Bioreactors (Fermenters) - Function, Designs and Types

1/1/2016
Bioreactors(Fermenters):Function,Designsandtypes
Bioreactors
(Fermenters): Function,
Designs and types
bySarithaPujariMicroBiology
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Bioreactors (Fermenters): Function, Designs and

types!
A bioreactor is a device in which a substrate of low
value is utilized by living cells or enzymes to generate a
product of higher value. Bioreactors arc extensively
used for food processing, fermentation, waste treatment,
etc.
On the basis of the agent used, bioreactors are grouped
into the following two broad classes: (i) those based on
living cells and, (ii) those employing enzymes. But in
terms of process requirements, they are of the following
types: (i) aerobic, (ii) anaerobic, (iii) solid state, and (iv)
immobilized cell bioreactors.
All bioreactors deal with heterogeneous systems dealing
with two or more phases, e.g., liquid, gas, solid.
http://www.yourarticlelibrary.com/microbiology/bioreactorsfermentersfunctiondesignsandtypes/33628/
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Therefore, optimal conditions for fermentation

necessitate efficient transfer of mass, heat and
momentum from one phase to the other. Chemical
engineering principles are employed for design and
operation of bioreactors. But, in general, theoretical
explanation usually lags behind technical realization.
A bioreactor should provide for the following: (i)
agitation (for mixing of cells and medium), (ii) aeration
(aerobic fermenters; for O2 supply), (iii) regulation of
factors like temperature, pH, pressure, aeration,
nutrient feeding, liquid level, etc., (iv) sterilization and
maintenance of sterility, and (v) withdrawal of
cells/medium (for continuous fermenters). Modern
fermenters are usually integrated with computers for
efficient process monitoring, data acquisition, etc.
The first truly large-scale aseptic anaerobic fermentation
vessels were developed in the wake of the process
developed (during the First World War, 1914-1918) by
Weizmann and co-workers of U.K. to produce acetone by
a deep liquid fermentation using Clostridium
acetobutylicum.
For this, large cylindrical vessels of mild steel that
permitted sterilization with steam under pressure were
constructed, and piping, joints and valves were specially
designed to maintain aseptic conditions, which were the
major problem; mixing was achieved by the large
volumes of gas produced during fermentation.
The large-scale aerobic fermentation vessels were first
used in Central Europe during 1930s for the production
of compressed yeast; these fermenters had large
cylindrical tanks in which air was introduced at the base
via a network of perforated pipes.
In later modifications, mechanical impellers were used
to improve mixing of broth and dispersal of air bubbles.
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Fermenter design was considerably improved during

1940s to accommodate the requirements of strict aseptic
conditions, and good agitation and aeration for
penicillin production from submerged cultures; for this,
steel fermenters with working volumes of 54,000 1 were
built in U.S.A. In 1944, Cooper and co-workers (and
several others) reported the findings from studies on
agitation in baffled stirred tank fermenters, which had a
major influence on the design of later fermenters.
BasicFunctionsofaFermenter:
1. It should provide a controlled environment for
optimum biomass/product yields.
2. It should permit aseptic fermentation for a number of
days reliably and dependably, and meet the
requirements of containment regulations. Containment
involves prevention of escape of viable cells from a
fermenter or downstream processing equipment into
the environment.
3. It should provide adequate mixing and aeration for
optimum growth and production, without damaging the
microorganisms/cells. The above two points (items 2 and
3) are perhaps the most important of all.
4. The power consumption should be minimum.
5. It should provide easy and dependable temperature
control.
6. Facility for sampling should be provided.
7. It should have a system for monitoring and regulating
pH of the fermentation broth.
8. Evaporation losses should be as low as possible.
9. It should require a minimum of labour in
maintenance, cleaning, operating and harvesting
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operations.
10. It should be suitable for a range of fermentation
processes. But this range may often be restricted by the
containment regulations.
11. It should have smooth internal surfaces, and joints
should be welded wherever possible.
12. The pilot scale and production stage fermenters
should have similar geometry to facilitate scale-up.
13. It should be contrasted using the cheapest materials
that afford satisfactory results.
14. There should be adequate service provisions for
individual plants.
FermenterDesign:
A bioreactor is a device in which a substrate of low
value is utilized by living cells or enzymes to generate a
product of higher value. Bioreactors are extensively
used for food processing, fermentation, waste treatment,
etc.
On the basis of the agent used, bioreactors are grouped
into the following two broad classes: (i) those based on
living cells and, (ii) those employing enzymes. But in
terms of process requirements, they are of the following
types: (i) aerobic, (ii) anaerobic, (iii) solid state, and (iv)
immobilized cell bioreactors.
All bioreactors deal with heterogeneous systems dealing
with two or more phases, e.g., liquid, gas, solid.
Therefore, optimal conditions for fermentation
necessitate efficient transfer of mass, heat and
momentum from one phase to the other. Chemical
engineering principles are employed for design and
operation of bioreactors.
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But, in general, theoretical explanation usually lags

behind technical realization. A bioreactor should
provide for the following: (i) agitation (for mixing of
cells and medium), (ii) aeration (aerobic fermenters; for
O2 supply), (iii) regulation of factors like temperature,
pH, pressure, aeration, nutrient feeding, liquid level,
etc., (iv) sterilization and maintenance of sterility, and
(v) withdrawal of cells/medium (for continuous
fermenters). Modern fermenters are usually integrated
with computers for efficient process monitoring, data
acquisition, etc.
AgitationandAeration:
In scaling up, both chemical (O2, pH, medium
constituents and removal of wastes) and physical (the
configuration of bioreactor and power supplied to the
reactor) factors have to be optimised for good results.
The medium must be suitably stirred to keep the cells in
suspension and to make the culture homogeneous; it
becomes increasingly difficult with the scaling up.
Various types of stirrers range from simple magnetic
stirrers, flat blade turbine impellers, to marine
impellers, to those using pneumatic energy, e.g., airlift
fermenter, and those using hydraulic energy, e.g.,
medium perfusion.
Improved mixing can be obtained by changing the
design of stirrer paddle or by using multiple impellers.
The objective of stirring is to achieve good mixing
without causing damage to the cells. Vibro-mixer
achieves stirring by vertical reciprocating motion of 0.13 mm at a frequency of 50 cycles/sec of a mixing disc
fixed horizontally to the agitator shaft. These stirrers
cause random mixing, less foaming and lower shear
forces.
It is important to supply sufficient O2 without damaging
the cells. Mean O2 utilization rate by cells is about 6 mg
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O2/106 cells/hour. But O2 is only sparingly soluble in

culture medium; the oxygen transfer rate (OTR) from gas
phase into medium is about 17 g/cm/hr.
Therefore surface aeration can support about 50 x 106
cells in I 1 culture vessel. Efficient aeration is achieved
by bubbling air through the medium (sparging), but this
may damage animal cells due to the high surface energy
of the bubble and on the cell membrane.
The damage can be reduced by using larger bubbles,
lower gassing rates and by adding non-nutritional
supplements like Pluronic F-68 (polyglycol) and sodium
carboxymcthyl cellulose (these protect cells from
damage due to shear forces and bubbles, respectively).
Silicone tubing (highly gas permeable) can be arranged
inside the culture vessel (2-5 cm tubing of 30 111 length
for a 1000 1 culture) and air is passed though the tube;
however it is inconvenient to use.
Aeration may be achieved by medium perfusion, in
which medium is continuously taken from culture
vessel, passed through an oxygenation chamber and
returned to the culture. The cells are removed from the
medium taken for perfusion so that the medium can be
suitably altered, e.g., for pH control. Perfusion is used
with glass bead and, more particularly, with microcarrier systems.
Where considered safe and desirable, O2 supply in the
culture vessel can be enhanced from the normal 21% to
a higher value and the air pressure can be increased by
1 atmosphere. This increases the O2 solubility and
diffusion rates in the medium, but there is a risk of O2
toxicity.
The basic objective of aeration is to provide
microorganisms growing in submerged cultures with
adequate oxygen for their metabolic needs. Agitation, on
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the other hand, aims to ensure a homogeneous

distribution of microorganisms and the nutrients in the
broth.
The type of aeration- agitation system used in the
fermenter is dictated by the characteristics of the
fermentation process. For example, in processes based
on low viscosity, low total solids broths, agitation may
not be needed as aeration itself would create the
necessary agitation.
Fine bubble aerators without mechanical agitation offer
the advantage of lower equipment and power costs.
Such fermentations are usually carried out in vessels
having height/diameter ratio of 5 : 1, but a tall column of
liquid would require a higher energy input for the
compression of air used for aeration.
However, mechanical agitation is usually necessary for
fermentation processes based on actinomycetes and
fungi. The following components of the fermenter are
required for aeration and agitation: (t) agitator
(impeller), (ii) stirrer glands and bearings, (iii) baffles,
and (iv) sparger (the aeration system).
1. Agitator (Impeller):
Agitators achieve the following objectives; (a) bulk fluid
and gas-phase mixing, (b) air dispersion, (c) oxygen
transfer, (d) heat transfer, (e) suspension of solid
particles, and (f) maintenance of a uniform environment
throughout the vessel.
These objectives are achieved by a suitable combination
of the most appropriate agitator, air sparger and baffles,
and the best positions for nutrient feeds, acid or alkali
for pH control and antifoam addition. Agitators are of
several different types, e.g., (i) disc turbines, (ii) vaned
discs, (iii) open turbines of variable pitch and (iv)
propellers.
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Disc turbine consists of a disc with a series of

rectangular vanes set in a vertical plane around its
perpheri (Fig. 14.1 A). The vaned disc turbine has a
series of rectangular vanes attached vertically to the
underside of the disc (Fig. 14. 1B). In case of variable
pitch open turbine, the vanes are attached directly to a
boss on the agitator shaft (Fig. 14.1C).
The marine propeller is similar to variable pitch open
turbine, except that it has blades in the place of vanes
(Fig. 14.1D). In case of disc and vaned disc turbines, the
air bubbles from the sparger first-hit the underside of
disc before being broken into smaller bubbles and
dispersed by the vanes.
But in the case of the latter two types of agitators, air
bubbles contact the vanes/blades directly and arc
broken up and dispersed by them. These basic agitation
devices have been variously modified. For example, the
variable pitch open turbine scheme has been modified
to develop four modern agitator types, viz., Scaba
6SRGT, Prochem Maxflo T, Lightning A315 and the Ekato
Intcrmig.
The Rushton disc turbine, having a diameter of one-third
the fermenter diameter, has been long considered
optimum for many fermentation processes. The disc
turbine was considered optimum because it was shown
to be able to break up a fast air stream without itself
becoming flooded in air bubbles; the latter situation
seriously hampers oxygen dispersal in the broth.
In contrast, the impeller and open turbine were found to
have the tendency to be flooded in air at higher aeration
rates. In subsequent studies, it was found that in low
viscosity broths, all the four agitator types can achieve
good gas dispersion provided the agitator speed is high
enough.
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In such broths, agitator type does not appear to be a

significant factor affecting oxygen transfer efficiencies.
In high viscosity broths, however, gas dispersal presents
problems and is greatly reduced. In view of this, a
number of agitators have been developed for high
viscosity broths, e.g., Scaba 6SRGT, Prochem Maxflow T,
Lightning A315 and Ekato Intermig (Fig. 14.2).
These agitators are larger, require lower power input
(they do not lose as much power as the Rushton turbines
when aerated), are able to handle higher air volumes
without flooding, and give better bulk blending and heat
transfer in more viscous media.
But they can cause mechanical problems mostly of
vibrational nature. Good mixing and aeration in high
viscosity broths may also be achieved by a dual impeller
combination in which the lower impeller primarily
dispenses the air, while the upper impeller primarily
enhances mixing of the broth.
2. Stirrer Glands and Bearings:
The satisfactory sealing of the stirrer shaft assembly has
been one of the most difficult problems; this is very
important for maintaining aseptic conditions over long
periods. Four basic types of seal assembly have been
used in fermenters: (1) the stuffing box (packed- gland
seal), (2) the simple bush seal, (3) the mechanical seal
and (4) the magnetic drive.
Most modern fermenters use mechanical seals; these
seals are more expensive, but they are more durable
and less prone to leakage or contaminant entry.
Magnetic drives, although quite expensive, are being
used in some animal cell culture vessels.
The mechanical seal consists of two parts; one part
remains stationery in the bearing housing, while the
other rotates on the shaft. The two components of the
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seal are pressed together by springs or expanding

bellows. Steam condensate is used to lubricate and cool
the seals during operation and servers as a contaminant
barrier.
3. Baffles:
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Baffles are metal strips roughly one-tenth of the vessel

diameter and attached radially to the fermenter wall
(Fig. 14.3). They are normally used in fermenters having
agitators to prevent vortex formation and to improve
aeration efficiency.
Usually, four baffles are used, but larger fermenters may
have 6 or 8 baffles. Extra cooling coils may be attached
to baffles to improve cooling. Further, the baffles may be
installed in such a way that a gap exists between the
baffles and the fermenter wall. This would lead to a
scouring action around and behind the baffles, which
would minimise microbial growth on the baffles and the
fermenter wall.
4. Aeration System (Sparger):
The device used to introduce air into the fermenter
broth is called sparger. Spargers are of the following
three basic types: (1) porous spargers, (2) orifice
spargers and (3) nozzle spargers. Porous spargers may
be made of sintered glass, ceramics or a metal.
They are used primarily on a laboratory scale in nonagitated vessels. The bubble size from such spargers is
always 10 to 100 limes larger than the pore size of the
sparger. These spargers have low air throughput
because pressure drops across the sparger, and the fine
holes often become blocked by microbial growth.
Orifice spargers consist of perforated pipes arranged in
various ways, e.g., the sparger pipe forming a ring below
the impeller. In most cases, air holes are drilled on the
underside of the pipe and the holes are arranged in the
form of ring or cross.
It is desirable that the holes are at least 6 mm in
diameter to avoid clogging by microbial growth. These
spargers (without agitation) have been used to a limited
extent in yeast manufacture, effluent treatment and in
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air-lift fermenters used for single-cell protein (SCP)

production.
Nozle sparger consists of an open or partially closed

pipe. Most modern fermenters (laboratory to production
scale) have a single open or partially closed pipe as a
sparger that is ideally placed centrally below the
impeller.
It provides a stream of air bubbles. The sparger should
be as far below the impeller as possible to avoid flooding
of the impeller in a stream of air bubbles. These
spargers cause a lower pressure loss than the other
spargers and they are not easily blocked.
In small fermenters, a combined sparger-agitator may
be used. In this case, the air is introduced via a hollow
agitator shaft, and it comes out through holes drilled in
the disc between the blades and connected to the base of
the main shaft. This design gives a good aeration in
baffled vessels over a range of agitator speeds.
TemperatureRegulation:
The fermenter must have an adequate provision for
temperature control. Both microbial activity and
agitation will generate heat. If this heat generates a
temperature that is optimum for the fermentation
process, then heat removal or addition may not be
required.
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But in most cases, this may not be the case; in all such
cases, either additional heating or removal of the excess
heat would be required. Temperature control may be
considered at laboratory scale, and pilot and production
scales.
1. In laboratory scale fermentations, normally little heat
is generated. Therefore, heat has to be added to the
system; this can be achieved in the following ways: (a)
the fermenter may be placed in thermostatically
controlled bath, (b) internal heating coils may be used,
(c) water may be circulated through a heating jacket, or
(d) a silicone healing jacket may be used. The silicone
jacket consists of two silicone rubber mats, and heating
wires between these mats. This jacket is wrapped
around the fermenter and is held in place by Velcro
strips.
2. In case of larger fermenters beyond a certain size,
excess heat is generated, and the fermenter surface
becomes inadequate for heat removal. The size at which
fermenter surface becomes inadequate for heat removal
will depend on the fermentation process and the
ambient temperature at which fermentation is being
carried out. In such cases, internal coils have to be used
to circulate cold water through them for removing the
excess heat.
The cooling surface area necessary for temperature
control will depend mainly on the following factors: (i)
temperature of cooling water, (ii) the culture
temperature, (iii) the type of microorganism, and (iv) the
energy provided by stirring. The average cooling area
for a 55,000 l fermenter may be considered to be around
50-70 m2; if the cold water temperature were 14C, the
broth temperature would cool down to 30C from 120C
in 2.5 to 4 hours without stirring. The cooling water
consumed during bacterial fermentation in a vessel of
this size would range between 500 to 2,000 l h-1. Fungal
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fermentation, however, may need 2,000 to 10,000 l

cooling water per hour as they have a lower optimum
temperature for growth.
The heating/cooling requirements for a specific
fermentation process can be accurately estimated by
taking into account the overall energy balance of the
process, which is described by the following formula.
Qmet + Qag + Qgas = Qacc + Qexch + Qevap + Qsen
where, Qmet the rate of heat generated by microbial
metabolism;
Qag = the rate of heat produced by mechanical agitation;
Qgas = the rate of heat generated by aeration power
input; Qacc = the rate of heat accumulation in the
system;
Qexch = the rate of heat transfer to the surroundings
and/or heat exchanger, i.e., heating/cooling device;
Qevap = the rate of heat loss due to evaporation; and
Qsen = the rate of sensible enthalpy gain by the flow
streams (exit-inlet). This equation may be arranged as
follows.
Qexch = Qmet + Qag + Qgas Qacc Qsen Qevap
In this equation, Qexch provides the estimate of heat
that has to be removed by the cooling system. The values
for Qmet are experimentally determined for different
substrates, while those of Qag, Qgas, Qevap,and Qsen are
computed using appropriate methods/formulae. For
example, estimates of these values for Bacillus subtilis
grown on molasses in one study are summarised in
Table 14.7.
Among these values, contributions due to Qevap and
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Qsen are quite small. In a steady-state system, Qacc is

zero; further, Qevup can be eliminated by using a
saturated air stream that has the same temperature as
the broth. In large fermenters, Qevap will depend on
operating temperature and flow conditions. Similarly,
Qag, will be determined by the choice of agitator and the
speed of agitation, while aeration rate and sparger
design will determine Qgas.
Once the value of Qexch is estimated, the cooling

requirement (jacket and/or pipes) can be computed
using appropriate formulae. The factors that will affect
the heat transfer surface area may be summarised as
follows: vessel geometry, fluid properties, flow velocity,
wall material and thickness, the temperature difference
between the cooling agent and the broth, and of course
the value of Qexch.
FoamControl:
Foam is produced during most microbial fermentations.
Foaming may occur either due to a medium component,
e.g., protein present in the medium, or due to some
compound produced by the microorganism. Proteins are
present in corn-steep liquor, pharma media, peanut
meal, soybean meal, etc.
These proteins may denature at the air-broth interface
and form a protein film that does not rupture readily.
Foaming can cause removal of cells from the medium;
such cell wills undergo autolysis and release more
proteins into the medium. This, in turn, will further
stabilize the foam. Five different patterns of foaming are
recognized; these are listed below.
1. Foaming remains at a constant level throughout the
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fermentation. Initial foaming is due to the medium, but

later microbial activity contributes to it.
2. Foaming declines steadily in the initial stages, but
remains constant thereafter. This type of foaming is due
to the medium.
3. The foaming increases after a slight initial fall, in this
case, microbial activity is the major cause of foaming.
4. The foaming level increases with fermentation
duration; such foaming pattern is solely due to microbial
activity.
5. A complex foaming pattern that combines features of
two or more of the above patterns.
Foaming may lead to several physical and biological
problems. Some examples of physical problems are
as follows:
(1) The working volume of the fermenter may decrease
due to a circulation of oxygen-depleted gas bubbles in
the system.
(2) The bubble size may also decrease, and
(3) The heat and mass transfer rates may also decline.
(4) Foaming may interfere with the functioning of
sensing electrodes resulting in invalid process data, and
incorrect monitoring and control of pH, temperature,
etc. The biological problems of foaming include (1)
deposition of cells in the upper parts of the fermenter, (2
problems of sterile operation as the air filter exits of the
fermenter become wet, and (3) increased risk of
contamination. In addition, (4) there may be product
loss due to siphoning of the culture broth.
Whenever excessive foaming occurs, the following
approaches may be used to resolve the problem:
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(1) A defined medium may be used to avoid foam

formation. This may be combined with modifications in
physical parameters like pH, temperature, aeration and
agitation. This approach will be successful in such cases
where medium is the main culprit, but will fail
whenever microbial activity is the main contributor.
(2) Often the foam may be unavoidable; in such case,
antifoam should be used. This is the most standard
approach to combat foaming.
(3) A mechanical foam breaker may also be used.
Antifoams are surface active agents; they reduce surface
tension in the foams and destabilize protein film by the
following effects: (a) hydrophobic bridges between two
surfaces, (b) displacement of the absorbed protein, and
(c) rapid spreading of the surface film. Ideal antifoam
should have the following properties.
1. It should disperse rapidly and act fast on existing
foam.
2. It should be used at a low concentration.
3. It should prevent new foam formation for a long time.
4. It should not be used up or degraded by the
microorganism.
5. It should be nontoxic (to the microorganism as well as
animals, including humans).
6. It should not interfere with downstream processing.
7. It should not cause problems in effluent treatment.
8. It should be safe to handle.
9. It should be cheap.
10. It should not affect oxygen transfer.
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11. It should be heat stable for heat sterilization.

Several compounds meet most of these requirements,
and have been found to be suitable for different
fermentation processes; these compounds are as follows:
alcohols (stearyl and octyl decanol), esters, fatty acids
and their derivatives (especially, triglycerides like
cottonseed oil, linseed oil, soybean oil, sunflower oil,
etc.), silicones, sulphonates, and miscellaneous
compounds like oxaline, Alkaterge C, and polypropylene
glycol.
Many of the antifoams are of low solubility; therefore,
they are added with a carrier like lard oil, liquid
paraffin and castor oil. There carriers, however, may be
metabolized, and they may affect the fermentation
process. Further, many antifoams would reduce oxygen
transfer by up to 50% when used at effective
concentrations.
Antifoams are generally added when foaming occurs
during fermentation. But foam control in fermentation
industry is still an empirical art. Therefore, the best
method of foam control for a particular process in one
factory is not necessarily the best for the same process
in other factories. Further, the design and operating
parameters of the fermenters may affect the properties
and the foams produced during the fermentation
process.
TypesofFermenters:
A variety of fermenters have been described in the
literature, but few of them have proved satisfactory for
large scale aerobic fermentations. The most commonly
used fermenters are based on a stirred upright cylinder
with sparger aeration (Fig. 14.3).
The volumes ranging from 1 l to several thousand I. A
general description of the following types of fermenter
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is given in the following sections: (1) stirred tank

reactor, (2) airlift fermenter, (3) tower fermenter and (4)
bubble up fermenter.
StirredTankFermenter:
These are glass (smaller vessels) or stainless steel (larger
volumes) vessels of 1-1,000 1 or even 8,000 1 (Namalva
cells grown for interferon; but in practice their
maximum size is 20 1 since larger vessels are difficult to
handle, autoclave and to agitate the culture effectively).
These are closed systems with fixed volumes and are
usually agitated with motor-driven stirrers with
considerable variation in design details, e.g., water
jacket in place of heater type temperature control,
curved bottom for better mixing at low speeds, mirror
internal finishes to reduce cell damage, etc. Many
heteroploid cell lines can be grown in such vessels.
The needs for research bio-chemicals from cells are met
from 2-50 1 reactors, while large scale reactors are
mainly used for growing hybridoma cells for the
production of monoclonal antibodies although their
yields from cultured cells is only 1-2% of those obtained
by passaging the cells through peritoneal cavity of mice.
Continuous-Flow culture systems, a type of stirred tank
reactors, are either of chemostat or turbidostat type. In
both the types, cultures begin as a batch culture. In a
chemostat type, inoculated cells grow to the maximum
density when some nutrient, e.g., a vitamin, becomes
growth limiting.
Fresh medium is added after 24-48 hours of growth, at a
constant rate (usually lower than the maximum growth
rate of culture) and at an equal rate the culture is
withdrawn. When the rate of growth equals the rate of
cell withdrawal, the cultures are in a steady state, and
both the cell density and medium composition remain
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constant. One of the constituents of the medium is used

at a lower concentration to make it growth-limiting.
However, chemostat is the least efficient or controllable
at the cells maximum growth rate hence the steadystate growth rates in them are much lower than the
maximum.
In contrast, in a turbidostat cells grow to achieve a predecided density (measured as turbidity using a
photoelectric cell). At this point, a fixed volume of
culture is withdrawn and the same volume of fresh
normal (not having a growth-limiting factor) medium is
added; this lowers the cell density or turbidity of the
culture.
Cells keep growing, and once the culture reaches the
preset density the fixed volume of culture is replaced by
fresh medium. This system works really well when the
growth rate of the culture is close to the maximum for
the cell line.
The continuous-flow cultures provide a continuous
source of cells, and are suitable for product generation,
e.g., for the production of viruses and interferons. It is
often necessary to use a two-stage system in which the
first stage supports cell growth, while the second stage
promotes product generation.
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AirliftFermenter:
An airlift fermenter consists of a gas light baffled riser
tube or draught tube (broth rises through this tube)
connected to a down-comer tube (broth flows down
through this tube). The riser tube may be placed within
the down-comer tube as shown in Fig. 14.4, or it may be
externally located and connected to the latter (Fig. 14.5).
Air/gas mixture is introduced into the base of the riser
tube by a sparger.
The aerated medium/broth of the riser tube has a lower
density, while that in the down-flow tube it is relatively
much less aerated and, as a consequence, has a higher
density. This density difference drives the circulation of
broth.
The lighter medium in the rise tube flows upward till it
reaches the gas disengagement space of the fermenter.
The O2 is continuously consumed by the cells and CO2 is
generated by respiration.
The bulk of CO2 and other gases move out of the

medium broth into the gas phase, and the un-aerated
medium flows down through the down-flow tube.
Circulation times in loops of 45 m height may be 120
seconds.
Single cell protein (SCP) production by Marlow Foods,
U.K uses an air-lift fermenter in which the riser tube is
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1/1/2016
externally placed (Fig. 14.6). Air and gaseous ammonia

are introduced at the base of riser tube, while sterilized
glucose, biotin and mineral salts are pumped into the
fermenter at the base of the down-flow tube.
An internal heat exchanger coil is located at the bottom
loop connecting the riser and down-flow tubes; it
maintains the temperature at 30C. The upper loop
connecting the riser and down-flow tubes acts as an air
outlet assembly through which CO2 is continuously
extracted. The removal of CO2 and continuous
consumption of O2 dissolved in the medium increases
the density of the culture broth, which causes it to settle
down through the down-flow tube.
SCP is harvested through a port at the base of riser tube,
which leads into an RNA reduction vessel; steam is
injected into the vessel to raise the temperature to 60C,
which reduces RNA content of SCP. After RNA reduction,
SCP is harvested and processed.
This air-lift fermenter of 43 m3 volume is used in a

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continuous mode for the production of mycoprotein

Quorn from Fusarium gaminareum grown on wheat
starch-based medium. It allows production of long
hyphae due to low shear, which is the preferred form of
the product.
However, it gives lower biomass yields (only 20 g l-1)
due to lower oxygen transfer rates in the high viscosity
broth resulting from fungal hyphae. This fermenter is a
modification of that designed by ICI pic, U.K. for SCP
production using methanol as substrate.
The fermenter was developed to reduce production costs
by minimising cooling costs since agitated vessels would
generate additional heat. ICI pic used it in a continuous
process to produce SCP for animal feed, but the process
had to be discontinued because of high methanol cost
and competition from animal feeds based on proteinrich crop produce. The mycoprotein production is,
however, primarily for animal food.
Modifications of airlift fermenters include various
modifications of draught (riser) tubes and multiple airlift fermenters.
(1) In one modification of draught tube, stainless steel
four-mesh tubes were placed at the top and bottom of
the tube. This fermenter was used for growing
Aspergillus terreus for itaconic acid production. The
sieves modulated the fungal morphology so that the
biomass was in an intermediate state between pellets
and pulp. The type of culture gave double the yields of
itaconic acid per unit volume per unit culture time.
(2) The multiple air-lift fermenters has three air-lift
fermenters placed in a single vessel. The medium is fed
into the central fermenter from where it flows in the
middle one and then finally into the outer compartment
from where it is eventually discharged.
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1/1/2016
(3) Another modification of air-lift fermenters is

described in Section 14.9.3.4.
Animal cell cultures are also grown in such vessels that
are both aerated and agitated by air bubbles introduced
at the bottom of vessels (Fig. 14.7). The vessel has an
inner draft lube through which the air bubbles and the
aerated medium rise since aerated medium is lighter
than non-aerated one; this results in mixing of the
culture as well as aeration. The air bubbles lift to the top
of the medium and the air passes out through an outlet.
The cells and the medium that lift out of the draft tube
move down outside the tube and are re-circulated. O2
supply is quite efficient but scaling up presents certain
problems. Fermenters of 2-90 1 are commercially
available but 2,000 1 fermenters are being used for the
production of monclonal antibodies.
TowerFermenter:
A tower fermenter has been defined by Green-shields
and co-workers as an elongated non-mechanically
stirred fermenter that has an aspect ratio (height to
diameter ratio) of at least 6 : 1 for the tubular section
and 10 ; 1 overall, and there is a unidirectional How of
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1/1/2016
gases through the fermenter. There are several different

types of tower fermenters, which are grouped as follows
on the basis of their design: (1) bubble columns, (2)
vertical-tower beer fermenter and (3) multistage
fermenter systems.
1. Bubble Column Tower Fermenters:
These are the simplest type of tower fermenters; they
consist of glass or metal tubes into which air is
introduced at the base. Fermenter volumes from 3 / to
up to 950 / have been used, and the aspect ratio may be
up to 16 : 1. These tower fermenters have been used for
citric acid and tetracycline production, and for a range
of other fermentations based on mycelial fungi.
2. Vertical-Tower Beer Fermenters:
These fermenters were designed for beer production
and to maximise yeast biomass yields. A series of
perforated plates are placed at intervals to maximise
yeast yields. It has a settling zone free of gas; in this
zone, yeast cells settle down to the bottom and return to
the main body of the tower fermenter, and clear beer
could be removed from the fermenter. Tower of up to
20,000 / capacity and capable of producing up to 90,000 I
beer per day have been installed.
3. Multistage Tower Fermenters:
In these fermenters, a column forms the body of vessel,
which is divided into compartments by placing
perforated plates across the fermenter. About 10% of the
horizontal area of plates is perforated. In a variant of
this type of fermenter (down-flow tower fermenter), the
substrate is fed in at the top and overflowed through
down spouts to the next section, and the air is supplied
from the base. These fermenters have been used for
continuous culture of E. coli, S. cerevisiae (bakers
yeast), and activated sludge.
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1/1/2016
BubbleupFermenter:
It is a bubble column fermenter that is fitted with an
internal cooling coil (Fig. 14.8). Air is introduced from
the bottom of the column. In this vessel, the cooling coil
effectively separates the column into an inner
riser/draught tube and the outer down-flow tube. The
cooling coil assembly functions as a leaky draught tube.
The culture broth rises in the compartment enclosed by
the cooling coils and it moves down in the compartment
outside the coil, although back- mixing also occurs
through the coils. The region above the cooling coil
shows good mixing, and there were no poorly
oxygenated zones in the vessel. It can generate liquid
velocities of 1 m sec-1, giving circulation times of 9-12
seconds and mixing times of 14-18 seconds.
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Bioreactors (Fermenters): Function, Designs and

Therefore, optimal conditions for fermentation

Fermenter design was considerably improved during

But, in general, theoretical explanation usually lags

O2/106 cells/hour. But O2 is only sparingly soluble in

the other hand, aims to ensure a homogeneous

Disc turbine consists of a disc with a series of

In such broths, agitator type does not appear to be a

seal are pressed together by springs or expanding

Baffles are metal strips roughly one-tenth of the vessel

air-lift fermenters used for single-cell protein (SCP)

Nozle sparger consists of an open or partially closed

fermentation, however, may need 2,000 to 10,000 l

Qsen are quite small. In a steady-state system, Qacc is

Once the value of Qexch is estimated, the cooling

fermentation. Initial foaming is due to the medium, but

(1) A defined medium may be used to avoid foam

11. It should be heat stable for heat sterilization.

is given in the following sections: (1) stirred tank

constant. One of the constituents of the medium is used

The bulk of CO2 and other gases move out of the

externally placed (Fig. 14.6). Air and gaseous ammonia

This air-lift fermenter of 43 m3 volume is used in a

continuous mode for the production of mycoprotein

(3) Another modification of air-lift fermenters is

gases through the fermenter. There are several different

Before publishing your

Cost of Capital: Concept

Divestitures: Concept and

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