PHARMACEUTICAL BIOTECHNOLOGY (BP502TT)

TOPIC: FERMENTATION TECHNOLOGY

Prepared By:
Ms. Disha Joshi
Assistant Professor
Department Of Pharmaceutical Technology
L.J. Institute Of Pharmacy

1
PHARMACEUTICAL BIOTECHNOLOGY (BP502TT)
 LIST OF CONTENTS

1. Introduction To Fermentation

2. Methods of Fermentation

3. General Requirements

4. Fermentation Media

5. Sterilization

6. Aeration Process And Stirring

7. Ideal Characteristics Of Fermenter

8. Design Of Fermenter And Its Various Control

FERMENTATION TECHNOLOGY 2
 1. INTRODUCTION
⤇ DEFINITION
⤇ Fermentation is a metabolic process of growing micro-organisms in a nutrient media by maintaining physico-chemical conditions and
thereby converting feed into a desired end product.
⤇ The selection of good medium is important to the success of an industrial fermentation which supplies nutrients for cell growth and
biosynthesis of fermentation products.
⤇ The vessels or containers in which fermentation processes are carried out are called fermenters. They are designed and operated under
suitable conditions of constant temperature, pH, dissolved oxygen and substrate concentration.

Major Fermentation Products

Group Product Producing micro-organisms
Antibiotics Penicillin Penicillium chrysogeneum
Streptomycin Streptomyces griseus
Enzymes Proteases Bacillus species
Amylases Aspergillus oryzae
Vitamins Vitamin B12 Pseudomonas dentrificans
Industrial chemicals Ethanol Saccharomyces cerevisiae
Citric acid Aspergillus niger
Food and Beverages Bread or beer Saccharomyces cerevisiae
Cheese Streptococcus species

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 2. TYPES/METHODS OF FERMENTATION

Fermentation Types

Batch Continuous Fed batch Aerobic Anaerobic Surface Submerged

↦ Closed culture system, initial and limited amount of nutrient medium is added into the fermenter for single time.
↦ Suitable micro-organism is incubated into the medium for definite time and under optimal physiological conditions.
↦ During the incubation period, the micro-organism culture undergoes multiplication and passes through the number of stages of growth in the batch
process.

FERMENTATION TECHNOLOGY 4
 ⤇ Batch Fermentation

LAG PHASE • Period of adaptation for organisms to new conditions before growth.

• Transition of organisms from lag to exponential growth phase.

ACCELERATION PHASE • Cell size increases and division of single cell occurs, thus the cycle continues.

• Under optimum conditions, growth rate is most rapid in this phase. Hence, the period of maximum growth rate
is known as exponential or log phase and the time required to complete the cell division is known as the
LOG PHASE generation time.
• Primary metabolites of microbial cells such as lactic acid, ethanol or amino acids, proteins, vitamins
(compounds required for cell synthesis) are produced during this phase.

• As the time increases, growth rate of organisms increases but the growth of the cell remains constant.
STATIONARY PHASE & • Since the environmental conditions of the nutrient culture are continuously changing, the micro-organisms are
ACCELERATED DEATH affected by the changing cultural conditions.
PHASE • Thus, the growth rate of organisms decreases due to reduction of nutrients (exhaustion of nutrients) or toxin
accumulation.

EXPONENTIAL DEATH • The microbial cells have efficiency to convert essential nutrients into biomass.
PHASE & SURVIVAL • Secondary metabolites are produced during this stage, since microbial cells produce bioactive molecules such as
PHASE antibiotics, enzymes or inhibitors.

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 ⤇ Batch Fermentation
↦ ADVANTAGES:
↦ Due to short growth period, less risk of contamination and cell mutation
↦ Simplicity of operation and more flexibility with different products
↦ Process is more economical because raw material conversion level is more

↦ DISADVANGES:
↦ For each fermentation process, the fermenter and other equipment are to be cleaned and sterilized
↦ Low productivity
↦ Running costs are high for preparing and maintaining stock cultures
↦ More focus on instrumentation due to frequent sterilization
↦ Fresh sterilized medium and pure culture are to be made for every fermentation process
↦ Larger industrial hygiene risks due to potential contact with pathogenic micro-organisms

⤇ Continuous Fermentation
↦ Fresh nutrient media is added continuously to the fermenter and equivalent amount of used medium with micro-organisms is withdrawn continuously for
recovery of cells or certain fermentation products.

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 ⤇ Continuous Fermentation
↦ ADVANTAGES:
↦ Less labor expense due to automation of fermentation process
↦ Little quantity of initial inoculum is needed
In continuous mode, ↦ Less toxicity risks to operator by any toxins producing micro-organisms
volume of medium and
↦ Maximum (high yield) and continuous production of good quality product
concentration of
nutrients at optimum due to invariable operating parameters
level are maintained
↦ DISADVANTAGES:
Micro-filtrations or ↦ More risk of contamination and mutation due to prolonged incubation and
screens are used to continuous fermentation
Starting medium and
return the cell mass ↦ Possibility of wastage of nutrient medium because of continuous
inoculum are added to
back to the fermenter, withdrawal for product isolation
the fermenter
thus constant volume of
broth is maintained ↦ Uniformity in media quality is necessary to ensure the continuous process
↦ Process becomes more complex and difficult to accomplish when the
desired products are antibiotics

↦ APPLICATIONS:
After the growth of ↦ Continuous culture fermentation has been used for the production of:
The vessel is fitted with culture, fermenter is fed ↦ Acetic acid
an overflow device, so with nutrients and
that the culture is culture broth is ↦ Ethanol
displaced by the withdrawn at the same ↦ Lactic acid
incoming fresh medium rate ↦ Hydrogen sulphide
↦ Penicillin
↦ Chloramphenicol
↦ Streptomycin
↦ Vitamin B₁₂

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 ⤇ Continuous Fermentation

↦Single stage Fermentation

Single fermenter is inoculated and the nutrient medium
with culture is kept in continuous operation by balancing
an input and output of nutrient medium and harvested
culture

↦Recycle fermentation ↦Multiple stage

A portion of the fermentation
withdrawn culture or Two or more fermenters
residue of unused are employed
substrate plus withdrawn simultaneously and the
culture is recycled to the fermentation is operated
fermentation vessel in sequence

FERMENTATION TECHNOLOGY 8
 ⤇ Fed Batch Fermentation
↦ Modification to the batch fermentation where substrate is added periodically in the installments as the fermentation progresses, due to which the
substratum is always at an optimal concentration.
↦ Three types of fed batch fermentation are:
↦ Variable volume fed batch culture- Same medium is added resulting in an increase in volume.
↦ Fixed volume fed batch culture- A very concentrated solution of the limiting substrate is added at a very little amount resulting in an insignificant
increase in volume of medium.
↦ Cyclic fed batch culture- Indirect methods are employed for controlling the feeding process. For e.g. In organic acid production, the pH value may be used
to determine the rate of glucose utilization
↦ E.g. of Fed batch culture products: Theostrepton by Streptomyces laurentii, Lysine by Corynebacterium glutamicum

⤇ Aerobic & Anaerobic Fermentation

↦ Fermentation process carried out in the presence of oxygen is known as aerobic fermentation.
↦ Fermentation process carried out in the absence of oxygen is known as an anaerobic fermentation.
↦ E.g. of anaerobic fermentation products: Ethyl alcohol by Saccharomyces, Acetic acid and succinic acid by E.coli
↦ Advantages:
↦ Production of economically valuable byproducts like carbon dioxide and hydrogen gas during anaerobic fermentation, which may fetch profits to the
manufacturers.
↦ Disadvantages:
↦ Manufacturers may have to spend more money in providing extra provisions to the fermenter like exhaust pump in order to enforce anaerobic conditions.

⤇ Surface & Submerged Fermentation

↦ Substratum may be solid or liquid in surface fermentation, thus the organisms grows on the substratum and draws the nutrients from it.
↦ Nutrient substratum is liquid in submerged fermentation and the organisms grow inside the substratum.
↦ Most of the industrial fermentations are of these type.

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 3. GENERAL/ IDEAL REQUIREMENTS OF FERMENTATION
i. Selection of suitable organism is important for conduction of fermentation
Basic requirements to conduct fermentation process are: process. Various varieties of organisms are first isolated from different sources
such as soil, ocean, river, plant, animal, air or non-living objects and further
improved strain of the same are used for fermentation process.
➢ By various methods such as protoplast fusion, mutation or genetic recombination,
Micro-organism improved strains are developed.
➢ Suitable strains are selected by serial dilution, spread plate, streak plate or pour
plate techniques.
ii. Important to develop inoculum and to increase the yield of desired product.
Growth media
Micro-organisms require various conditions for growth such as nutrients, oxygen,
temperature, pH, salinity, where nutrients to the organism are provided by using
either synthetic, semi synthetic or natural media.
➢ Water: clean water is required for media prep., to dissolve chemicals, for
Equipment
measuring and adjusting pH.
➢ Carbon: sugarcane molasses, beet molasses, vegetable oil, starch, glucose,
sucrose, lactose
➢ Nitrogen: slaughter house waste, urea, ammonium salts, nitrate, peanut granules,
soyabean meal or yeast extract

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 3. GENERAL/ IDEAL REQUIREMENTS OF FERMENTATION

➢ Growth factors: Vitamins and amino acids are added to the media
Basic requirements to conduct fermentation process are:

➢ Trace elements: Zn, Mo, Co, Mn, Cu are required for metabolism or in proteins
(haemoglobin)
➢ Inducers: Required for enzyme function to perform metabolic process
➢ Precursors: To enhance production of secondary metabolite. Eg. Streptomycin
production may be induced by yeast extract
Growth media
➢ Repressors: To repress production of enzymes
➢ Antifoam: To supress the problem of foam formation in fermentation.
➢ Sterilization: To avoid contamination of culture, equipment, media.
➢ Physical parameters: Temp., pH, agitation and aeration
Equipment
iii. For development of culture, optimization of physical parameters
➢ Once the desired product is obtained from the suitable organism, suitable
equipment is provided for cell separation, collection of cells and finally in product
purification

FERMENTATION TECHNOLOGY 11
 4. Fermentation Media Design
➢ For high yield of product, choice of optimum micro-organisms and fermentation media is important.
➢ Fermentation media provides nutrients and energy for the growth of micro-organisms thus, its quality is equally important
➢ Nutrients required for fermentation media depends upon the type of fermentation organisms as well as the type of fermentation process to be used.
➢ Major and minor components of fermentation media are: Minor components: inorganic salts, vitamins,
growth factors, antifoaming agents, buffers,
growth inhibitors and enzymes
Major components: Carbon
and Nitrogen source

Synthetic media

Fermentation media

Crude media
Uses of Fermentation
media

Contains low amount of

nutrients which is useful for
Growth media
creating raw material that can
be used in fermentation process

FERMENTATION TECHNOLOGY 12
 4. Fermentation Media Design
➢ Useful in field of research because exact composition of nutrients is predetermined and every component of media is chemically
known. Variation in levels and concentration of nutrients can be controlled, also the effect of nutrients on growth and yield of
Synthetic media product can be analysed.
➢ Could be redesigned as per the fermentation needs. Example: Peptone-water, Glucose salts, Czapek Dox media
➢ Advantages: Chemically defined and sterile
➢ Pure cultures can be grown
➢ No foam formation and less chances of contamination
➢ Product recovery is easier because synthetic media contains pure compounds
➢ Disadvantages: Expensive, thus cannot be used for industrial scale

➢ Used on industrial scale for fermentation process, contains rough composition of media and sources thus gives high yield of product.
➢ Ingredients of crude media are:
Crude media ➢ Inorganic nutrients: Inorganic salts containing cations and anions along with a carbon source. Specific ions required are:
Magnesium, phosphates or sulphates.
➢ Carbon source: Mannitol, sorbitol, corn sugar molasses, beet molasses, starch corn, rice, wheat potatoes, etc
➢ Nitrogen source: Salts of urea, ammonia, nitrate, animal and plant raw materials such as casein, peptons, yeast extract and
soyabean meal.
➢ Growth factors: Yeast or beef extract, when there is lack of any kind of vitamins or nutrients.
➢ Precursors: Cobalt chloride is added in fermentation of vitamin B₁₂
➢ Buffers: To control changes in pH. Inorganic buffers like K2HPO4, CaCO3 and KH2PO4 can be added.

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 5. STERILIZATION

It is required to ensure sterility of

following for carrying out successful
fermentation

Prevention of
Sterility of culture Sterility of incoming Sterility of
contamination
media and outgoing air equipment
during process

Air sterilization by
Heat sterilization By filtration
heat

Physical methods Depth filter

Membrane cartridge
filter

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 5. STERILIZATION

A. Sterilization of culture media: Constituents of media, water and container contribute towards the contamination through
bacteria and spores. Sterilization of media before use in fermentation can be achieved by:
➢ Heat Sterilization- Vegetative cells are destroyed at lower temperature (around 60º C) in a short time (5-10 mins). But destruction of
spores require higher temperature (around 80º C) for 15-20 mins.
➢ Factors influencing the success of heat sterilization are: quality and quantity of contamination, composition of media and its pH.
➢ Physical methods- Filtration, centrifugation and adsorption are mostly used physical methods where filtration is the most widely
used. Certain components such as vitamins, or antibiotics are heat labile, therefore they can be destroyed along with micro-organisms
through heat sterilization. Such components need to subjected to filter sterilization.
➢ Limitations of filtration technique: Application of high pressure during filtration may be unsuitable
➢ It is possible that during filtration some of the essential media components may be lost.
B. Sterilization of Air: For an effective fermentation, the air should be completely sterile and free from all MO’s and suspended
particles. Wide variation in the quantity of microbes and suspended particles of outdoor air can be seen such as:
➢ Micro-organisms- 10-2000/m³ and Suspended particles- 20-10,000/m³
➢ Air can be sterilized by heat, filtration or UV radiation where heat is generally cost effective for full scale production.
➢ Air Sterilization by filters- Depth filters comprising of glass wool are used for trapping and removing of the contaminated particles
present in the air.
➢ Membrane cartridge filter: made up of cellulose ester, nylon or polysulfone

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 5. STERILIZATION

A. Sterilization of fermenter: In the fermenter, possible contamination source is all the entry and exit points. Thus, they should be
sterilized with steam excluding the air outlet through which the air is coming out of fermenter.
➢ For small scale fermenter, media and fermenter both are sterilized by steam under pressure in autoclave. Sterilization of media and
vessel is done using steam at 121ºC for 15 mins. If the medium is sterilized in a separate batch cooker, or continuously then the
fermenter has to be sterilized separately before the media is added to it.
➢ This process is carried out by heating the coils or jacket of the fermenter with steam and passing the steam further into the vessel
through all the entries at 15 psi pressure for 20 mins.
B. Prevention of contamination during fermentation: By adopting physical and chemical sterilization methods, the initial
contamination gets prevented. Possibility of contamination occurs through:
➢ Improper cleaning of the sparger
➢ Poor tightening of the fermenter top lid screws and improperly connected air vent filters
➢ Silicone tubing used to deliver feeds to the fermenter where insufficient care has been taken with tubing connections.
➢ Sometimes contamination is not easy to recognize thus, collecting samples from all the processes and performing proper test for the
presence of contaminants is highly recommended.

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 6. EQUIPMENTS
In fermentation industries, microbes are to be grown in specially designed vessels loaded with particular type of nutrient media. These vessels are referred
to as Fermenters

AERATION PROCESS AGITATION/ STIRRING PROCESS

➢ The majority of fermentation process are aerobic and continuously require the delivery of oxygen during growth at a rate sufficient to satisfy the
organisms demand.
➢ This requirement for oxygen of fermentation procedure is generally fulfilled by aerating and agitating the fermentation broth.
➢ Oxygen is normally supplied to microbial culture in the form of air, which is the cheapest source of the gas.
➢ At industrial scale, air is provided to the culture by providing sparger into the fermenter.

SPARGER: A device used for introducing air as a source of oxygen into the contents of the fermenter.

POROUS SPARGER ORIFICE SPARGER NOZZLE SPARGER

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 6. EQUIPMENTS

POROUS SPARGER: is made up of It has thousands of tiny pores which Main demerit of porous sparger is
1. sintered glass; ceramics like material release numerous and 10 to 100 getting blocked due to microbial
or metals and is generally used in times larger size bubbles than the growth into the fine holes of the
non-agitated vessels. pore size of the aerator. sparger.

ORIFICE SPARGER: used in small Air holes are drilled on the under Used with agitation or to a limited
stirred fermenters where perforated surfaces of the tubes and the holes extent in yeast manufacture, effluent
2. pipes are used and attached below the should be at least 6mm diameter to treatment and production of single-cell
impeller in the form of a ring.. avoid blockage proteins.

NOZZLE SPARGER: used in industrial-

Thus, have advantage of causing a
scale fermenters that contains a single Pipe is positioned centrally below and
lower pressure and prevents clogging
open or partially closed pipe as an air far away from the impeller.
3. outlet .
of pores.

FERMENTATION TECHNOLOGY 18
 AGITATION/ STIRRING PROCESS
6. EQUIPMENTS

➢ Synonym: IMPELLER
➢ The objectives of the impeller used in fermenters are: Bulk fluid and gas phase mixing,
Air dispersion,
Heat transfer and oxygen transfer,
Suspension of solid particles,
Maintain the uniform environment inside the vessel.
Four different classes of agitators are:

Disc turbine Variable pitch open Marine propellers

Vanned disc
turbine

➢ Series of rectangular vanes arranged in vertical plane around ➢ This type of agitator lacks a disc and the vanes are directly
circumference. connected to a center shaft.
➢ Disk turbines are most successful because these are able to ➢ Air bubbles hit any surface by their action
breakdown fast air stream without getting flooded with air ➢ Floods only when superficial velocity exceeds 21m/h
bubbles.

FERMENTATION TECHNOLOGY 19
 6. EQUIPMENTS
Vanned disc

➢ A series of rectangular vanes attached vertically to the underside.

➢ Air from sparger hits its underside & the air gets displaced
towards the vanes.
➢ Results in the destruction of air bubbles.

Marine propellers

➢ Blades are attached directly to a boss on the agitator shaft

➢ Air bubbles hit the surface and are mainly used in animal cell
culture vessels.

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 Modern Agitators 6. EQUIPMENTS

➢ Rushton disc turbine

➢ Scaba 6SRGT
➢ Prochem max flow T
➢ LighteningA315
➢ Useful for high viscosity broth, where gas
dispersal presents a problem
➢ Breaks up faster air stream, without
itself becoming flooded with air bubbles
➢ Able to handle higher air volume, due to
large surface area
➢ Gives better bulk blending in viscous media
and heat transfer
➢ Sometimes, can cause mechanical
problems due to its vibrational nature

FERMENTATION TECHNOLOGY 21
 7. IDEAL CHARACTERISTICS OF FERMENTER
➢ Used for fabrication of fermenter should be strong enough to withstand interior pressure due to fermentation media
MATERIALS
➢ Should be resistant to corrosion
➢ Free from toxic effect for the microbial culture and the product formed by the microbial culture

➢ Should be provided with the inoculation point for aseptic transfer of the inoculum
➢ Equipped with the aerating device (spargers), stirring device (Impellers) for uniform distribution of air, nutrients
and microbes
PROVISIONS ➢ Equipped with baffles to avoid vortex formation
➢ Provided with sampling valve for aseptic withdrawing of sample for different laboratory tests
➢ Posses a device for controlling temperature; pH controlling device for monitoring and maintaining pH of the medium
(pH probe and acid base reservoir)
➢ Facility for addition of antifoam agents for controlling foam formation or mechanical foam breakers
➢ Facility for feeding of various media components (Precursors) during the fermentation progress
➢ For further progressing, drain at the bottom of fermenter to remove used fermentation broth
➢ Exit valve provision at the top for the removal of metabolic gases produced during fermentation process
➢ For purposes such as repairing and thorough cleaning of fermenters, man hole access should be provided at the top of
the fermenter

FERMENTATION TECHNOLOGY 22
 8. DESIGN OF FERMENTER
Fermenter or bioreactor refers to a device that provides all the basic necessities 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. Therefore the main objective of
a fermenter is to maintain a controlled environment that supports the growth of the bacteria or any other organism.

Labelled diagram of fermenter design Design of Industrial fermenter

FERMENTATION TECHNOLOGY 23
8. DESIGN OF FERMENTER

FERMENTATION TECHNOLOGY 24
8. DESIGN OF FERMENTER

FERMENTATION TECHNOLOGY 25
8. DESIGN OF FERMENTER

FERMENTATION TECHNOLOGY 26
 8. DESIGN OF FERMENTER
MATERIALS USED IN CONSTRUCTION OF FERMENTER
▪ Non-toxic
▪ Corrosion proof
▪ 2 types of material STAINLESS STEEL

GLASS VESSEL (Borosilicate glass)

▪ Can withstand repeated sterilization cycles
▪ Used for small-scale fermentation mainly at a laboratory scale
▪ Gives a smooth surface and it is easy to examine the interior of the
vessel
▪ E.g. Pyrex® & Kimax®
▪ Different variants of glass fermenter are:
1. Glass Bioreactor (without jacket) with an upper stainless steel lid
2. With jacket and upper stainless steel lid ▪ STAINLESS STEEL: used as a vessel construction material with
different modifications such as
3. Without jacket, upper & lower ss lid
▪ >4% chromium may be added
4. Two-part bioreactor (glass & SS) where the stainless steel part has a ▪ Film of thin hydrous oxide
jacket & ports for electrodes installation ▪ Inclusion of nickel- improves resistance and engineering properties
▪ Presence of molybdenum for resistance against halogen salts, brine,
and sea water
▪ Tungsten, silicon

FERMENTATION TECHNOLOGY 27
 8. DESIGN OF FERMENTER
MATERIALS USED IN CONSTRUCTION OF FERMENTER
▪ Materials for pilot scale and large scale bioreactors are sterilized
in-situ and are assessed for their ability to withstand sterilization
pressure and corrosion
▪ They are normally constructed of Stainless Steel, where steel
containing <4% chromium is classified as steel alloys, and those
with >4% are SS (American Iron & Steel Institute)
▪ Corrosion resistance of SS is due to the presence of a thin hydrous
oxide film on the surface which is stabilized by chromium and is
considered to be continuous, non-porous, and self-healing.
▪ Increasing the concentration of chromium by 10-13% develops
effective film and enhances resistance to corrosion by acid,
alkalis, gases, soil, salt, water
▪ Thickness of construction material increases with scale, such as at
▪ AISI grade 317 (SS with 3-4% Mo²)- used for citric acid fermentation
3,00,000 dm³ capacity, 7mm plate for sides of vessel and 10mm (pH 1-2), to prevent the leaching of heavy metals from steel.
plate for top and bottom to withstand pressure ▪ AISI grade 304 (SS with 10% Ni² & 18.5% Cr³)- used in the brewing
industry.
▪ SS type 316L (low carbon version)- for plant and animal cell tissue
culture

FERMENTATION TECHNOLOGY 28
 8. DESIGN OF FERMENTER
➢ BAFFLES: They are metal strips of ideally one-tenth of the diameter of the vessel & attached radially to the wall of the fermenter
➢ To augment mixing and gas dispersion
➢ Incorporated into agitated vessels to prevent vortex formation and improve aeration efficiency
➢ Generally 4-8 baffles are incorporated
➢ Installed in fermenters by providing a gap between them and the vessel walls, thus to prevent microbial growth and scouring could be provided around
and behind the baffles.
➢ To improve the cooling capacity of the fermenter, extra cooling coils are sometimes attached to the baffles.

FERMENTATION TECHNOLOGY 29
 8. DESIGN OF FERMENTER
➢ FOAM CONTROL:
➢ Most problem offered in fermentation is foaming, because when it becomes excessive then there is a danger of filters wetting, resulting in contamination,
increasing pressure drop, and decreasing gas flow.
➢ Foam can be controlled by adding: ANTIFOAM AGENTS & MECHANICAL FOAM BREAKERS
➢ MECHANICAL FOAM BREAKER (turbosep): Foam is directed over stationery turbine blades in a separate vessel & the liquid is returned to fermenter.
➢ ANTIFOAM AGENTS: either added during media makeup or during the fermentation process
➢ Egs: Animal & vegetable oils, lard oil, corn & soyabean oil, long-chain alcohols (octadecanol) or silicone compounds & polyglycols
➢ During the fermentation process, antifoam agents are either added manually or electrically
➢ Where manual addition requires continuous observation of the tank and addition of antifoaming agents as required
➢ Thus electrical addition is more preferred
➢ To accomplish that a sensing mechanism is employed that determines the foam risen into the headspace of the fermenter thus, provides automatic
addition of antifoaming agents.

FERMENTATION TECHNOLOGY 30
 8. DESIGN OF FERMENTER
➢ TEMPERATURE CONTROL:
➢ Normally heat in the fermenter vessel is produced by the microbial activity and mechanical agitation, but for ideal heat transfer extra provisions
has to be provided by placing the fermenter vessel in a thermostatically controlled bath, on laboratory scale.
➢ Internal heating coils or by a heating jacket through which water is circulated is provided.
➢ When surface area covered by the jacket is too small that possess problem in removal of heat produced during fermentation, in that case cold water is
circulated to maintain correct temperature.
➢ Many a times temperature sensor are placed directly with the pH sensors and used directly for automatic correction of pH & temp.
➢ pH CONTROL:
➢ In order to grow desired microorganisms for product formation, it is very essential to maintain certain pH.
➢ pH control sensors are used in fermenter for periodically checking of pH.

FERMENTATION TECHNOLOGY 31
9. MICROBIAL FERMENTATION PROCESS
✓ Study for the production of:
A. PENICILLIN
B. CITRIC ACID
C. VITAMIN B12
D. GRISEOFULVIN
E. GLUTAMIC ACID

General procedure

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