Bioprocess Engineering
43
tissue that is damaged by disease, injures,
or old age. Tissue cell reactors for these
purposes require precise control compared
to those used for the production of food
or pharmaceutical products, but the princi-
ples of operation build upon the knowledge
learned from existing whole-cell bioreac-
tors. A more controversial area of research
is the use of stem cells for medicinal pur-
poses. The ethical issues surrounding this
type of work may slow its development but
these areas will be an important part of the
next few decades of research.
Various models ranging from unstruc-
tured, nonsegregated to structured, segre-
gated are used to describe cell growth. The
most common kinetic expression is the
Monod equation:
µ
=
µ
max
S
K
s
+
S
(
3
)
where
µ
is the speciFc growth rate,
µ
max
is the maximum speciFc growth rate,
K
s
is
the saturation constant, and S is the sub-
strate. This growth expression is inserted
into batch, continuous, bioFlm, scaffold, or
immobilized reactor equations to predict
the rate of utilization of substrate, cell con-
centration, and growth-associated product
concentration. The semi-empirical expres-
sion assumes that a single chemical
species,
S
, is limiting, while changes in
other nutrient concentrations have no ef-
fect; and that a single enzyme system with
Michaelis–Menten kinetics is responsible
for the uptake of
S
. Although this premise
is seldom true, the Monod equation is used
routinely to describe bioreactor behavior
of everything from well-deFned recom-
binant bacterial or mammalian systems
to wastewater treatment systems. Growth
rates are affected by temperature, pH, and
media composition.
Chemically structured models provide a
more general approach with greater pre-
dictive power by relating cell growth and
product production not to just one sub-
strate, but to nitrogen, carbon, and oxygen
uptake, as well as including expressions
that relate important kinetic interactions
among cellular subcomponents such as
RNA, DNA, lipids, and proteins. These
more sophisticated models predict growth
rates better and, thus, reactor behavior,
but consist of between 4 and 40 equations.
Segregated models typically differentiate
between productive and nonproductive
cells within one reactor system. The very
complex models are not typically used by
industry but are used in some research
laboratories.
4
Transgenic Animals and Plants
A technology that has made great strides
in the past decade is the use of transgenic
animals and plants for production of
proteins.
The
living
animal
or
plant
becomes the ‘‘bioreactor’’. The use of
transgenic animals is less developed than
that of plants. Animals have the advantage
of performing complex posttranslational
processing steps that cannot be done
in animal cell culture. How it works is
that new genetic information is inserted
into the embryo of the animal and the
nontoxic protein is expressed by the
mature animal – typically in the milk.
High concentrations of complex proteins
are achieved, and the processes can be
made cost effective. Sheep, goats, and pigs
are the primary species being evaluated
for this task. Harvesting the milk and
downstream processing technologies are
areas of current study. In addition, there
are some serious concerns about the use of
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