516 Bioreactions and Bioreactor OperationImage of Figure 1 Image of Figure 1 Image of Figure 1 Image of Figure 1 Image of Figure 1 Image of Figure 1 Image of Figure 1 Image of Figure 1 Image of Figure 1 Image of Figure 1Image of Figure 1 Image of Figure 1 Image of Figure 1Image of Figure 1 Image of Figure 1 Image of Figure 1Image of Figure 1Image of Figure 1 Image of Figure 1Figure 1 Schematic of (a) batch, (b) fed-batch, and (c) continuous cultivation. X: concentration of biomass (g/l); P: concentration of product (g/l); F : volumetric feed rate at which nutrients are added (l/h); V0: initial volume of the medium in the bioreactor (l ); V: final volume of the medium in the bioreactor (l); S: instantaneous substrate concentration in the Bioreactor (g/l); S0: Substrate concentration in the feed.formed by catalysts by their interaction with the substrate; besides, they catalyze their own synthesis. Based on the environment, type of cell, and typical characteristics of substrate and its feed strategy, the mode of reactor operation could be batch, fed batch, or continuous cultivation (Figure 1).2.38.1.1 Batch FermentationBatch fermentation is highly dynamic yet a closed system in which all the medium components, except gases such as oxygen, acid or base for pH control, and antifoaming agents, are placed in the reactor at the start of the cultivation. During the process there is neither any addition nor any withdrawal of nutrients. The nutrient concentrations are continuously changing with time and the system remains in a dynamic unsteady state. The major disadvantage of batch cultivation is its low productivity due to its high downtime (nonproduction time which is used for cleaning, sterilization, and startup of another batch cultivation) during two batch cultivations.2.38.1.2 Continuous Mode of CultivationIn continuous mode of cultivation, fresh medium is continuously added in the fermenter with a simultaneous removal of spent medium containing residual nutrients from the bioreactor. This keeps the reactor volume constant and helps in maintaining the cells in a predefined growth phase (physiological state). Thus, a steady state is achieved, which helps to establish the relationship between microbial behavior (physiology) depending on the limiting nutrient availability conditions. At the same time, they feature continuous product formation with higher productivity. However, continuous cultivation may not be suitable for the production of secondary metabolites primarily because of difficulty in maintenance of low dilution rates, that is, specific growth rates in the bioreactor. Also contamination or mutation could also result in a failure of continuous cultivation process.2.38.1.3 Fed-Batch FermentationThe fed-batch cultivation processes generally feature no removal of broth from the reactor during the entire fermentation period; however, the rate of addition of the limiting nutrient helps to control the reaction rate. Sterilized conditions are maintained throughout the process and the product is generally withdrawn only at the end of the batch.However, fed-batch processes are relatively more labor intensive because of the need to sterilize the equipment after every batch and require precise nutrient feed at the time when they are disappearing and maintenance of the specific growth conditions for the production of a particular metabolite. This gives rise to the batch-to-batch product concentration variability in quality. Nonetheless, this mode of operation is preferred as it can eliminate excessive substrate feed which might inhibit microorganism growth and product formation. Thus, fed-batch cultivation is the preferred mode of cultivation as it has higher operational flexibility as compared to continuous operation. Fed-batch cultivation has been used successfully in the production of lactic acid [1], poly-(β-hydroxybutyrate) [2, 3], biomass, antibiotics [4], and recombinant proteins [5].2.38.2 Different Types of Fed-Batch CultivationsThe fed-batch fermentation consists of growth and production phases. The initial batch growth is followed by the addition of one or more limiting nutrients to the fermenter without the removal of cells or product from the fermenter. Under these circumstances, the rate of production of biomass can be given by eqn 1:dðVXÞ
μXð1−αXÞV ¼½1
dt where μ is the specific growth rate, X is the concentration of biomass at any time t, V is the volume of the medium, and α is a constant. An increase in the biomass concentration in the fermenter results in a slow down of growth which can be explained by the
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