Fed-batch

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A fed-batch is a biotechnological batchprocess which is based on feeding of a growth limiting nutrient substrate to a culture. The fed-batch strategy is typically used in bio-industrial processes to reach a high cell density in the bioreactor. Mostly the feed solution is highly concentrated to avoid dilution of the bioreactor. 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). In most cases the growth-limiting nutrient is glucose which is fed to the culture as a highly concentrated glucose sirup (600-850 g/l).

Why is the fed-batch principle used? - 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, catabolite repression and overflow metabolism of side products.

Different strategies can be used to control the growth in a fed-batch process:

Control Parameter Control Principle
DOT (pO2) DOstat (DOT= constant), F~DOT
Oxygen uptake rate (OUR) OUR=constant, F~OUR
Glucose on-line measurement of glucose (FIA), glucose=constant
Acetate on-line measurement of acetate (FIA), acetate=constant
pH (pHstat) F~pH (acidification is connected to high glucose)
Ammonia on-line measurement of ammonia (FIA), ammonia=constant
Temperature T adapted according to OUR or pO2

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