agitation

1. 15 Agitation in fermenters and bioreactors
R.J. McDONOUGH
15.1 Mechanically stirred fermenters
15.1.1 Introduction
Agitators have been used in fermenters for many years. The functions of the
mixer in fermentation processes requiring dispersion of air or oxygen in a
broth are that they:
• Provide uniform dispersion of gas bubbles
• Produce small gas bubbles by shearing the inlet gas with fluid velocity
gradients
• Maximize retention time of the gas in the broth by driving the gas bubbles
to the bottom of the tank
• Produce good bulk velocity and top-to-bottom turnover to:
~create the driving force for driving bubbles to tank bottom
~ enhance heat transfer
~ reincorporate nutrients from the surface froth back into the tank
contents
~ provide uniform nutrient and broth concentrations and temperature
profile throughout the broth.
The biological products of fermentation are living organisms with a cell
wall of limited resistance to fluid shear stress damage. The sensitivity of
microbial cells to shear varies greatly. There has been great concern over the
effect that fluid shear has on yield and productivity of various fermented
products. When in doubt as to the threshold ofshear sensitivity ofa particular
microbial organism, the fermenter mixer should be designed to minimize
fluid shear. Shear rate in mechanically agitated fermenters will be discussed
in section 15.1.2.
Animal cell fermentations are encountered in biotechnical processes, and
the fermenter is often called a bioreactor. Animal cells frequently must attach
themselves to a surface for growth and reproduction. Inert solids have been
used successfully to increase the surface area on which these cells can attach
and grow. Depending on the size of the cell and surface irregularities in the
inert carrier (microcarrier), the animal cells may grow either internally or
exterior to the surface of the inert solid.
The cultivation of animal cells that must be attached to the surface has
revealed an intriguing set of problems. In addition, there are very sensitive
E. Goldberg (ed.), Handbook of Downstream Processing
© Chapman & Hall 1997

2. 358 HANDBOOK OF DOWNSTREAM PROCESSING
cells made using genetic engineering techniques that have more diverse
requirements for cultivation. This has led to the proliferation of many mixing
devices other than impeller mixers (i.e. airlifts and bubble columns), in part
because many animal cell cultures require 7-20 weeks for processing rather
than the 5-7 days that is common to antibiotic fermentations. This requires
that attention be given to developing equipment that can be maintained
aseptic for long periods of time. Airlifts and bubble-column fermenters will
be presented later in this chapter.
Anaerobic and aerobic processes are involved in fermentation. Anaerobic
processes require low oxygen uptake rates (low mass-transfer rates of gas to
liquid). The mixer design is controlled by mass transfer across the liquid-solid
slurry boundary, possible effects of fluid shear on the organisms, and overall
blending or bulk mixing ofnutrients in the tank. Mammalian cell fermentation
is an example of an anaerobic process.
Aerobic fermentation processes, on the other hand, require moderate to
high oxygen rates between gas and liquid phases. The controlling factor in
mixer design is mass transfer across the liquid-gas boundary, usually
accommodated by uniform physical dispersion of gas in the fermented broth
or medium. Products of aerobic fermentations are not usually shear sensitive
and heat transfer can often be a major consideration in agitator design.
Unlike mammalian cell bioreactors that are typically small in scale (10 liter
to perhaps as large as 1000 gallon (45371) in capacity), aerobic fermenters
are much larger with commercial scales typically ranging from 5000 up to
50000 gallons (22685-226850 I). Bacterial fermentation of Escherichia coli
strains and yeasts, and mycelial fermentations to produce antibiotics such
as penicillin, are examples of aerobic fermentations.
Process and agitation requirements for various fermentation processes are
tabulated in Table 15.1.
15.1.2 Fluid dynamics - flow and shear
Impeller-type mixers are essentially pumps (albeit not very efficient ones)
having many of the same characteristics. The most fundamental of these is
that the mixer-impeller power consumption is proportional to its flow and
head development.
Poc QH (15.1)
where: P = power; Q= flow rate; and H = head. All the power supplied from
the agitator to the fermenter media produces flow, velocity, head, or shear.
Usually, impeller flow is expressed as the pumping capacity normal to the
discharge plane of a turbine.
The discharge area ofa typical constant pitch axial flow turbine is a conical