There are many different types of bioreactors including bubble column bioreactors, continuous stirred tank bioreactors, fluidized bed bioreactors, packed bed bioreactors, and photobioreactors. The most common bioreactors are the stirred tank, airlift, and fixed-bed types. 

Bioreactors are essential tools in biotechnology and have revolutionized research in various fields. They are most commonly used in the production of vaccines, biopharmaceuticals, and biofuels, and there are several types of bioreactors, each with its own advantages and limitations. 

In this article, we will explore six types of bioreactors to understand why it is crucial to choose the most appropriate system for your particular application.

What Are Bioreactors?

Bioreactors are specialized vessels designed for the growth and cultivation of microorganisms, plant and animal cells, and tissues. They are important tools in biotechnology, used for a variety of purposes such as the production of pharmaceuticals, vaccines, biofuels, and food products. Essentially, a bioreactor is a system that provides a controlled environment for cells or microorganisms to grow and multiply.

The design of a bioreactor is dependent on the type of organisms being cultivated and the intended use of the final product. Typically, bioreactors are equipped with sensors to monitor and control factors such as temperature, pH, oxygen, and nutrient levels. They may also have mechanical agitators or impellers to ensure that the cells or microorganisms are evenly distributed throughout the reactor.

Bioreactors come in various shapes and sizes, ranging from small benchtop units to large industrial-scale vessels. Some bioreactors are single-use, while others are designed for multiple uses, so the choice of bioreactor depends on the specific application and the level of production you require.

Bioreactor Working Principle

The bioreactor working principle is relatively simple, but the technology behind it is incredibly complex. As mentioned, essentially, a bioreactor is a vessel in which living cells or organisms are grown under controlled conditions to produce a particular product.

The first step in understanding how bioreactors work is to understand what they are made of. Typically, a bioreactor consists of a container, an agitator, and a means of controlling temperature, pH, and other environmental factors. The container can be made of glass or stainless steel and has ports for adding nutrients, removing waste, and monitoring the progress of the culture. The agitator is used to mix the contents of the bioreactor to ensure that all cells receive an equal supply of nutrients and oxygen.

The bioreactor working principle involves creating an environment that is conducive to the growth of the cells or organisms being cultured. For example, if you were trying to produce a particular protein using bacteria, you would need to provide them with the right nutrients, such as glucose and amino acids. You would also need to control the temperature and pH of the culture to ensure that the bacteria grow optimally.

Once you have set up the bioreactor with the right conditions, you would then inoculate it with the bacteria. Over time, the bacteria would multiply and produce the protein that you are interested in. As they do so, they will consume nutrients and produce waste products, such as carbon dioxide and lactic acid. These waste products can build up in the culture and affect its growth, so it is essential to remove them periodically.

Airlift Bioreactors

One type of bioreactor that has gained popularity in recent years is the airlift bioreactor. This type of bioreactor is similar to a bubble column reactor, however, airlift bioreactors contain a draft tube. The draft tube can either be an inner tube (with an internal loop) or an external tube (with an external loop), but the functionality is the same: to improve circulation and oxygen transfer. The draft tube also equalizes shear forces into the bioreactor. 

Airlift bioreactors with internal loops create interior liquid circulation channels via a single container. They are simple and have a fixed rate during fermentation processes. Airlift bioreactors with external loops circulate through separate channels.

The performance of the bioreactor relies on the pumping or injection of air/gas, and the media circulation. Airlift bioreactors are different from stirred-tank bioreactors as they do not need a heat coat or plate to control the temperature. For temperature-dependent formations, a two-stage airlift bioreactor is used. 

Airlift Bioreactor Applications

• Culturing sensitive organisms/cells and single-cell protein production
• Methanol productions
• Wastewater treatment
• Aerobic bioprocessing 

Advantages

• Extremely energy efficient; low energy requirement
• They use a simple design 
• They have no moving parts, so less maintenance is required
• Less risk of defects 
• As they have no agitator shaft parts they have easier sterilization

Disadvantages

• They can be expensive to run; the greater the air pressure, the more energy is consumed
• Agitation of the bioreactor is controlled from the air supply so a greater pressure is required 
• During higher pressures, a greater air throughput is needed
• When foaming happens, an inefficient break of the foam occurs
• As there are no blades, there is no bubble breaker 

Bubble Column Bioreactors

Bubble column bioreactors consist of a tall vertical column filled with liquid, which is aerated from the bottom to create bubbles. These bubbles provide oxygen and mixing and aeration to the system, allowing for the growth and viability of microorganisms.

The design of a bubble column bioreactor is quite simple, making it an attractive option for many applications. The vessel used is typically cylindrical and the size can be adjusted based on the desired scale of production, between an aspect ratio of 4-6. 

Inside the bioreactor, air or gas is added at the base of the bioreactor column via perforated plates or pipes, or microporous spargers. Perforated plates are typically preferred as they improve the bubble column bioreactor’s performance. By adding air or gas into the cylinder, it enables gaseous exchange. The flow rate of the air or gas is influenced by mixing and oxygen transfer. The products are produced using a fermentation method where the reactants are compacted using a finely dispersed catalyst.

Bubble Column Bioreactor Applications

• Fermentation processes 
• Producing pharmaceuticals and chemicals 
• Culturing sensitive organisms/cells like plant cells

Advantages

• Self-regulating 
• Excellent heat management
• High volumetric productivity
• Good flow distribution 

Disadvantages

• Less efficient than other types of bioregulators 
• They do not have a draft tube 
• They are expensive to install 
• They have a higher catalytic consumption than fixed-bed bioreactors

Continuous Stirred-Tank Bioreactors

Continuous stirred tank bioreactors, also known as CSTRs, are the most common type of bioreactor most widely used today. They have an aspect ratio, typically between 3-5. CSTRs use turbid static or chemo static principles to control the flow rate, and when under pressure, the air is added to the culture via a sparger device. 

Bubbles are formed by the sparger, which are then later broken down into smaller bubbles and evenly spread throughout the medium. This process allows the creation of a homogeneous and uniform environment inside the bioreactor. This enables a bioprocess reaction. 

Continuous Stirred Tank Bioreactor Applications

• Hydrocarbon-rich industrial wastewater treatments
• Pharmaceutical industry
• Fermentation processes
• Biological processes, such as cell cultures

Advantages

• Continuous operation, making them ideal for large-scale production of biotech products where consistency and efficiency are key factors 
• Good temperature control, so they require minimal supervision
• The process can easily be adapted to two-phase runs
• Easy to clean 
• They allow efficient gas transfer for growing cells and content mixing 

Disadvantages

• They require bearings and shaft seals 
• Some users have issues with foaming 
• You are limited in terms of motor size, weight, and the shaft length
• They consume a lot of power because of the mechanical pressure pumps used

Fluidized Bed Bioreactors

Fluidized Bed Bioreactors (FBBRs) are similar to bubble column bioreactors however, the top position of the FBBR is expanded and the column is narrowed to reduce the fluid velocity. This is so that the solids are maintained in the reactor while the liquid can flow out. 

Inefficient FBBR operations, gas is provided to create a ‘gas-liquid-solid’ fluid bed and a good suspended state. If using a FBBR, it is also important that suspended solid particles are heavy enough to prevent them from floating. The same goes for dense particles. You do not want too many dense particles otherwise they may lay at the bottom. 

The good thing with FBBRs is that you can recycle the liquid. This is essential to maintain continuous contact between the biocatalysts inside the bioreactor and the reaction contents. This is a good habit for bioprocessing, and it is important for good efficiency.

Fluidized Bed Bioreactor Applications

• Producing gasoline and other fuels 
• Chemical engineering 
• Food processing industries 
• Bulk drying of materials 
• Anaerobic and aerobic wastewater treatments

Advantages

• They can operate in a continuous state
• They use uniform temperature gradients
• Uniform particle mixing 
• Small footprint 

Disadvantages

• Some users face pressure loss/drop
• The reactor vessel is large 
• They have specific pumping requirements 

Packed Bed Bioreactors

Packed bed bioreactors contain a confined bed of solid particles with biocatalysts. These solids can either consist of porous or non-porous (rigid) gels. The biocatalyst is immobilized on the solids and a medium (typically called a nutrient broth) flows constantly over it, either upward or downward. When the fluid runs upward, the velocity must not exceed the minimum fluidization velocity, which is why gravitational downward flow is preferred. 

The products and metabolites inside the bioreactor are dispersed into the media fluid and during the outflow, they are removed.

Packed Bed Bioreactor Applications

• Immobilized/particular biocatalysts
• Wastewater treatments
• Catalytic reactors; fermentors
• Can handle high-density cultures

Advantages

• Low operating cost
• They offer continuous operations (constant flow rate of nutrients and oxygen)
• They have no moving mechanical parts that will wear out 
• The catalyst stays within the bioreactor
• The design is simple and therefore they are effective at high temperatures and pressures
• Compared to other catalytic bioreactors, packed bed bioreactors have a higher conversion per unit mass
• They are highly versatile, so they can be adapted to a wide range of biological systems

Disadvantages

• They are very difficult to clean
• Unwanted heat gradients and poor temperature control
• It is difficult to replace the catalyst

Photobioreactors

Photobioreactors are a relatively new technology that has revolutionized the way we think about sustainable energy. These bioreactors are an innovative reactor that uses photosynthetic organisms to convert sunlight into usable energy, which can then be harvested and used to power a variety of different applications. Unlike traditional bioreactors which rely on chemical reactions to produce energy, photobioreactors rely solely on the power of the sun, making them incredibly eco-friendly and efficient.

The most common use is to cultivate microalgae in wastewater treatment facilities (WWTPs). The photobioreactor usually has a light source like an LED or fluorescent bulb to allow enough light for photosynthesis and a culture media. The light intensity and spectrum can be adjusted to the maximize growth of the microorganisms.

Photobioreactors may also use a mechanical stirrer or bubbling mechanism to mix the culture medium and allow air through the medium. During use, the temperature, and the pH of the culture medium must be carefully controlled accordingly to the microorganism growth. The photobioreactor being used must also be designed to prevent possible contamination. 

The specific design used depends on the specific microorganism being cultivated and the final product, and there are four basic types of photobioreactors to select from:

• Open raceway pond
• Flat-plate photobioreactor
• Inclined tubular photobioreactor
• Horizontal tubular photobioreactor

Photobioreactor Applications

• Pharmaceutical industry
• Biofuel production; growing algae and cyanobacteria 
• Bioplastics
• Food additives
• Wastewater treatments (remediation)
• Carbon capture
• Aerobic and anaerobic processes

Advantages

• They are highly efficient at nutrient removal
• Sufficient mixing conditions
• Low cost and simple operation 
• Easy maintenance
• No other carbon resources are required
• Small environmental footprint
• They are not weather limited; they can operate all year 
• They are simple to integrate into WWTPs
• They can be used in large-scale applications
• They can be used at both high and low density

Disadvantages

• The initial cost is very high
• They are challenging to sterilize

Summary

Bioreactors are essential tools in biotechnology, providing a controlled environment for the growth and cultivation of cells and microorganisms. These specialized vessels play a crucial role in the production of a wide range of products, from pharmaceuticals to biofuels. 

If you are unsure which bioreactor is best suited, do not hesitate to contact the world-class team at Atlas Scientific.

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