Design of Fermentation Processes
In all the previous chapters the bioreactor has been invisibly present, waiting in the wings for a cue
to enter central stage. The discussion of rate measurements in chapters 3 and 5 and of kinetics in
chapters 6 to 8 would not have been meaningful without the short introduction to basic mass
balancing for stirred tank reactors in steady state (chapters 3 and 5) and extended to include also
transients in Chapter 7. Now the bioreactor itself will be given full attention. The kinetics of
Chapter 7 will be used as part of the description of the behavior of typical reactor configurations
used in the laboratory and in industry. Steady state- and transient operation of bioreactors will be
the main subject of the present chapter, and optimization problems, typical topics of texts on
chemical reaction engineering, will be treated. In particular we shall solve the mass balances for the
most popular reactor configurations and look for the maximum productivity
rather than for
the maximum specific productivity
Also optimal start-up procedures for bioreactors are
discussed, and it will be shown how stability of the process can be assured and how infection of the
culture or spontaneous mutation of the producing strain will influence the outcome of the process.
The bioreactor is still claimed to be “ideal” following the definition given in Section 3.1.There is no
shunt of substrate from inlet to outlet, no dead zones or clumps of undissolved solid substrate
floating around. A drop of substrate is instantaneously distributed throughout the entire reactor
volume, and the sparger provides an intimately mixed gas-liquid medium with no air bubbles
sliding up along the reactor wall. Some laboratory reactors approach the ideal. Mixing time is on
the order of 1-2 s, and the gas-liquid mass transfer rate is very high [see, e.g., Sonnleitner and
Fiechter (1988)]. These reactors may be abundantly equipped with on-line measuring and control
systems, and one is able to follow the effect of steep transients imposed on the microbial
environment. These units, the true bioreactors, are used for scientific investigations, to learn more
about the cell metabolism, and to study the cell as the ultimate biochemical reactor. Other
experiments are carried out - often without involvement of an actual fermentation - in the
equipment that is going to be used for industrial production. Here the interaction between
mechanical devices such as agitators, draught tubes, static mixers with or without corrugated
surfaces, and a fluid of given properties can be studied. The outcome is a series of time constants
for mixing, for circulation, for gas-to-liquid transport and the like. As discussed in Chapter 11, it
may be hoped that both the chemical interactions between the cell and its microenvironment, and
the physical interactions between the cell or the cell culture and the macroenvironment will
eventually be clarified in enough detail to allow a new bioprocess to be designed with only minimal
scale-up problems.
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