Cell batch fermentor

Cell Growth in Batch Fermentors and Continuous Stirred-Tank Fermentors (CSTF) S3... 

Suppose that a well-mixed stirred tank is being used as a fed-batch fermentor at a constant feed rate F (m h ), substrate concentration in the feed C j (kg m ), and at a dilution rate D equal to the specific cell growth rate p. Ihe cell concentration Cjj (kgrn ) and the substrate concentration (kgm ) in the fermentor do not... 

Figure 1. Cellulose degradation, cell growth and extracellular filter-paper activity in a culture of Thermoactinomyces sp., strain YX. 40 L batch fermentor, 55°C, pH 7.2 (5).

The simple fermentor model has three state variables that change with time during the batch. The first is the concentration of cells X (grams of cells per liter of reactor liquid) that grow during the batch from some initial small value. This is provided by a seed fermentor that is itself a small batch fermentor in which a small number of cells are grown. 

It may also be economical to remove the inhibitory product directly from the ongoing fermentation by extraction, membranes, or sorption. The use of sorption with simultaneous fermentation and separation for succinic acid has not been investigated. Separation has been used to enhance other organic acid fermentations through in situ separation or separation from a recycled side stream. Solid sorbents have been added directly to batch fermentations (18,19). Seevarantnam et al. (20) tested a sorbent in the solvent phase to enhance recovery of lactic acid from free cell batch culture. A sorption column was also used to remove lactate from a recycled side stream in a free-cell continuously stirred tank reactor (21). Continuous sorption for in situ separation in a biparticle fermentor was successful in enhancing the production of lactic acid (16,22). Recovery in this system was tested with hot water (16). 

ABE production was studied by Qureshi et al [3.91] in a laboratory PVMBR system, which coupled a fed-batch fermentor (using C. acetobutylicum) with an UF membrane and a PV product recovery system using a silicalite-silicone composite membrane. Cells of C. acetobutylicum were removed from the culture using the 500,000 molecular weight... 

Kluyveromices fragilis. The behavior of the fermentor is similar to that of a cell recycle reactor with the same fermentation system. Higher productivity and yields than with a batch fermentation are obtained (Tables 7.1, 7.2). The long term cell stability in an HFF (Figure 7.46) is also better than in a batch fermentor. However, even with HFF, reactor productivity is increased at the expense of low substrate conversions, at least at low dilution rates. 

The N. rustica hairy roots were successfully grown in a packed-bed fermentor, yielding biomass densities (DW) of 10 g/liter (90). The growth rate was comparable with a cell suspension culture. The fermentor was operated as a batch fermentor for 11 days, after which is was run as a continuous culture. Nicotine was isolated from the medium during the continuous operation. The alkaloid production rate was estimated to be 1.54 mg/liter/day during this phase. To improve the release of alkaloids by the hairy roots, a continuous removal of the alkaloids from the medium with XAD-4 as an adsorbent was tested. Hairy roots cultured in flasks did not produce more alkaloids in the presence of sachets with XAD-4. However, the amount of alkaloid released into the medium increased in other words, the accumulation ratio was affected by the adsorbent. 

Park et al. [251, 252] used a mutant strain of R. eutropha capable of using alcohols as a carbon source for the production of PHB and PHBV in fed-batch fermentors. With phosphate limitation as inducing factor, ethanol was used for the production in 7 L of 46.6 g PHB L (74% of the CDM) in 50 h [251]. When 1-propanol was added to the medium, up to 15.1 mol% in 3HV units were incorporated to the polymer, and when propanol was the sole carbon source, the cells accumulated about 85% of their CDM in P(3HB-co-35.2-mol% 3HV). Both alcohols were completely consumed. In computer-controlled fermentations [252], switches between the alcohols or mixtures thereof led to improved copolymer yield from the substrates and production rates. 

Example 7.1 Nonlinear Regression Using the Marquardt Method. In Prob. 5.5, we described the kinetics of a fermentation process that manufactures penicillin antibiotics. When the microorganism Penicillium chrysogenum is grown in a batch fermentor under carefully controlled conditions, the cells grow in a rate that can be modeled by the logistic law... 

The alternative to batch mode operation is continuous operation. In the continuous mode there is a continuous flow of medium into the fermentor and of product stream out of the fermentor. Continuous bioprocesses often use homogenously mixed whole cell suspensions. However, immobilised cell or enzyme processes generally operate in continuous plug flow reactors, without mixing (see Figure 2.1, packed-bed reactors). 

Fig. 6 shows a fed batch fermentation of sweet sorghum juice (SSJ) by Bacillus aryabhattai in 3 L fermentor under cultivating condition with agitation rate at 200 rpm, air rate of 1.5 1/min, at 30° C and feeding time at 18 and 24 hr during log phase of the culture. It was found that the cell could continuously produce both biomass and PHAs. Maximum cells were obtained at about 14.20 g/1 at 54 hr when PHAs content reached 4.84 g/1 after 66 hr (Tanamool et al., 2011). In addition, in Table 2, fed batch fermentation by A, latus was used for the production of PHAs (Yamane et al, 1996 Wang Lee, 1997). It could yield high productivity with the use of cheap carbon sources. 

Carbon dioxide produced in an aerobic fermentor should be desorbed from the broth into the exit gas. Figure 12.2 [11] shows, as an example, variations with time ofthe dissolved CO2 and oxygen concentrations in the broth, CO2 partial pressure in the exit gas, and the cell concentration during batch culture of a bacterium in a stirred fermentor. It can be seen that CO2 levels in the broth and in the exit gas increase, while the dissolved oxygen (DO) concentration in the broth decreases. 

In a fed-batch culture (semi-batch culture, see Figure 7.1b), a fresh medium that contains a substrate but no cells is fed to the fermentor, without product removal. The fed-batch operation has special importance in biotechnology, as it is the most... 

Thus, if D is made equal to fi, the cell concentration would not vary with time. For a given substrate concentration in the fermentor C, fi is given by the Monod equation (i.e.. Equation 4.6). Alternatively, we can adjust the substrate concentration Cj for a given value of fi. Practical operation usually starts as batch culture and, when an appropriate cell concentration is reached, the operation is switched to a fed-batch culture. 

Fed-batch culture is not a steady-state process, as the liquid volume in the fermentor increases with time and withdrawal of products is not continuous. However, the feed rate and the concentrations of cells and substrate in the broth in a fermentor can be made steady. 

The characteristics of the fed-batch culture, shown by Equations 12.21 and 12.23, make it possible to keep the concentrations of the substrate and/or the cell at the desired values. For example, after a batch culture, a feed medium that contains the substrate at a high concentration can be fed, either continuously or intermittently, to the fermentor under a fed-batch operation. The values of the dilution rate and the substrate concentration in the feed medium can be determined using Equation 12.23. Thus, by using the fed-batch operation, the yield and/or productivity can be greatly improved in a variety of areas of biotechnology by controlling the concentrations of substrate and cell. Some examples of where the fed-batch operation can be effectively used are as follows. 

Bioreactors that use enzymes but not microbial cells could be regarded as fermentors in the broadest sense. Although their modes of operation are similar to those of microbial fermentors, fed-batch operation is seldom practiced for enzyme reactors. The basic equations for batch and continuous reactors for... 

Batch cultivation is perhaps the simplest way to operate a fermentor or bioreactor. It is easy to scale up, easy to operate, quick to turn around, and reliable for scale-up. Batch sizes of 15,000 L have been reported for animal cell cultivation [2], and vessels of over 100,000 L for fermentation are also available. Continuous processes can be classified into cell retention and non-cell retention. The devices typically used for cell retention are spin filters, hollow fibers, and decanters. Large-scale operation of continuous processes can reach up to 2,000 L of bioreactor volume. Typically, the process is operated at 1-2 bioreactor volumes... 

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