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REVIEW ON BIOREACTORS

About Author:
Kambham Venkateswarlu
Graduate Student
Sri Lakshmi Narasimha College of Pharmacy,
Palluru, Chittoor District, Andhra Pradesh-517132, India.
k.v.reddy9441701016@gmail.com

ABSTRACT:
Many different types of laboratory fermentors and bioreactors are used worldwide. The selection of a good quality bioreactor is not easy. Some advantageous parameters found in one product are cancelled out by other draw backs in the same system. Good high quality bioreactors are very expensive. Even then ease of use is not assured. The question arises, whether it is possible to construct a bioreactor, which would satisfy most requirements. The most important are high quality and easy to use, perfect sterility, precise measurement, control and recording of all important culture parameters and lasts but not lasts, and the bioreactor shouldn’t expensive!

Based on long personal practical experience in the field, we have tried to analyse the requirements and select technical solutions, which would lead to the satisfaction of the criteria presented above. In the following sections several important parameters will be briefly described and new solutions suggested.

Reference Id: PHARMATUTOR-ART-1601

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 presence or absence of oxygen and requirement of stirring.
• Non stirred non aerated bioreactors are used for production of traditional products 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 which 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 types.
• Batch reactors 
• Fed batch 
• Continuous e.g.: chemostat

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 immobilized bioreactors are used for commercial manufacturing of metabolites. They include 
- Moving bed
- Fibrous bed
- Packed bed
- Membrane

4. On the basis of the microbial agent used, the bioreactors can be classified into 
• Those based on living cells
• Which employ enzymes

5. Based on the process requirements, bioreactors can be classified into 
a. Aerobic
b. Anaerobic
c. Solid state
d. Immobilized

I. Aerobic fermentation
These reactors should have adequate provisions for supply of sterile air and also need a mechanism of stirring up and mixing the medium and cells.
a. Stirred tank or
b. Air lifts 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 stainless steel. The stirrer can be either at the top or bottom of the reactor. The dimensions of the reactor depend on the amount of heat to be removed from the vessel. Baffles in the centre of the tank prevent formation of vortex and effective mixing of the ingredients.

The continuous stirred-tank reactor(CSTR), also known as vat- or back mix reactor, is a common ideal reactor type in chemical engineering. A CSTR often refers to a model used to estimate the key unit operation variables when using a continuous[†]agitated-tank reactor to reach a specified output. (See Chemical reactors.) The mathematical model works for all fluids: liquids, gases, and slurries.

The behavior of a CSTR is often approximated or modeled by that of a Continuous Ideally Stirred-Tank Reactor (CISTR). All calculations performed with CISTRs assume perfect mixing. In a perfectly mixed reactor, the output composition is identical to composition of the material inside the reactor, which is a function of residence time and rate of reaction. If the residence time is 5-10 times the mixing time, this approximation is valid for engineering purposes. The CISTR model is often used to simplify engineering calculations and can be used to describe research reactors. In practice it can only be approached, in particular in industrial size reactors.

Assume:
·         perfect or ideal mixing, as stated above
Integral mass balance on number of moles Ni of species i in a reactor of volume V.

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1. Cross-sectional diagram of Continuous stirred-tank reactor


Where Fio is the molar flow rate inlet of species i, Fi the molar flow rate outlet, and stoichiometric coefficient. The reaction rate, r, is generally dependent on the reactant concentration and the rate constant (k). The rate constant can be determined by using a known empirical reaction rates that is adjusted for temperature using the Arrhenius temperature dependence. Generally, as the temperature increases so does the rate at which the reaction occurs. Residence time, , is the average amount of time a discrete quantity of reagent spends inside the tank.

Assume:

  • constant density (valid for most liquids; valid for gases only if there is no net change in the number of moles or drastic temperature change)
  • isothermal conditions, or constant temperature (k is constant)
  • steady state
  • single, irreversible reaction (νA = -1)
  • first-order reaction (r = kCA)

A → products

NA = CA V (where CA is the concentration of species A, V is the volume of the reactor, NA is the number of moles of species A)

2. The values of the variables, outlet concentration and residence time, in Equation 2 are major design criteria.

To model systems that do not obey the assumptions of constant temperature and a single reaction, additional dependent variables must be considered. If the system is considered to be in unsteady-state, a differential equation or a system of coupled differential equations must be solved.

CSTR's are known to be one of the systems which exhibit complex behavior such as steady-state multiplicity, limit cycles and chaos.

3. Non-ideal CSTR
The actual reaction volume will be affected by the non-uniform mixing (short-circuiting) or existence of dead zone areas. Temperature effect will also cause significant effect on the reaction rate.
Advantages:
• Low investment needs 
• Low operating costs 
Disadvantages:
• Foaming is often a problem. But this can be overcome using proper antifoaming agents. However, this has to be exercised with caution since some antifoaming agents inhibit the growth of microbes.

Air lift bioreactors in the airlift bioreactor, the medium of the vessel is divided into two interconnected.

Zones by means of baffle or draft tube. In one two zones referred to a riser, the air/gas is pumped. The other zone that receives no gas is down comer. The dispersion flows up the riser zone while down occurs in the down comers. There are two types of airlift bioreactors.

Internal –loop airlift bioreactors has a single container with a central draft tube that creates interior liquid circulation channels. These bioreactors are simple in design, with volume and circulation at a fixed rate for fermentation .

External loop airlift bioreactor possesses an external loop so that circulates through separate independent channels. These reactors can be suitably modified to suit the requirements of different fermentations. In general, the airlift bioreactors are more efficient than bubble columns, particularly for denser suspensions of microorganisms. This mainly because in these bioreactors, the mixing of the contents is better compared to bubble columns.

Airlift bioreactors are commonly employed for aerobic bioprocess technology. They ensure a controlled liquid flow in a recycle system by pumping. Due to high efficiency, airlift bioreactors are some times preferred example methanol production, waste water treatment, single-cell protein production. In general, the performance of the airlift bioreactors is dependent on the pumping (injection) of air and liquid circulation.

The stirred tank bioreactors lack well defined flow of air. In these, air is pumped from below. This creates the bubbles in the medium which rises up through the draught tube by buoyancy and drags the surrounding fluid up. The air that is used 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 released from the media is sufficient to provide mixing.

In case of enzyme production, the recovery has to be strictly under anaerobic conditions since for most of the enzymatic activity is sensitive to the presence of oxygen.

III. Immobilized cell bioreactors:
·         Packed bed
·         Moving bed
·         Fibrous bed
·         Membrane bed

Packed bed:-
In chemical processing, a packed bedis a hollow tube, pipe, or other vessel that is filled with a packing material. The packing can be randomly filled with small objects like Raschig rings or else it can be a specifically designed structured packing. Packed beds may also contain catalyst particles or adsorbents such as zeolite pellets, granular activated carbon, etc.

The purpose of a packed bed is typically to improve contact between two phases in a chemical or similar process. Packed beds can be used in a chemical reactor, a distillation process, or a scrubber, but packed beds have also been used to store heat in chemical plants. In this case, hot gases are allowed to escape through a vessel that is packed with a refractory material until the packing is hot. Air or other cool gas is then fed back to the plant through the hot bed, thereby pre-heating the air or gas feed.

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 reactor:


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These reactors can utilize high density of particles and reduce bulk fluid density. The design of fluidized bed reactor such that the solid are retained in the reactor while the liquid flows out .this bioreactors are suitable for use to carry out reactions involving fluid suspended bio catalyst Such as immobilized enzymes, immobilized cells, microbial flocs.

For an efficient operation of fluidized beds,gas is spragedto create a gas-liquid-solid fluid bed.it is also necessary to ensure to that suspended particles are not too light are to dense and they are good suspended state. Recycling of liquid is important to maintain continuous contact between the reaction contents and biocatalyst .this unable good efficiency of bioprocessing.

Advantages
• Heat and mass transfer are efficient 
• The mixing of the media between the liquid, solid and gaseous phases are effective. 
• The reactor requires less energy. 
• Low shear rates and hence suitable for cells which are more sensitive to friction like the plant cells and mammalian cells. 

2. Hollow fiber membrane bioreactors
These reactors have hollow fibers are made from cellulose acetate, acrylic polymers, 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 growth of microbes.

POTENTIAL ADVANTAGES OF BIOREACTOR LANDFILLS:-
Decomposition and biological stabilization of the waste in a bioreactor landfill can occur in a much shorter time frame than occurs in a traditional “dry tomb” landfill providing a potential decrease in long-term environmental risks and landfill operating and post-closure costs.

 Potential advantages of bioreactors include:

  • Decomposition and biological stabilization in years vs. decades in “dry tombs”
  • Lower waste toxicity and mobility due to both aerobic and anaerobic conditions
  • Reduced leachate disposal costs
  • A 15 to 30 percent gain in landfill space due to an increase in density of waste mass
  • Reduced post-closure care
  • Bioreactors are used for carrying out biochemical processes which employ microbes, fungus, plant cells or mammalian cell systems for production of biological products.

The bioreactors provide a controlled environment for the production of metabolites which can help to achieve the optimal growth of microbes. The term fermentor is used as synonym to bioreactors.

Applications:-
·         AT Bioreactors can be employed in a wide variety of situations.
·          There is high BOD, COD or organic suspended solids to be removed and treated in order to avoid draining the pollutant into the sewers, we could potentially use AT Bioreactors.

Conclusion:-
The review of the bioreactors for the application of wastewater treatment has proven that this emerging technology has developed a niche in the wastewater treatment sector while concentration.

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