Bioreactors for cultivating mammalian cells are typically aerobic bioreactors and oxygen is usually a limiting nutrient because
of its low solubility in culture media. When bioreactors are scaled up from laboratory to production size, their design must
meet both oxygen distribution and oxygen mass transfer requirements.
One engineering parameter that could be used to compare the newly developed disposable bioreactors with established stainless
steel cell-culture bioreactors could be the oxygen transfer rate (OTR). Because of its low solubility, only 0.3 mM O2, equivalent
to 9 mg/L, dissolves in one litre of water at 20 °C in an air/water mixture. This amount of oxygen will be depleted in a few
seconds by an active and concentrated growing culture unless oxygen is supplied continuously. In contrast, during the same
period the amount of other nutrients used is negligible compared with the bulk of concentrations. Therefore, most aerobic
processes are oxygen-limited. This is the reason why the concept of gas–liquid mass transfer in bioprocesses is centered on
oxygen transfer even if other gasses such as carbon dioxide, hydrogen, methane and ammonia can also be involved.
The mass transfer of oxygen into liquid can be characterized by the OTR or by the volumetric oxygen transfer coefficient (KLa).
The larger the KLa, the higher the aeration capacity of the system. These values have been thoroughly examined as a critical
parameter for bioreactor function.
Conclusion
Figure 4. Disposable system approach.
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Disposable bioreactors with wave agitation are used for commercial and R&D applications for the production of cell-derived
products using animal, insect, plant and virus cultures in good manufacturing practice (GMP) and non-GMP applications. Because
of their flexibility, single-use cultivation bags are especially suitable for screening new cell lines, media optimization
and vaccine production. Basically, two strategies can be implemented when considering the use of disposable bioreactors:
- A partially disposable strategy; for example, preparation of inoculum in disposable cultivation bags for process-scale cultivation
in conventional stirred tank reactors (Figure 4).
Figure 5. Disposable system approach.
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- A completely disposable strategy, where inoculum as well as plant bioreactors are disposables based on the rocking-motion
principle (Figure 5).
Table 2. Oxygen uptake rate values for mammalian cells and E. coli.
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In addition, the use of multiple large-scale disposable bioreactors instead of one conventional stirred tank reactor can be
considered, particularly in view of their ease-of-use and process safety against contaminations of disposable bioreactors.
Finally, the parameter that will document the merits of using conventional bioreactors or disposable bioreactor systems for
biotechnology processes are yield of production, expenditure of time and process costs.8 The cultivation of yeast and aerobic microorganisms is, however, a challenge in disposable bioreactors. As shown in Table
2, because of the published Kla or OTR values, it is unlikely that a wave agitated system can be used for the most common
microbial expression systems because of the Kla or OTR values inherent in this method.
Even if the market for disposable bioreactors has grown rapidly in recent years, full acceptance will only be reached when
the entire production process from media preparation, inoculum preparation and downstream processes can be done using disposable
equipment. Some suppliers are focusing on this issue to become a total solution provider for disposable biotech factories.
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