Bioreactor: Design, Principle, Parts, Types, Uses, Diagram

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A bioreactor serves as a fermentation vessel, essential for various chemical and biological reactions. It is designed as a closed container with systems for aeration, mixing, temperature and pH adjustments, along with drainage to eliminate waste biomass and product byproducts.

Key functionalities of a bioreactor include:

1. Agitation (mixing of cells and medium), 

2. Aeration (for aerobic fermentors); facilitating O2 supply,

3. Regulation of critical factors such as temperature, pH, pressure, aeration, nutrient supply, and liquid levels.

4. Sterilization and upkeep of sterility, 

5. Withdrawal of cells/medium

Bioreactors play a pivotal role in generating biomass, metabolites, and antibiotics.

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Bioreactor Design

• The design and operational mode of a bioreactor are contingent upon the organism choice, optimal environmental conditions for product generation, product value, and the required production scale.

• Effective bioreactor design contributes to heightened productivity and superior product quality at reduced costs.

• The structure of a bioreactor incorporates various features such as an agitation system, oxygen supply mechanism, foam control system, temperature and pH control systems, sample ports, and systems for cleaning and sterilization.

• Materials used in bioreactor construction must possess the following essential characteristics:

  • Non-corrosive properties.

  • No introduction of toxins into the fermentation medium.

  • Resistance to steam sterilization.

  • Tolerance to high pressure and pH fluctuations.

• Depending on the application, bioreactors can range widely in size.

• They can be tailored for small-scale fermentations or large-scale industrial applications, from micro-scale (a few mm³) to lab-scale (1-50 L) and pilot (0.3-10 m³) to plant scale (2-500 m³) for larger volumes.

Bioreactor Principle

• A bioreactor is the centerpiece of any biochemical process, providing an environment for microorganisms to thrive and produce metabolites, facilitating the conversion of substrates into desirable end products.

• Reactors can be engineered based on the specific growth requirements of the employed organisms.

• Bioreactors can be adapted to transform biological materials into preferred end products.

• They are instrumental in producing a variety of enzymes and other biocatalytic processes.

Parts of the Bioreactor and Their Function

• These reactors are designed to maintain essential parameters such as flow rates, aeration, temperature, pH, foam control, and agitation speed.

• The capacity to monitor and control these variables is limited by the quantity of sensors and control elements integrated into the bioreactor.

• Additional considerations must be taken into account before designing a fermenter, as depicted below.

Figure: Bioreactor. Image Source: Kuila, A., & Sharma, V. (). Principles and applications of fermentation technology. John Wiley & Sons, Inc.

1. Fermenter Vessel

• A fermenter is designed as a large cylinder, closed at both ends, interconnected with multiple pipes and valves.

• The vessel is engineered to function under controlled conditions.

• Common materials for fermenter vessels include glass and stainless steel.

• Glass vessels are typically utilized in small-scale applications due to their non-toxic and corrosion-resistant properties.

• In contrast, stainless steel vessels are preferred for large-scale operations due to their ability to withstand pressure and resist corrosion.

2. Heating and Cooling Apparatus

• The exterior of the fermenter vessel features a cooling jacket, which encases the vessel and supplies cooling water.

• Thermostatically controlled baths or inner coils are typically employed for heating, while silicone jackets help dissipate excess heat.

• A cooling jacket plays a vital role in sterilizing the nutrient medium and counteracting the heat generated during fermentation.

3. Aeration System

• An aeration system is crucial for maintaining appropriate aeration and oxygen availability within the culture.

• It incorporates two distinct aeration devices: sparger and impeller, ensuring optimal aeration within the fermenter.

• The agitation serves two primary functions:

  • Facilitating the mixing of gas bubbles throughout the liquid culture medium

  • Ensuring proper distribution of microbial cells in the medium for uniform nutrient access.

4. Sealing Assembly

• The sealing assembly secures the stirrer shaft to ensure effective agitation.

• There are three predominant types of sealing assemblies in the fermenter:

  • Packed gland seal

  • Mechanical seal

  • Magnetic drives

5. Baffles

• Baffles are incorporated into fermenters to prevent vortex formation and enhance aeration.

• These consist of metal strips attached radially to the internal wall of the fermenter.

6. Impeller

• Impellers are utilized for maintaining a consistent suspension of microbial cells in various nutrient media.

• These are constructed with impeller blades connected to a motor situated on the lid.

• Impeller blades play a significant role in reducing air bubble size and ensuring uniform distribution within the fermentation media.

• Variable impellers used in fermenters are classified as follows:

  • Disc turbines

  • Variable pitch open turbine

7. Sparger

• A sparger is employed for introducing sterile air into the fermentation vessel, ensuring adequate aeration.

• The sparger pipes have small holes (5-10 mm) through which pressurized air is released.

• Three sparger types include:

  • Porous sparger

  • Nozzle sparger

  • Combined sparger/agitation system

8. Feed Ports

• Feed ports are utilized for adding nutrients and adjusting acid/alkali levels within the fermenter. 

• These ports consist of tubes made from silicone material.

• In-situ sterilization is executed prior to the addition or removal of products.

9. Foam-Control

• Minimizing foam levels is crucial to prevent contamination, making this an important function of the fermentor.

• Foam control is achieved through two components: a foam sensing unit and a control unit.

• A foam-control device is installed at the top of the fermentor, equipped with an inlet leading into the vessel.

10. Valves

• Valves regulate the movement of liquid within the fermentor.

• There are five principal types of valves used:

  • Globe valve

  • Butterfly valve

  • Ball valve

  • Diaphragm valve

• Furthermore, a safety valve is integrated into the air and pipe layout to maintain functionality under pressure.

11. Controlling Devices for Environmental Factors

• A range of devices is employed to regulate environmental factors, including temperature, oxygen concentration, pH, cell mass, essential nutrient levels, and product concentrations.

12. Use of Computer in Fermenter

• For enhanced operational efficiency, monitoring, and data collection, fermenters are often integrated with modern automated or semi-automated computer systems and databases.

Types of Bioreactor

The bioreactor types commonly utilized across various industries include:

1. Continuous Stirred Tank Fermentor

• A continuous stirred tank bioreactor consists of a cylindrical vessel with a central shaft driven by a motor that accommodates one or more impellers (agitation devices).

• The combination of sparger and impellers enhances gas distribution within the vessel.

• A stirred tank bioreactor can operate continuously with effortless temperature control, cost-effective construction, ease of operation, thus minimizing labor costs and simplifying cleaning procedures.

• It is among the most frequently employed bioreactor types in industrial applications.

Figure: Continuous Stirred Tank Fermentor. Image Source:

Saran, S., Malaviya, A., & Chaubey, A. (). Introduction, scope and significance of fermentation technology.

High Value Fermentation Products

, 1'25. https://doi.org/10./.ch1

2. Airlift Fermentor

• The airlift reactor is primarily used for gas-liquid or gas-liquid-solid interactions, also referred to as a tower reactor.

• This bioreactor operates by segregating the fluid volume into two zones to enhance circulation, oxygen transfer, and force equalization within the reactor.

• In a two-zone system, one zone is sparged with gas (the riser), while the other remains unstirred (the downcomer).

• Airlift bioreactors are applicable for aerobic bioprocessing, allowing for regulated liquid flow within a recycling system using pumps.

• Benefits of this system include a simplistic design free of moving parts or agitators, easy sterilization, reduced energy requirements, and affordability.

Figure: Airlift Fermentor. Image Source:

Kuila, A., & Sharma, V. (). Principles and applications of fermentation technology. John Wiley & Sons, Inc.

3. Bubble Column Fermentor

• A bubble column fermentor is composed of a cylindrical vessel outfitted with a gas sparger that injects gas bubbles into a liquid phase or liquid-solid suspension.

• Gas is introduced at the base of the column via perforated pipes or plates, or metal micro-porous spargers.

• The fluid’s rheological properties and gas flow rates crucially impact oxygen mixing and performance factors.

• To enhance mass transfer, internal devices such as perforated plates, baffles, and corrugated sheet packings can be incorporated within the vessel design.

• Bubble column reactors are straightforward in design, low in maintenance, and economically viable.

• They are widely used in biochemical processes like fermentation and biological wastewater treatment, and they also find applications in numerous chemical, petrochemical, and biochemical industries.

Figure: Bubble Column Fermentor. Image Source:

Kuila, A., & Sharma, V. (). Principles and applications of fermentation technology. John Wiley & Sons, Inc.

4. Fluidized-Bed Fermentor

• Fluidized bed bioreactors encompass packed beds containing smaller particles, alleviating issues related to clogging, high liquid pressure drops, channeling, and bed compaction common in packed bed reactors.

• The catalyst is positioned at the reactor's bottom, with reactants pumped through a distributor to fluidize the bed.

• In these systems, cells are immobilized on small particles that move with the fluid, enhancing mass and oxygen transfer and nutrient accessibility for the cells.

• These bioreactors are effective for processes involving fluid-suspended biocatalysts such as immobilized enzymes and microbial flocs.

• Key advantages include consistent temperature maintenance, simple catalyst replacement and regeneration, continuous operation, and reduced gas-solid contact times, compared to other catalytic reactors.

Figure: Fluidized-Bed Fermentor. Image Source:

Singh, J., Kaushik, N., & Biswas, S. ().

Bioreactors ' Technology & Design Analysis

.

April .

5. Packed Bed Fermentor

• A packed bed fermentor consists of a solid particle bed, featuring biocatalysts on or within the solid matrix.

• This system can operate in submerged mode (with or without aeration) or in trickle flow mode.

• Often utilized in chemical processing applications—absorption, distillation, separation processes—the packed bed reactor is alternatively known as a fixed bed reactor.

• In packed bed bioreactors, air is introduced through a sieve supporting the substrate.

• Benefits include high catalyst conversion rates, straightforward operation, low construction and operational costs, and enhanced contact between reactants and catalysts, capable of functioning under high-temperature and high-pressure conditions.

Figure: Packed Bed Fermentor. Image Source:

Kuila, A., & Sharma, V. ().

Principles and applications of fermentation technology

. John Wiley & Sons, Inc.

6. Photobioreactor

Figure: Photobioreactor. Image Source: Singh, J., Kaushik, N., & Biswas, S. (). Bioreactors ' Technology & Design Analysis. April .

• A photobioreactor is a specialized fermentation unit illuminated by sunlight or artificial lighting.

• These reactors typically consist of glass or transparent plastic tubes or flat panels designed for optimal light reception.

• Centrifugal pumps or airlift pumps can be utilized to circulate the medium through the solar receivers in this type of bioreactor.

• Photobioreactors are generally operated in a continuous mode, with temperatures maintained between 25-40 °C.

• They are primarily used for the photosynthetic culture of microalgae and cyanobacteria, producing compounds like astaxanthin and β-carotene.

Figure: Types of Photobioreactor. Image Source: Singh, J., Kaushik, N., & Biswas, S. (). Bioreactors ' Technology & Design Analysis. April .

7. Membrane Bioreactor

• This system integrates standard treatment with membrane filtration, facilitating the removal of organics, suspended solids, and excess nutrients.

• In this setup, membranes are submerged within an aerated biological reactor, with pore sizes ranging from 0.035 to 0.4 microns.

• Using pure oxygen enhances the efficiency of this bioreactor, yielding high biological treatment rates while allowing for compact control of COD and microorganisms.

Figure: Membrane Bioreactor. Image Source: Kuila, A., & Sharma, V. (). Principles and applications of fermentation technology. John Wiley & Sons, Inc.

Applications of Bioreactor

Significant applications of bioreactors are:

Type of Bioreactor

Applications

Stirred Tank Fermentor

Antibiotics, citric acid, exopolysaccharides, cellulose, chitinase enzymes, laccase, xylanase, pectolytic enzymes, tissue mass culture, lipase, polygalacturonases, succinic acid

Bubble Column Fermentor

Algal culture, chitinase enzymes 

Airlift Fermentor

Antibiotics, chitinase enzymes, exopolysaccharides, gibberellic acid, laccase, cellulase, lactic acid, polygalacturonases, tissue mass culture

Fluid Bed Fermentor

Laccase

Packed Bed Fermentor

Laccase, hydrogen, organic acids, mammalian cells, 

Photobioreactor

Wastewater treatment, water quality management, soil remediation

Membrane Bioreactor

Alginate, antibiotics, cellulose hydrolysis, hydrogen production, water treatment, VOC treatment

Limitations of Bioreactor

Types of Bioreactor

Limitations 

Stirred Tank Fermentor

High shear stress

High power consumption

Moving internal components

Bubble Column Bioreactor 

Low photosynthetic efficiency

Airlift 

Non-uniform nutrient distribution

Insufficient mixing

High viscosity limits bulk circulation

Fluid Bed Fermentor

Particle breakage is common

Increased reactor vessel size

Bubbling beds of fine particles are unpredictable and less efficient.

Pipe and vessel walls are susceptible to erosion from particle collisions

Packed Bed Bioreactor

Undesirable temperature gradients

Poor temperature regulation

Difficult catalyst replacement 

Photobioreactor 

Scalability issues

Require temperature control due to lack of evaporative cooling

Periodic cleaning needed due to light exposure

Maximal light exposure is essential

Membrane Bioreactor

Biofilm overgrowth necessitates periodic cleaning

 

The membrane is prone to rupture at elevated flow rates

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