Bioreactor industrial scale

Until recently most industrial scale, and even bench scale, bioreactors of this type were agitated by a set of Rushton turbines having about one-thind the diameter of the bioreactor (43) (Fig. 3). In this system, the air enters into the lower agitator and is dispersed from the back of the impeller blades by gas-fiUed or ventilated cavities (44). The presence of these cavities causes the power drawn by the agitator, ie, the power requited to drive it through the broth, to fall and this has important consequences for the performance of the bioreactor with respect to aeration (35). k a has been related to the power per unit volume, P/ U, in W/m and to the superficial air velocity, in m/s (20), where is the air flow rate per cross-sectional area of bioreactor. This relationship in water is... 

The combination of kinetics, hydrodynamics and transport phenomena that provide the proper scale-up of bioreactors from laboratory to the industrial scale also has to be taken into account [4]. Different process solutions will be discussed within this chapter in detail, starting from concrete problem and illustrating possibilities to overcome this problem. 

Biomass containment in continuously operated bioreactors is an essential prerequisite for the feasibility of practical industrial-scale dye biodegradation. Biofilm airlift reactors have demonstrated excellent performance for their ability to control mixing, interphase mass transfer and biofilm detachment rate. Further studies are required to further exploit the potential of this type of reactors with either aggregated cells or biofilm supported on granular carriers. 

In the development of cell or enzyme-based processes, many process configurations exist, including batch, fed batch and continuous operation. In general, the conversion and the separation processes (downstream processing) are regarded as separate units, and most industrial processes are based on this approach. In the last decades, however, more attention is paid to the integration of conversion and separation, leading to the development of membrane bioreactors [49, 50], and some of these concepts have reached an industrial scale. The membranes used for this type of reactors are almost exclusively polymeric, as temperatures seldomly exceed 100 °C for obvious reasons. 

Figure 3.9. Generalized overview of the industrial-scale manufacture of recombinant E2 classical swine fever-based vaccine, using insect cell culture production systems. Clean (uninfected) cells are initially cultured in 500-1000 litre bioreactors for several days, followed by viral addition. Upon product recovery, viral inactivating agents such as /i-propiolactone or 2-bromoethyl-iminebromide are added in order to destroy any free viral particles in the product stream. No chromatographic purification is generally undertaken as the product is substantially pure the cell culture media is protein-free and the recombinant product is the only protein exported in any quantity by the producer cells. Excipients added can include liquid paraffin and polysorbate 80 (required to generate an emulsion). Thiomersal may also be added as a preservative. The final product generally displays a shelf-life of 18 months when stored refrigerated...

Figure 13.1 Schematic representation of a fully instrumented bioreactor system for an industrial-scale fed-batch culture (solid line - fluid flow and air flow dotted line - ana-log/digital signals).

In order to make a decision on the most appropriate operation mode for a bioreactor, several factors must be taken into consideration. At industrial scale, the most important factors are ... 

Inner surface of an industrial-scale stirred-tank bioreactor for animal cell cultivation. Photo taken by Dr. Ernesto Chico, Center of molecular Immunology, Cuba. 

The optimization of culture parameters and the scale-up of a human hetero-hybridoma in a stirred bioreactor are described in this section. From the viewpoint of scale-up and handling, a stirred bioreactor is chosen as the most practical approach for industrial-scale production of monoclonal antibodies (MAbs). Furthermore, stirred bioreactors are very flexible with regard to the optimization of culture parameters, i.e. oxygen supply (bubble free, air sparging) and culture mode (e.g. batch, fed-batch, chemostat and perfusion). They also give easy access to cell samples at any time of culture, and keep cells homogeneously supplied with nutrients and oxygen. 

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. 

As a basic in B LMs for the wastewater treatment the author presents two-phase partitioning bioreactors. He presents the main criteria which must be considered in the selection of the LM solvent biocompatibility (toxicity of the solvent to the microorganism), bioavailabihty (resistance of the solvent to biodegradation by the microorganism used), immiscibility in the aqueous phase, high solubility of pollutant in the solvent, favorable mass-transfer characteristics, etc. Biodegradation mechanisms and kinetics are discussed. Apphcations of bioreactors in wastewater treatment in laboratory, phot, and industrial scale are reviewed. Potential applications are considered also. 

The solvent should be readily available from a local supplier and be cost-effective for pilot- and/or industrial scale [7]. The solubility of the pollutant in question in the diluent should be as high as possible to allow maximum pollutant loadings in the two-phase partitioning bioreactor system, that is, make the biodegradation system perform most effectively [1]. As the last criterion, the diluent should not form emulsion with the treated wastewater. This is required to minimize the entrainment of the cells of the MO used in the organic phase of the system, potentially leading to decrease in the rate of biodegradation [12]. 

On the laboratory-scale, batch cell culturing is mainly conducted in flasks, dishes or microtiter plates (Fig. 1), however industrial-scale bioreactors with perfusion (continuous culture) are also available for production of, e.g. antibodies and other proteins. In both laboratory- and industrial-scale systems, a large volume of cell medium is available in comparison with the cell volume to provide the cultured cells with sufficient amount of nutrients. 

As the consequence of this, the metabolic waste products are initially distributed evenly in the bulk medium but accumulated with time in batch culture systems. Furthermore, as a part of normal culture operations, the vessels are taken out from the incubator for microscopic observations, which can cause movement of the bulk medium and formation of temperature gradients, consequently contributing to forced and natural convection, respectively. In industrial-scale bioreactors, the applied perfusion creates forced convection, which is the primary mode of mass transfer. The common feature of all the conventional systems, laboratory- or industrial scale, is that due to the long distances and the large medium volume in comparison with the cell volume, the significance of convection is pronounced. Consequently, mass transfer in such systems takes place in all directions (x-, y- and z-direction) with a comparable magnitude, as is schematically shown in Fig. 2a. 

The introduction of the koji process to the West is chiefly due to the work of Takamine, which started in 1891 in the USA using wheat bran to make the preparation named Taka-Koji. Takamine introduced the technique of acclimatizing the mold to various antiseptics in order to minimize growth of contaminants during the process. The process was carried out on an industrial scale in rotating drum bioreactors. Large scale trials of the use of Taka-Koji instead of malt in distilleries were carried out in the plant of Hiram Walker Sons in Ontario Canada in 1913. This was marketed as a digestive aid imder the name of Takadiastase [8]. 

The term bioreactor can be apphed to various types of industrial-scale equipment, but there is no commonly... 

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