Fermentation processes large-scale

Other Processes. Isopropyl alcohol can be prepared by the Hquid-phase oxidation of propane (118). It is produced iacidentaHy by the reductive condensation of acetone, and is pardy recovered from fermentation (119). Large-scale commercial biological production of isopropyl alcohol from carbohydrate raw materials has also been studied (120—123). 

Figure 9.6 Examples of fermenters, (a) Large-scale fermenter for the production of ethanol (Copsright Lurgi AG, Germany), (b) Hi -tech industrial scale fermenter only the top part with the connections for loading and downstream processing is shown, the lower part extends to the floor below (right). Source Lonza Biologies Portsmouth USA)...

As can be seen from the four different examples, the choice of purification steps and procedures depends on the product location and properties and ultimately very much on the target application. Considerations are if the molecule is intracellular, cell associated, or extracellular and if it is soluble in the aqueous fermentation liquid or not. Other considerations are the fermentation medium itself and the fermentation organism. Large-scale industrial fermentation media often relies on complex, crude feedstocks as nutrient sources, as using defined nutrient sources is usually cost prohibitive. One of the major challenges is that complex fermentation media can lead to more variability in the fermentation output. To consistently deliver a robust product, downstream processing and formulation need to be able to normalize the upstream variability. 

Some of the economic hurdles and process cost centers of this conventional carbohydrate fermentation process, schematically shown in Eigure 1, are in the complex separation steps which are needed to recover and purify the product from the cmde fermentation broths. Eurthermore, approximately a ton of gypsum, CaSO, by-product is produced and needs to be disposed of for every ton of lactic acid produced by the conventional fermentation and recovery process (30). These factors have made large-scale production by this conventional route economically and ecologically unattractive. 

The ultimate goal of process development is to achieve feasibility where it is possible to produce amino adds on a large scale at a production cost per kg of amino add comparable to, or cheaper than, the processes currently used by other companies. If we presume that the technical performance (fermentation and recovery) are sorted out on a laboratory scale and scaling up looks promising, then it is time to find out whether it is possible to operate economically on a large scale. 

A bioreactor is a vessel in which an organism is cultivated and grown in a controlled manner to form the by-product. In some cases specialised organisms are cultivated to produce very specific products such as antibiotics. The laboratory scale of a bioreactor is in the range 2-100 litres, but in commercial processes or in large-scale operation this may be up to 100 m3.4,5 Initially the term fermenter was used to describe these vessels, but in strict teims fermentation is an anaerobic process whereas the major proportion of fermenter uses aerobic conditions. The term bioreactor has been introduced to describe fermentation vessels for growing the microorganisms under aerobic or anaerobic conditions. 

The power per unit volume is constant. From power consumptions in a bench-scale bioreactor, the necessary agitation rate is calculated for the scale up ratio, using Equation (13.2.1). The choice of criterion is dependent on what type of fermentation process has been studied. The following equation expresses relations for the impeller size and agitation rate in small and large bioreactors. 

The 1980 s and the early 1990 s have seen the blossoming development of the biotechnology field. Three-phase fluidized bed bioreactors have become an essential element in the commercialization of processes to yield products and treat wastewater via biological mechanisms. Fluidized bed bioreactors have been applied in the areas of wastewater treatment, discussed previously, fermentation, and cell culture. The large scale application of three-phase fluidized bed or slurry bubble column fermen-tors are represented by ethanol production in a 10,000 liter fermentor (Samejima et al., 1984), penicillin production in a 200 liter fermentor (Endo et al., 1986), and the production of monoclonal antibodies in a 1,000 liter slurry bubble column bioreactor (Birch et al., 1985). Fan (1989) provides a complete review of biological applications of three-phase fluidized beds up to 1989. Part II of this chapter covers the recent developments in three-phase fluidized bed bioreactor technology. 

The most widespread biological application of three-phase fluidization at a commercial scale is in wastewater treatment. Several large scale applications exist for fermentation processes, as well, and, recently, applications in cell culture have been developed. Each of these areas have particular features that make three-phase fluidization particularly well-suited for them Wastewater Treatment. As can be seen in Tables 14a to 14d, numerous examples of the application of three-phase fluidization to waste-water treatment exist. Laboratory studies in the 1970 s were followed by large scale commercial units in the early 1980 s, with aerobic applications preceding anaerobic systems (Heijnen et al., 1989). The technique is well accepted as a viable tool for wastewater treatment for municipal sewage, food process waste streams, and other industrial effluents. Though pure cultures known to degrade a particular waste component are occasionally used (Sreekrishnan et al., 1991 Austermann-Haun et al., 1994 Lazarova et al., 1994), most applications use a mixed culture enriched from a similar waste stream or treatment facility or no inoculation at all (Sanz and Fdez-Polanco, 1990). 

Table 21. Examples of Pilot and Large Scale Applications of Three-Phase Biofluidization to Fermentation Processes...

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