6.

THE DISTANT AND RECENT PAST

Long before anyone understood the concept of bioreaction, humans were taking advantage of its
results.Bread, cheese, wine and beer were ali made possible through what was traditionally
known as fermentation a little-understood process, successful more by chance than design. It
was, in fact, the failure and frustration of French vintners who found they were too often
producing vinegar not wine, which led the famous French chemist and microbiologist Louis
Pasteur to study the fermentation process at their request.
What Pasteur discovered was that fermentation occurred as a result of the biological activity of a
microscopic plant called yeast. When unwanted microbes infiltrated the wine and "fed "on the
alcohol produced by the yeast, the microbes left behind distasteful and harmful wastes, which
ruined the wine's flavor. Pasteur's work laid the foundation for bioreactors as we know them
today, because once the process was identified and understood, it could be controlled. And it is
the control of the process that concerns chemical engineers first and foremost. The scope of
bioengineering has grown from simple wine-bottle microbiology to the industrialization of not
only beer, wine, cheese and milk production, but also the production of biotechnology's newer
products antibiotics, enzymes, steroidal hormones, vitamins, sugars and organic acids.

6.2

Bioreactors vs. Chemical Reactors

By definition, a bioreactor is a system in which a biological conversion is effected. Although

this definition can apply to any conversion involving enzymes, microorganisms, and animal or
plant cells, for the purposes of this article, we will limit the definition. The bioreactors referred
to here include only mechanical vessels in which (a) organisms are cultivated in a controlled
manner and/or (b) materials are converted or transformed via specific reactions.
Quite similar to conventional chemical reactors, bioreactors differ in that they are
specifically designed to influence metabolic pathways. Traditional chemical reactor models and
designs that may be used for bioreaction as well include: continuous stirred-tank reactors,
continuous flow stirred-tank reactors, and plug-flow reactors, singularly or in series; ebullizedbed (i.e., "bubbling and boiling") reactors; and fluidized-bed reactors. The term "bioreactor" is
often used synonymously with "fermenter;" however, in the strictest definition, a fermenter is a
system that provides an anaerobic process for producing alcohol from sugar.
Bioreactors differ from conventional chemical reactors in that they support and control

38

biological entities. As such, bioreactor systems must be designed to provide a higher degree of
control over process upsets and contaminations, since the organisms are more sensitive and less
stable than chemicals. Biological organisms, by their nature, will mutate, which may alter the
biochemistry of the bioreaction or the physical properties of the organism. Analogous to
heterogeneous catalysis, deactivation or mortality occur and promoters or coenzymes influence
the kinetics of the bioreaction.
Although the majority of fundamental bioreactor engineering and design issues are similar,
maintaining the desired biological activity and eliminating or minimizing undesired activities
often presents a greater challenge than traditional chemical reactors typically require.
Organisms, influenced by their morphology and the bioreaction medium, are shear-sensitive to
varying degrees.
A number of bacteria, yeast and fungi cultures that can be relatively tolerant of high-shear
environments exhibit robustness in high-energy mixing vessels. Animal, fish, insect and plant
cells are delicate and usually require low-shear environments for viability. The viscosities of
bioreaction masses may change during growth and production phases, and, often, the medium
becomes non-Newtonian as a cycle progressed. Mixing within the bioreactor is integral to
efficient heat and mass transfer during the production phases, which places
additional

constraints

on

the

suitable

agitation

mechanism

and rheology of the

bioreaction medium.
Other key differences between chemical reactors and bioreactors are selectivity and rate. In
bioreactors, higher selectivity that is, the measure of the system's capability for producing the
preferred product (over other outcomes) is of primary importance. In fact, selectivity is
especially important in the production of relatively complex molecules such as antibiotics,
steroids, vitamins, proteins and certain sugars and organic acids. Frequently, the activity and
desired selectivity occur in a substantially smaller range of conditions than are present in
conventional chemical reactors. Further, deactivation of the biomass often poses more severe
consequences than a chemical upset. Rate is of secondary importance. For many biological
systems, an incubation period is needed to prepare a culture used to inoculate the bioreactor with
the producing microbes or their precursors. Although a bioreaction can be brief, in systems
where organism or biomass growth is necessary, the bioreaction can take 10-20 d for completion
of the batch. Further, the bioreactor should not be regarded as an isolated unit, but as part of an

39

integrated unit operation with both upstream (preparation) and downstream (recovery) unit
operations.

6.3

Products of Bioreactions

Bioreaction products are formed by three basic processes: 1. Processes in which the product is
produced by the cells is either extra cellular, e.g., alcohols or critic acid, or Intracellular, e.g., a
metabolite or enzyme. Production of cellular products is divided into two types, based on when
they are produced within a biological cycle. Primary metabolites are produced during growth and
are essential for continuing growth. Secondary metabolites are produced after growth has ceased.
Primary metabolites include amino acids, nucleotides, nucleic acids, proteins, lipids and
carbohydrates.
Examples of primary products for industrial use include ethanol, citric acid, acetone,
butanol, lysine, polysaccharides and vitamins.
Secondary cellular products are formed from the intermediates and products of primary
metabolism, and tend to be specific to a species or group of organisms. Not all microorganisms
produce secondary metabolites, but they are widespread among the filamentous fungi and plants.
Many secondary products have toxic or antibiotic properties and are, as such, the basis of much
of the antibiotic industry.
Production of enzymes via bioreactions has displaced inefficient extraction techniques with
mutation and genetic manipulation. Industrial
brewing,

enzymes

find

their

home

in

baking,

grain processing, dairy making, and in the production of detergents, juices, wines and

other products.
2. Processes that produce a cell mass. Bakers' yeast, used in the baking industry, is an example
of a produced cell mass. Others include single-cell proteins for food sources.
3. Processes that modify a compound that is added to the fermentation process are referred to as
biotransformation. Biotransformation occurs using the inherent enzymatic capability of most
cells. Cells of all types can be employed to biocatalyze a transformation of certain compounds
via dehydration, oxidation, hydroxyfation, amination or isomerization. Enzymatic conversions
frequently exhibit lower activation energies and higher selectivity than their chemical
counterparts. Steroids, antibiotics and prostaglandins can all be produced via biotransformation.

40

6.4. Key Issues in Bioreactor Design and Operation

The goal of an effective bioreactor is to control, contain and positively influence the biological
reaction. To accomplish this, the chemical engineer must take into consideration two areas. One
is the suitable reactor parameters for the desired biological, chemical and physical
(macrokinetic) system. The macrokinetic system includes microbial growth and metabolite
production. Microbes can include bacteria, yeast, fungi, and animal, plant, fish and insect cells,
as well as other biological materials.
The other area of major importance in bioreactor design involves the bioreaction parameters,
including:

controlled temperature optimum pH

sufficient substrate (usually a carbon source), such as sugars, proteins and fats

water availability

salts for nutrition

vitamins

oxygen (for aerobic processes)

gas evolution and product and byproduct removal

Flow behaviors (rheology), broth viscosity and type of fluid (e.g. Newtonian,
viscoelastic, pseudoplastic, Bingham plastic).

6.5

Nature and amount of suspended solids in broth.

Mixing requirements.

Heat-transfer needs. Shear tolerance of microorganism, substrate and product.

Sterility requirements

Process kinetics, batch or continuous operation, single-stage or multistage fermentation

Local technological capability and potential for technology transfer.

Desired process flexibility.

Capital and operational costs

Types of Fermentation

Before we continue with our discussion on fermenter Design, let's review the different Types of
Fermentation.
41

Large scale cell cultivation is performed in specialized reaction vessels known as

bioreactors or fermenters. The term fermentation is often used to describe the cultivation of cells
in fermenters. Most commercially useful fermentations may be classified as:
1. solid-state
2. submerged cultures
v Solid State
In solid-state fermentations, the microorganisms grow on a moist solid with little or no 'free'
water, although capillary water may be present. Examples of this type of fermentation are seen in
mushroom cultivation, bread-making and the processing of cocoa, and in the manufacture of
some traditional foods, e.g. miso (soy paste), sake, soy sauce, tempeh (soybean cake) and gari
(cassava), which are now produced in large industrial operations, v Submerged cultures
Submerged fermentations may use a dissolved substrate, e.g. sugar solution, or a solid substrate,
suspended in a large amount of water to form slurry. Submerged fermentations are used for
pickling vegetables, producing yoghurt, brewing beer and producing wine and soy sauce.
Solid-state and submerged fermentations may each be subdivided - into oxygen-requiring
aerobic processes, and anaerobic processes that must be conducted in the absence of oxygen.
Examples of aerobic fermentations include submerged-culture citric acid production by
Aspergillus Niger and solid-state koji fermentations (used in the production of soy sauce).
Fermented meat products such as bologna sausage (polony), dry sausage, pepperoni and salami
are produced by solid-state anaerobic fermentations utilizing acid-forming bacteria, particularly
Lactobaciilus, Pediococcus and Micrococcus species. A submerged-culture anaerobic
fermentation occurs in yoghurt-making.
Fermentations may require only a single species of microorganism to effect the desired
chemical change. In this case the substrate may be sterilized, to kill unwanted species prior to
inoculation with the desired microorganism. However, most food fermentations are non-sterile.
Typically fermentations used in food processing require the participation of several microbial
species, acting simultaneously and/or sequentially, to give a product with the desired properties,
including appearance, aroma, texture and taste. In non-sterile fermentations, the culture
environment may be tailored specifically to favour the

42

desired microorganisms. For example, the salt content may be high, the pH may be low, or the
water activity may be reduced by additives such as salt or sugar.

6.6

Fermentation systems

Industrial fermentations may be carried out either batch wise, as fed-batch operations, or as
continuous cultures (Fig. 1). Batch and fed-batch operations are quite common, continuous
fermentations being relatively rare. For example, continuous brewing is used commercially, but
most beer breweries use batch processes of the three systems,
1. Fed batch bioreactors are most commonly used to produce biological products.
2. Batch reactors are the second most commonly used.
3. Although continuous reactors are rarely used for large scale production of biochemicals,
they are widely used in waste treatment processes. In addition, natural ecosystems, such
as the rumen and gut, soil and rivers, are more closely represented by a continuous
culture system.

6.7

Continuous vs. Batch

There are several major advantages to using continuous bioreactions as

opposed

to

the

batch mode. First, continuous reactions offer

increased opportunities for system investigation and analysis. Because the variables remain
unchanged, a benchmark can be determined for the process results, and then the effects of even
minor changes to physical or chemical variables can be evaluated. Also, by changing the growthlimiting nutrient, changes in cell composition and metabolic activity can be tracked. The
constancy of continuous bioreaction also provides a more accurate picture of kinetic constants,
maintenance energy and true growth yields.
Secondly, continuous bioreaction provides a higher degree of control than does batch.
Growth rates can be regulated and maintained for extended periods. By varying the dilution rate,
biomass concentration can be controlled. Secondary metabolite production can be sustained
simultaneously along with growth. In steady-state continuous bioreaction, mixed cultures can be
maintained using chemostat cultures unlike in batch bioreaction, where one organism usually
outgrows another. Chemostats are continuous- flow stirred-tank bioreactors (CFSTRs) in an
idealized steady-state, i.e., the feed-and outlet-stream compositions and flows are constant, and
perfect mixing occurs within the CFSTR vessel. In Chemostats, the outlet stream composition is

43

considered to be the same as within the bioreactor.

Bioreactors operated as Chemostats can be used to enhance the selectivity for thermophiles,
osmotolerant strains, or mutant organisms with high growth rates. Also, the medium
composition can be optimized for biomass and product formation, using a pulse-and-shift
method that injects nutrients directly into the chemostat. As changes are observed, the nutrient is
added to the medium supply reservoir and a new steady state is established.
A third advantage is the quality of the product. Because of the steady-state of continuous
bioreaction, the results are not only more reliable, but also more easily reproducible. This
process also results in higher productivity per unit volume, because time-consuming tasks, such
as cleaning and sterilization, are unnecessary. The ability to automate the process also renders it
less labor-intensive, and, therefore, more cost-efficient and less sensitive to the impact of human
error.Along with the strengths of continuous bioreaction, there are inherent disadvantages that
may make this process unsuitable for some types of bioreaction. For example, one challenge lies
in controlling the production of some non-growth-related products. For this reason, the
continuous process often requires feed-batch culturing, and a continuous nutrient supply. Wall
growth and cell aggregation can also cause wash-out or prevent optimum steady-state growth.
Another problem is that the original product strain can be lost over time, if it is overtaken by a
faster-growing one.
The viscosity and heterogeneous nature of the mixture can also make it difficult to maintain
filamentous organisms.Long growth periods not only increase the risk of contamination, but also
dictate that the bioreactor must be extremely reliable and consistent, incurring a potentially
larger initial expenditure in higher-quality equipment.

44

6.8

Types of Submerged-Culture Bioreactor

The major Types of submerged-culture bioreactor are:

a stirred-tank fermenter
a bubble column
a airlift fermenter
a fluidized-bed fermenter
a Trickle-bed fermenter
The figure on the next page shows various types of bioreactors.

6.9

Stirred Tank Reactors (The selected fermenter for the process)

6.9.1

Introduction

A typical bioreactor used for microbial fermentations is shown in the following figure:

Laboratory scale bioreactors with liquid volumes of less than 10 liters are constructed out of
Pyrex glass. For larger reactors, stainless steel is used.
6.9.2

Basic features of a stirred tank bioreactor

A modern mechanically agitated bioreactor will contain:

1. An agitator system
2. An oxygen delivery system (Required for Aerobic Fermentations)
45

3. A foam control system

4. A temperature control system
5. A pH control system
6. Sampling ports
7. A cleaning and sterilization system.
8. A sump and dump line for emptying of the reactor.
Agitation Systern The function of the agitation system is to

Provide good mixing and thus increase mass transfer rates through the bulk liquid
and bubble boundary layers.

Provide the appropriate shear conditions

required for the

breaking up of bubbles.
The agitation system consists of the agitator and the baffles. The baffles are used to break
the liquid flow to increase turbulence and mixing efficiency. The role of the baffles is discussed
in depth in a later section.
The

agitator

consists

of

the

components

shown

in

the

following

diagram:

The number of impellers will depend on the height of the liquid in the reactor. Each impeller
will have between 2 and 6 blades. Most microbial fermentations use a Rushton turbine impeller.

46

A single phase (ie. 240 V) drive motor can be used with small reactors. However for large
reactors, a 3 phase motor (ie 430 V) should be used. The latter will tend to require less current
and therefore generate less heat.
V TYPES OF IMPELLERS
Agitators

are

classified

as

having

radial

flow

or

axial

flow characteristics.

With radial flow mixing, the liquid flow from the impeller is initially directed towards the
wall of the reactor; ie. along the radius of the tank.
With axial flow mixing, the liquid flow from the impeller is directed downwards towards
the base of the reactor, ie. in the direction of the axis of the tank.
1. Radial flow impellers are primarily used for gas-liquid contacting (such as in the mixing
of sparged bioreactors) and blending processes. Radial flow impellers contain two or
more impeller blades which are set at a vertical pitch:
Four baffled system
The liquid flow from the blades is directed towards the walls of the reactor; ie. along the
radius of the tank. With radial flow impellers, vertical (or axial) mixing is achieved with the use
of baffles.
Radial flow mixing is not as efficient as axial flow mixing. For radial flow impellers, a
much higher input of energy input is required to generate a given level of flow as compared to
axial flow impellers.

47

Radial flow impellers do and are designed to, generate high shear conditions. This is
achieved by the formation of vortices in the wake of the impeller:

The high shear is effective at breaking up bubbles. For this reason, radial flow impellers are
used for the culture of aerobic bacteria.
High shear can also damage shear sensitive materials such as crystals and precipitates and
shear sensitive cells such as filamentous fungi and animal cells.

2. Axial flow impeller blades are pitched at an angle and thus direct the liquid flow towards the
base of the tank. Examples of axial flow impellers are pitched-blade turbines, marine
impellers and hydrofoil impellers.

48

49

The resultant flow pattern is thus predominantly vertical; i-e along the tank axis.

Axial flow mixing is considerably more energy efficient than radial flow mixing.
They are also more effective at lifting solids from the base of the tank. Axial flow impellers have
low shear properties. The angled pitch of the agitators coupled with the thin trailing edges of the
impeller blades reduce formation of eddies in the wake of the moving blades.

Axial flow impellers are used for mixing shear sensitive processes such as crystallization
and precipitation reactions. They are also used widely in the culture of animal cells.
Their low shear characteristics generally make them ineffective at breaking up bubbles and
thus unsuitable for use in aeration of bacterial fermentations.

50

Temperature Control System

The temperature control system consists of

temperature probes

heat transfer system

Typically the heat transfer system will use a "jacket" to transfer heat in or out of the reactor.
The jacket is a shell which surrounds part of the reactor. The liquid in the jacket does not come
in direct contact with the fermentation fluid.

The jacket will typically be "dimpled" to encourage turbulence in the jacket and thus
increase the heat transfer efficiency. An alternative to using jackets are coils. Coils have a much
higher heat transfer efficiency than jackets. However coils take up valuable reactor volume and
can be difficult to clean and sterilize. The heating/cooling requirements are provided by the
following methods In pilot and production scale reactors, heating is typically only required
during the initial stages and final stages of the fermentation as most processes which occur
during a fermentation process, including

the biological reactions (eg. growth)

chemical reactions

mixing are exothermic.

51

The oxygen delivery system consists of

a compressor

inlet air sterilization system

an air sparger

exit air sterilization system

Foam Control System

Foam control is an essential element of the operation of a sparged bioreactor. The following
photograph shows the accumulation of foam in a 2 liter laboratory reactor.

Excessive foam formation can lead to blocked air exit filters and to pressure build up in the
reactor. The latter can lead to a loss of medium, damage to the reactor and even injury to
operating personnel.
Foam is typically controlled with aid of antifoaming agents based on silicone or on
vegetable oils. As discussed previously, excessive antifoam addition can however result in poor
oxygen transfer rates.
The following factors affect the foam formation and the requirement to antifoam addition.

the fermentation medium

products produced during the fermentation

52

 the aeration rate and stirrer speed.

the use of mechanical foam breakers
the head space volume
condenser temperature
The characteristics of the fermentation medium and the nature play an important role in
determining foam formation. Media rich in proteins will tend to foam more readily than simple
media. For example, the use of whey powder and corn steep liquor, two common nitrogen
sources will contribute significantly to rate of foam formation and the antifoam requirement.
Many cells also produce detergent-like molecules. These molecules can be nucleic acids and
proteins released upon the death of the cells or proteins and lipid compounds produced during the
growth of the cells.
Higher stirrer speeds and higher aeration rates increase foaming problems. These problems
can in fact be so significant that they limit the stirrer speeds or aeration rates that can be used in
process. A fast stirrer speed will lead to the faster formation of foam.

Mechanical foam breakers can eliminate or at least reduce the antifoam requirement. These
devices generate sit above the liquid and generate high shear forces which break the bubbles in
the foam. High shear agitators and nozzles connected to high shear pumps are often used.

53

For small scale reactor systems such as those used in the culture of animal cells, ultrasonic
foam breakers are sometimes used. These generate high frequency vibrations which break the
bubbles in the foam.
A bioreactor is divided in a working volume and a head-space volume. The working volume
is the fraction of the total volume taken up by the medium, microbes, and gas bubbles.
The remaining volume is called the headspace.

Typically, the working volume will be 70-80% of the total fermenter volume.
This value will however depend on the rate of foam formation during the reactor. If the
medium or the fermentation has a tendency to foam, then a larger headspace and smaller
working volume will need to be used.
The headspace plays an important role in foam control. In systems which readily foam, the
working volume must be reduced to facilitate better foam control.
The larger headspace volume, then the greater the tendency for the foam to collapse under
its own weight. For example, for fermentations in which high foam formation can be rapid, a
50% headspace volume may be required.

54

pH Control System
The pH control system consists of

a pH probe

alkali delivery system

acid delivery system

The pH probe is typically steam sterilizable. The neutralizing agents used to control pH
should be non-corrosive. They should also be non-toxic to cells when diluted in the medium.
Potassium hydroxide is preferred to NaOH, as potassium ions tend to be less toxic to cells than
55

sodium ions. However KOH is more expensive than NaOH. Sodium carbonate is also commonly
used in small scale bioreactor systems.
Hydrochloric acid should never be used as it is corrosive to most stainless steel.
Likewise sulphuric acid concentrations should not be between 10% and 80% as between this
range, sulphuric acid is most corrosive. For fermentations that produce large amounts of acids,
for example lactic acid, high concentrations of alkali (4 M and above) are used. This prevents
dilution of the medium due to the addition of excessive addition of the alkali solution.
For laboratory fermenters, a peristaltic pump is used to add the pH adjusting agents.
Silicone tubing is often used. However, note that silicone tubing will decay in the presence of
high alkali concentrations. Thick walled slicone tubing should be used.
Alternatively Tygon or Neoprene tubing can be used. Tygon is not autoclavable but can be
sterilized by passing the NaOH through the tubing for about 1 hour. Neoprene is autoclavable
but is not transparent or translucent as is Tygon and silicone.

Flow Descriptio
INTRODUCTION
Fluid mixing is described as existing one of three states:

Laminar flow

Turbulent flow
Transient flow.
In laminar flow, the fluid tends to flow in one direction as visualized as "flow lines". There
is little mixing between these flow lines.
In turbulent flow, the flow lines breakdown to form eddies. These eddies carry the fluids
away from the flow lines leading to mixing of materials through the reactor.

56

Laminar Row

Fluirf stay* It* orrieri>*} flnw

Turbulent flow

Ax tbs fluid moves lurliulunl

lines. There Is no significant are formed. These eddies break

mixing between the flow lines

down forming smaller eddies. On a

mieroscale, Htjtiid movs in ratidom directions, feadlny to mixing.

In between laminar and turbulent flow is a state called transient
flow. In this state, the fluid moves randomly moves between laminar
and turbulent states.
A turbulent flow condition are required for good mass and heat transfer
and is thus most often the desired mixing state.
LAMINAR FLOW IN STIRRED TANK BIOREACTORS
Turbulence is characterized by the formation of randomly moving turbulent eddies. Turbulence
breaks the liquid flow lines and leads to good mixing of the fermenter fluid.
At low stirring speeds, a phenomenon known as circulation or swirling occurs. During
circulation, the fluid follows the laminar flow lines, moving in circles around the tank; the result
being ineffective mixing .

57

In an unbaffled tank, as the stirrer speed is increased, the liquid will continue to circulate,
although at a faster speed. Eventually the liquid and air will be drawn into impeller leading to a
phenomenon known as vortexing.

PREVENTING VORTEX FORMATION

In an unbaffled tank, as the stirrer speed is increased, the li< continue to circulate,
although at a faster speed. Eventually the liquid and air will be drawn into impeller leading to
a phenomenon known as vortexing.
Vortexing is generally an undesirable phenomenon. Firstly, although high stirring
speeds are used, mixing is still poor as the bulk of the fluid is simply circulating throughout
the tank. Secondly, the collisions between the cells, air-bubbles and the impeller can lead to
cell damage.
Vortexing can be prevented with:

58

Off-centre impellers Baffles

The formation

of a vortex can be seen in the following photographs. Note

the formation of a whirlpool in the reactor. This whirlpool grows larger as the stirrer speed
increases.
OFF CENTRE IMPELLERS
The simplest method to avoid vortexing is to move the impeller into an off-centre
position or side entry position or by tilting the impeller at an angle.

Off-centre and side-entry impellers are suited oniy for stirred tanks with small liquid
volumes (less than 10,000 litres).
With off-centre impellers, the forces acting on the impeller are unevenly distributed. This can
lead to shaft, impeller and motor damage.

59

60

BAFFLES
The alternative to off-center impellers are baffles.

Baffles break the liquid flow a line causing the formation of turbulent eddies.
The stirring speeds required for turbulence in a baffled reactor is many magnitudes less
than that required for an unbaffled fermenter.

6.10 Standard Geometry of a Stirred Tank Bioreactor

A stirred tank reactor will either be approximately cylindrical or have a curved base. Stirred
tank bioreactors are generally constructed to standard dimensions.
That is, they are constructed according to recognized standards such as those published
by the International Standards Organisation and the British Standards Institution.
These dimensions take into account both mixing effectiveness and structural
considerations.

61

A mechanically stirred tank bioreactor fitted with

a sparger and

a Pitched-blade turbine will typically have the following relative

dimensions:

A tank's height: diameter ratio is often referred to as its aspect ratio.

7.11,Selection of Agitator
Grain fermentation requires agitator with moderate shear stresses due to shear sensitive
substances. It also requires an agitation system that prevents massive settling of solids; axial flow
impellers are the best choice. Marine propellers. Pitched-blade turbine and hydrofoil impellers
are the axial flow impellers. Marine Propellers are used for small vessels. For tank volumes (4200 m3), the pitched-blade turbines are the initial choice for proper heat transfer, blending and
solid suspension services. As design calculations in Appendix A show the tank volume to be
within this range, so we chose top-entering pitched-blade turbine impeller for this fermentation.

62

7.12.Selection of Cooling System

Cooling is necessary, especially in large fermenter, to keep temperatures within the prescribed
limits., External-Jacketed Systems are not used because in large tanks these are inadequate for
cooling from sterilization temperature to operating temperature in reasonable time. Internal
cooling coils are no used also as they are difficult to clean and create low circulation areas in the
liquid also. An external cooling system is chosen liquid is drawn from the tank through
recirculating pumps and passed through heat exchanger.

7.13. Foam control system

Special provision is made for foaming by proper headspace - about 50% of tank volume above
the liquid. The foam collapses under its own weight due to this provision. If excessive foaming
occurs, suitable antifoaming agent may also be used.

63