Fed-batch culture

Fed-batch bioreactor symbol

A fed‑batch culture is, in the broadest sense, defined as a bioprocessing operation in which one or more nutrients (substrates) are supplied to the bioreactor during cultivation of microorganisms or animal cells, while no culture broth (cells and medium) is taken out until the final harvest. An alternative description of the method is that of a culture in which "a base medium supports initial cell culture and a feed medium is added to prevent nutrient depletion". In some fed‑batch cultures, the entire culture medium or a precursor of the target metabolite serves as the feed substrate. It is also called semi-batch culture.
While the term "semi-batch" is well-established in the field of chemical reaction engineering, "fed-batch" is considered the most appropriate term for microbial reactions, as the supplied substrates are typically nutrients consumed by the microorganisms. Indeed, this terminology is widely adopted in numerous English-language research papers and reviews. In modern bioprocess engineering, batch, fed-batch, and continuous cultures are typically described as the three fundamental modes of cultivation. Given these characteristics, fed-batch culture is essentially a variant of batch culture.
The advantage of the fed-batch culture is that one can control concentration of fed-substrate in the culture liquid at arbitrarily desired levels (in many cases, at low levels).
Generally speaking, fed-batch culture is superior to conventional batch culture when controlling concentrations of a nutrient (or nutrients) affects the yield or productivity of the desired metabolite. In other words, the primary advantage of fed-batch culture is the ability to arbitrarily control the concentration of the fed substrate within the culture broth. In batch culture, all necessary medium components are added at the outset, leaving their concentrations uncontrolled and subject to only the metabolic activity of the microorganisms. In contrast, fed-batch culture allows for the gradual supply of substrates, enabling the optimal maintenance of concentrations—most often at low levels—according to the specific objectives of the process. Meanwhile, in continuous culture (chemostat), all medium components, including the growth-limiting substrate, are maintained at constant values. Therefore, from the perspective of environmental control, fed-batch culture can be positioned as an intermediate between batch and continuous cultivations. Currently, due to risks such as bacterial or phage contamination and genetic mutation, industrial-scale continuous culture is restricted to a limited number of specific fermentations. Consequently, fed-batch culture is increasingly emphasized as an essential improvement over traditional batch culture.
In industrial fed-batch processes, the specific substrates used and the feeding strategies employed are often treated as highly confidential proprietary know-how. Consequently, while it is difficult to obtain detailed information on industrial applications, a significant number of commercial fermentations are being conducted using this method.