Bioreactors are used for carrying out biochemical processes which employ microbe s, fungus, plant cells or mammalian

cell systems for production of biological pr oducts. The bioreactors provide a controlled environment for the production of m etabolites which can help to achieve the optimal growth of microbes. The term fe rmentor is used as synonym to bioreactors. Classification of bioreactors There are numerous types of bioreactors - batch, sequence, continuously stirred tanks, anaerobic contact processes, anaerobic filters, etc. 1. They can be conveniently classified into three major types based on the prese nce or absence of oxygen and requirement of stirring. Non stirred non aerated bioreactors are used for production of traditional produ cts such as wine, beer, cheese etc. Non stirred aerated reactors are used much rarely. Stirred and aerated reactors are most often used for production of metabolites w hich require growth of microbes which require oxygen. Most of the newer methods are based on this type of bioreactors.

Bioreactors are used for carrying out biochemical processes which employ microbe s, fungus, plant cells or mammalian cell systems for production of biological pr oducts. The bioreactors provide a controlled environment for the production of m etabolites which can help to achieve the optimal growth of microbes. The term fe rmentor is used as synonym to bioreactors. Classification of bioreactors There are numerous types of bioreactors - batch, sequence, continuously stirred tanks, anaerobic contact processes, anaerobic filters, etc. 1. They can be conveniently classified into three major types based on the prese nce or absence of oxygen and requirement of stirring. Non stirred non aerated bioreactors are used for production of traditional produ cts such as wine, beer, cheese etc. Non stirred aerated reactors are used much rarely. Stirred and aerated reactors are most often used for production of metabolites w hich require growth of microbes which require oxygen. Most of the newer methods are based on this type of bioreactors. 2. Based on mode of operation, the bioreactors can be classified into three type s. Batch reactors Fed batch Continuous e.g.: chemo stat 3. Based on the method of growing of microbes, bioreactors can be either Suspended or Immobilized The Petri dish is the simplest immobilized bioreactor. The large scale immobiliz ed bioreactors are used for commercial manufacturing of metabolites. They includ e - Moving bed - Fibrous bed - Packed bed - Membrane 4. On the basis of the microbial agent used, the bioreactors can be classified i

nto Those based on living cells Which employ enzymes 5. a. b. c. d. Based on the process requirements, bioreactors can be classified into Aerobic Anaerobic Solid state Immobilized

I. Aerobic fermentation These reactors should have adequate provisions for supply of sterile air and als o need a mechanism of stirring up and mixing the medium and cells. These can be either a. Stirred tank or b. Air lift type Generally, they are either closed type or batch reactors. Some special cases use continuous flow reactors also. 1. Stirred tank bioreactor This is the conventional mixing reactor which is made of either glass or stainle ss steel. The stirrer can be either at the top or bottom of the reactor. The dim ensions of the reactor depend on the amount of heat to be removed from the vesse l. Baffles in the centre of the tank prevent formation of vortex and effective m ixing of the ingredients. Advantages Low investment needs Low operating costs Disadvantages Foaming is often a problem. But this can be overcome using proper antifoaming ag ents. However, this has to be exercised with caution since some antifoaming agen ts inhibit the growth of microbes. 2. Air lift bioreactors The stirred tank bioreactors lack well defined flow of air. In these, air is pum ped from below. This creates the bubbles in the medium which rises up through th e draught tube by buoyancy and drags the surrounding fluid up. The air that is u sed to lift up is sufficient to stir up the contents. Advantages Low friction Less energy requirements The mechanical parts are easy to construct. There is no need of special aseptic seals. Scaling up is easier Metabolic performance does not drastically reduce on scale up. Disadvantages Capital needed is more Difficulty of sterilization Efficiency of mixing is low II. Anaerobic fermentation

These reactors do not require aeration except in a few where initial preparation of inoculums requires aeration. Once the fermentation starts off, the gas relea sed from the media is sufficient to provide mixing. In case of enzyme production, the recovery has to be strictly under anaerobic co nditions since for most of the enzymatic activity is sensitive to the presence o f oxygen. III. Immobilized cell bioreactors These are based on immobilized cells. Advantages Useful fro manufacture of intracellular enzymes. When the extracted enzymes are unstable For preparing low weight products which are released into the medium. Reduction of pollution Allow continuous operation of bioreactors Suitable for production of amino acids, organic acids etc. Commonly fluidized bed reactors and hollow fiber membrane bioreactors are used 1. Fluidized bed reactors These reactors can utilize high density of particles and reduce bulk fluid densi ty. Advantages Heat and mass transfer are efficient The mixing of the media between the liquid, solid and gaseous phases are effecti ve. The reactor requires less energy. Low shear rates and hence suitable for cells which are more sensitive to frictio n like the plant cells and mammalian cells. 2. Hollow fiber membrane bioreactors These reactors have hollow fibers are made from cellulose acetate, acrylic polym ers, polysulphone etc. Advantages Extracellular products can be separated from cells at the same time. The productivity is high. Scale up is easy since several parallel fiber units can be added. Disadvantages Sometimes, the pores get plugged. Cell growth around the lumen can sometimes distort and rupture the fibers. Nutrients and products can diffuse through the membrane and limit the growth of microbes. If the toxic products happen to accumulate in the fiber it may inhibit the growt h of microbes. 2. Based on mode of operation, the bioreactors can be classified into three type s. Batch reactors Fed batch Continuous e.g.: chemo stat 3. Based on the method of growing of microbes, bioreactors can be either Suspended or

Immobilized The Petri dish is the simplest immobilized bioreactor. The large scale immobiliz ed bioreactors are used for commercial manufacturing of metabolites. They includ e - Moving bed - Fibrous bed - Packed bed - Membrane 4. On the basis of the microbial agent used, the bioreactors can be classified i nto Those based on living cells Which employ enzymes 5. a. b. c. d. Based on the process requirements, bioreactors can be classified into Aerobic Anaerobic Solid state Immobilized

I. Aerobic fermentation These reactors should have adequate provisions for supply of sterile air and als o need a mechanism of stirring up and mixing the medium and cells. These can be either a. Stirred tank or b. Air lift type Generally, they are either closed type or batch reactors. Some special cases use continuous flow reactors also. 1. Stirred tank bioreactor This is the conventional mixing reactor which is made of either glass or stainle ss steel. The stirrer can be either at the top or bottom of the reactor. The dim ensions of the reactor depend on the amount of heat to be removed from the vesse l. Baffles in the centre of the tank prevent formation of vortex and effective m ixing of the ingredients. Advantages Low investment needs Low operating costs Disadvantages Foaming is often a problem. But this can be overcome using proper antifoaming ag ents. However, this has to be exercised with caution since some antifoaming agen ts inhibit the growth of microbes. 2. Air lift bioreactors The stirred tank bioreactors lack well defined flow of air. In these, air is pum ped from below. This creates the bubbles in the medium which rises up through th e draught tube by buoyancy and drags the surrounding fluid up. The air that is u sed to lift up is sufficient to stir up the contents. Advantages Low friction Less energy requirements The mechanical parts are easy to construct. There is no need of special aseptic seals.

Scaling up is easier Metabolic performance does not drastically reduce on scale up. Disadvantages Capital needed is more Difficulty of sterilization Efficiency of mixing is low II. Anaerobic fermentation These reactors do not require aeration except in a few where initial preparation of inoculums requires aeration. Once the fermentation starts off, the gas relea sed from the media is sufficient to provide mixing. In case of enzyme production, the recovery has to be strictly under anaerobic co nditions since for most of the enzymatic activity is sensitive to the presence o f oxygen. III. Immobilized cell bioreactors These are based on immobilized cells. Advantages Useful fro manufacture of intracellular enzymes. When the extracted enzymes are unstable For preparing low weight products which are released into the medium. Reduction of pollution Allow continuous operation of bioreactors Suitable for production of amino acids, organic acids etc. Commonly fluidized bed reactors and hollow fiber membrane bioreactors are used 1. Fluidized bed reactors These reactors can utilize high density of particles and reduce bulk fluid densi ty. Advantages Heat and mass transfer are efficient The mixing of the media between the liquid, solid and gaseous phases are effecti ve. The reactor requires less energy. Low shear rates and hence suitable for cells which are more sensitive to frictio n like the plant cells and mammalian cells. 2. Hollow fiber membrane bioreactors These reactors have hollow fibers are made from cellulose acetate, acrylic polym ers, polysulphone etc. Advantages Extracellular products can be separated from cells at the same time. The productivity is high. Scale up is easy since several parallel fiber units can be added. Disadvantages Sometimes, the pores get plugged. Cell growth around the lumen can sometimes distort and rupture the fibers. Nutrients and products can diffuse through the membrane and limit the growth of microbes. If the toxic products happen to accumulate in the fiber it may inhibit the growt

h of microbes.

Correlation for Mass Transfer Coefficient, KLA Note: An important consideration in the design of diffused air systems is that t he overall mass transfer coefficient changes with changing air flow rate; that i s, KLa is not "constant". Under dynamic loading conditions, over periods when th e oxygen demand is high, and a higher air flow is required, there is a drop-off in transfer efficiency. This is an important factor when determining blower peak air delivery requirements. Manufacturers generally provide diffuser performance data in the form of a set o f curves for a range of diffuser densities showing SOTE/depth (%/m or %/ft) vers us air flow rate per diffuser. Typically, for fine bubble systems the curves sta rt in the region of 8%/m (2.5%/ft) for low air flow rates, decrease with increas ing air flow, and level off at higher air flows. An example is shown in the diag ram below.

These data reflect the change in the mass transfer coefficient, KLa , with incre asing air flow and diffuser density. The data points in the plot below are from aeration tests conducted at two diffuser densities in a 20 foot by 20 foot test tank for diffuser submergences of 9, 14 and 19 feet. [The diffusers used in thes e tests were 18 inches in diameter, and the numerical values in the plots below should not be seen as typical for other diffuser types]. In the plot the cluster s of data points correspond to KLa values for different submergences. Note that the diffuser density, DD%, is defined in terms of the coverage: Calculation DD% = diffusers.area per diffuser*100/bioreactor area = 1/ATAD *100 where AT = Area of aeration tank. Therefore: ATAD= AT/AD=100/DD% Where ad=Total area of diffusers in aeration tank.

Research has shown that the mass transfer coefficient, KLa correlates with the s uperficial gas velocity i.e. the air flow rate per unit aerated tank area. In Bi oWin the KLa value is estimated using a correlation of the form: Calculations Kla = C. U ^YSG where C = parameter depending on diffuser density (see below), Y = parameter [De fault value in BioWin = 0.82], USG = Superficial gas velocity (m3/m2/day) = QAIR / Area of bioreactor, QAIR = Air flow rate (m3/day). The parameter C is a function of the diffuser density. In BioWin the C value is determined as follows:

Calculations C=K1 . DD% 0.25 +K2 where K1 = parameter [Default value in BioWin = 2.5656/day], K2 = parameter [Def ault value in BioWin = 0.0432]. The diagrams below show how BioWin predicts the relations between (a) KLa and su perficial gas velocity, and (b) SOTE (%/m) and air flow per diffuser, for K1 = 1 .8 /day and the other parameters presented above.