Bioreactor- Definition, Design, Principle, Parts, Types, Applications, Limitations

Biotechnology is the application of biological systems, organisms, or processes to produce useful products or services. Biotechnology has a wide range of applications in various fields such as medicine, agriculture, food, environment, and industry. However, biotechnology often requires the use of specialized equipment and devices to manipulate and control the biological systems or processes involved. One of the most important and widely used devices in biotechnology is the bioreactor.

A bioreactor is a device that supports a biologically active environment, where biochemical reactions or biological transformations take place. A bioreactor can be a vessel, a tank, a column, a pipe, or any other container that can hold a liquid, a gas, or a solid medium with living cells or enzymes. A bioreactor can also be a system that mimics the natural conditions of a specific tissue or organ, such as a heart, a liver, or a bone.

The main purpose of a bioreactor is to provide optimal conditions for the growth and activity of the biological agents (such as microorganisms, animal cells, plant cells, or enzymes) and to facilitate the production of the desired products (such as biomass, metabolites, proteins, drugs, biofuels, or bioplastics). A bioreactor can also be used for other purposes such as waste treatment, bioremediation, biosensing, or bioartificial organs.

Depending on the type and scale of the bioprocess involved, different types of bioreactors can be used. Some of the common types of bioreactors are:

• Continuous stirred tank reactor (CSTR): A bioreactor that operates in a continuous mode, where fresh medium is added and product is removed at a constant rate. The bioreactor is equipped with an agitator that provides mixing and aeration. CSTRs are widely used for aerobic fermentation processes such as ethanol production.
• Airlift reactor: A bioreactor that uses air bubbles to provide mixing and aeration. The bioreactor consists of two zones: a riser zone where air is sparged and a downcomer zone where air is separated. Airlift reactors are suitable for aerobic processes involving gas-liquid or gas-liquid-solid systems such as algal cultivation.
• Bubble column reactor: A bioreactor that consists of a cylindrical vessel with a gas sparger at the bottom. The gas bubbles rise through the liquid medium and provide mixing and mass transfer. Bubble column reactors are simple and low-cost devices that can be used for aerobic processes such as wastewater treatment.
• Fluidized bed reactor: A bioreactor that uses small particles as carriers for immobilized cells or enzymes. The particles are fluidized by an upward flow of liquid or gas and form a dense bed with good mass transfer and mixing characteristics. Fluidized bed reactors are used for high-rate anaerobic processes such as methane production.
• Packed bed reactor: A bioreactor that uses solid particles as carriers for immobilized cells or enzymes. The particles are packed in a fixed bed and the liquid or gas flows through the interstices. Packed bed reactors have high surface area and low pressure drop but may suffer from clogging and channeling problems. Packed bed reactors are used for low-rate anaerobic processes such as hydrogen production.
• Photobioreactor: A bioreactor that uses light as an energy source for photosynthetic organisms such as microalgae or cyanobacteria. The bioreactor can be illuminated by natural sunlight or artificial light sources. Photobioreactors can be designed in various shapes and configurations such as tubular, flat panel, helical, or vertical. Photobioreactors are used for the production of high-value products such as pigments, antioxidants, or biofuels.
• Membrane bioreactor: A bioreactor that combines conventional biological treatment with membrane filtration. The membrane acts as a physical barrier that retains the biomass and separates the product from the medium. Membrane bioreactors can achieve high-quality effluent and high biomass concentration but may require frequent cleaning and maintenance. Membrane bioreactors are used for wastewater treatment and water reuse.

Bioreactors are essential tools for modern biotechnology as they enable the efficient and controlled conversion of raw materials into valuable products by biological means. Bioreactors also offer opportunities for innovation and discovery in various fields of science and engineering. By understanding the principles and design of bioreactors, one can harness the potential of biological systems for various applications.

A bioreactor is a type of fermentation vessel that is used for the production of various chemicals and biological reactions. It is a closed container 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 bioreactor should provide for the following:

• Agitation (for mixing of cells and medium),
• Aeration (aerobic fermentors); for O2 supply,
• Regulation of factors like temperature, pH, pressure, aeration, nutrient feeding, and liquid level.
• Sterilization and maintenance of sterility, and
• Withdrawal of cells/medium

Bioreactors are used for the production of biomass, metabolites, and antibiotics.

The design and mode of operation of a bioreactor are based on the production of an organism, optimum conditions required for desired product formation, product value, and its scale of production. A good bioreactor design will help to improve productivity and provide higher quality products at lower prices.

A bioreactor is a device that consists of various features such as an agitator system, an oxygen delivery system, a foam control system, and a variety of other systems such as temperature & pH control system, sampling ports, cleaning, and sterilization system, and lines for charging & emptying the reactor.

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.

The sizes of the bioreactor vary widely depending on the application. Some bioreactors are designed for small scale fermenters and some for large scale industrial applications from the microbial cell (few mm3) to shake flask (100-1000 ml) to the laboratory-scale fermenter (1 – 50 L) to pilot level (0.3 – 10 m3) to plant scale (2 – 500 m3) for large volume).

The shape of the reactor is critical for its performance as it affects the power transmission and fluid dynamics that drive heat and mass transfer within the system. A critical design parameter related to reactor shape is the height-to-diameter ratio H/D, or H:D. Tall, thin reactors with H:D > 3:1 enable long liquid residence times of gas bubbles sparged from the bottom, allowing an effective gas-to-liquid mass transfer. However, in tall and thin reactor designs, the headspace surface area is limited, and consequently this can lead to limitations in the associated partial pressure driving forces. Conversely, a short and wide reactor with H:D < 1:1 has a short residence time for gas bubbles and a large headspace surface area. In microbial fermentations, where gas flow rates are high and mixing is vigorous, vessels with an H:D ratio of 3:1 are typical. In cell culture, where gas flow rates are lower and mixing is gentle, a common range for H:D is 1.5:1–2.1:1.

Autoclavable and sterilize-in-place bioreactors are designed with top and bottom heads, whereas current single-use vessel designs only have bottom heads. Top and bottom heads can have many different profiles, which affect the mixing characteristics in the system.

Mass transfer in the reactor is related to the flow pattern in the process liquid, which in turn is affected by the interior design of the reactor and the agitation system. Mass transfer during turbulent flow is greater than during laminar flow conditions. However, too much turbulence can be detrimental to delicate bioprocesses. Turbulence can be introduced in several different ways, for example,

• through the design of the agitation system
• through the use of internal baffles.

Baffles establish fluid resistance and break up laminar flow.

The bioreactor is the heart of any biochemical process as it provides an environment for microorganisms to obtain optimal growth and produce metabolites for the biotransformation and bioconversion of substrates into desirable products. The reactors can be engineered or manufactured based on the growth requirements of the organisms used. Reactors are machines that can be made to transform biological-based materials into desirable products. They can be used for the production of various enzymes and other bio-catalysis processes.

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. The bioreactor provides a suitable growth environment for the growth and reproduction of bacteria and promotes the bacteria to produce the products people need.

The bioreactor also controls various environmental factors that affect the growth and productivity of the organisms, such as temperature, nutrient concentrations, pH, dissolved gases (especially oxygen for aerobic fermentations), agitation, aeration, and sterilization. The bioreactor should also allow for monitoring and sampling of the culture and product, as well as removal of waste biomass and by-products.

The bioreactor should be designed in such a way that it allows for efficient mass transfer, heat transfer, mixing, and oxygen transfer between the phases (gas-liquid-solid) involved in the fermentation process. The bioreactor should also minimize the formation of foam, shear stress, and contamination.

The bioreactor should be operated in a mode that suits the type of fermentation process and product desired. The common modes of operation are batch, fed-batch, and continuous. In batch mode, all the nutrients are added at the beginning of the fermentation and no further addition or removal is done until the end of the process. In fed-batch mode, nutrients are added periodically or continuously during the fermentation to maintain a constant or optimal concentration. In continuous mode, nutrients are added and products are removed continuously at a constant rate throughout the fermentation. Each mode has its own advantages and disadvantages depending on the process parameters and product characteristics.

A bioreactor is a device that consists of various features such as an agitator system, an oxygen delivery system, a foam control system, and a variety of other systems such as temperature & pH control system, sampling ports, cleaning, and sterilization system, and lines for charging & emptying the reactor. These reactors have been designed to maintain certain parameters like flow rates, aeration, temperature, pH, foam control, and agitation rate. The number of parameters that can be monitored and controlled is limited by the number of sensors and control elements incorporated into a given bioreactor. Some essential parts of a bioreactor are discussed below:

• Fermenter vessel: Most fermented containers are made of glass and stainless steel to reduce pressure and corrosion. Glass vessels are usually used in small-scale industries. They are non-toxic and corrosion-proof. Stainless steel vessels are used in large-scale industries. They can resist pressure and corrosion.
• Heating and cooling apparatus: The cooling jacket and silicon in a reactor help to remove excess heat, while internal coils provide heat during fermentation. A cooling jacket is necessary for sterilization of the nutrient medium and removal of the heat generated during fermentation in the fermentor.
• Aeration system: An aeration system is one of the very important parts of a fermentor. It contains two separate aeration devices (sparger and impeller) to ensure proper aeration in a fermentor. The sparger pipes contain small holes of about 5-10 mm, through which pressurized air is released. The stirring accomplishes two things: It helps to mix the gas bubbles through the liquid culture medium and It helps to mix the microbial cells through the liquid culture medium which ensures the uniform access of microbial cells to the nutrients.
• Sealing assembly: The sealing assembly is used for the sealing of the stirrer shaft to offer proper agitation. There are three types of sealing assembly in the fermenter: Packed gland seal, Mechanical seal, Magnetic drives.
• Baffles: The baffles are incorporated into fermenters to prevent a vortex improve aeration in the fermenters. It consists of metal strips attached radially to the wall.
• Impeller: Impellers are used to provide uniform suspension of microbial cells in different nutrient mediums. They are made up of impeller blades attached to a motor on the lid. Impeller blades play an important role in reducing the size of air bubbles and distribute them uniformly into the fermentation media. Variable impellers are used in the fermenters and are classified as follows: Disc turbines, Variable pitch open turbine.
• Sparger: A sparger is a system used for introducing sterile air to a fermentation vessel. It helps in providing proper aeration to the vessel. Three types of sparger are used: Porous sparger, Nozzle sparger, Combined sparger–agitator.
• Feed ports: They are used to add nutrients and acid/alkali to the fermentor. Feed ports are tubes made up of silicone. In-situ sterilization is performed before the removal or addition of the products.
• Foam-Control: The level of foam in the vessel must be minimized to avoid contamination, this is an important aspect of the fermentor. Foam is controlled by two units, foam sensing, and a control unit. A foam-controlling device is mounted on top of the fermentor, with an inlet into the fermentor.
• Valves: Valves are used in the fermentor to control the movement of liquid in the vessel. There are around five types of valves are used, that is: globe valve, butterfly valve, ball valve, diaphragm valve, and safety valve.
• Controlling Devices for Environmental Factors: A variety of devices are utilized to control environmental elements like temperature, oxygen concentration, pH, cell mass, essential nutrient levels, and product concentration.
• Use of Computer in Fermenter: For an efficient process, monitoring, and data collecting, fermentors are generally coupled with modern automated and semi-automated computers and databases.

Bioreactors are widely used in various fields of biotechnology, such as:

• Cell growth: Bioreactors provide a suitable environment for the cultivation of animal, plant, and microbial cells for the production of biopharmaceuticals, vaccines, antibodies, hormones, enzymes, and other valuable products. For example, bioreactors are used for the production of insulin, erythropoietin, interferon, monoclonal antibodies, and recombinant vaccines .
• Enzyme production: Bioreactors are used for the production of enzymes by immobilized or free cells or by cell-free systems. Enzymes are important biocatalysts that have applications in various industries such as food, detergent, textile, leather, paper, and biofuel. For example, bioreactors are used for the production of amylase, protease, cellulase, lipase, lactase, and pectinase .
• Biotransformation and bioconversion: Bioreactors are used for the conversion of substrates into desired products by using whole cells or enzymes as biocatalysts. Biotransformation and bioconversion processes have advantages over chemical synthesis such as high specificity, selectivity, efficiency, and environmental friendliness. For example, bioreactors are used for the conversion of glucose to fructose, lactose to galacto-oligosaccharides, starch to ethanol, and phenol to catechol .
• Biosensors: Bioreactors are used for the development of biosensors that can detect and measure various analytes such as glucose, lactate, urea, ethanol, and toxins. Biosensors consist of a bioreceptor (such as an enzyme or an antibody) that binds to the analyte and a transducer (such as an electrode or an optical device) that converts the binding signal into a measurable output. For example, bioreactors are used for the development of glucose biosensors based on glucose oxidase immobilized on electrodes .
• Food production: Bioreactors are used for the production of various food products by using microorganisms or enzymes as biocatalysts. Food biotechnology can improve the quality, safety, nutrition, and diversity of food products. For example, bioreactors are used for the production of cheese, yogurt, bread, beer, wine, vinegar, soy sauce, and fermented vegetables .
• Milk processing: Bioreactors are used for the processing of milk by using microorganisms or enzymes as biocatalysts. Milk processing can enhance the shelf life, flavor, texture, and functionality of milk products. For example, bioreactors are used for the production of lactose-free milk by using lactase enzyme .
• Extrusion: Bioreactors are used for the extrusion of various materials by using high temperature and pressure. Extrusion can modify the physical and chemical properties of materials such as starches, proteins, fibers, and plastics. For example, bioreactors are used for the extrusion of starch-based materials for food packaging applications .
• Tissue engineering: Bioreactors are used for the engineering of artificial tissues and organs by using living cells and biomaterials. Tissue engineering can provide solutions for organ transplantation, drug testing, disease modeling, and regenerative medicine. For example, bioreactors are used for the engineering of skin grafts , cartilage, bone, blood vessels, heart valves, and liver tissue.
• Algae production: Bioreactors are used for the cultivation of algae by using light and nutrients. Algae are photosynthetic microorganisms that can produce various valuable products such as biofuels, pigments, antioxidants, omega-3 fatty acids, and proteins. For example, bioreactors are used for the production of biodiesel from microalgae.
• Protein synthesis: Bioreactors are used for the synthesis of proteins by using cell-free systems or recombinant cells. Protein synthesis can produce various proteins that have applications in biotechnology such as enzymes, antibodies, vaccines, hormones, and growth factors. For example, bioreactors are used for the synthesis of human serum albumin from yeast cells.
• Anaerobic digestion: Bioreactors are used for the digestion of organic waste by using anaerobic microorganisms. Anaerobic digestion can produce biogas (a mixture of methane and carbon dioxide) that can be used as a renewable energy source. Anaerobic digestion can also reduce greenhouse gas emissions and produce organic fertilizer. For example, bioreactors are used for the digestion of municipal solid waste, agricultural waste, sewage sludge, and industrial waste.

Bioreactors are powerful tools for bioprocessing and biotechnology, but they also have some limitations that need to be considered. Some of the common limitations of bioreactors are:

• Scalability: Scaling up bioreactors from laboratory to industrial scale is not a straightforward process, as it involves many factors such as mass transfer, mixing, heat transfer, oxygen transfer, shear stress, and hydrodynamics. These factors may affect the performance and productivity of the bioreactor at different scales and require careful optimization and design .
• Cost: Bioreactors can be expensive to construct, operate, and maintain, especially for large-scale applications. The cost of bioreactors depends on the type, size, material, configuration, and accessories of the bioreactor. For example, stainless steel bioreactors require high initial investment, cleaning and sterilization costs, and maintenance costs. Single-use bioreactors can reduce some of these costs, but they also have drawbacks such as limited size range, disposability issues, and potential leaching of plasticizers .
• Contamination: Bioreactors are susceptible to microbial contamination, which can compromise the quality and yield of the product. Contamination can occur from various sources such as raw materials, air, water, equipment, personnel, and environment. To prevent contamination, bioreactors must be designed with proper aseptic features and operated under strict sterile conditions. Moreover, bioreactors must be monitored and controlled for various parameters such as pH, temperature, dissolved oxygen, nutrient concentration, and product concentration to ensure optimal growth and activity of the desired microorganisms .
• Fouling: Fouling is the accumulation of unwanted materials on the surfaces of the bioreactor or its components. Fouling can affect the heat transfer, mass transfer, mixing, and oxygen transfer efficiency of the bioreactor. It can also cause corrosion, clogging, and biofilm formation. Fouling can be caused by various factors such as chemical reactions, precipitation, adsorption, sedimentation, and biological growth. To avoid fouling, the bioreactor must be easily cleaned and sanitized. Interior surfaces are typically made of stainless steel or other non-corrosive materials for easy cleaning .

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