Bioreactors are fundamental in extraction, analytical and production processes in the biotechnology sector. Researchers and industrialists must understand the fundamental principles of bioreactors, their different typologies, the multiple applications in different sectors and the challenges associated with their use to obtain the best operating conditions to optimize the production of the metabolites of interest. However, they have some limitations that must be addressed to optimize their efficiency and performance.
Understanding these different elements is fundamental for optimizing industrial processes, obtaining biomedical and pharmaceutical engineering products, as well as in environmental biotechnologies.
What is a Bioreactor?
Bioreactors are the main unitary operations of industrial biochemical transformation in which the chosen substrates are biotransformed by the action of living cells (microorganisms) or from their cellular components such as enzymes. They are reservoirs in which cells or cell-free enzymes, or both, transform raw materials into biochemical products and, sometimes, in less unwanted by-products.
Commonly cylindrical and of variable dimensions from one liter to a few cubic meters, they differ depending on operational needs. Microorganisms include bacteria, yeast, fungi, algae, plant or animal cells, including tissue-like matrices. [1]
What are the Principles of a Bioreactor?
The design and all parts of the bioreactors are specially designed to create a vessel within which biological reactions take place in a constantly controlled environment. Kernel sensors allow continuous monitoring of key parameters (pH, dissolved oxygen, temperature, nutrient concentration) necessary for growth and metabolic or enzymatic activities. Sensors and alarms allow the adjustment of parameters in real time and guarantee reproducibility, constant output and high quality of production, in particular pharmaceuticals, biofuels and food additives, reducing contamination to a minimum. [2]
The conditions can vary depending on the needs of the reactions, they may not be constant over time but create ramps or accompany the different reaction phases. Very often the obtained metabolic products are removed from the reaction environment to overcome what could be negative feedback signals that reduce the rate or even realization of reactions.
Mixing mechanisms provide uniform distribution of nutrients while avoiding gradients that would affect system performance. Aeration systems regulate oxygen in aerobic processes, fundamental for the initial reaction and growth phases of microorganisms. [1]
Types of Bioreactors
The applications of bioreactors are very vast as we have anticipated, and the specialization is determined by the conditions applied: cultivation of photosynthetic microorganisms, anaerobic fermentation or intensive production of cells in controlled environments, as well as the production of metabolites of industrial or pharmaceutical interest.
Each of these intended uses will have its specific parameters, they can often be directly provided by the manufacturer, other times they will be implemented within the specific process following research and development of new methods, this is why they are so widespread in use, even for their manageability. [1]
Stirred Tank Reactor (STR)
Stirred tank reactors are widely used: they consist of a cylindrical vessel equipped with a stirrer, often a mechanical shovel, which allows complete and continuous mixing of the nutrients, as well as a transfer of oxygen to the entire culture medium and to the cells that contains. STRs are perfect for aerobic processes where the presence of oxygen is a limiting factor for the reactions.
The design allows an easy transition from the minimum laboratory dimensions to those on an industrial scale, this makes them ideal for the production of compounds of high pharmaceutical interest, enzymes, bioproducts of high economic value (microbial cultures, animal cells and tissue-like matrices, plant cells, etc). [1]
Bubble Column Bioreactor
These reactors consist of a vertical column filled with culture broth, into which air or other gas is injected to create bubbles that will mix the solution without mechanical agitation. The insertion occurs from the bottom and the ascending bubbles mix and supply oxygen making this type of setup suitable for aerobic fermentation processes and wastewater treatment.
Wastewater treatment
- In the first phase, suspended solids are removed by sedimentation plus filtration.
- The second step sees the biological degradation of organic pollutants, in bioreactors containing microorganisms such as activated sludge or biofilm.
- The third step involves further purification through chemical (chlorine disinfection), physical (UV treatment) or biological (membrane filtration) processes.
- The fourth step concerns the removed sludge which can be stabilized, dehydrated, disposed of or reused, often in agriculture as fertilizers.
They are particularly advantageous for processes involving shear-sensitive organisms since they generate low shear forces. Their simple design also results in lower capital and operating costs compared to more complex bioreactor systems. [1]
Airlift Bioreactor
Airlift bioreactors utilize air circulation to mix the culture medium gently and efficiently. The design typically includes a central riser and an outer downcomer, creating a loop for natural fluid circulation. This setup reduces mechanical stress on cells, making airlift bioreactors ideal for cultivating shear-sensitive organisms like animal cells and certain types of plant cells.
These bioreactors are commonly used in wastewater treatment and large-scale cell culture processes. Their energy-efficient operation and lower maintenance requirements widen their appeal for industrial applications, where maintaining cell viability and productivity are high priorities. [1]
Fluidized Bed Bioreactor
Fluid bed bioreactors are characterized by their structure: solid particles and fluid are contained inside the tank or column; the cylindrical shape facilitates uniformity of movement. Solid particles can be glass, ceramic or polymer spheres on which microorganisms or enzymes are attached.
The ascending flow (liquid or gas) is introduced from the bottom, the flow speed is adjustable and allows the particles to be kept in a “fluid bed” state.
Ancillary aeration and mixing systems are used to improve oxygen transfer and promote particle-fluid contact. There are also control systems (sensors and alarms) for all the fundamental parameters, and an enriched fluid outlet from which the metabolites of interest will then be separated. This model can operate continuously, offering advantages in scalability and sustained productivity for various industrial applications. [1]
Packed Bed Bioreactor
Packed bed bioreactors contain immobilized cells or enzymes within a packed column, optimizing substrate conversion and product yield. The structure of the equipment is suitable for processes involving a high density of cells and prolonged stability of the enzymes or biocatalysts. Packed bed bioreactors are primarily used in the production of active molecules or biopharmaceuticals, biofuels or high-purity chemicals, where consistent quality and high productivity are essential.
It is precisely the immobility of cells or enzymes that allows continuous operation, efficient use of substrates while containing costs and all this makes the application ideal for the industrial scale. [1]
Photobioreactor
Photobioreactors are equipment designed for the growth of algae or plant tissue-like matrices. In fact, under controlled light conditions it is possible to optimize the photosynthesis process and maximize biomass production. They may have open tank-like structures or closed systems with artificial lighting. The result? Constant production and high efficiency products.
Biopharmaceuticals, biofuels and food supplements are produced with this technology and the sustainability of the system is one of the reasons why it is so widely used. This last characteristic, added to the possibility of precisely controlling the environmental conditions in photobioreactors, makes them an applicable technology for the development of renewable energy and bioproducts. [3]
Membrane Bioreactor
The combination of bioprocessing and filtration with biological membranes is the basis of the membrane bioreactor model, in this way in a single step it is possible to efficiently treat the effluent and then separate the biomass. Also in this case, wastewater treatment is one of the most common applications because they offer superior performance in terms of effluent quality and operational efficiency.
The integrated membranes allow high concentrations of microorganisms responsible for improving the rate of biodegradation, or biological conversion, as well as a reduction in the environmental impact of the entire production system. [3]
Bioreactor Applications: What are Typically Used For?
Now that we know the various types of bioreactors models, we can delve into the many production applications at an industrial and scientific level.
The main drugs produced are antibiotics (from Streptomyces) such as penicillin, or recombinant human hormones such as growth hormone or insulin (from bacteria or yeasts). [3]
Biofuels such as bioethanol are produced by fermentation of sugars from corn or sugar cane; Biodiesel is obtained by converting vegetable oils produced by algae. [3]
In the food industry sector, bioreactors are exploited for the production of enzymes used for cheese production processes or additives for bakery dough. They find application in the production of bacterial strains beneficial to human health (such as Lactobacillus and Bifidobacterium) used widely as food supplements, but also in the production of dairy products and yogurt. Let’s not forget bioproducts such as organic lactic and citric acids which are the main antioxidant additives in packaged food.
In scientific research, bioreactors are used to provide researchers with proteins of interest for structural or functional studies (e.g. for new drugs), furthermore genetically modified cells can be cultivated to test new generation gene therapies. [3]
What are the Limitations of Bioreactors?
In addition to the many benefits, there are also application and performance limitations. The initial costs and ongoing operational and maintenance expenses for complex systems is certainly a challenge, implementing automatic mechanisms or management software could be a solution. The transition from the small laboratory scale to the industrial one can bring to problems related to the mass or heat transfer process, causing inconsistency and lower reaction yields.
On an industrial scale the risks of contamination are higher. To overcome this problem companies should implement rigorous sterilization protocols and containment strategies. Even small variations in environmental parameters (pH, temperature or nutrient availability) can lead to suboptimal performance or the inability to adapt these systems to all types of cells or microorganisms, the a priori failure of the system therefore limits its applications.
Regulations and constraints of following Good Manufacturing Practices (GMP) further reduce the possibility of achieving implementation and scalability of biotransformation processes in the biotechnology and pharmaceutical sectors.
Although all these challenges and risks exist, advances in bioreactor design continue to enhance their efficiency and reliability. More sustainable bioproduction processes for companies could lead to greater implementation of biotechnology in scalable and innovative processes in industrial and environmental sectors.
References:
- Christy, Y. Basic Biotechnology. Cambridge University Press. 2006. Third Edition.
- Jaibiba P., et al. Chapter 10 – Working principle of typical bioreactors. Bioreactors Sustainable Design and Industrial Applications in Mitigation of GHG Emissions. 2020
- Spier M.R., et al. Application of Different Types of Bioreactors in Bioprocesses. Bioreactors: Design, Properties and Applications. 2011
