Fed-Batch Cultivation - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 664

S , X , P

Q , S F

V E , S , X , P

V , S , X , P

V 0 , S 0 ,
X 0 , P 0

(a)

Start-up

(b)

Fill

(c) Harvest

FIGURE 13.1 A schematic of fed-batch reactor operation. (a) Reactor preparation, seed culture ready; (b) reactor
filling with a sterile concentrated substrate; (c) harvest both before starting the next round of filling operation.

In Chapter 11, we learned how cells grow in a batch reactor andmicrobial growth kinetics. In
a batch reactor, one is not exertingany control on the systemother than the environmental condi-
tions such as temperature. In Chapter 12, we learned cell growth and fermentation in chemo-
stats, where cell growth and/or fermentation is actively controlled by the feed of the
substrate(s) into and products withdrawing from the reactor. Continuous fermentation is
only suitable for cases where mass production is warranted, such as fuel ethanol fermentation.
Inmost bioreactor operations for food,medicine, and specialty chemical production, batchoper-
ations are preferreddue to the relatively small productiondemands and the concern over uncer-
tainty in feed variation. How do we exert control over a batch reactor? The alternative is by
modifying the batch operation with a gradual feeding or withdrawing scheme as was discov-
ered by the yeast producers in the early 1900s. In this chapter, we shall focus on the control
scheme for batch reactors and provide means to increase productivity up to a modest level.
While batch operation may be desired for extremely valuable product handling, the lack of
control in batch operations can significantly reduce the productivity and product yield. In
this case, fed-batch operation is desired. For example, when cells are strongly inhibited by
the substrate, low substrate concentration is desired in the reactor. However, low substrate
concentration also means low biomass concentration is achievable. To counter this conflict,
one can feed rich medium gradually into the reactor to maintain growth at low substrate
concentrations. The controlled addition of the nutrient directly affects the growth rate of
the culture and allows the avoidance of overflow metabolism (or Crabtree effect: formation
of side metabolites, such as acetate for Escherichia coli , lactic acid in cell cultures, ethanol in
S. cerevisiae ) and oxygen limitation (anaerobiosis). Therefore, fed-batch operation can be
employed to control the growth and/or desired product yield.
The feeding mode influences a fed-batch fermentation by defining the growth rate of the
microorganisms and the effectiveness of the carbon cycle for product formation and minimi-
zation of by-product formation. Inherently related with the concept of fed-batch, the feeding
mode allows many variances in how substrate and/or medium is introduced into the reactor
and consequently better control over inhibitory effects of the substrate and/or product. The
feedmode can be defined based on an open loop, if an exact mathematical model is at disposal
(not very common and usually insufficient), a feedback control (e.g. pH or DO) or in any other
way depending on the specific kinetics of each fermentation and evenwithin the time frame of