Continuous Cultivation - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 651

biomass concentration near the washout limit either if there are endogenous requirements or
if the death rate is not zero.
The growth and/or product formation patterns can be different between batch and
continuous cultivations. In a batch system, lag phase is commonly observed which is
absent in a continuous system. On the other hand, Crabtree effect can be observed
with changing flow rates in a continuous system, which is absent in a batch cultivation
curve.
Bioreactors using suspended cells can be operated in many modes intermediate between
a batch reactor and a single-stage chemostat. Although a chemostat has potential produc-
tivity advantages for primary products, considerations of genetic instability, process flexi-
bility, low quantities of product demand, and process reliability (such as biocontamination
and biostability) have greatly limited the use of chemostat units. The use of cell recycle
with a CSTR increases volumetric productivity and has found use in large-volume, consistent
production demand and low-product value processes (e.g. waste treatment and fuel-grade
ethanol production).
Multistage continuous systems improve the potential usefulness of continuous processes
for the production of secondary metabolites and for the use of genetically unstable cells. The
perfusion system is another option that is particularly attractive for animal cells.
Immobilized cell systems offer a number of potential processing advantages, and the
commercialization of such systems is proceeding rapidly where cell culture is expensive
and difficult (e.g. animal cell tissue culture). Physical entrapment or encapsulation is used
in most cases, although adsorption onto surfaces or covalent binding of cells to surfaces is
possible.
In some cases, self-immobilization on surfaces is possible and a biofilm is formed. Biofilm
reactors can apply to tissue culture, mold, and bacterial systems. Biofilm-based reactors are
very important in waste treatment applications and in natural ecosystems. The analysis of
immobilized cell reactors is analogous to that for immobilized enzyme reactors except for
the feature of biocatalyst replication.
Solid-state fermentations share some characteristics with immobilized cell systems but
differ in that no discernible liquid is present. SSFs have found important uses in the
production of some traditional fermented foods and may have use in upgrading agricul-
tural or forest materials and in the production of mold products requiring full mold
differentiation.
Further Reading
Bailey, J.E., 1998. Mathematical Modeling and Analysis in Biochemical Engineering: Past Accomplishments and
Future Opportunities, Biotechnol. Prog. 14:8.
Bailey, J.E., Ollis, D.F., 1986. Biochemical Engineering Fundamentals, 2nd ed. Mc-Graw-Hill Book Co., New York.
Blanch, H.W., Clark, D.S., 1996. Biochemical Engineering. Marcel Dekker, Inc., New York.
Herbert, D.R., Ellsworth, R., Telling, R.C., 1956. The Continuous Culture of Bacteria: ATheoretical and Experimental
Study, J. Gen. Microbiol. 14:601.
Mitchell, D.A., Krieger, N., Berovic, M., (Eds.). 2006. Solid State F ermentation Bioreactors: Fundamentals of Design and
Operation , Springer.
Pandey, A., Soccol, C.R., Larroche, C., (Eds.). 2008. Current Developments in Solid State Fermentation , Springer.
Shuler, M.L., Kargi, F., 2006. Bioprocess Engineering, Basic Concepts. 2nd ed. Prentice Hall: Upper Saddle
River, NJ.