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Bioreactor Types, Design, Parts, Applications, Limitations

A bioreactor can be described as a kind of fermenter vessel used to produce diverse biological and chemical reactions. It is a...

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This article writter by MN Editors on February 02, 2022

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

Contents

What is Bioreactor? /Definition of Bioreactor 

The bioreactor can be described as a vessel-like apparatus which provides a stable environment for microorganisms to flourish and maintains a steady balance in the biochemical processes that these microorganisms carry out to create desired substances.

  • The bioreactors’ applications can be expanded to include biomass production like single cell proteins baker’s yeast, animal microalgae, and cells and also for the production of metabolites like organic acids as well as antibiotics, ethanol, pigments, aromatic compounds as well as to alter substrates such as steroids and to even produce both extracellular and intracellular enzymes.
  • They can be utilized for any biocatalytic process, including making enzymes, as well as the growth of cells, tissues and organelles in the cell.
  • Bioreactors are usually constructed as cylindrical tanks equipped with an agitator as well as an integral cooling or heating systems with sizes ranging from less than 1 liter to over 50,000 L usually comprised of glass-lined steel or glass.
  • The reactors are constructed to keep certain parameters, such as Aeration rates, flow rates temperatures as well as pH, foam control and the rate of agitation.
  • Reactors are able to provide an output to the specified process parameters to fix any deviation in the values for these variables from the value.
  • The amount of parameters that can be controlled and monitored can be limited only by the amount of control and sensors that are integrated into a particular bioreactor.
  • The efficiency of any bioreactor is dependent on the following main elements: Agitation rate oxygen transfer, temperature, foam production and pH.

An ideal Bioreactor Should Have Following Qualities 

  • The vessel is can be operated aseptically for a few days.
  • Proper agitation and aeration.
  • The power consumption must remain as minimal as is possible.
  • Control of temperature and pH must be made available.
  • Facilities for sampling should be made available.
  • The losses of the fermentation process from evaporation shouldn’t be too high.
  • A minimal amount of labor is required during production cleaning, harvesting, and maintenance.
  • Internal smooth surfaces.
  • Containment is the process of preventing the leakage of cells that are viable from fermenters or equipment downstream.
  • Aseptic operations require protection from contamination.

Important factors need to be consider in designing Bioreactors

Low value and large volume alcohol-based beverages require simple fermenters. They don’t require aseptic conditions. The high-value and low-volume products require a more complex process and aseptic conditions. The design of a bioreactor must also be able to take into account the specific Biochemical Processes’ Characteristics:

  1. The levels of the starting substances (substrates) and the products that are in the reaction mixture are usually inadequate; both substrates and products can hinder the process. Cell development, the structure of intracellular enzymes and their production of products are influenced by the nutritional requirements that the cell has (salts and oxygen) and the maintenance of the optimal conditions for biological activity (temperature as well as the concentration of reactants and pH) within a narrow range.
  2. Specific substances or inhibitors and effectors and metabolic products, such as precursors, can influence the rate and nature of the reactions and intracellular regulation.
  3. Microorganisms can be metabolized by metabolizing unconventional or even contaminants in raw substances (cellulose Molasses, cellulose minerals oil, starch ore waste, air pollution and biogenic waste) this process is often carried out in highly viscous mediums.
  4. Contrary to isolated enzymes and chemicals, the mo’s adjust the structure and function of their enzymes in response to process conditions, and thus the their productivity and selectivity can alter. The microorganisms are susceptible to mutations, which can occur under low conditions in the biological world.
  5. Microorganisms are usually vulnerable to high shear stress, as well as chemical and thermal influences.
  6. Reactions are typically seen in gas-liquid solid systems, with the liquid phase typically being Aqueous.
  7. Continuous bioreactors typically exhibit complex dynamic behavior.
  8. The mass of microbial cells can grow when biochemical conversion is progressing. There are many effects, such as growth on walls, flocculation, and autolysis of microorganisms could be observed during the process.

Fermenter Design

A good fermenter must have the following features: Heat and oxygen transfer settings Sterilization processes and foam control, a fast and thorough cleaning system A proper monitoring and control system.

Parts of the bioreactor and their function
Parts of the bioreactor and their function
  • Traditional designs are open-circular or rectangular vessels constructed from stone or wood.
  • The majority of fermentations are conducted in close systems to prevent contamination.
  • It should be constructed of non-toxic and corrosion-resistant materials.
  • Small fermenters with a capacity of just a few liters are made of glass or stainless steel.
  • Pilot scales and a variety of production vessels are constructed from stainless steel, with polished internal surfaces.
  • Large fermenters are usually constructed of mild steel, and then lined with plastic or glass to cut down on costs.
  • If an aseptic process is required the pipelines that transport inoculum, air and ingredients for fermentation have to be sterilized, normally with steam.
  • The majority of vessel cleaning processes are now automated with spray jets and are referred to as Cleaning in Place (CIP). It is located inside the vessel.
  • The pipework must be designed to limit the chance of microbial contamination. There shouldn’t be joints in the horizontal direction, or any unnecessary pipes and stagnant spaces that are dead where substances can gather; otherwise, the result could be ineffective sterilization.
  • Typically, fermenters with a capacity of 1000 liters capacity are equipped with an outer jacket. larger vessels come with internal coils.
  • Safety and pressure gauges valves should be used, (required during sterilization and operation).
  • To transfer media, pumps are employed. Centrifugal pumps (generate high shear forces and provide a routes for easy contaminations) magnetically coupled jet and the peristaltic pumps.
  • Alternative methods for liquid transfer include gravity feeding or vessel pressure
  • In ferments operating at high temperatures or that contain volatile compounds A sterilizable condenser could be needed to stop the loss of evaporation.
  • Fermenters are usually operated with positive pressure to stop the entry of contaminants.

Different Parts of Bioreactor

Different Parts of Bioreactor
Different Parts of Bioreactor

1. Fermenter Vessel/Vessel

The vessel is designed so that it uses the least work and maintains it and work is carried out in a clean manner under carefully controlled conditions. The inside that the vessel has is smooth, and is constructed of low-cost substances that provide the best outcomes. There are two kinds of fermentor vessels such as glass fermenter and stainless steel fermenter, for small-scale glass is the preferred choice, and for industrial use stainless steel is employed.

  • Glass is not toxic and is resistant to corrosion. It is easy to study the internal reaction within the vessel. Sterilization is performed using autoclave. They are small fermentors that measure around 60 centimeters.
  • The majority of stainless steel is employed for large-scale fermentations. The vessels are able to withstand corrosion and pressure. The sterilization process is performed in situ.

2. Heating and Cooling Apparatus

The vessel that is used to ferment food is generated by the activity of microbes and the an agitation. The temperature in the vessel is controlled by adding or removing heating from the unit. Baths that are thermostatically controlled and internal coils usually employed to supply heat, and silicone jackets are utilized to eliminate heat. It features a double-silicon mats with heating wires sandwiched in between mats. If the dimensions are exceeded and the mat is covered with a surface with the jacket the removal of heat is a pain in the internal coils cold water must be circulated to keep the temperature at a constant level.

3. Sealing Assembly

The sealing assembly is utilized for the sealing of stirrer shafts to ensure proper agitation. it is able to function for longer periods of time aseptically. There are three kinds of seals used within the fermenter. Seals for the packed gland The shaft is sealed by many asbestos packing rings which are pulled by a glands that are pushed to the shaft. To ensure that the heat is not absorbed packing rings are periodically tested and replaced.

Mechanical seals: This kind of seal is composed of two components, one stationary within the bearing, and a rotating shaft. Two components are joined using springs. In the process, stem condensate is utilized to cool and lubricate the seals. Magnet drives comprise two types of magnets which is a driving magnetic and driven. The driving magnet is secured to the exterior of the head plate within a bearing and linked with the shaft of drive. A second, the magnet that is driven is located on the other side of the shaft, and secured in bearings on the face of the head plate’s interior.

4. Baffles

Baffles stop vortex from expanding the capacity of aeration and are composed of metal strips welded in a radial direction to the wall. Baffles are able to reduce the growth of microbial colonies on the sides of the fermenter.

5. Impeller

Impellers are utilized to provide homogeneous suspensions of microbial cells in a homogeneous medium for nutrient delivery by stirring. Impellers mix the bulk liquid with solid particles and gas phases of the culture of suspension. Impellers with variable impellers are employed in fermenters and can be classified according to.

  • Disc turbines: They comprise disc with a set of rectangular vanes. They allow an air stream from the sparger to strike on the disc’s underside and then move the air toward the vanes, breaking large air bubbles down into smaller ones.
  • Variable pitch open turbine: They also comprise a an agitator shaft that is vanned and joined to propeller blades of the marine on the shaft for the agitator. The air bubbles that make up this turbine don’t touch any surface prior to dispersing.

6. Sparger

  • The sparger is used during fermentation to stir and aerate the wort. 
  • It lets oxygen in the fermenter, allowing yeast to convert sugars from fruits, vegetables, grains, and juices into alcohol. 
  • Spargers made from stainless steel, brass and glass are the best. 
  • It must fit into the fermenter’s opening without clogging. 
  • Two main functions of the sparger are: It creates air bubbles that help disperse oxygen throughout wort during fermentation. And it pushes out unwanted trub from the fermenter. This makes it easier to clean the equipment and keep the beer clear.
  • It pushes air through pipes into fermenters to aerate them. 
  • The sparger keeps the contents of fermenters mixed so they don’t get clumped together. 
  • This prevents oxygen from getting into the fermenter. This could cause bad smells.
  • Three kinds of spargers are utilized. Porous spargers consist of sintered or ceramic and are used in vessels that do not have agitation at the scale of a laboratory.
    • Nozzle Sparger: It’s an open or partially opened single pipe. This kind of sparger is typically employed because they don’t block and offer less pressure.
    • Combined sparger-agitator: They insert air through a hollow shaft, and then release it from the holes in the disc that is drilled to connect directly to the bottom of the primary shaft. If the agitator operates in a range of rpm they will provide an adequate amount of air in an agitator with a baffle.

7. Feed Ports

  • Feed ports help you to add ingredients at the right times to the bioreactor.
  • Feed ports allow for small amounts of liquid to pass through them, so nutrients can be added to or removed from fermenters without having to open them. 
  • This allows you to monitor your fermentation process continuously and makes it easy to add nutrients or remove byproducts.
  • Feed ports enable you to add feeds at various stages of fermentation to your fermenters. You can control the characteristics of your beer by controlling when each ingredient is added. You can add malt extract to your wort at the beginning of the brewing process to give it time to turn sugars into alcohol. However, if you wait too long, the beer may taste flat and lack character.
  • The feed ports consist of tubes made of silicone.
  • In-situ sterilization is carried out prior to either the removal or the addition of ingredients.

8. Foam Control

This is among the most important components of the fermenter, as the volume of foam within the vessel must be reduced to prevent contamination. The level of foam can be controlled with two components: foam sensing and control. In the fermenter the probe is placed through the top and is set to a certain level that is above the surface of the broth. If the level of foam rises and it touches the probe’s tip there will be a current carried across the circuit. The current will activate the pump, and antifoam will be released immediately to fight the issue.

9. Valves

Valves are employed in the fermentor for controlling the flow of liquid inside the vessel. There are around five kinds of valves used including globe valves, butterfly valves ball valve diaphragm and butterfly valve. Globe valves can be used for general use, but they don’t control flow. Butterfly valves are not appropriate for use in aseptic conditions. They are utilized for pipes with large diameters that operate at low pressure. Ball valves can be used in aseptic conditions. They can handle mycelial broths and operate at a high temperatures. Diaphragm valves aid in adjusting flow.

10. Safety Valves

The safety valve is integrated into the pipe and air layout to function under pressure. Through these valves, the pressure remains within the safe boundaries.

11. Aeration System

Anaerobic digestion requires oxygen for microorganisms that metabolize organic matter into biogas. Methane gas is formed when biodegradable materials are broken down. Carbon dioxide, which is produced during the oxidation process, is the main component of the gas. The bacteria won’t be able to grow and digest the material if there is no air. This will lead to lower production of biogas as well as higher levels of carbon dioxide.

To keep cells alive and growing, oxygen is added through spargers (aerating device) during aerobic fermentation. The rate at which yeast consumes sugar during fermentation is affected by the level of aeration. Higher levels of dissolved oxygen allow yeast to grow more quickly, but with a lower cell density. High cell concentrations result in a decreased space per cell, and therefore lower productivity.

  • A fermentor’s aeration system can be one of its most important components.
  • To ensure adequate oxygen supply throughout the culture, it is crucial to select a reliable aeration system.
  • It has two separate aeration devices, an impeller and a sparger, to ensure that fermentors are properly aerated.
  • Two things are accomplished by the stirring:
    • It allows you to mix the gas bubbles in the liquid culture medium.
    • It allows the microbial cells to be mixed through the liquid culture medium, which makes sure that they have equal access to the nutrients.

12. Foam-Control

  • Two functions are provided by the foam control system in the bioreactor. It prevents foaming by removing air from the solution. 
  • It also helps stabilize bubbles that form during fermentation by adding gas. Because less oxygen diffuses through liquid, this results in a better product. It’s also useful for high yields of fermentable sweeteners; adding CO2 to the liquid will increase sugar intake without affecting yield.
  • The continuous feedback loop of the foam control system optimizes foam generation and stability according to input flow rates. 
  • This device produces foam that has been shown to increase cell growth and proliferation. It creates a favorable environment for the growth of cells from different tissue/organ sources.
  • The foam control system adjusts the air supply to maintain the desired levels of dissolved oxygen. 
  • This system makes the most of energy and reduces water consumption by half compared to manual operations. This reduces costs and greenhouse gas emissions.
  • North Carolina State University’s Dr. Robert Davis designed a foam-control system. A computer algorithm is used to regulate the flow of air into the bioreactor based on the level of dissolved oxygen in the vessel. This keeps cells alive and prevents them growing too large.
  • To avoid contamination, the foam level in the vessel should be reduced. This is an important aspect to the fermentor.
  • Two units control foam: a foam sensing unit and a control device.
  • An inlet is provided to the fermentor that allows for the installation of a foam-controlling device.

13. Controlling devices for environmental factors

  • Bioprocess industries have always struggled with controlling devices. Bioreactor design must consider many parameters such as temperature, pH, dissolved oxygen and carbon dioxide concentrations. These should all be controlled at certain levels during the process. This will control growth, reduce contamination, improve production rate and increase product-quality.
  • This will allow you to better control the environment in a bioreactor. 
  • These devices will enable us to monitor the temperature, carbon dioxide, oxygen concentration, and pH of the reactor at any time. 
  • We also want to offer an interface that allows users to program parameters such as the amount of nutrients provided and the rate at which these are added.
  • Many devices can be used to regulate environmental elements such as temperature, oxygen concentrations, pH, cell mass and essential nutrients levels.

14. Fermenter using Computer

  • Fermentors can be paired with semi-automatic and automated computers to improve process efficiency, data collection, and monitoring.
  • Students will have more information because computers are used in fermenters. The output of each fermentation chamber will be visible to students. Students will be able view temperature and progress of each fermenter, keep track of activity and compare results between batches. This will help them understand how microbiology works at every stage of the process.
  • Although the fermenter’s computer cannot be used continuously, some users claim that it can do a decent job maintaining temperature stability if it is switched off between batches.
  • The fermenter is a computer-controlled device that monitors fermentation activity and automatically adjusts pH levels. It also pumps CO2 into the mixture to maintain a constant level.

Classification of Bioreactor

The different types of fermentors are the continuous stirred tanks including airlift, the fluidized bed membrane fermenter, photobioreactor along with bubble column fermenters.

1. Continuous Stirred Tank Bioreactors 

Its Continuous Stirred Tank bioreactor is the most traditional design and is the most frequently utilized bioreactor. Many manufacturing facilities and FDA approved manufacturing processes for biopharmaceuticals use bioreactors in the stirred tank. The process of scaling-up from laboratory-scale to production systems is also designed around this concept too. The bioreactor is cylindrical and has either a bottom or top fixed rotating mixer. The typical aspect ratio is between 3 and 5.

  • In the Continuous Stirred Tank Bioreactor the contents of the vessel will no more change with the time. This applies to the encapsulation of microorganisms and the amount of elements of the medium within the fermentor.
  • Stable state conditions can be obtained using one of two methods: Chemo statically or by Turbid principles , which can be used to regulate your flow speed.
Continuous stirred tank fermentor
Continuous stirred tank fermenter | Source: https://upload.wikimedia.org/wikipedia/commons/thumb/b/be/Agitated_vessel.svg/342px-Agitated_vessel.svg.png

Features of Stirred Tank Bioreactors

  • The microbial reactors are equipped with impellers that create agitation. They also usually contain baffles on the walls to stop vortexing of the liquid.
  • Mechanical stress is high on the shaft of the stirrer, seals and bearings.
  • Bioreactors used to grow animal cells generally do not include baffles (to lessen the amount of turbulence).
  • The aspect ratio (height-to-diameter ratio) of the vessel is usually 3-5 for microbial cultivation, however it typically lower than 2 in the culture of animal cells.
  • Gas is sucked in the bottom by an insulated pipe ring.
  • Impellers of various types (Rustom disc concave bladed, marine propeller, etc.) are used.

Working Mechanism of Stirred Tank Bioreactors

  • In bioreactors with stirred tanks, it is possible to add air into the medium under pressure using an instrument called a sparger.
  • The sparger could be a ring with a number of holes or a tube having only one orifice.
  • The sparger in conjunction together with the impellers (agitators) allows for a better gas distribution throughout the vessel.
  • The bubbles produced by the sparger are crushed down to smaller ones through impellers and scattered across the medium.
  • This creates an even and uniform environment within the bioreactor. This allows the bioprocess to run efficiently.
  • The bioprocess continues to produce the desired end product through the vent.

Advantages of Stirred Tank Bioreactors

  • Continuous operation.
  • Excellent temperature control.
  • It is easy to adapt easily to easily adapt to.
  • Control of parameters is good and also the environmental conditions.
  • The simplicity of construction 6. Flexible and low operating (labor) costs and investment requirements.
  • Clean and easy to maintain.
  • can handle the highest concentrations thanks to its high heat transfer.
  • Efficacious gas transfer to developing cells, and mixing of contents.

Disadvantages of Stirred Tank Bioreactors

  • The requirement for bearings and shaft seals.
  • Limitation of size by motor size as well as shaft length and weight.
  • The problem of foaming can be a major one.
  • Power consumption is increased because of the Mechanical pressure pumps.

Application of Stirred Tank Bioreactors

  • The most effective continuous methods to date have relied on the yeast and bacteria where the most desired products are cells.
  • Production of the primary metabolites, enzymes and amino acids.
  • The process of producing alcohol(product evidently linked with growing or energy-producing mechanisms).
  • The most popular is the process of activated sludge employed in the wastewater treatment industries.

2. Bubble column bioreactors 

The bubble column is employed in numerous chemical, petrochemical and biochemical industries. They are easy in construction, simple maintenance and operate at a low cost. They have a cylindrical shape with a ratio of 4:6 (height:diameter proportion) and at the base of the column, air and gas are introduced through perforated pipes or plates or a metal micro porous sparger. The rate of flow of gas or air is monitored to ensure proper mixing or transfer of O2 is accomplished. Perforated plates are inserted into the fermentor in order to enhance the performance that of the unit.

Bubble column fermentor
Bubble column fermentor | Source: https://upload.wikimedia.org/wikipedia/commons/thumb/9/93/Bubble_column.svg/1200px-Bubble_column.svg.png

Features of Bubble column bioreactors 

  • The ratio for height-to-diameter is usually between 4-6.
  • Gas is sucked at the bottom by perforated pipes or plates , or metal spargers with porous materials.
  • O2 transfer, mixing , and other performance parameters are affected mostly by the gas flow rate as well as the rheological characteristics of the gas.
  • Mixing and mass transfer could be improved by putting perforated plates, or baffles with vertical sides within the vessel.
  • Doesn’t contain any draft tubes.

Mechanisms of Bubble column bioreactors 

  1. In the bioreactor bubble column the gas or air is introduced into the bottom of the column by perforated pipes, plates, or through metal micro porous spargers. This creates an unstable stream that allows gas exchange.
  2. The flow rate of gas or air affects the performance factors O2 transfer mixing.
  3. The bubble column bioreactors can be equipped with perforated plates for improved the efficiency.
  4. The reactants are compressed by a finely dispersed catalyst , and so create the product using the process of fermentation.

Advantages of Bubble column bioreactors 

  • High volumetric efficiency and outstanding heat management.
  • Greater utilization of the plate’s area as well as flow distrubution.
  • Self-regulating.

Disadvantages of Bubble column bioreactors 

  • Inefficient compared to other bioreactors.
  • Doesn’t have draft tube
  • A higher consumption of catalysts that the bed fixed
  • Installation costs are higher, and the design is difficult to create

Applications of Bubble column bioreactors 

  • The reactor is used extensively for the cultivation of herring-sensitive organisms. E.g. Plant cells and mould
  • Chemical and pharmaceutical production.
  • Also, for fermentation processes.

3. Air-lift bioreactors

Air-lift bioreactors are like bubble column reactors, however they differ in that they have draft tubes. It is an internal tube (this kind of bioreactor for airlift is known as “air-lift bioreactor with an internal loop”) or an external tube (called “air-lift bioreactor with an external loop”), which enhances circulation and oxygen transfer , and also equalizes the shear force in the reactor.

  • The internal loop airlift bioreactor consists of one container that has an internal draft tube that allows for internal channels for liquid circulation. The bioreactors are straightforward in their design, and feature a volumes and circulation that is at a predetermined rate of fermentation.
  • The external loop airlift bioreactor has an external loop that allows the liquid flows through distinct independent channels.
  • They can be modified to meet the demands of various fermentations.
  • In general, bioreactors that use airlift are more effective as bubble column systems, especially for the more dense suspensions of microorganisms.
  • This is due to the fact that in these bioreactors the mixing of the ingredients is superior to bubble columns.
Airlift fermenter
Airlift fermenter | Source: https://www.researchgate.net/profile/Tomas-Branyik/publication/277047195/figure/fig1/AS:[email protected]/Schematic-representation-of-the-airlift-bioreactor.png

Features of Air-lift bioreactors

  • Two zones are separated The zone that is sparged is referred to as the riser and the zone that is fueled by no gas is called the downcomer.
  • The density in the region of riser is less than in the downcomer area which causes the circulation (so the circulation will be enhanced when there is less or no gas in the region down).
  • For maximum mass transfer the riser-to-downcomer cross-sectional area ratio should fall between 1.8 to 4.3.
  • The rate of circulation of liquid increases by an increase in the square of an airlift system. Thus the reactors are built with large aspect ratios.
  • A gas-liquid separator located in the head-zone could reduce gas carry-over to the downstream and, consequently, improve the capacity of the

Mechanisms of Air-lift bioreactors

  1. The performance of the bioreactors with airlift depend on pumping (injection) by air as well as the circulation of liquid.
  2. It differs than that of the Stirred tank bioreactor, which requires the heating coat or plate around the tank to create a an insulated bioreactor. It is obvious to see that Airlift bioreactor is more efficient in removing heat in comparison to the Stirred tank.

Two-stage airlift bioreactors

Two-stage airlift bioreactors
(b) Two-stage airlift bioreactors | Source: https://www.researchgate.net/profile/Marcos-Gonzalez-Llanes/publication/316598115/figure/fig1/AS:[email protected]/Airlift-bioreactor-with-a-internal-and-with-b-external-circulation-loop_Q640.jpg
  • Two-stage airlift bioreactors are utilized for the formation of temperature-dependent batches of substances.
  • Cells that are growing from an individual bioreactor (maintained at 30degC) are transferred to another bioreactor (at temperature of 42degC).
  • There is a need for the airlift bioreactor with two stages as it is difficult to quickly raise the temperature from 30degC up to 42degC in an identical vessel.
  • Each of the bioreactors is equipped with valves and are connected via pumps and transfer tubes.
  • The cells are produced within the bioreactor, and the bioprocess itself is carried out in the second one.

Advantages of Air-lift bioreactors

  • Highly efficient in terms of energy efficiency and productivity. are similar to stirred tank bioreactors.
  • Simple design, no moving parts or an agitator to ensure lower maintenance and less chance of a defect.
  • Easier sterilization (no agitator shaft parts)
  • Low energy requirement vs. stirred tank clearly doesn’t require energy for the moving components (agitator shaft).
  • More efficient heat removal vs. stirred tank In the Airlift bioreactor, there is no need for the heat plate in order to control the temperature since the Draught-Tube that is within the bioreactor is able to function as an the internal exchanger of heat.

Disadvantages of Air-lift bioreactors

  • More air flow and higher pressures are needed.
  • The agitation in the Airlift bioreactor is controlled by the supply air . This allows it to regulate the supply air, and the required pressure.
  • the greater pressure of air required, then more energy consumption required and more costs must be paid.
  • Ineffectively break the foam when foaming takes place.
  • There aren’t any bubble breakers, there aren’t any blades used to break the bubbles that result from in the supply of air (sparger).

Applications of Air-lift bioreactors

  • The reactor is commonly used in the culture of shear sensitive organisms.
  • Airlift bioreactors are commonly employed for aerobic bioprocessing technology. They ensure a controlled liquid flow in a recycle system by pumping.
  • Due to high efficiency, airlift bioreactors are sometimes preferred e.g., methanol production, waste water treatment, single-cell protein production.

4. Packed Bed Reactors

A bed of solid particles, with biocatalysts on or within the matrix of solids, packed in a column constitutes a packed bed bioreactor. The solids used may be porous or non- porous gels, and they may be compressible or rigid in nature. A nutrient broth flows continuously over the immobilized biocatalyst. The products obtained in the packed bed bioreactor are released into the fluid and removed. While the flow of the fluid can be upward or downward, down flow under gravity is preferred.

  • The concentration of the nutrients (and therefore the products formed) can be increased by increasing the flow rate of the nutrient broth.
  • Because of poor mixing, it is rather difficult to control the pH of packed bed bioreactors by the addition of acid or alkali.
  • However, these bioreactors are preferred for bioprocessing technology involving product-inhibited reactions.
  • The packed bed bioreactors do not allow accumulation of the products to any significant extent.
Packed bed fermentor
Packed bed fermentor | Source; https://ars.els-cdn.com/content/image/3-s2.0-B9780444636638000094-f09-02-9780444636638.jpg

Features of Packed Bed Reactors

  • A bed of particles are confined in the reactor. The biocatalyst (or cell) is immobilized on the solids which may be rigid or macroporous particles.
  • A fluid containing nutrients flows through the bed to provide the needs of the immobilized biocatalyst. Metabolites and products are released into the fluid and removed in the outflow.
  • The flow can be upward or downward. If upward fluid is used, the velocity can not exceed the minimum fluidization velocity.

Advantages of Packed Bed Reactors

  • Higher conversion per unit mass of catalyst than other catalytic reactors
  • Low operating cost.
  • Continuous operation.
  • No moving parts to wear out.
  • Catalyst stays in the reactor 6. Reaction mixture/catalyst separation is easy
  • Design is simple
  • Effective at high temperatures and pressures

Disadvantages of Packed Bed Reactors

  • Undesired heat gradients.
  • Poor temperature control.
  • Difficult to clean.
  • Difficult to replace catalyst.
  • Undesirable side reactions.

Application of Packed Bed Reactors

  • These are used with immobilized or particulate biocatalysts.
  • High conservation per weight of catalyst than other catalytic reactors. Thus mostly preferred fermentor.
  • Used is waste water treatment.

5. Fluidized Bed Bioreactor

Fluidized bed bioreactor is comparable to bubble column bioreactor except the top position is expanded to reduce the velocity of the fluid. The design of the fluidized bioreactors (expanded top and narrow reaction column) is such that the solids are retained in the reactor while the liquid flows out. These bioreactors are suitable for use to carry out reactions involving fluid suspended biocatalysts such as immobilized enzymes, immobilized cells, and microbial flocks.

  • This is a characteristic of beds of regular particles suspended in an up flowing liquid stream.
  • If an additional gas phase is involved, there is a tendency for the particles in the bed to become less evenly distributed.
  • The fermentor consists of a vertical cylinder with an aspect ratio is 10:1.
  • At the top of the tower a separator is provided to induce the gas bubbles produced by the reaction, to coalesce and escape from the liquid phase.
  • There are two important features of the beds of mixed particle sizes: (i) The increase in porosity from the bottom to the top of the bed, and (ii) The decreased particle movement when compared with beds containing particles of constant size.
Fluidized-bed fermentor
Fluidized-bed fermentor | Source: https://upload.wikimedia.org/wikipedia/commons/thumb/9/91/Fluidized_Bed_Reactor_Graphic.svg/1200px-Fluidized_Bed_Reactor_Graphic.svg.png

Features of Fluidized Bed Bioreactor

  • Suitable for reactions involving a fluid-suspended particulate biocatalyst such as immobilized enzyme and cell particles.
  • Similar to the bubble column reactor except that the top section is expanded to reduce the superficial velocity of the fluidizing liquid to a level below that needed to keep the solids in suspension.
  • Consequently, the solids sediment in the expanded zone and drop back, hence the solids are retained in the reactor whereas the liquid flows out.
  • The properties include:
    • Extremely high surface area contact between fluid and solid per unit bed volume
    • High relative velocities between the fluid and the dispersed solid phase.
    • High levels of intermixing of the particulate phase.
    • Frequent particle-particle and particle-wall collisions.

Mechanism of Fluidized Bed Bioreactor

  • For an efficient operation of fluidized beds, gas is spared to create a suitable gas-liquid-solid fluid bed.
  • It is also necessary to ensure that the suspended solid particles are not too light or too dense (too light ones may float whereas to dense ones may settle at the bottom), and they are in a good suspended state.
  • Recycling of the liquid is important to maintain continuous contact between the reaction contents and biocatalysts. This enable good efficiency of bioprocessing.

Advantages of Fluidized Bed Bioreactor

  • Uniform Particle Mixing
  • Uniform Temperature Gradients
  • Ability to Operate Reactor in Continuous State

Disadvantages of Fluidized Bed Bioreactor

  • Increased Reactor Vessel Size
  • Pumping Requirements and Pressure Drop
  • Particle Entrainment
  • Lack of Current Understanding
  • Erosion of Internal Components
  • Pressure Loss Scenarios

Application of Fluidized Bed Bioreactor

  • These reactors can utilize high density of particles and reduce bulk fluid density.
  • Fluidized beds are used as a technical process which has the ability to promote high levels of contact between gases and solids.
  • In a fluidized bed a characteristic set of basic properties can be utilized, indispensable to modern process and chemical engineering
  • The food processing industry: fluidized beds are used to accelerate freezing in some individually quick frozen (IQF) tunnel freezers.
  • The fluid used in fluidized beds may also contain a fluid of catalytic type.
  • Fluidized beds are also used for efficient bulk drying of materials.
  • Fluidized bed technology in dryers increases efficiency by allowing for the entire surface of the drying material to be suspended and therefore exposed to the air.

6. Photobioreactor

Although some models of photobioreactors are planned, only few of them can utilize biomass from algae. The photobioreactors array from laboratory to industrial scale models and more over they are classified into;

  1. closed photobioreactor,
  2. open ponds,
  3. flat-plate,
  4. horizontal/serpentine tubular airlift, and
  5. inclined tubular photobioreactors.

The introduction of more complicated cultivating methods of microalgae with higher production value and capable of providing sterile conditions, which is accessible by different types of closed photobioreactors, applied outdoors. In general, laboratory-scale photobioreactors are artificially illuminated using fluorescent or other light lamp distributors.

Some of these reactors include open ponds, flat-plate, tubular, bubble column, airlift column, helical tubular, conical, torus, stirred-tank, seaweed type photobioreactors. The only disadvantage which limits their practical application in algal mass cultures is mass transfer that is required for proper processing of mass algal cultures. The algal biomass is mainly used in water treatment, in aquaculture, production of fine chemicals and useful supplements in humansand animals, for biosorption of heavy metals and CO2 fixation.

Photobioreactor
Photobioreactor | Source: https://ars.els-cdn.com/content/image/3-s2.0-B9780124095489093738-f09373-04-9780124095489.jpg

Advabtages of Photobioreactor

  • Higher productivity
  • Large surface-to-volume ratio
  • Better control of gas transfer.
  • Reduction in evaporation of growth medium.
  • More uniform temperature. Powerpoint Templates

Disadvantages of Photobioreactor

  • Capital cost is very high.
  • The productivity and production cost in some enclosed photobioreactor systems are not much better than those achievable in open-pond cultures.
  • The technical difficulty in sterilizing Powerpoint Templates

Application

  • The main applications of photobioreactors are in photosynthetic processes, involving vegetable biomass growth or microalgae growth under restricted conditions.

7. Membrane Bioreactor

Membrane bioreactors (MBR) are been used since 90s. It basically combines traditional treatment system with filtration via membranes resulting in removal of organic and suspended solid matters that also removes high level of nutrients.

Membranes in the MBR system are submerged in an aerated biological reactor. The pore size of the membrane ranges from 0.035 microns to 0.4 microns.

However, membrane fouling is a chief obstacle to the extensive application of MBRs. Moreover large-scale use of MBRs in waste water treatment will involve a notable worthy decrease in price of the membranes

Membrane bioreactor
Membrane bioreactor | Source: https://upload.wikimedia.org/wikipedia/en/thumb/c/c0/MBRvsASP_Schematic.jpg/550px-MBRvsASP_Schematic.jpg

Advantages

  • The loss of enzyme is reduced.
  • Enzyme lost by denaturation can be made up by periodic addition of enzyme.
  • Substrate and enzyme can be easily replaced.

Applications

  • The use has widely extended and is rapidly growing both in research and commercial applications.
  • Several variations of MBR systems have evolved and presently, an MBR system is widely used in treatment of waste water from several sources.

8. Rotary Drum Bioreactor

The rotating-drum bioreactors comprise a horizontally rotating drum, that may or may not have a paddle mixer and rotates slowly for proper mixing of fermentation substrate. For scaling-up purposes, many assumptions need to be made concerning the rotating-drum bioreactors.

  • The bioreactor is cylindrical (with a length L and diameter D) and partially filed;
  • since the solid materials are degraded during fermentation, it will be considered that only the density of the bed is affected;
  • the dry gas remains constant in the headspace;
  • the gas flow rates remain the same between the inlet and the outlet of the bioreactor;
  • the solid particles and gas phase are in equilibrium (moisture and thermal) and the diffusion from the axe is negligible.
Rotary Drum Bioreactor diagram
Rotary Drum Bioreactor diagram | Source: https://d3i71xaburhd42.cloudfront.net/a543ef33e6a3689a346442341d0b357bba640397/3-Figure1-1.png

Advantages of Rotary Drum Reactor

  • High oxygen transfer.
  • Good mixing facilitates better growth and impart less hydrodynamic stress.

Disadvantages of Rotary Drum Reactor

  • Difficult to scale up.

9. Mist Bioreactor

Mist bioreactors are hydraulically-driven bioreactors for root cell cultures (see plant cell cultures). Their key feature is a disposable bag (single-use or multi-use) in which the roots are immobilized and aerated on a frame. A two-component jet or an ultrasonic atomizer befogs the culture medium which gets distributed around the supporting frame. The largest disposable mist-bioreactors are currently the 60 liter systems produced by former ROOTec.

Mist Bioreactor diagram
Mist Bioreactor diagram | Source: https://www.researchgate.net/profile/Nivedita-Patra/publication/316994372/figure/fig1/AS:[email protected]/Schematic-of-Mist-Bioreactor.png

Advantages of Mist Bioreactor

  • High oxygen transfer.
  • Hydrodynamic stress elimination.
  • Low production cost.

Disadvantages of Mist Bioreactor

  • Mesh trays and cylindrical stainless steel meshes are required.

10. Immobilized cell bioreactor

  • The immobilized cell reaction (ICR) operates in accordance with the principle of immobilization. The process of limiting the cell’s mobility within a certain space.
  • The interaction between hydrogen and hydrophobic and the formation of salt bridges between the adsorbent as well as the cells are the driving factors for immobilization.
  • In general, immobilization can be divided into two kinds which are passive and active.
    • In the passive model cells, they are stuck naturally in the matrix of solids, leading to the creation of biofilm.
    • In active techniques Immobilization can be induced by a physical or chemical method. This can occur in a variety of ways like attachment, entrapment gathering, and confinement.
  • The management of cells that are immobilized inside the reactor is difficult since these cells are not dependent on liquid or gas phases.
  • The performance of these immobilized cells may be enhanced by a an appropriate design of the reactor.
  • To design a good reactor various criteria must be considered.
  • The amount of shear forces must be minimal.
  • The reactor should be able to hold the maximum amount of particles.
  • The heat and mass transfer must be kept in check.
  • Immobilization is usually done with sodium alginate (2 percent) where cell beads immobilized are made.
  • The substrate or nutrient is introduced into a reaction vessel that includes the cells that are immobilized, they interact and then create a product and a byproduct.
  • In the majority of cases, ICRs are created with two stages. These include an enricher stage as well as an a stripper stage. This stage is utilized to remove and treat the byproducts when they are they are present in large amounts
  • After the process of fermentation is complete then the inner and outside surface of the beads will be examined to determine whether the cells initially resided in the inner part of the beads but as time passes, the cells move and are located on the outside of the beads.
  • ICRs are employed in the industry of fermentation in which the production and growth phases are easily separated.
Immobilized cell bioreactor diagram
Immobilized cell bioreactor diagram | Source: https://www.researchgate.net/publication/329804458/figure/fig1/AS:[email protected]/Immobilized-cell-bioreactor-system-with-infi-nite-recirculation.png

Advantages

  • The harvesting of the product you want is a breeze and requires any effort if the substances are released in the medium

Disadvantages

There are some restrictions in the ICR like;

  • A limitation in mass transfer due to the intraparticle diffusion resistance, which restricts the ability of the substrate to get to cells. This type of problem occurs in aerobic reactions, where there is an oxygen shortage to cells, resulting in lower reactor performance.
  • Another issue is inhibition of the product in which the concentration of the product is reduced within the inner core and, consequently, the rate of reaction is also decreased.

11. Activated sludge bioreactor

When an active sludge bioreactor is used the proportion of microbes as well as the amount of oxygen and substrate are all the same as the reactor is equipped with a homogeneous tank in which the feed is dispersed throughout the. In the active sludge with plug flow, the reactor has an extended channeled inlet which restricts any growth in microorganisms as well as improves the ability of sludge to settle.

Step feed reactors are an improvement that is a variation of the plug flow system, in where sewage is injected in multiple points in the Aeration tank. Food-to-microbes (F/M) ratio of the step feed reactor is significantly higher than those using the plug flow. Oxidation ditches are a different kind that is an activated sludge-based bioreactor. It uses a modified activated sludge treatment procedure employing long SRTs to eliminate organic matter that is biodegradable. It is fitted with an aeration rotor , or brushes to ensure adequate circulation and Aeration. The reactor is similar to the whole mix reactor.

Activated sludge bioreactor
Activated sludge bioreactor | Source: https://www.suezwaterhandbook.com/var/degremont/storage/images/procedes-et-technologies/procedes-biologiques/procedes-a-cultures-libres/types-et-configurations-des-reacteurs-de-boues-activees/33289-30-eng-GB/activated-sludge-reactor-type-and-configurations.png

Mechanism/Process of activated sludge reactor

The activated sludge system consists of:

  • water being pumped to the aeration tank an microbial suspension
  • solidliquid separation,
  • the disposal of treated waste and
  • the remaining biomass is returned to the Aeration tank.

In the process of activated Sludge in the activated sludge process, sewage with organic matter is pumped to the tank for aeration that is then metabolized because it is filled with microorganisms. The organic matter that is metabolized is converted to CO2 and water in order to generate energy. A portion of the cells that have formed during the process are eliminated from the process in sludge. The remaining sludge returns to an aeration tank in which this process is carried on.

Application

  • The reactor is employed in the treatment of wastewater and sewage.
  • This particular reactor is used to produce biofuels such as biogas, bioethanol and so on. such as biofuels that are made by milk-based waste.

Advantage

  • The reactor can be operated with high organic loading rates.

Limitation

  • This reactor is a major consumer of energy and also capital.
  • The operating expenses are high.

11. Immersed membrane bioreactor

Immersed membrane bioreactors (IMBRs) are a form of membrane bioreactor where two fundamental principles, suspended growth bioreactor and the separation are performed in tandem to create an effect synergistically. The IMBR is built on a filtration system which has membranes that are encased within the biomass. The filtration is accomplished through the application of a vacuum on the membrane’s interior. The membranes are placed in the bioreactor, or in an additional tank. The membranes may be hollow, flat, or a mixture of both. An online backwash system is integrated to reduce the possibility of surface fouling. Additionally, aeration is needed to ensure air scour and lessen the possibility of fouling. Membrane reactors with hollow fibers are typically used in large-scale and medium-sized facilities.

Process of immersed membrane bioreactor

The procedure of the IMBR relies on five fundamental components. They are:

  1. it’s membrane and its structure and its maintenance of permeability
  2. the feedwater, their properties and pretreatment
  3. Aeration of the bulk biomass and the membrane;
  4. Sludge withdrawal and residence time and
  5. Bioactivity and the nature of biomass.

Advantage

  • Low energy consumption
  • lower capital costs.

Application

  • This kind of bioreactor is mainly used to treat textile and tannery wastes along with wastewaters and for the reuse of aquaculture wastes. 

12. Reverse membrane bioreactor

Bioreactors with reverse membranes (rMBRs) are a unique method of combining the traditional membrane bioreactor as well as cell encapsulation methods wherein cells are separated from feed and then encased within the form of a membrane which is then fixated within the reactor. The basic principle behind this type of system is similar the membrane reactor with an immersed design in which that membrane gets submerged within the reactor. However, within the rMBR microorganisms are enclosed inside membrane layers which create an Sachet.

The integrated permeate channels (IPC) along with packed columns are two other types of membrane setting. The choice of the configuration for the membrane is based on the product you want to produce and the byproducts it produces. For example, a multilayer membrane column is utilized to create biogas, and for the production of ethanol it is an IPC membrane-configuration-based reactor is utilized. A majority of synthetic membranes are utilized to allow certain nutrients to flow through, for example, in plants where the cytoplasm is separate from the other components of the cell.

The goal of surrounding cells within this membrane layer is increasing cell’s density and tolerance. For example, the yeast cell concentration can be increased as high as 309 grams/L. Because of this dense concentration the cells could be exposed to greater stress because of the deficiency of nutrition. This results in an immune response to stress through the expression of stress-related genes.

Reverse membrane bioreactor
Reverse membrane bioreactor | Source: https://ars.els-cdn.com/content/image/1-s2.0-S0734975016300660-gr4.jpg

Mechanism

In general, in rMBRs, the diffusion mechanism is carried out in three distinct stages.

  1. The dispersion of the substrate from the feed side of the membrane’s surface, and the reverse process to the product
  2. the transport of substances (substrate or metabolites) through the membrane and
  3. the dispersal of feed and products on the cell’s side via biofilm.

The rate at which compounds diffuse through the membrane is influenced by different parameters, including hydrophilicity, tortuosity and porosity and concentration gradient etc.

What is the Difference between conventional membrane bioreactor and reverse membrane bioreactor?

Conventional membrane bioreactor

The design of the traditional membrane bioreactor is either internal or external. The pressure gradient functions as an accelerating force. The mechanism for mass transfer occurs via the process of convection as well as diffusion. Microbial or other types in living cells get fed with the feed , and they are able to freely circulate within the medium.

Reverse membrane bioreactor

For RMBR, it’s an type of bioreactor with an embedded structure in which the concentration gradient functions as a force driving the process and the mechanism for mass transfer occurs by diffusion. Living cells are not able to be fed alongside the feed. They have to be isolated and kept inside their membranes.

Application of Bioreactor

  • A bioreactor could be a reference to the device or system that is designed to produce tissues or cells within an environment of cell cultivation.
  • They are currently being developed to be used in tissue engineering.
  • Bioreactors are modular and performs all process of fermentation in one enclosed environment.
  • Bioreactors play a crucial part in bioprocess.
  • Bioreactors with stirred tanks are often employed in the process of fermentation.
  • Because of the simplicity of technology and better yield, solid state bioreactors are extensively used in the industry.
  • Ethanol is produced by Saccharomyces cerevisiae, a fungus that lives.
  • Organic acids e.g. butyric acid and acetic acid are produced in bioreactors by Eubacterium limosum.
  • Thienamycine an antibiotic that is also made in a bioreactor.
  • The production of glucomylase occurs in Auerobasidium pullulans, a bioreactor.

FAQ

What is bioreactor?

A bioreactor is an apparatus for growing cells under controlled conditions.

What is a bioreactor used for?

A bioreactor is an apparatus that allows bacteria growth and fermentation at controlled conditions. They are commonly used in industry to manufacture pharmaceuticals and foodstuffs such as beer and wine. It is an industrial device that uses microorganisms such as bacteria to break down organic materials into useful chemicals and energy, like hydrogen gas for fuel cells. Bioreactors can be found in wastewater treatment plants, producing pharmaceuticals, and food processing facilities.

How does a bioreactor work?

A bioreactor works by pumping nutrients into a solution of water and microorganisms, such as bacteria, algae, yeast, fungi, or protozoa. The organisms consume the nutrients until they reach a certain density, at which point they produce additional waste products. Bioreactors can be used to produce hydrogen for fuel cells, ethanol from sugarcane molasses, or synthetic chemicals. An example of a typical bioreactor setup would include: an air compressor, a reservoir of water containing microbes, a pump, a tube, diffuser plates that spread out the flow of nutrient solution, and monitoring equipment.

What does a bioreactor do?

A Bioreactor is used for culturing cells within the lab. The growth of cells in a bioreactor is much faster compared to those grown outside in Petri dishes or flasks. Also, the ability to control the temperature and pH level within a bioreactor enables scientists to study cell growth under controlled conditions.

References

  • Principles and Applications of Fermentation Technology, Arindam Kuila, Vinay Sharma, DOI:10.1002/9781119460381
  • Mist reactors: Principles, comparison of various systems, and case studies, January 2008
  • Chisti, Y. (2006). Bioreactor design. In C. Ratledge & B. Kristiansen (Eds.), Basic Biotechnology (pp. 181-200). Cambridge: Cambridge University Press. doi:10.1017/CBO9780511802409.009
  • Working principle of typical bioreactors, P.JaibibaS.Naga VigneshS.Hariharan, https://doi.org/10.1016/B978-0-12-821264-6.00010-3
  • Scaling-up and Modelling Applications of Solid State Fermentation and Demonstration in Microbial Enzyme Production Related to Food Industries: An Overview, 2016, DOI:10.1201/9781315368405-29
  • Anthony H. Rose (1985). Principles of fermentation technology: by P. F. Stanbury and A. Whitaker, Pergamon Press, 1984. doi:10.1016/0167-7799(85)90016-2 
  • https://www.engr.colostate.edu/CBE101/topics/bioreactors.html
  • https://www.researchgate.net/profile/Tomas-Branyik/publication/277047195/figure/fig1/AS:[email protected]/Schematic-representation-of-the-airlift-bioreactor.png
  • https://www.slideshare.net/PoorvajaGanesan/bioreators
  • http://a-z-singleuse.org/singleuse/en/Glossary/M/Mist+bioreactors.html#:~:text=are%20hydraulically%2Ddriven%20bioreactors%20for,and%20aerated%20on%20a%20frame.
  • https://www.slideshare.net/kanishjay/bioreactors-18087061
  • https://www.slideshare.net/ajithnandanam/types-of-bioreactors-fermenters
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