Chapter 13 - Fed-Batch Cultivation

Abstract

Fed-batch reactor is based on feeding of a growth limiting nutrient substrate to a culture. Cell growth and fermentation can be controlled by the feeding strategy. The fed-batch strategy is typically used to reach a high cell density in the bioreactor or mimic a continuous culture. Mostly the feed solution is highly concentrated. In essence, fed-batch reactor is applied in such a fashion that a chemostat is simulated with a seemingly batch operation. The controlled addition of the nutrient directly affects the growth rate of the culture and allows to avoid overflow metabolism (formation of side metabolites, such as acetate for Escherichia coli , lactic acid in cell cultures, ethanol in Saccharomyces cerevisiae ), oxygen limitation (anaerobiosis). Substrate limitation offers the possibility to control the reaction rates to avoid technological limitations connected to the cooling of the reactor and oxygen transfer. Substrate limitation also allows the metabolic control, to avoid osmotic effects and catabolite repression. Therefore there are different operation strategies for fed-batch: 1) constant feed rate; 2) exponential feed rate or constant specific growth rate. The exponential growth with fed-batch operation can be at any rate, up to the maximum rate in the exponential growth phase of a batch growth. Usually, maximum growth rate is not wanted for undesired by-product production can be high at maximum growth. Analysis of fed-batch reactors is more complex than either a chemostat or a batch reactor. Solutions of differential equations are usually required. When long operation time is employed, a pseudo-steady state may be assumed, simplifying the analysis. The pseudosteady state is found to correspond to biomass steady state or time derivative of biomass concentration is zero. Some solutions to the biomass concentration and product formation are listed for constant feed and exponential feed at pseudo-steady state conditions.