Single-use bioreactors

The bags employed in single use bioreactors are presterilized prior to use in cultivation of cells. Several forms of disposable bag bioreactors are available from multiple vendors. Examples include physically stirred bag bioreactors and wave-mixed bag bioreactors. A schematic diagram of a wave-mixed bag bioreactor is shown in Figure 13.13. Bag bioreactors are used in the production of therapeutic recombinant proteins and monoclonal antibodies. Other types of single use bioreactors include permselective membrane reactors in both hollow-fiber and flat-sheet membrane configurations (see Section 13.2.7). 

Only a few of these techniques are both sufficiently inexpensive and sufficiently advanced in their development that they are economically viable for use in single-use bioreactors (even if only a portion of the instrumentation is actually considered disposable). Individuals with responsibilities in this area have to utilize not only their knowledge of biochemistry and engineering, but also creativity and imagination in facilitating further evolution of disposable bioreactor technology. 

Additional descriptive material concerning single-use bioreactors is provided in the publications of Eibl and Eibl (82), Eibl et (83), Zhou et al. (50), and Warnock and Al-Rubeai (29). 

Characterization and scale-up considerations of single-use bioreactors http //www.youtube.com/watch v= v5DZpEwkHLM... 

The steps between the cell bank and the production fermentation serve the purpose of expanding the seed volume (biomass) to finally provide sufficient cells to inoculate the main fermenter. Early seed stages, also referred to as precultures, are often run in shake flasks or in T-flasks and roller bottles in the case of cell culture, whereas subsequent stages are performed in stainless steel or single-use bioreactors. The dimensions of the seed bioreactors are adjusted to the biological system, as shown in Table 1.5. 

Figure 1.22 Comparison of cost structures of a recombinant biopharmaceutical production (monoclonal antibody) in a 1000-1 stainless steel stirred-tank reactor (SS STR) and in single-use bioreactor (SUB) of the same scale.

Kaiser, A.C., Jossen, V., Schirmaier, C., Eibl, D. et al. (2013) Eluid flow and cell proliferation of mesenchymal adipose-derived stem cells in small scale, stirred, single use bioreactors. Chem. Ing. Tech., 85 (1-2), 95-102. 

Odeleye AOO, Marsh DTJ, Osborne MD, Lye GJ, Micheletti M. On the fluid dynamics of a laboratory scale single-use stirred bioreactor. Chemical Engineering Science 2014 111 299-312. 

To date, stirred-tank bioreactors providing low shear environment by especially designed agitation and aeration systems have been developed [34]. Cultivation systems for immobilized cells such as hollow-fiber, fluidized-bed, and fixed-bed bioreactors are intended to protect the cells from stressful conditions. Nowadays, mammahan cells can be cultivated in volumes up to 20 0001 to produce the necessary quantities of a desired protein. The single-use technology for bioreactor has been successfully implemented on the industrial scale. 

Some bioreactor systems must be completely protected from microbial contamination, meaning that not a single alien bacterium or virus particle can be allowed to penetrate the system. Reliable and economical systems need to be developed to achieve this level of contamination prevention. Along with the need for prevention is the need to be able to detect contamination at a level of a few microorganisms in a hundred kiloliters of medium. This degree of detection is not yet achievable. Research could vastly improve the crude detection methods that are used today. 

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