Bioreactors for animal cell cultures

Commercial manufacturing operations in biotechnology usually employ bioreactors or fermentors for product expression. In this discussion, the term fermentor will refer to bacterial or fungal processes and the term bioreactor to animal cell cultures. While extensive description of the operation... 

Laboratory-scale stirred-tank bioreactor for animal cell cultiavaion. Photo taken by Dr. Rodrigo C. V. Pinto, Cell Culture Engnieering Laboratory, Federal University of Rio de Janeiro, Brazil. 

Stirred bioreactors are common in animal cell culture, as they offer a homogenous enviroiunent, representative sampling, better access to process control and an increased oxygen transfer. Several of these techniques (spinner flasks and stirred vessel bioreactors) have been tested successfully for the cultivation of hematopoietic cells [58,64-67]. 

Dilution rate values higher than Dwask 0ut cause a progressive decrease in cell concentration, until no more cells are found inside the bioreactor. Thus, Dwash-out is the upper limit that should not be exceeded in a continuous culture. Since the Pmax values for animal cells are between 0.02 and 0.04 h-1 (0.5-1 d 1), the maximum cell concentration usually does not surpass 2 X 106 cell mL"1. Considering that productivity in a contin-... 

Gueza JS, Cassar JP, Wartelle F, Dhulster P, Suhr FF (2004), Real time in situ microscopy for animal cell-concentration monitoring during high density culture in bioreactor, J. Biotechnol. 111 335-343. 

In spite of these hurdles, the last two decades have seen an immense leap in animal cell culture technology both at the laboratory scale as well as the industrial scale. A variety of bioreactors and instrumentation have been ingeniously been devised for the scale up and process control of animal cell cultures. Serum-free media development has considerably reduced the downstream processing costs in the recombinant protein production and purification process. The capability to induce some cell lines to lose anchorage dependence has also been an important breakthrough. 

Airlift reactors are an alternative bioreactor in which the agitation is accomplished by a clear cyclic pattern of air flow through both a riser and a downflow reactor compartment. Stirred tank and airlift reactors are most often used for aerobic cell cultures. Airlift reactors are often utilized to culture plant and animal cells because they typically have lower shear levels. ... 

Measurement and control systems used in the bioreactor for plants are essentially the same as those for microbial or animal cell cultures, but, in special cases, where the mineral components influence the productivity of secondary metabolites, the kind of salts used for the electrode must be taken into consideration. 

Colhgnon M-L, Delafosse A, Crine M, Toye D. (2010) Axial impeller selection for anchorage dependent animal cell culture in stirred bioreactors methodology based on the impeller comparison at just-suspended speed of rotation. Chem. Eng. Sci., 65 5929-5941. 

Animal and Plant Cell Cultures. Bioprocess engineering incorporating animal cell culture is used primarily for the production of health care products such as viral vaccines or antibodies in traditional fermenters or bioreactors with immobilized cells. Antibodies, for example, are produced in bioreactors with hoUow-fiber immobilized animal cells. Plant cell culture is also an important target of bioprocess engineering. However, only a few processes have been successfully developed. One successful process is the production of the pigment shikonin in Japan. Shikonin is used as a dye for coloring food and has applications as an anti-inflammatory agent. 

Continuous flow operation of a bioreactor such that the cells are recycled or retained within the reactor, is sometimes known as perfusion culture. Many different kinds of devices are available for cell retention and recyele. These devices may be loeated within or outside the bioreactor vessel. External sedimentation tanks (Fig. 23b) are often used to recycle biomass in wastewater treatment processes. External and internal enhanced-rate sedimentors are also employed in animal cell culture bioreactors, as shown in Fig. 26a, b. Because of the small differences in... 

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