Batch Sterilization - Process, Advantages and Disadvantages

What are Bioreactors? Definition, Principle, Design, Parts, Types, Applications :

What is Bioreactor?

• The fermentation process is carried out in a special type of vessel known as a Fermenter or Bioreactor.

• A bioreactor is a device used for microbial fermentation, which can improve fermentation efficiency by optimizing the fermentation conditions of microorganisms. 

• These bioreactors are commonly cylindrical, ranging in size from a few milliliters to cubic meters, and are usually made of stainless steel.

• According to the aerobic and anaerobic properties of the cultured microorganisms, fermenters can be divided into aerobic and anaerobic types.

• There are different types of bioreactors, The major types are Continuous Stirred Tank Bioreactors, Bubble Column Bioreactor, Fluidized Bed Bioreactors, Packed Bed Bioreactors, etc.

• The size of the biological fermenter is usually different according to the application from a small scale to a large scale ranging from 50ml to 5000L, which can be independently customized according to the user's requirements. 

• Generally, biological fermenters are vertical, with standard jackets, and flat-round turbine stirring devices. 

• A typical bioreactor consists of various systems such as a temperature & pH control system, sterilization system, sampling system agitator system, oxygen delivery system, foam control system Cooling system, etc.

• Fermentation tanks are widely used in the pharma industry, alcoholic beverages, chemicals, food, dairy, brewing, and other industries to play a fermenting role.

Bioreactor Definition: 

• A bioreactor is defined as a vessel that carries out a biological reaction and provides a controlled environment such as temperature, pH, substrate, salts, vitamins, oxygen, etc for the growth of microorganisms and product formation.

• Bioreactors are device in which biological or biochemical processes takes place under controlled environmental conditions such as pH, temperature, nutrient supply, etc.

Principle of Bioreactor:

• The bioreactor is the core heart of the fermentation process.
• The bioreactor provides a suitable growth environment for the growth and reproduction of microorganisms to produce suitable products.
• The main principle of the bioreactor is to make the gas well dispersed in the liquid phase so that the materials can be mixed more evenly, and the uneven other liquid can be evenly suspended or fully emulsified; so that the solid particles can be evenly suspended in the liquid phase.
• In the future, fermenters will be more widely used, and customers should apply them more rationally and scientifically.
• Biological bioreactors are widely used in dairy products, beverage bioengineering, pharmaceutical, dairy products, alcoholic beverages, and other industries.

Characteristics of Ideal Bioreactor:

1. The ideal Bioreactor should be simple, easy to use and provide proper environmental conditions.
2. Keep the temperature constant and homogeneous.
3. Minimize nutrient concentration gradients.
4. Prevent sedimentation and flocculation.
5. Keep the culture pure without contamination.
6. Maintain an aseptic environment.
7. Maximize performance and production.
8. Minimize spending and production costs.
9. It should Minimize the time.
10. The bioreactor must be designed to prevent the entry of contaminating organisms and to contain the desired organisms.
11. Bioreactors must resist corrosion, and sterilization pressure and meet the demands of the cultivation of different types of microorganisms.
12. A good Bioreactor must Control temperature, agitation, pH, and dissolved oxygen of the culture medium necessary to optimize the multiplication of microorganisms.

Structure and Design of Bioreactor:

• The fermenter is a container of a closed type, usually cylindrical in shape. Inside this tank, the medium and microorganism are mixed, and the process of fermentation takes place.

• Bioreactors are a vessel in the fermentation process carried out for the production of biomass, antibiotics metabolites, and vitamins.

• Generally, the Fermentation vessel is made up of Glass and stainless steel.

• The sizes of the bioreactor can vary from small scale to large scale according to application. shake flask (100-1000 ml), laboratory fermenter (1 – 50 L), to plant scale (2 – 500 m3) are some examples of bioreactors.

• An aeration system is one of the very important parts of the Bioreactor which includes in sparger and an impeller for mixing the gas bubbles and microbial cells through the liquid culture medium for uniform circulation of Nutrients.

• In a fermentation vessel, four baffles are present inside of an agitation vessel to prevent a vortex and improve aeration efficiency for the growth of microorganisms.

• Heating devices use for temperature control and sterilization. similarly, cooling jackets are used for sterilization of media and to control the temperature.

• The foam control unit is used to control the level of foam in the fermenter vessel and minimize or avoid contamination.

• Different types of valves are used in Bioreactors such as globe valves, butterfly valves, ball valves, diaphragm valves, and safety valves to control the movement of liquid in the vessel. 

• A variety of computer monitoring sensors are used to control environmental conditions like temperature, pH, dissolved oxygen concentration, nutrient levels, cell mass, and product concentration.

Types of Bioreactors: 

There are different types of bioreactors according 

• Depending on the input and output flows, the operation of a bioreactor can be done in three different ways: continuous (chemostat), semi-continuous (fed-batch), and discontinuous (batch). 

• Depending on the biological culture you want to carry out, they can be divided into aerobic, anaerobic, or facultative organisms. In each of the bioreactors, the aeration or insulation system will vary. In the same way, depending on the organism, its growth will be favored by aeration with bubbles, as in the case of lichens, or with agitation, the most normal aeration in bacterial growth.

• According to the types of organisms in bioreactors: microbial reactors, plant cell reactors, animal cell reactors, and enzyme reactors.

The main types of Breactors are : 

1. Continuous Stirred Tank Reactors (CSTR).
2. Plug flow Reactor, also known as tubular flow reactor.
3. Tube Reactor. 
4.  Bubble Column Reactor 
5. Airlift Bioreactor.
6. Packed Bed Reactor. 
7. Fluidized Bed Reactor.
8. Tower Reactor.

1. Continuous Stirred Tank reactors :

Image source: Wikipedia

• Continuous Stirred Tank reactors are reaction vessels in which the substrate and other materials are continuously added and the products continuously removed. 
• The continuous stirred-tank reactor is also known as a continuous-flow stirred-tank reactor or mixed flow reactor.
• The CSTR reactor is designed with full consideration of the research on the fermentation state of different materials and is equipped with a variety of feeding and discharging methods, which can complete continuous feeding or semi-continuous feeding and fermentation research.
• CSTR is High strength acid and alkali corrosion-resistant stainless steel tank.
• It has an easy modular system, easy to clean and maintain.
• CSTR is suitable for scientific researchers, biogas plants, and for continuous simulation experiments.
• CSTRs are most commonly used in industrial fermentation processing, primarily inhomogeneous liquid-phase flow reactions where constant agitation is required.
• Continuous reactors are used for a wide variety of chemical and pharmaceutical industries and for biological processes, such as cell cultures and fermenters.
• Large-scale production should use continuous reactors as much as possible. 
• The advantages of continuous reactors are stable product quality and easy operation and control. 
• The disadvantage is that there are different degrees of back mixing in the continuous reactor, which is an unfavorable factor for most reactions and should be suppressed by reasonable selection and structural design of the reactor.

2. Plug Flow Reactor : 

• A plug flow reactor (PFR) is a continuous type reactor in which materially is added continuously inside the reactor and it flows in a “plug-like” manner.
• The plug flow reactor model (PFR) is also known as a Continuous tubular reactor (CTR).
• The plug flow reactor is suitable for large-scale and continuous chemical production.
• It is composed of an empty tube or a filled tube with a relatively large length and diameter, which can be used to perform gas-phase or liquid-phase reactions.
• The plug flow reactor operates under steady-state conditions.
• The plug flow reactor has a small volume, a large specific surface, and a large heat transfer area per unit volume, which is especially suitable for reactions with large thermal effects.
• Since the reactant has a fast reaction speed and a fast flow rate in the tubular reactor, its production capacity is high.
• The continuous tubular reactor is suitable for both liquid phase reactions and gas-phase reactions. 
• It is particularly suitable for pressurized reactions.

3. Tube Reactor: 

• The tubular reactor is a continuous operation reactor with a tubular shape and a large aspect ratio, which belongs to the plug flow reactor.
• The tubular reactor has small back mixing and the production capacity per unit volume is high.
• This type of reactor is especially suitable for occasions requiring a high conversion rate or a series of side reactions. 
• Tubular bioreactors are used in gasoline production, oxidation of sulfur dioxide, oil cracking, and synthesis of ammonia from its elements. 
• Its main disadvantage is that when the reaction rate is very low, the required pipeline is too long, which is not easy to realize in the industry.

4. Bubble Column Reactor: 

• A bubble column reactor is basically a cylindrical structure. 
• In Bubble Column Reactor the tank is filled with liquid and the gas is introduced from the bottom of the tank. 
• Bubble Column Reactor is suitable for gas-liquid reactions and slow and medium-speed exothermic reactions. 
• A bubble column reactor cannot be used for a highly viscous medium.
• Bubble Column Reactor has a simple structure, easy to use, low cost, and easy to control and maintain with no difficulty at high-pressure use.
• It has low efficiency due to the liquid phase of the bubble column reactor being over-mixed and the bubbles are easily fused.

5. Airlift Bioreactor : 

• Airlift bioreactors are a type of bioreactor without mechanical agitation that is widely used. 
• The airlift bioreactor is developed based on the bubble column reactor. 
• Airlift bioreactors can be further divided into four types: airlift and external circulation fermenters, airlift circulation fermenters, belt lift fermenters, and tower fermenters 
• Airlift bioreactor is one of the important reactors used in the field of plant cell culture. 
• Its fluidity is more uniform than other bioreactors, and its structure is simple. 
• The structure of the airlift bioreactor is relatively simple, easy to clean and maintain, not easy to contaminate bacteria, has low energy consumption, high dissolved oxygen efficiency, and low operating cost.
• The disadvantages are relatively few, mainly because the mixing is not uniform enough during high-density culture.

6. Packed bed reactor :

• A packed bed reactor PBR is also known as a fixed bed reactor. 
• A Packed bed composed of small granular materials (such as fine sand, activated carbon, and coke) or immobilized enzymes is stacked in the container. 
• The Packed bed reactor tank is filled with an immobilized enzyme to form a stable column bed and then add substrate into the tank.
• This causes enzyme-catalyzed reactions under certain reaction conditions and collects the output conversion liquid at a certain flow rate.
• It is suitable for immobilized enzymes of various shapes and substrate solutions with no solid particles and low viscosity, as well as conversion reactions with product inhibition.
• This type of equipment is widely used in gas-solid phase reactions and liquid-solid phase reaction processes. 
• PBR is the most commonly used reactor in industrial production and research. 
• Packed bed reactors can be used for stripping, air aeration, sand filtration, activated carbon adsorption, or nitrification.

7. Fluidized Bed Reactor: 

• A fluidized bed reactor is a type of reactor device that can be used to carry out a variety of heterogeneous chemical reactions.
• A fluidized bed reactor is a reactor that uses gas or liquid to pass through a granular solid layer to keep solid particles in a suspended motion state and conducts a gas-solid phase reaction process or a liquid-solid phase reaction process. 
• When we used it in a gas-solid system, it is also called a fluidized bed reactor.
• It can realize the continuous input and output of solid materials.
• FBR is easy to control and suitable for strong exothermic reactions. 
• Fluidized bed reactors have been widely used in chemical, petroleum, metallurgy, nuclear industry, and other sectors.

8. Tower fermenters :

• A tower fermenter is also known as a column fermenter.
• The tower fermentation tank is a hollow cylinder with a high tank body and a height-diameter ratio.
• Tower Fermenter was defined by Greenshields et al. in 1971. They described it as an elongated non-mechanically stirred fermenter with an aspect ratio of 6:1 for the tubular section or 10:1 overall.
• It has a simple structure, low energy consumption, is simple to clean and maintain, is not easy to contaminate bacteria, and is suitable for large-scale production.
• Tower fermenters are generally used for the production of single-cell proteins, alcohol production, and the cultivation of plant cells.

Applications of Bioreactor: 

The fermenter was invented to obtain drinks with natural carbonation. The direct purpose of fermenters is the fermentation of various materials. In this case, fruit, sugar, or grain raw materials are used. With the help of an effective fermentation process, drinks such as beer, wine, and other fermented products are obtained.

1. Bioreactors are used for the production of drugs, the cultivation of cells or microorganisms in 
2. Bioreactors are useful in Tissue Engineering.
3. Use in the food industry:  production of food additives and fermented products such as beer, fruit wine, vinegar, etc.
4. Use in the pharmaceutical industry: By use of a variety of drugs have been developed, such as human growth hormone, recombinant hepatitis B vaccine, certain varieties of monoclonal antibodies, etc.
5. They are mainly used in the fermentation of dairy products and alcohol. 
6. Bioreactors are generally used for the production of glutamic acid, antibiotics, xanthan gum, saccharification enzymes, and citric acid.
7. Application in the field of environmental science: municipal and domestic wastewater treatment, industrial wastewater, water purification treatment, and others.
8. Bioreactors are also used for gas removal, sludge treatment, and enhancement of microorganisms in sewage treatment.
9. Treatment of polluted air (bio-purification).

Limitations of Bioreactor: 

1. The biological fermenter requires a very large air throughput.
2. It has Poor interphase mixing and contact.
3. The number of substrates, nutrients, and oxygen cannot be kept consistent when the circulating organisms and operating conditions change.
4. Mixing and ventilation are coupling problems, and it is difficult to improve the mixing condition without changing ventilation.

Frequently Asked Questions on Bioreactor:

1. What do you mean by fermentor?

Answer: The fermentor is a vessel that is used for the process of fermentation. Fermentor provides a controlled environment for the activity of the microorganisms for the commercial production of certain substances. There are different types of fermentors depending on the type of product and the volume of the product to be produced.

2. What is a Fermenter?

Answer: A fermenter is a specialized vessel designed for fermentation and enzymatic processes in the production of wine. The fermenter is also used as a container for storing wine and other food products.

3. What does a bioreactor do?

Answer: The purpose of any bioreactor is to create optimal conditions for the vital activity of the cells and microorganisms cultivated in it, namely, to ensure respiration, supply of food, and removal of metabolites by uniform mixing of the gas and liquid components of the contents of the bioreactor.

4. How is a fermenter different from a bioreactor?

Answer: The apparatus for growing live cultures has two names - bioreactor and fermenter. In different countries, they are called differently, and experts distinguish them according to the functions that these devices perform. If the fermenter is used for cultivating bacteria, then the bioreactor is needed for growing cell cultures.

5. Why fermenter is used?

Answer: Because fermenter maintains the optimum environment for the growth and development of significant microorganisms used in the large-scale fermentation process and the commercial production of products like Alcoholic beverages, Enzymes, Antibiotics, Organic acids, vaccines, etc.

6. What are the parts of the bioreactor?

Answer: The following components of the bioreactor are pH & temperature control system, agitator (impeller), stirrer and bearings, baffles and sparger, etc.

7. Is bioreactor and fermentor the same?

Answer: Bioreactor and fermentor are two words for basically the same thing. Scientists who cultivate bacteria, yeast, or fungi often use the term fermentor. The term bioreactor often relates to the cultivation of mammalian cells but is also generically used.