable for high-density, shear-tolerant cultures. Selection of the appropriate system depends on the biological system, process requirements, and scale of production.
Table 1: Key differences between OSB and STR
Feature | Orbital Shaken Bioreactor (OSB) | Stirred Tank Bioreactor (STB) |
---|---|---|
Mixing principle | Orbital motion, surface aeration | Mechanical impellers and gas sparging |
Shear stress | Low (gentle) | High (can damage shear-sensitive cells) |
Oxygen transfer | Surface-gassing, dependent on shaking dynamics | Enhanced by sparging and agitation |
Scale-up | Simplified (same principles as shake flasks) | Engineering intensive |
Cultivation volumes | Single-Use: 100 µL– 2500 L | Single-Use: 10 mL – 2000 L Stainless steel: 10 mL– 100 m³ |
Suitable for | Mammalian cells, plant cells, insect cells, stem cells | Microbial cells, mammalian cells, insect cells, plant cells, stem cells |
Equipment complexity | Simple, single-use | Complex, stainless steel, glass or single-use |
ABEC CSR® Single-Use Fermenters. (n.d.). ABEC. Retrieved 3 July 2025, from https://www.abec.com/b_a_goals/abec-csr-single-use-bioreactors-and-fermenters/
Ambr® 250. (2025). Sartorius. https://www.sartorius.com/en/products/fermentation-bioreactors/ambr-multi-parallel-bioreactors/ambr-250-high-throughput
Eibl, R., Löffelholz, C., & Eibl, D. (2010). Single-Use Bioreactors—An Overview. In Single-Use Technology in Biopharmaceutical Manufacture (pp. 33–51). John Wiley & Sons, Ltd. https://doi.org/10.1002/9780470909997.ch4
Garcia-Ochoa, F., & Gomez, E. (2009). Bioreactor scale-up and oxygen transfer rate in microbial processes: An overview. Biotechnology Advances, 27(2), 153–176. https://doi.org/10.1016/j.biotechadv.2008.10.006
Hu, W., Berdugo, C., & Chalmers. (2011). The potential of hydrodynamic damage to animal cells of industrial relevance: Current understanding. Cytotechnology, 63(5). https://doi.org/10.1007/s10616-011-9368-3
Klöckner, W., & Büchs, J. (2012). Advances in shaking technologies. Trends in Biotechnology, 30(6), 307–314. https://doi.org/10.1016/j.tibtech.2012.03.001
Klöckner, W., Lattermann, C., Pursche, F., Büchs, J., Werner, S., & Eibl, D. (2014). Time efficient way to calculate oxygen transfer areas and power input in cylindrical disposable shaken bioreactors. Biotechnology Progress, 30(6), 1441–1456. https://doi.org/10.1002/btpr.1977
Kuhner – SB2500-Z. (2025, June 24). https://kuhner.com/en/products/data/SB2500-X.php
OGI3 BioReactor System. (n.d.). Retrieved 3 July 2025, from https://ogibiotec.com/product/ogi3-bioreactor-system/
Raval, K., Liu, C.-M., & Büchs, J. (2006). Large-Scale Disposable Shaking Bioreactors.
Zhang, X., Bürki, C.-A., Stettler, M., De Sanctis, D., Perrone, M., Discacciati, M., Parolini, N., DeJesus, M., Hacker, D. L., Quarteroni, A., & Wurm, F. M. (2009). Efficient oxygen transfer by surface aeration in shaken cylindrical containers for mammalian cell cultivation at volumetric scales up to 1000 L. Biochemical Engineering Journal, 45(1), 41–47. https://doi.org/10.1016/j.bej.2009.02.003
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