Page 84 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioTechnology

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Encyclopedia of Physical Science and Technology EN002G-67 May 25, 2001 20:8

266 Bioreactors

FIGURE 26 Cell retention by sedimentation in perfusion culture: (a) internal sedimentor, (b) inclined channel
sedimentor.

is a cylinder formed of wire meshing. The openings of the Spinfilters and sedimentation devices do not retain all
wire screen are significantly larger (e.g., 25 µm) than the cells within a bioreactor and some washout occurs. To-
cells which are retainedby a hydrodynamic mechanism re- tal retention of biomass is feasible by using an external
quiring rapid rotation (e.g., 500 rpm) of the spinfilter. The microfilter to continuously harvest a cell-free stream, as
mostly cell-free spent medium is withdrawn from the zone shown in Fig. 28. The cells are returned to the bioreac-
within the rotating screen. Depending on the specifics of tor. The bioreactor operational schemes identified here are
design and operation, a spinfilter may preferentially retain the ones most commonly used; other variations on these
the viable cells. Also, a noninvasive acoustic sedimenta- schemes are encountered occasionally.
tion device has been developed and this is installed on the
outside of the bioreactor harvest pipe. This device uses
sound waves to aggregate the cells which sediment back E. Medium Composition
into the bioreactor vessel.
The composition of the nutrient medium used to grow
cells determines the rate of production, the type of prod-
ucts produced, and the yield of biomass and products. The
medium also influences the cost of production, the quality
of the product, and factors such as the broth rheology. The
medium must provide all the elements that compose the
product and the biomass. These elements (e.g., C, N, O,
S, P) must be provided in a suitable form and ratios that
are designed to achieve specific effects. The growing cells
may require additional complex organic molecules (mi-
cronutrients) that they are unable to synthesize but that are
essential to growth. In addition, the medium may contain
specificprecursorcompounds,thesubstratesthatarebeing
biotransformed, and inhibitors or inducers of specific en-
zymes. While the medium needs many components, care
is necessary to prevent contamination with others that may
affect the process performance. For example, presence of
iron in Aspergillus niger fermentation broth greatly sup-
presses the production of citric acid. Proper formulation
of the medium is also important in cell-free enzyme reac-
tors, where the rate of reaction and the extent of substrate
(or/and product) inhibition depend on the composition of
FIGURE 27 A spinfilter device of cell retention in perfusion cul- the reaction medium. Some enzyme reactions are carried
ture of animal cells. out in organic solvents containing small amounts of water.