Fermentor (Bioreactor): History, Design, Construction and types
1. Meaning of Fermentor 2. History of Fermentors 3. Design 4. Construction 5. Use of
Computer in Fermentor 6. Types.
Meaning of Fermentor:
A fermentor (bioreactor) is a closed vessel with adequate arrangement for aeration, agitation,
temperature and pH control, and drain or overflow vent to remove the waste biomass of cultured
microorganisms along-with their products.
A fermentor is used for commercial production in fermentation industries and is a device in
which a substrate of low value is utilized by living cells or enzymes to generate a product of
higher value. Fermentors are extensively used for food processing, fermentation, waste
treatment, etc.
History of Fermentors:
De Beeze and Liebmann (1944) used the first large scale (above 20 litre capacity) fermentor for
the production of yeast. But it was during the first world war, a British scientist named Chain
Weizmann (1914-1918) developed a fermentor for the production of acetone.
Since importance of aseptic conditions was recognised, hence steps were taken to design-and
construct piping, joints and valves in which sterile conditions could be achieved and
manufactured when required.
For the first time, large scale aerobic fermentors were used in central Europe in the year 1930’s
for the production of compressed yeast (de Becze and Leibmann, 1944). The fermentor consisted
of a large cylindrical tank with air introduced at the base via network of perforated pipes.
In later modifications, mechanical impellers were used to increase the rate of mixing and to
break up and disperse the air bubbles. This process led to the compressed air requirements.
Baffles on the walls of the vessels prevented forming a vortex in the liquid. In the year 1934,
Strauch and Schmidt patented a system in which the aeration tubes were introduced with water
and steam for cleaning and sterilization.
The decision to use submerged culture technique for penicillin production, where aseptic
conditions, good aeration and agitation were essential, was probably a very important factor in
forcing the development of carefully designed and purpose-built fermentation vessels.
In 1943, when the British Govt. decided that surface culture was inadequate, none of the
fermentation plants were immediately suitable for deep fermentation. The first pilot fermentor
was erected in India at Hindustan Antibiotic Ltd., Pimpri, Pune in the year 1950.
Design of Fermentors:
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.
A bioreactor should provide for the following:
(i) Agitation (for mixing of cells and medium),
(ii) Aeration (aerobic fermentors); 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 fermentors).
Modern fermentors are usually integrated with computers for efficient process monitoring, data
acquisition, etc.
Generally, 20-25% of fermentor volume is left unfilled with medium as “head space” to allow
for splashing, foaming and aeration. The fermentor design varies greatly depending on the type
and the fermentation for which it is used. Bioreactors are so designed that they provide the best
possible growth and biosynthesis for industrially important cultures and allow ease of
manipulation for all operations.
Size of Fermentors:
The size of fermentors ranges from 1-2 litre laboratory fementors to 5,00,000 litre or,
occasionally, even more, fermentors of upto 1.2 million litres have been used. The size of the
fermentor used depends on the process and how it is operated. A summary of fermentor or size
of fermentor (litres) Industrial product sizes for some common microbial fermentations is given
in Table 39.6.
        Construction of Fermentors:
        Industrial fermentors can be divided into two major classes, anaerobic and aerobic. Anaerobic
        fermentors require little special equipment except for removal of heat generated during the
        fermentation process, whereas aerobic fermentors require much more elaborate equipment to
        ensure that mixing and adequate aeration are achieved.
         The material used for the construction of a bioreactor must have the
          following important properties:
       It should not be corrosive.
       It should not add any toxic substances to the fermentation media.
       It should tolerate the steam sterilization process.
        It should be able to tolerate high pressure and resist pH changes
        Since most industrial fermentation process are aerobic, the construction of a typical
        aerobic fermentor (Fig. 39.1) is the following:
1. Cooling Jacket:
Large-scale industrial fermentors are almost always constructed of stainless steel. A fermentor is
a large cylinder closed at the top and the bottom and various pipes and valves are fitted into it.
The fermentor is fitted externally with a cooling jacket through which steam (for sterilization) or
cooling water (for cooling) is run.
Cooling jacket is necessary because sterilization of the nutrient medium and removal of the heat
generated are obligatory for successful completion of the fermentation in the fermentor. For very
large fermentors, insufficient heat transfer takes place through the jacket and therefore, internal
coils are provided through which either steam or cooling water is run.
2. Aeration System:
Aeration system is one of the most critical part of a fermentor. In a fermentor with a high
microbial population density, there is a tremendous oxygen demand by the culture, but oxygen
being poorly soluble in water hardly transfers rapidly throughout the growth medium.
It is necessary, therefore, that elaborate precautions are taken using a good aeration system to
ensure proper aeration an oxygen availability throughout the culture. However, two separate
aeration devices are used to ensure proper aeration in fermentor. These devices are sparger and
impeller.
The sparger is typically just a series of holes in a metal ring or a nozzle through which filter-
sterilized air (or oxygen-enriched air) passes into the fermentor under high pressure. The air
enters the fermentor as a series of tiny bubbles from which the oxygen passes by diffusion into
the liquid culture medium.
The impeller (also called agitator) is an agitating device necessary for stirring of the fermenter.
The stirring accomplishes two things:
(i) It mixes the gas bubbles through the liquid culture medium and
(ii) It mixes the microbial cells through the liquid culture medium. In this way, the stirring
ensures uniform access of microbial cells to the nutrients.
The size and position of the impeller in the fermentor depends upon the size of the fermentor. In
tall fermentors, more than one impeller is needed if adequate aeration and agitation is to be
obtained. Ideally, the impeller should be 1/3 of the fermentors diameter fitted above the base of
the fermentor. The number of impeller may vary from size to size to the fermentor.
3. Baffles:
The baffles are normally incorporated into fermentors of all sizes to prevent a vortex and to
improve aeration efficiency. They are metal strips roughly one-tenth of the fermentors diameter
and attached radially to the walls.
4. Controlling Devices for Environmental Factors:
In any microbial fermentation, it is necessary not only to measure growth and product formation
but also to control the process by altering environmental parameters as the process proceeds. For
this purpose, various devices are used in a fermentor. Environmental factors that are frequently
controlled includes temperature, oxygen concentration, pH, cells mass, levels of key nutrients,
and product concentration.
Use of Computer in Fermentor:
    Computer technology has produced a remarkable impact in fermentation work in recent years
    and the computers are used to model fermentation processes in industrial fermentors. Integration
    of computers into fermentation systems is based on the computers capacity for process
    monitoring, data acquisition, data storage, and error-detection.
    Some typical, on-line data analysis functions include the acquisition measurements, verification
    of data, filtering, unit conversion, calculations of indirect measurements, differential integration
    calculations of estimated variables, data reduction, tabulation of results, graphical presentation of
    results, process stimulation and storage of data.
    Types of Fermentor:
    The fermentor (bioreactor) types used extensively in industries are the stirred tank fermentor,
    airlift fermentor, and bubble column fermentor.
    (i) Stirred Tank Fermentor:
     A continuous stirred tank bioreactor is made up of a cylindrical vessel with a
      central shaft controlled by a motor that supports one or more agitators
      (impellers).
     The sparger, in combination with impellers (agitators), allows for improved
      gas distribution throughout the vessel.
     A stirred tank bioreactor can be operated continuously in the fermentor,
      temperature control is effortless, construction is
      cheap, easy to operate, resulting in low labor cost, and it is easy to clean.
     It is the most common type of bioreactor used in industry
     (ii) Airlift Fermentor:
    In airlift fermentor (Fig. 39.2) the liquid culture volume of the vessel is divided into two
    interconnected zones by means of a baffle or draft tube. Only one of the two zones is sparged
    with air or other gas and this sparged zone is known as the riser.
    The other zone that receives no gas is called down-comer. The bulk density of the gas-liquid
    dispersion in the gas-sparged riser tends to be lower than the bulk density in the down-comer,
    consequently the dispersion flows up in the riser zone and down-flow occurs in the down-comer.
Airlift fermentors are highly energy-efficient and are often used in large-scale manufacture of
biopharmaceutical proteins obtained from fragile animal cells. Heat and mass transfer
capabilities of airlift reactors are at least as good as those of other systems, and airlift reactors are
more effective in suspending solids than are bubble column fermentors.
All performance characteristics of airlift -fermentor are related ultimately to the gas injection rate
and the resulting rate of liquid circulation. Usually, the rate of liquid circulation increases with
the square root of the height of the airlift device.
Because the liquid circulation is driven by the gas hold-up difference between the riser and the
down-comer, circulation is enhanced if there is little or no gas in the down-comer. All the gas in
the down-comer comes from being entrained in with the liquid as it flows into the down-comer
from the riser near the top of the reactor.
(iii) Bubble Column Fermentor:
A bubble column fermentor (Fig. 39.3) is usually cylindrical with an aspect (height-to-diameter)
ratio of 4-6. Gas is sparged at the base of the column through perforated pipes, perforated plates,
or sintered glass or metal micro-porous spargers.
O2transfer, mixing and other performance factors are influenced mainly by the gas flow rate and
the rheological properties of the fluid. Internal devices such as horizontal perforated plates,
    vertical baffles and corrugated sheet packing’s may be placed in the vessel to improve mass
    transfer and modify the basic design.
    The column diameter does not affect its behaviour so long as the diameter exceeds 0.1 m. One
    exception is the axial mixing performance. For a given gas flow rate, the mixing improves with
    increasing vessel diameter. Mass and heat transfer and the prevailing shear rate increase as gas
    flow rate is increased.
    4. Fluidized-bed fermentor
    Fluid bed bioreactors constitute packed beds with smaller particles. This
     prevents problems such as clogging, high liquid pressure drop, channeling,
     and bed compaction associated with packed bed reactors.
    Catalyst is laid on the bottom of the reactor and the reactants are pumped
     into the reactor through a distributor pump to make the bed fluidized.
    In these reactors, the cells are immobilized small particles which move with
     the fluid as a result, mass transfer, oxygen transfer, and nutrition to the cells
     are enhanced.
    The bioreactors can be used for reactions involving fluid-suspended
     biocatalysts, such as immobilized enzymes, immobilized cells, and microbial
     flocs.
    Its main advantages include its ability to maintain even temperatures, easy
     replacement and regeneration of the catalyst, continuity, and automaticity of
     operation, and reduced contact time between gas and solid, compared to
     other catalytic reactors.
                                                               5. Packed bed
    fermentor
    A packed bed fermentor is a bed of solid particles, having biocatalyst on or
     within, the matrix of solids.
    It can either be run in the submerged mode (with or without aeration) or the
     trickle flow mode.
    Frequently used in chemical processing processes such as absorption,
     distillation, stripping, separation process, and catalytic reactions, packed bed
     reactors are also called fixed bed reactors.
    In packed-bed bioreactors, the air is introduced through a sieve that
     supports the substrate.
    This reactor has many benefits, like a high conversion rate for the catalyst,
     ease of operation, low construction and operation costs, increased contact
     between reactant and catalyst, and the ability to work in high temperatures
     and pressures.
Figure: Packed bed fermentor. Image Source: Kuila, A., & Sharma, V. (2018). Principles and
applications of fermentation technology. John Wiley & Sons, Inc.
6. Photobioreactor
                                                                    Figure: Photobioreactor. Image
    Source: Singh, J., Kaushik, N., & Biswas, S. (2014). Bioreactors – Technology & Design
    Analysis. April 2016.
    A photobioreactor is a specialized unit for fermentation that is either
     illuminated by direct sunlight or artificially illuminated
    They are made up of glass or more commonly transparent plastic and the
     tubes or flat panels is consist of light receiving systems.
    In this bioreactor, centrifugal pumps or airlift pumps can be used to circulate
     the medium through solar receivers.
    Photo-bioreactors are usually operated in a continuous mode at a
     temperature in the range of 25–40 °C.
    Photobioreactors are used for the photosynthetic culture of microalgae and
     cyanobacteria to produce products such as astaxanthin and β-carotene.
                                                                                           Figure:
    Types of photobioreactor. Image Source: Singh, J., Kaushik, N., & Biswas, S. (2014).
    Bioreactors – Technology & Design Analysis. April 2016.
    7. Membrane bioreactor
    This system combines traditional treatment with membrane filtration,
     resulting in the removal of organics and suspended solids as well as the
     removal of high nutrient levels.
    Membranes in this system are submerged in an aerated biological reactor.
     The pore size of the membrane ranges from 0.035 microns to 0.4 microns.
    With pure oxygen, the benefits of this bioreactor are enhanced resulting in
     even higher rate biological treatment systems that provide compact control
     of COD, microorganisms.
Type of
                    Applications
bioreactor
Stirred tank        Antibiotics, citric acid, Exopolysaccharides, cellulose, Chitinolytic enzymes, Laccase, Xylanase, Pectic, and pecta
fermenter           lyase, Tissue mass culture, Lipase, Polygalacturonases, Succinic acid
Bubble column
                    Algal culture, Chitinolytic enzymes
fermentor
                    Antibiotics, Chitinolytic enzymes, Exopolysaccharides, Gibberelic acid, Laccase, Cellulase, Lactic acid,
Airlift fermentor
                    Polygalacturonases, Tissue mass culture
Fluid bed
                    Laccase
fermentor
Packed bed
                    Laccase, Hydrogen, Organic acids, Mammalian cells,
fermentor
Photobioreactor     Wastewater treatment, water quality management, remediation of contaminated soil
Membrane
                    Alginate, Antibiotic, Cellulose hydrolysis, Hydrogen production, Water treatment, VOCs treatment
bioreactor