17.10 Beyond the batch culture

Although we have occasionally mentioned other culture systems in previous pages, most of the discussion so far has concentrated on batch cultures, so we now want to turn to other types of culture system.

The term fed-batch culture (or simply, ‘fed-batch’) is used to describe a batch culture which is fed with medium either intermittently or continuously. Nothing is removed until final harvest, so the volume of the culture increases with time (Fig. 23A). Fed-batch is a way of obtaining very slow growth rates resulting from substrate limitation; the penicillin fermentation is the classic fed-batch industrial process, best described by Nielsen (1996).

Diagrams of fed-batch cultures
Fig. 23. A, sketch diagram of a fed-batch culture. The right-hand panel (B) records the basic kinetics of biomass concentration (x), substrate (glucose) concentration (S) and dilution rate (D) in such a fed-batch culture. Adapted from Stanbury, Whitaker & Hall, 1998.

Although the total biomass in the culture increases with time, biomass concentration remains virtually constant because medium is added and the volume of the culture increases with time. Providing the dilution rate (D) is less than µmax and Ks is much smaller than substrate concentration in the inflowing medium, a quasi-steady state may be achieved. However, unlike a continuous culture, D (and therefore µ) decreases with time, because the tank has a finite volume and as nothing is removed feeding with medium must stop at some stage in the cultivation (it was stopped at the 6 hour mark in the culture illustrated in Fig. 23B).

The dilution rate of a fed-batch culture is given by:

3

Where, D = dilution rate, V0 = original volume of culture, and F = flow rate of medium into the culture.

The next development of the fed-batch culture is to remove some of the culture at intervals but to keep feeding the culture with more medium; this is a repeated fed-batch culture. In repeated fed-batch cultures the culture volume and consequently the dilution rate and specific growth rate undergo cyclical variations as parts of the culture are removed.

Because it is technically easier to obtain substrate limited growth in fed-batch culture than in chemostat culture, this type of culture is used for many industrial fermentations. In particular, feeding a batch culture with fresh medium can be used to:

  • relieve catabolite repression when this is an issue in a production process; and
  • avoid toxic effects of some medium components, that may be required for particular production processes, on the growth of the biomass; for example sodium phenylacetate, a toxic precursor of penicillin, can be kept at sub-inhibitory concentration by feeding it gradually to the culture.

Updated December 17, 2016