Basic Fermenter Design : External, Agitation & Aeration, Inlets and Outlets

  De Becze and Liebmann (1944) used the first large scale (above 20 litre capacity) fermenter for the production of yeast. But it was during the First World War, a British scientist named Chain Weizmann (1914-1918) developed a fermenter 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.
  The first pilot fermenter was erected in India at Hindustan Antibiotic Ltd., Pimpri, Pune in the year 1950.

Basic criteria of the fermenter

  • The vessel should be capable of being operated aseptically for a number of days and should be reliable in long-term operation and meet the requirements of containment regulations.
  • Adequate aeration and agitation should be provided to meet the metabolic requirements of the microorganism.
  • However, the mixing should not cause damage to the organism.
  • Power consumption should be as low as possible.
  • A system of temperature control should be provided.
  • A system of pH control should be provided.
  • Sampling facilities should be provided.
  • Evaporation losses from the fermenter should not be excessive.
  • The vessel should be designed to require the minimal use of labour in operation, harvesting, cleaning and maintenance.
  • Ideally the vessel should be suitable for a range of processes, but this may be restricted because of containment regulations.
  • The vessel should be constructed to ensure smooth internal surfaces.
  • The vessel should be of similar geometry to both smaller and larger vessels in the pilot plant to facilitate scale-up.
  • The cheapest materials which enable satisfactory results to be achieved should be used.
  • There should be adequate service provisions for individual plants.

Parts of fermenter

1. Materials used for body construction.
2. Seals 
3. Mixing components
  •  Impellers
  •  Spargers
  •  Baffles
4. Sampling point
6. Bottom drainage system (outlet)
7. Air filter.


1. Material used for fermenter

Properties of the material used for fermenter designing :

  • Non-corrosive
  • Non-toxic
  • Tolerable to repeated steam sterilization Cycles
  • Withstand high pressure
  • Resist pH changes
  • Selection of the material also depends on the type of fermentation process to be carried.
Mainly two types of materials are used worldwide for the manufacture of fermenters:
  1. Glass
  2. Stainless steel

i]. Glass fermenters

  • On a small scale (Laboratory scale) (1 to 30 dm³), it is possible to use glass.
  • Glass is useful because it gives smooth surfaces, is non-toxic, corrosion proof and it is usually easy to examine the interior of the vessel.
  • These can be of two types:
  1. > A glass vessel with a round or flat bottom and a top flange carrying plate. All vessels of this type have to be sterilized by autoclaving.
  2. > A giass cylinder with stainless-steel top flange carrying and bottom solid plates. Vessels with two stainless steel plates cost approximately 50% more than those with just a top plate.
  • These top flange carrying plates provides port for the entrance of media, inoculum, buffers and anti-foam agents.
  • At pilot and large scale, when all fermenters are sterilized in situ, any materials used will have to be assessed on their ability to withstand pressure sterilization and corrosion and on their potential toxicity and cost.

ii]. Stainless steel fermenters

  • Fermenters are normally constructed of stainiess steel or at least have a stainless-steel cladding (or layering) to limit corrosion.
  • The American Iron and Steel Institute (AISI) states that steels containing less than 4% chromium are cliassified as steel alloys and those containing more than 4% are classified as stainiess steels.
  • Mild steel coated with glass or phenolic epoxy materials has occasionally been used.
  • Stainless steel - 304 and 316 grade coated with epoxy or glass lining are into use.
  • The corrosion resistance of stainless steel is thought to depend on the existence of a thin hydrous oxide film on the surface of the metal.
  • The composition of this film varies with different steel alloys and different manufacturing process treatments such as rolling, pickling (removal of impurities, such as stains, inorganic contaminants, rust) or heat treatment.
  • The film is stabilized by chromium and is considered to be continuous, non-porous, insoluble and self healing.
  • If damaged, the film will repair itself when exposed to air or an oxidizing agent.
  • The minimum amount of chromium needed to resist corrosion will depend on the corroding agent in a particular environment, such as acids, alkalis, gases, soil, salt or fresh water.
  • Increasing the chromium content enhances resistance to corrosion, but only grades of steel containing at least 10 to 13% chromium develop an effective film.
  •  The inclusion of nickel in high percent chromium steels enhances their resistance and improves their engineering properties.
  •  The presence of molybdenum improves the resistance of stainless steels to solutions of halogen salts and pitting (small holes) by chloride ions in brine or sea water.
  • Corrosion resistance can also be improved by tungsten, silicone and other elements.
  • AISI grade 316 steels which contain 18% chromium, 10% nickel and 2-2.5% molybdenum are now commoniy used in fermenter construction.
  •  Increasing the chromium content enhances resistance to corrosion, but only grades of steel containing at least 10 to 13% chromium develop an effective film.
  • The inclusion of nickel in high percent chromium steels enhances their resistance and improves their engineering properties.
  • The presence of molybdenum improves the resistance of stainless steels to solutions of halogen salts and pitting (small holes) by chloride ions in brine or sea water.
  • Corrosion resistance can also be improved by tungsten, silicone and other elements.
  • AISI grade 316 steels which contain 18% chromium, 10% nickel and 2-2.5% molybdenum are now commonly used in fermenter construction.

2. Types of Seals

  It is important to consider the ways in which a reliable aseptic seal is made between glass and glass, glass and metal or metal and metal joints such as between a fermenter vessel and a detachable top or base plate.

  • Between a fermenter vessel and a detachable top or base plate.
  • Sealing assembly for stirrer shaft.

i]. Between a fermenter vessel and a detachable top or base plate

a) Gasket seals are suitable with glass to glass joints.
  • Nitryl or butyl rubbers are normally used for these seals as they will withstand fermentation process conditions.
b) Lip seals are suitable with glass metal joints.
  • These are generally made of silicone and are fluorosilicone elastomers.
c) O ring seals are suitable with metal to metal joints.
  • These are made of Polytetrafluoroethylene (PTFE) and Neoprene.

ii]. Sealing assembly for stirrer shaft

• Stirrer shaft is a device providing agitation.
• It must be sealed properly ensuring a long term aseptic operation

There are various types of sealing assembly such as:

  • Mechanical seal
  • Packed gland seal
  • Magnetic drive.

3. Mixing components

• Structural components involved in mixing such as :
  1. Impellor for agitation
  2. Sparger for aeration
  3. Baffles for breaking vortex

Importance of Agitation and Aeration

  • Important factor in a fermenter. 
  • Provides a provision for adequate mixing of the contents of a fermenter.
  • Mixing helps to disperse the air bubbles, suspend cells, enhance heat and mass transfer in the medium.

Location of mixing components are

  • Impeller : shaft in the centre of the fermenter
  • Sparger : below the impeller (at base)
  • Baffles : Along the side walls of the fermenter

i]. Impellors or agitators

Agitation should ensure that a uniform suspension of microbial cells is achieved in a homogenous nutrient medium.
  • Agitation is done using impellers.
  • These are mounted on the drive shaft and into the fermenter through its lid (flange).
  • These are made up of impellor biades and the position may be varying according to the need and size of the fermenter.
  • These impellors or blades are attached to a motor on lid.
  • Impellors may not be required in small scale fermenters.

The major function of an impellor is to aid in proper mixing of the following components uniformly throughout the fermentation vessel :

  1. > Suspended microorganisms (microbial cells),
  2. > Media components
  3. > Oxygen (air bubbles)
  4. > Heat transfer.
  • Impellor blades reduce the size of the air bubbles by breaking them and distributes them uniformly into the fermentation media.
  • Impellors also helps in breaking of foam bubbles in the head space of fermenter.
  • This foam formed during fermentation process can cause a major problem of contamination. Therefore, it is important to breakdown these foam so that they don't over flow out of the fermenter and cause contamination.

Impellors classification : Basic impellors

a] Disc turbines or Rushton turbines consists of a disc of a disc with a series of rectangular vanes set in a vertical plate around the circumference.

b] Vaned discs has a series of rectangular vanes attached vertically to the underside. Air from the sparger hits the underside of the disc and is displaced towards the dreamstim vanes where the air bubbles are broken up into smaller bubbles.

c] Open turbines of variable pitch

d] Marine propellerss - The vanes of a variable pitch open propeller are attached directly to a boss on the agitator shaft. In this case the air bubbles do not initially hit any surface before dispersion by the vanes or blades.

Modern Agitator Developments 

Four other modern agitator developments are derived from open turbines. The new turbine designs make it possible to replace Rushton turbines by :

  • larger low power agitators which do not lose as much power when aerated,
  • Which are able to handle higher air volumes without flooding and give better bulk blending and heat transfer characteristics in more viscous media.
  • Good mixing and aeration in high viscosity broths may also be achieved by a dual impeller combination, where the lower impeller acts as the gas disperser and the upper impeller acts primarily as a device for aiding circulation of vessel contents.

ii]. Spargers or aerators

  •  A sparger is an aeration system through which sterile air is introduced in the medium of fermentation tank.
  •  Spargers are located at the bottom of the fermentation tank.
  • Glass wool filters are used in a sparger for sterilization of air and other gases.
  • The sparger pipes contain small holes of about 5-10 mm.
  • Through these small holes pressurized air is released in the aqueous fermentation media.
  • The air released is the form of tiny air bubbles.
  • These air bubbles helps in mixing of media.
  • Impeller blades disperses air released through sparger into medium.

Types of spargers

1. Porous sparger
  • These type of spargers are used mainly in laboratory scale non- agitated fermenter (without impellors).
  • These are mainly made up of ceramics.
  • Pressure drop occurs across the sparger.
  • Fine holes may become blocked due to microbial growth around holes with low pressure.

2. Orifice sparger (a perforated pipe)

  • These are used in small or large scale, agitated/non- agitated fermenters.
  • Spargers have holes of at least 6mm diameter.

3. Nozzle sparger (an open or partially dosed pipe)

  • It is used in most modern mechanically stirred fermenter design from lab to industrial scale.
  • It has a single open or partially closed pipe to provide the stream of air bubbles.

iii]. Baffles

Baffles are mounted on the walls of a fermenter.
  • 4, 6 or 8 baffles may be used in a fermenter.
  • Baffles are metal strips roughly 1/10th of vessel diameter and attached radially to the fermenter wall.
  • The major function of baffles is to break the vortex formed during agitation process by the impellors.
  • If the vortex, formed during agitation, is not broken, the fermentation media may spill out of fermenter and be a major cause of contamination. Therefore, it is important to break the vortex using a barrier in the form of baffles.


It is recommended that baffles should be installed so that a gap existed between them and the vessel wall, so that there is a scouring action around and behind the baffles thus minimizing microbial growth on the baffles and the fermenter walls.

4. Ports

  Ports are located on the top flange carrying plate of the fermentation vessel.
Different ports are present for the supply of different components via silicone tubes:
  • Feeding port: for fermentation media (in case where media is sterilized ex-situ),
  • Inoculation port : for seed culture (microorganism).
  • Buffer port : for buffers (acid/ alkali)
  • Anti-foam port: for anti-foaming agents.
Care should be taken that the port provides aseptic transfer.
The reservoirs for the nutrients and inoculum and associated piping are steam sterilized in situ.
Addition is done using peristaltic pump only after aseptic connection has been established.

5. Sampling point

  • Sampling point is used for time to time withdrawal of samples to monitor fermentation process and quality control.
  • This sampling point should provide aseptic withdrawal of sample.

6. Bottom drainage system

  • It is aseptic outlet present at the bottom of fermenter for removal of entire fermented media and products formed after the fermentation process is completed.
  • It is different from the sampling point.

7. Air Filter

  • Oxygen-enriched air is used for sparging fermenters, to achieve the desired broth aeration and dissolved oxygen levels.
  • Fermenter air should be free of unwanted airborne microorganisms and bacteriophage contamination.
  • It is important to prevent the entry of unwanted microorganisms from the environment, that could interfere with the growth and multiplication of the selected fermentation organisms; contamination would impact fermentation yield and compromise product quality.
  • Depending on the nature of the fermenter microbial cultures in use, it may also be important to remove undesirable microorganisms from fermenter air exhaust before releasing it into the environment.
    Fermenter air filtration involves filtration of both inlet and exhaust air with pre-filtration and final filtration procedure.
  • Fermenter air filtration involves filtration of both inlet and exhaust air with pre-filtration and final filtration procedure.

i]. Inlet air filter

It is used to filter the air that is coming inside the fermenter to prevent any contamination of the fermentation broth.
It consists of following components:
  • > Compressor : A compressor is a mechanical device that increases the pressure of a gas by reducing its volume.
  • > Conditioner : a system for controlling the humidity and temperature.
  • > Pre-filters : Fermenter air pre-filtration of compressed air protects downstream final air filters. It is composed of fibrous materials which removes solid particulars such as dust pollen, mould and bacteria from air.
  • > Final sterile filters : Final fermenter air filtration provides a sterile barrier between compressed inlet gas supply to fermenters and fermenter broth contents via sparger.

II). Exhaust air filter

  It is used to filter the air that is going out of the fermenter to prevent the environment from being contaminated by any biohazards.
  • >Pre-filters : Removes undesirable microorganisms to avoid their escaping out of the fermenter.
  • > Final sterile filters : Final fermenter air filtration provides a sterile barrier between fermenter air exhaust and the surrounding environment.

Also read

No comments: