Bioreactors are essential tools in modern biotechnology, enabling researchers to cultivate cells, microorganisms, or tissues in a controlled environment. Whether you’re working on producing proteins, biofuels, or bioplastics, bioreactors create the optimal conditions necessary for biological reactions to occur at scale. These highly engineered systems are central to the success of numerous industries, from pharmaceuticals and biomedicine to environmental science and industrial processing. In this article, we´ll answer what is a bioreactor and break down how it works by exploring its key components, functionality, and different steps involved in the bioprocess workflow. Understanding these core concepts is essential for researchers and scientists aiming to harness bioreactors for their research and development goals, driving innovation and achieving advancements. By mastering these technologies, researchers can push the boundaries of science, leading to more efficient processes, higher yields, and groundbreaking discoveries.
WHAT IS A BIOREACTOR?
At its core, a bioreactor is a device that provides a controlled environment where biological processes can take place. These processes are typically used to produce bioproducts such as proteins, vaccines, biofuels, and other valuable compounds. The bioreactor’s main purpose is to maintain optimal conditions for the growth of cells or microorganisms by regulating key parameters such as temperature, pH, oxygen levels, and nutrient supply.Bioreactors can be found in a range of sizes and designs, from small benchtop units used in academic research to industrial-scale systems designed for mass production. No matter the scale, the principles behind bioreactor operation remain the same: maximizing productivity by providing an ideal growth environment. To fully leverage their potential, it’s important to understand their essential components and how they function.
ESSENTIAL BIOREACTOR COMPONENTS AND THEIR FUNCTIONALITY
To understand how a bioreactor works, we need to explore its key components. Each part plays a critical role in maintaining the optimal environment for biological growth and production. Here’s a detailed breakdown of the most important components:
1. Vessel
The vessel is the chamber where the cellular growth takes place. The size and material of the vessel depend on the scale of production and the nature of the biological process. Small lab-scale vessels may be made from glass or plastic, offering the advantage of transparency for monitoring, while industrial bioreactors often use stainless steel for its durability and ease of sterilization.
For mammalian cells: These cells are particularly sensitive to shear stress, so bioreactors designed for mammalian cell culture use gentle mixing via axial flow impellers such as pitched-blade or marine impellers, to avoid damaging the cells.For microorganisms: More robust cultures like bacteria or yeast may require vigorous mixing to ensure the even distribution of oxygen and nutrients. For this purpose, radial flow impellers, such as Rushton are ideal due to their efficiency in high-shear mixing.
2. Agitation and mixing systems
In bioreactors, maintaining uniform conditions throughout the culture medium is vital. Impellers or stirrers, combined with the right mixing systems – including a motor and a drive shaft with impeller – ensure that gases, nutrients, and heat are evenly distributed. This is especially important in large-scale systems where inconsistencies in temperature or nutrient supply can affect the outcome of the process. Additionally, baffles within the vessel are often used to improve mixing efficiency and stability by preventing vortex formation.
3. Sensors and real-time monitoring
The ability to monitor key parameters such as temperature, pH, dissolved oxygen (DO), and nutrient levels in real-time is one of the major strengths of modern bioreactors. Integrated sensors provide real-time data, allowing the system to make automated adjustments to maintain optimal conditions.
Advanced monitoring: In some systems, remote monitoring allows researchers to oversee experiments without being physically present, offering convenience and reducing the risk of errors due to manual intervention.
4. Automated control systems
Bioreactors use automated control systems to regulate conditions based on the data provided by sensors. These systems can adjust the flow of gases, nutrients, and pH-balancing agents to ensure that the environment remains stable.
Automation in action: For instance, if the oxygen level drops below a certain threshold, the system will automatically increase the oxygen supply by pumping more gas and/or increasing stirrer speed. Similarly, if the pH level starts to drift, acid or base solutions can be added to bring it back into range.
5. Gas supply and exchange systems
Gas exchange is crucial for aerobic processes. In many bioreactors, spargers are used to introduce gases such as oxygen into the culture medium, while exhaust systems, often equipped with a condenser, remove carbon dioxide and other waste gases. Proper gas exchange is vital for maintaining the respiratory needs of the culture.
Sparger: The sparger ensures that oxygen is distributed throughout the medium, while minimizing foaming or shear stress. This is particularly important for sensitive cell cultures like mammalian cells.Gas control: Gas flow can be precisely managed using mass flow controllers (MFCs) or rotameters, depending on the setup requirements. Additionally, a condenser in the exhaust system helps keeping the liquid volume stable by preventing water vapor to leave the system.
6. Heating and cooling systems
Maintaining a stable temperature is essential for bioprocesses. Bioreactors often incorporate a thermostat, heating jacket, or cooling finger to regulate the temperature within the vessel, ensuring optimal growth conditions for the biological material.
7. Pumps and feed systems
Pumps are used to add nutrients, oxygen, or other media into the bioreactor as needed. Bioreactors can be used in a fed-batch strategy where nutrients are periodically added to prolong the growth phase and increase yields. Others may use continuous feeding, where fresh medium is constantly supplied, and product is continuously removed.
Continuous vs. Fed-batch: In continuous bioreactors, the process is ongoing with constant input and output, ideal for long-term production. Fed-batch systems, on the other hand, allow the culture to grow over a fixed period while being fed intermittently, making them ideal for optimizing yields in shorter cycles.
THE BIOPROCESS WORKFLOW: FROM PREPARATION TO HARVEST
Bioprocessing with bioreactors follows a well-defined workflow that involves several stages, each designed to maintain optimal conditions for the target cells or microorganisms:
1. Sterilization: Sterilizing the bioreactor and its components is critical to prevent contamination. The vessel, piping, and associated equipment must be thoroughly sterilized using methods such as steam-in-place (SIP) or autoclaving to ensure that no unwanted microorganisms interfere with the process.
2. Inoculation: Once the system is sterilized, the desired cells or microorganisms are introduced into the vessel. This stage, known as inoculation, marks the start of the bioprocess. The inoculum (starter culture) is carefully prepared in advance to the actual bioprocess, e.g. by creating an overnight culture in a shake flask. This is done to give the bioprocess the best possible start and allow for an even growth of the cells.
3. Cultivation: During cultivation, the bioreactor maintains ideal conditions for the growth of the organisms. Parameters such as temperature, pH, dissolved oxygen, and nutrient levels are constantly monitored and adjusted to keep the culture in its most productive phase. Bioreactors can employ batch, fed-batch, or continuous feeding strategies to optimize production.
4. Harvesting: Once the culture has reached the desired density or the product concentration is optimal, it is time to harvest. Downstream processing methods such as filtration, centrifugation, or chromatography are used to separate the cells or the product from the culture medium.
CONCLUSION
Bioreactors are complex systems that play a vital role in biotechnology, providing the controlled environments necessary for a wide range of biological processes. By understanding the different components—such as the vessel, mixing systems, sensors, and control units—one can better appreciate how these systems work to optimize the growth and productivity of cells and microorganisms.
For researchers and scientists, mastering the operation of a bioreactor is critical to achieving consistent, high-quality results, whether developing new pharmaceuticals, producing biofuels, or conducting academic research.
