The function of the fermenter or bioreactor is to provide a suitable environment in which an organism can efficiently produce a target product—the target product might be cell biomass,metabolite and bioconversion Product. It must be so designed that it is able to provide the optimum environments or conditions that will allow supporting the growth of the microorganisms. The design and mode of operation of a fermenter mainly depends on the production organism, the optimal operating condition required for target product formation, product value and scale of production. The choice of microorganisms is diverse to be used in the fermentation studies. Bacteria, Unicellular fungi, Virus, Algal cells have all been cultivated in fermenters. Now more and more attempts are tried to cultivate single plant and animal cells in fermenters. It is very important for us to know the physical and physiological characteristics of the type of cells which we use in the fermentation. Before designing the vessel, the fermentation vessel must fulfill certain requirements that is needed that will ensure the fermentation process will occur efficiently. Some of the actuated parameters are: the agitation speed, the aeration rate, the heating intensity or cooling rate, and the nutrients feeding rate, acid or base valve. Precise environmental control is of considerable interest in fermentations since oscillations may lower the system efficiency, increase the plasmid instability and produce undesirable end products.

1. DESIGN OF FERMENTER
AND TYPES
BY
LIKHITH K
BiSEP – 2021
Dept of Biotechnology
St Aloysius College
Mangaluru, Karnataka

2. CONTENTS
 Introduction
 History
 Factors required for designing a fermenter
 Design
a) Construction material
b) Size of fermentation vessel
c) Temperature control
d) pH Control sensors
e) Foam control
f) Agitation and aeration
• Parts of fermenter
• Types of fermenter
• Conclusion
• Reference

3. INTRODUCTION
 Fermenter or bioreactor refers to a device that provides all the basic necessities in a controlled system,
important for biological product extraction
 A fermenter contains different devices that help to maintain the environmental factor inside it which in turn
leads to the production of biological products.
 The main objective of the fermenter or bioreactor is to provide a suitable environment in which an organism
can efficiently produce a target product—the target product might be cell biomass, metabolite and
bioconversion Product.
 It must be so designed that it is able to provide the optimum environments or conditions that will allow
supporting the growth of the microorganisms.
 The design and mode of operation of a fermenter mainly depends on the production organism, the optimal
operating condition required for target product formation, product value and scale of production.

4.  The choice of microorganisms is diverse to be used in the fermentation studies. Bacteria, Unicellular fungi,
Virus, Algal cells have all been cultivated in fermenters.
 Now more and more attempts are tried to cultivate single plant and animal cells in fermenters.
 It is very important for us to know the physical and physiological characteristics of the type of cells which we
use in the fermentation.
 Before designing the vessel, the fermentation vessel must full fill certain requirements that is needed that will
ensure the fermentation process will occur efficiently.
 Some of the actuated parameters are: the agitation speed, the aeration rate, the heating intensity or cooling rate,
and the nutrients feeding rate, acid or base valve.
 Precise environmental control is of considerable interest in fermentations since oscillations may lower the
system efficiency, increase the plasmid instability and produce undesirable end products.

5.  Fermentation technology: - Fermentation Technology could be defined simply as the study of the fermentation
process, techniques and its application. Fermentation should not be seen merely as a process that is entirely
focused on the happenings occurring in the fermenter alone!
 There are many activities that occur upstream leading to the reactions that occur within the bioreactor or
fermenter, despite the fermenter is regarded as the heart of the fermentation process.
 Fermentation technology is the whole field of study which involves studying, controlling and optimization of
the fermentation process right up from upstream activities, mid stream and downstream or post fermentation
activities.
 The study of fermentation technology requires essential inputs from various disciplines such as biochemistry,
microbiology, genetics, chemical and bioprocess engineering and even a scatter of mathematics and physics.

6.  Fermentation in terms of biochemistry and physiology:- Fermentation is now defined as a process of energy
generation by various organisms especially microorganisms. The fermentation process showed unique
characteristics by which it generates energy in the absence of oxygen. The process of energy generation utilizes
the use of substrate level phosphorylation (SLP) which do not involved the use of electron transport chain and
free oxygen as the terminal electron acceptor.
 Engineers definition of fermentation:- It is only up to recently with the rise of industrial microbiology and
biotechnology that the definition of fermentation took a less specific meaning. Fermentation is defined more
from the point of view of engineers. They see fermentation as the cultivation of high amount of microorganisms
and biotransformation being carried out in special vessels called fermenter or bioreactors. Their definitions
make no attempt to differentiate whether the process is aerobic or anaerobic. Neither are they bothered whether
it involves microorganisms or single animal or plant cells. They view bioreactors as a vessel which is designed
and built to support high concentration of cells.

7. HISTORY
• In 1944 De becze and Liebmann used the primary large-scale fermenter for the growth of yeast.
• But, during the time of world war, a British scientist Chain Weizmann designed a fermenter for the
production of acetone.

9. Father of fermentation
Louis Pasteur

10. FACTORS REQUIRED FOR THE DESIGN OF FERMENTOR
 The vessel should be well equipped to maintain aseptic conditions inside it for a number of days.
 Aeration and agitation are important for the production of biological metabolites. However, controlled
agitation is required to prevent any damage to the cells.
 It should be less expensive in terms of power consumption.
 Temperature is an important environmental factor required for microbial growth. Therefore, a temperature
control system is required.
 Optimum pH is important for the growth of the organism; therefore, the fermenter must be equipped with
a pH controller.
 The fermentation of a huge culture is a time-consuming process. It needs to be contamination-free until
the process is complete. Apart from that, it is also important to monitor the growth rate of the organism.
Therefore, an aseptic sampling system is needed to design a fermenter.
 Facility for sampling should be provided.
 The fermenter vessel should be designed properly to minimize the labor involved in cleaning, harvesting,
etc.

12. DESIGN
A bioreactor should consist of the followings
1. Agitation- for mixing of cells and medium.
2. Aeration – used for oxygen supply.
3. Temperature, pH, pressure, nutrients feeding, etc.
4. Sterilization and maintenance of sterility.
5. Withdrawal of cells or media.
What should be the basic points of consideration while designing a fermenter?
 Fermenter operability and reliability ƒ
 Productivity and yield ƒ
 Product purification ƒ
 Water management ƒ
 Energy requirements ƒ
 Waste treatment

13. The Designing of a Bioreactor also has to take into Considerations the Unique Aspects of Biological
Processes
 The concentrations of starting materials (substrates) and products in the reaction mixture are frequently low;
both the substrates and the products may inhibit the process. Cell growth, the structure of intracellular enzymes,
and product formation depend on the nutritional needs of the cell (salts, oxygen) and on the maintenance of
optimum biological conditions (temperature, concentration of reactants, and pH) within narrow limits.
 Certain substances inhibitors effectors, precursors, metabolic products influence the rate and the mechanism of
the reactions and intracellular regulation.
 Microorganisms can metabolize unconventional or even contaminated raw materials (cellulose, molasses,
mineral oil, starch, wastewater, exhaust air, biogenic waste), a process which is frequently carried out in highly
viscous, non-Newtonian media.
 In contrast to isolated enzymes or chemical catalysts, microorganisms adapt the structure and activity of their
enzymes to the process conditions, whereby selectivity and productivity can change. Mutations of the
microorganisms can occur under sub optimal biological conditions.
 Microorganisms are frequently sensitive to strong shear stress and to thermal and chemical influences.

14.  Reactions generally occur in gas-liquid -solid systems, the liquid phase usually being aqueous.
 The microbial mass can increase as biochemical conversion progresses. Effects such as growth on the walls,
flocculation, or autolysis of microorganisms can occur during the reaction.
 Continuous bioreactors often exhibit complicated dynamic behaviour

15. Few Significant things of concern that should be taken into account while designing a fermenter: ƒ
• Design in features so that process control will be possible over reasonable ranges of process variables. ƒ
• Operation should be reliable ƒ
Operation should be contamination free. ƒ
• Traditional design is open cylindrical or rectangular vessels made from wood or stone. ƒ
• Most fermentation is now performed in close system to avoid contamination. ƒ
• Since the fermenter has to withstand repeated sterilization and cleaning, it should be constructed from non-
toxic, corrosion-resistant materials. ƒ
• Small fermentation vessels of a few liters capacity are constructed from glass and/or stainless steel. ƒ
• Pilot scale and many production vessels are normally made of stainless steel with polished internal surfaces. ƒ
• Very large fermenter is often constructed from mild steel lined with glass or plastic, in order to reduce the
cost. ƒ
• If aseptic operation is required, all associated pipelines transporting air, inoculum and nutrients for the
fermentation need to be sterilizable, usually by steam.

16.  Most vessel cleaning operations are now automated using spray jets, which are located within the vessels. They
efficiently disperse cleaning fluids and this cleaning mechanism is referred to as cleaning-in-place CIP. ƒ
 Associated pipe work must also be designed to reduce the risk of microbial contamination. There should be no
horizontal pipes or unnecessary joints and dead stagnant spaces where material can accumulate; otherwise this
may lead to ineffective sterilization.
 Overlapping joints are unacceptable and flanged connections should be avoided as vibration and thermal
expansion can result in loosening of the joints to allow ingress of microbial contaminants. Butt welded joints
with polished inner surfaces are preferred. ƒ
 Normally, fermenters up to 1000 L capacity have an external jacket, and larger vessels have internal coils. Both
provide a mechanism for vessel sterilization and temperature control during the fermentation. ƒ
 Other features that must be incorporated are pressure gauges and safety pressure valves, which are required
during sterilization and operation.
 The safety valves prevent excess pressurization, thus reducing potential safety risks. They are usually in the
form of a metal foil disc held in a holder set into the wall of the fermenter. These discs burst at a specified
pressure and present a much lower contamination risk than spring-loaded valves. ƒ
 For transfer of media pumps are used. However pumps should be avoided if aseptic operation is required, as
they can be a major source of contamination.

17.  Centrifugal pumps may be used, but their seals are potential routes for contamination. These pumps generate
high shear forces and are not suitable for pumping suspensions of shear sensitive cells. Other pumps used
include magnetically coupled, jet and peristaltic pumps. ƒ
 Alternate methods of liquid transfer are gravity feeding or vessel pressurization. ƒ
In fermentations operating at
high temperatures or containing volatile compounds, a sterilizable condenser may be required to prevent
evaporation loss.
 For safety reasons, it is particularly important to contain any aerosols generated within the fermenter by filter
sterilizing the exhaust gases. ƒAlso, fermenters are often operated under positive pressure to prevent entry of
contaminants

18. CONSTRUCTION MATERIAL
 Fermentation requires adequate aseptic conditions, for better yield of biomass or product.
 It is important to select a material for the body of the fermenter, which restricts the chances of contamination. it
needs to be non-toxic and corrosion free.
 Glass is a material that provides a smooth surface inside the vessel and also non-toxic in nature. Apart from
that, it is corrosion-proof and due to the transparency, it is easy to examine the inside of the vessel.
 There are mainly two types of glass fermenters
 A glass vessel with a flat bottom and a top plate with a diameter of 60 cm (approximately)
 The second glass vessel contains stainless steel plates at the top and bottom of the glass vessel.
SIZE OF FERMENTOR VESSEL
 The sizes of the bioreactor vary widely from the microbial cell (fewmm3 ) to shake flask (100-1000 ml) to
laboratory scale vessel (1 – 50L) to pilot level (0.3 – 10 m3 ) to industrial scale (2 – 500 m3 ) for large volume
industrial applications.

19. TEMPERATURE CONTROL
 Normally in the design and construction of a fermenter there must be adequate provision for
temperature control which will affect the design of the vessel body.
 Heat will be produced by microbial activity and mechanical agitation and if generated by these two
processes is not ideal for the particular manufacturing process then heat may have to be added to or
removed from, the system.
 On laboratory scale little heat is normally generated and extra heat has to be provided by placing
fermenter in a thermostatically controlled bath, or by use of internal heating coils or by a heating jacket
through which water is circulated or a silicone heating jacket.
 When certain size has been exceeded, the surface area covered by the jacket becomes too small to
remove the heat produced by the fermentation. When this situation occurs internal coils must used and
cold water is circulated to achieve correct temperature. Available heating/ cooling approaches are : -
Welded to the outside -in the fermenter
• Jacket Pillow plates,
• External coils tube coils
• Pillow Plate Thermo channels Tube bundles (vertical calandria).

20.  A new-patented IR radiator with a glided parabolic reflector is used to warm the culture broth. The heat
radiation (150 W) is concentrated on the bottom of the vessel where it is absorbed by the medium in a similar
way to the sun heating water.
 There is no overheating of culture common with heater placed directly in the medium. Thanks to the low heat
capacity of the IR source, overshooting of the temperature is reduced and the temperature can be controlled
more precisely.
 The temperature sensor is placed directly in the pH sensor and is used at the same time for an automatic
correction of pH and pO2 electrodes.

21. pH CONTROL SENSORS
 All types of fermenters are attached with a pH control sensor which consists of a pH sensor and a port to
maintain the pH inside of the fermenter.
 pH alteration can lead to death of the organism which leads to product loss.
 Therefore, it is a crucial instrument for a fermenter and needs to be checked regularly.

22. FOAM CONTROL
 It is very important to control foaming. When foaming becomes excessive, there is a danger that filters
become wet resulting in contamination, increasing pressure drop and decreasing gas flow.
 Foam can be controlled with mechanical foam breaker or the addition of surface active chemical agents,
called anti foaming agents. Foam breaking chemicals usually lowers KLa values, reducing reactors
capacity to supply to supply oxygen or other gases, and some cases they inhibit the cell growth.
 Mechanical foam breaker available is “turbosep”, in which foam is directed over stationary turbine blades
in a separator and the liquid is returned to fermenter.
 Foam is also controlled by addition of oils. Control of foams by oil additions is of large economic
importance to the fermentation industry.
 Excessive foaming causes loss of material and contamination, while excessive oil additions may decrease
the product formation.
 Antifoam oils may be synthetic, such as silicones or polyglycols, or natural, such as lard oil or soybean
oil. Either will substantially change the physical structure of foam, principally by reducing surface
elasticity.
 Industrial antifoam systems usually operate automatically from level-sensing devices. Methods for
metering of oil under aseptic conditions are: timed delivery through a solenoid, two solenoids with an
expansion chamber between, a motor-driven hypodermic syringe, and certain industrial pumps.

23. AGITATION AND AERATION
 The main aim of agitation to ensure similar distribution of microorganisms and the nutrients in the broth.
 Aeration provides microorganisms growing in submerged culture with adequate oxygen supply.
The following components of the fermenter which is required for aeration and agitation:
1. Agitator (impellers)
2. Stirrer glands and bearings
3. Baffles
4. Sparger (the Aeration system)

24. 1. Agitator (Impeller)
 The objectives of the impeller used in fermenters are bulk fluid and gas mixing, air dispersion, heat
transfer, oxygen transfer, maintain the uniform environment inside the vessel.
 Air bubbles often cause problems inside the fermenter. Impellers involved in breaking the air bubbles
produced in a liquid medium.

25. Various impellers use in bioreactors
 Flat blade disk turbine
 45° Flat blade disk turbine
 Curved blade disk turbine
 Pitched blade turbine
 curved blade turbine
 Marine propeller
 Large pitch blade impeller
 Intermig
 3 segment blade impeller
 Gate with turbine
 Maxblend
 Helical Ribbon

26. 2. Stirrer glands and Bearings
 The most important factor of designing a fermenter
is to maintain aseptic conditions inside the vessel.
 Therefore stirrer shafts are required.
 These stirrer shafts play an important role to seal the
openings of a bioreactor. As a result, it restricts the
entry of air from outside.

27. 3. Baffles
 There are four baffles that are present inside of an agitated vessel
to prevent a vortex and improve aeration efficiency.
 Baffles are made up of metal strips roughly one-tenth of the
vessel diameter and attached to the wall.
 The agitation effect is slightly increased with wider baffles but
drops sharply with narrower baffles.
 After installation of the baffle there a gap between them and the
vessel wall which facilitates scouring action around the baffles
and minimizes microbial growth on the baffles and the fermenter
wall.
 Baffles are often attached to cooling coils to increase the cooling
capacity of the fermenter.

28. 4. Airation system (Sparger)
 Aeration supports the growth of the organism by providing
appropriate amount of oxygen in the fermenter.
 The device such as sparger is used to introduce the air in
the fermenter.
 Aerators producing fine bubble should be used.
 Oxygen is easily transfer through the sparger to greater
amount with the large bubbles which has less surface area
than the smaller bubbles.
 Sparger contains air filter to supply sterile air into the
fermenter.

29. There are three main types of sparger used in industrial-scale bioreactors such as
 Nozzle Sparger: This is used in industrial-scale fermenters. The main characteristic of this kind of sparger
is that it contains a single open or partially closed pipe as an air outlet. The pipe needs to be positioned
below the impeller. The design helps to overcome troubles related to sparger blockage.
 Orifice Sparger: These are used in small stirred fermenters where perforated pipes are used and attached
below the impeller in the form of a ring.
 Porous Sparger: It is made up of sintered glass, ceramics or metals’ and are mostly used in laboratory-
scale bioreactors. As it introduces air inside a liquid medium, bubbles are formed. These bubbles are
always 10 to 100 times larger than the pore size of the aerator. The air pressure is generally low in these
devices and a major disadvantage of using porous sparger is that microbial growth may occur on the pores
which hamper the airflow.

32. TYPES OF FERMENTER
 Stirred tank fermenter
 Airlift fermenter
 Fluidised bed fermenter
 Packed bed fermenter
 Photo fermenter

33. Stirred Tank Fermenter
 It consists of the motor driveshaft and a variable number of impellers (more than one). The impellers have a
1/3rd diameter of the vessel. The height and diameter ratio of this bioreactor is between 3:5. Air passes into the
culture medium through a single orifice from the tube attached externally. It enables better distribution of the
contents throughout the vessel. Its basic functions include:
 Homogenization
 Suspension of solid material
 Aeration to the medium
 Heat exchange
 In stirred tank fermenter, rotating stirrer and baffle are found either at the top or the bottom. It mainly uses the
batch process of fermentation.

34.  Advantages
 It is easy to operate and easy to clean.
 Provides a good temperature control.
 The construction of stirred tank fermenter is quite simple.
 It has a low operating cost.
 It does not cause shear damage to the cells.
 Disadvantages
 It cannot be used for immobilized cells or enzymes.
 It has low volumetric productivity.

35. Airlift Fermenter
 It consists of a single container inside which a hollow tube is present. This hollow tube called “Draft tube”.
There is a gas flow inlet present at the bottom of the fermenter, which allows the passage of oxygen. Gas flow
inlet is attached with the perforated disc or tube that allows continuous distribution of air.
 This type of bioreactor lacks the mechanical stirring arrangements for agitation. As from the name airlift, it is
clear that the air lifts the medium upwards. There are internal liquid circulation channels, which enable
continuous circulatory motion of the medium. Here, the fermentation occurs at a fixed rate of volume and
circulation

36.  Advantages
 It ensures adequate mixing.
 Consumes less energy.
 It favours the growth of aerobic cultures.
 Construction is simple.
 It can use both free and immobilized cells and enzymes.
 Widely used in SCP production.
 Avoids excessive heat generation.
 Disadvantages
 Lacks mechanical stirring arrangements.
 High energy requirements
 Excessive foaming
 Cell damage due to bubble bursting; particularly with
animal cell culture

37. Fluidized Bed Fermentor
 The top portion of this bioreactor is more expanded. This expansion reduces the velocity of the fluid. Its
bottom part is slightly narrow. It is designed in such a way where:
 The solid retain inside the vessel.
 And, liquid flows out.
 An adequate amount of gas introduces into the medium to form a suitable gas-liquid-solid fluidised bed. By
using this kind of biofermenter one should note that the suspended particles should not be too light or too
heavy and secondly, there should be continuous recycling of the medium for good bioprocessing.
 Advantages
 Mixes the contents uniformly.
 Maintains the uniform temperature gradient.
 It can be used for continuous operation.
 Produces higher volumetric productivity.
 There is little or no clogging of particles.

38. Disadvantages
•Expensive to construct and maintain.
•Erosion of reactor walls may occur.
•Regeneration equipment for catalyst is
expensive.
•Catalyst may be deactivated.
•Can't be used with catalyst solids that won't
flow freely.
•Large pressure drop.
•Attrition, break-up of catalyst pellets due to
impact against reactor walls, can occur.

39. Packed Bed Fermenter
 It consists of a cylindrical vessel and a packed bed with biocatalysts. The solid matrix that is used for the
packed bed fermentor possess the following properties:
 Porous or non-porous
 Highly compressible
 Rigid
 In this kind of biofermenter, a nutrient broth continuously flows over the immobilized biocatalyst. After that, a
product releases into the fluid at the bottom of the culture vessel and finally, it can be removed. Here, the flow
of fluid can be upward or downward.
 Advantages
 It has a low operation cost.
 Provides continuous operation.
 Separation of the biocatalyst is easy.
 It is widely used in wastewater engineering.

40.  Disadvantages
 There are undesired heat gradients.
 Poor temperature control.
 There is an alternation in the bed porosity.
 Involves higher risk of particles clogging

41. Photo Fermenter
 This fermenter works under the principle of light energy that involves direct exposure to
the sunlight or through some artificial illumination. It is extensively used for the production of p-
Carotene, astaxanthin etc. This type of bioreactor is basically made of glass or plastic. Photo fermenter
consists of:
 A single container
 Number of tubes or panels
 Tubes act as “Solar light receivers or trappers”. In this, culture transfers through solar trappers with the
help of a centrifugal pump. Inside photo fermenter, adequate penetration of sunlight is maintained and
after that, it is cooled when there is a rise in temperature. Here, the microalgae and cyanobacteria are
the common microorganisms that are used. These microorganisms grow in the presence of solar light
and then product forms during the night.

42.  Advantages
 It gives higher productivity.
 Provides a large surface and volume ratio.
 Provides better control over the gas transfer.
 Maintains uniform temperature gradient.
 Disadvantages
 Expensive method to carry out.
 There is a technical difficulty in the process of sterilization.
 Low gas exchange
 High shear stress
 Accumulation of biomass in the tubes
 High energy input

43. CONCLUSION
 Bioreactors are vessels that have been designed and produced to provide an effective environment for enzymes
or whole cells to transform bio chemicals into products. In some cases, inactivation of cells or sterilization is
carried out in the bioreactor such as in water treatment. Many different bioreactors and bioreactor applications
are described, including those for cell growth, enzyme production, bio catalysis, biosensors, food production,
milk processing, extrusion, tissue engineering, algae production, protein synthesis, and anaerobic digestion.
 Methods to classify bioreactors are presented, including operational conditions and the nature of the process.
References are included to enable the reader to find more information on each of the types of bioreactors and
selected products. The emphasis is on reactors that are produced commercially rather than on reactors that have
evolved in the natural world. Bioreactors used for DNA and protein synthesis (bio molecular synthesizers) are
included. Commodity products include all substances that are produced in bioreactors and marketed; however,
the emphasis is on general principles and more widely used bioreactor types and products.

44. REFERENCES
 Stanbury P., Whitaker A., Hall S. Principle of fermentation technology (1975) third edition, pp: 441-460
 Doran P.M. Bioprocess engineering principles (1995) U.S. Edition published by academic press INC, pp: 165-
166
 An Overview of Fermenter and the Design Considerations to Enhance Its Productivity, Hitesh Jagani etal.
Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences Manipal
University, Manipal, Karnataka, India. Pharmacologyonline 1: 261-301 (2010)

45. THANK YOU