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248 Bioreactors

organic chemical (e.g., sugar and penicillin), an inorganic are carried out with a moistened solid substrate in the ab-
chemical such as carbon dioxide, or a poorly defined com- sence of free water, e.g., during composting, making of
plex material such as meat and animal manure. The prod- hard cheeses, and fermentation of cocoa beans for choco-
uct of the conversion may be cells (or biomass), viruses, late. Submerged processing is widely used in treatment
and chemicals of various kinds. The processes occurring of wastewater and production of vaccines, antibiotics, and
in a bioreactor may be summarized as follows: many other useful products. Bioreactors for submerged
and solid-state processes are discussed next.
biocatalyst(s)
Substrates −−−−−−−−→ products.
Many different kinds of bioreactors are available and A. Submerged Culture
sometimes a given type may be operated in different ways 1. Mechanically Stirred Tank Bioreactors
to obtain different results. The different bioreactor de-
signs are needed to accommodate the great diversity of Stirred tank bioreactors consist of a cylindrical vessel with
substrates, products, and biocatalysts and the different re- a motor driven central shaft that supports one or more ag-
quirements of the different bioconversion processes. itators (Fig. 1). Different kinds of agitators are used in
different applications. Microbial culture vessels are gen-
erally provided with four baffles placed equidistant around
I. INTRODUCTION the periphery of the tank. The baffles project into the ves-
sel from near the walls (Fig. 1). The baffles run the entire
working height of the vessel and they prevent swirling and
Bioreactors are used in all kinds of bioprocesses, includ-
ing those for making foods such as soy sauce; those for vortexing of the fluid. The baffle width is 1/10 or 1/12 of
treating domestic and industrial wastewater; and ones for the tank diameter. A gap of about 1.5% of tank diameter
making vaccines, antibiotics, and many other useful chem- is left between the wall and the baffle to prevent stagna-
icals. Bioreactors that produce microbial cells and cells of tion of fluid near the wall. The working aspect ratio of the
animals and plants, are known as fermenters. In addition vessel is between 3 and 5, except in animal cell culture
to cells, a fermenter may also produce other chemicals, applications where aspect ratios do not normally exceed
or convert (or biotransform) a chemical added to the fer- 2. Often, the animal cell culture vessels are unbaffled.
menter, to a different molecule. A fermenter may contain The number of impellers used depends on the aspect
either a single cell type (i.e., monoseptic operation), or a ratio of the vessel. The lowermost impeller is located
mixed population of different kinds of cells. Fermenters about one third of the tank diameter above the bot-
that operate monseptically are designed as sealed units, tom of the tank. Additional impellers are spaced with
with barriers that prevent ingress of contaminating mi-
croorganisms from the environment. Other types of biore-
actors may contain only nonviable entities (i.e., ones that
cannot multiply) including cells, isolated enzymes, and
organelles obtained from cells. The cells and organelles
may be freely suspended in an aqueous medium, or they
may be confined by various methods of immobilization.
Unlike cells and organelles, enzymes are usually solu-
ble in aqueous media; for repeated use, a soluble enzyme
may be retained in the bioreactor by ultrafiltration mem-
branes, or the enzyme may be immobilized in an insoluble
matrix.

II. BIOREACTOR SYSTEMS

In most bioprocessing situations cells and biocatalysts are
submerged and suspended in a broth that sustains live cul-
tures and dissolves the chemicals that are being modi-
fied by the action of the biocatalyst. Bioreactors for sub-
merged processing are generally quite different from those
used in solid-state cultivation. Solid-state fermentations FIGURE 1 Mechanically stirred bioreactor.