Classification and Types of Bioreactors
Biological reactor can be broadly classified based on their mode of operation into two major types – batch biological reactor and continuous biological reactor. Batch biological reactor involve cultivation of microorganisms or cell cultures in a closed system without replenishment of media or removal of products during the process. Continuous biological reactor, on the other hand, facilitate a continuous influx of fresh media and outflow of effluents or harvested products while maintaining the culture at a steady state.
Within these two major classifications, Bioreactors are further differentiated based on operational parameters like geometry, mixing mechanism, scale of operation, oxygen transfer capability etc. Common bioreactor configurations include surface aerated biological reactor, mechanically agitated biological reactor, air-lift biological reactor, bubble column biological reactor, roller bottle biological reactor, fluidized bed biological reactor and hollow fiber biological reactor. Each configuration has its inherent advantages and suitability for specific applications.
Advancements in Bioreactor Design
Over the decades, extensive research has led to major advancements in bioreactor design for improved process efficiency and product quality. Early biological reactor were often mechanically simple and had limited monitoring and control capabilities. Today’s biological reactor feature sophisticated real-time controllers, process analytical technologies and single-use disposable designs.
Advancements like computer controlled agitation and aeration systems along with in-built sensors for online monitoring of critical process parameters have enabled precise control over culture conditions. Single-use biological reactor using disposable flexible bags provide the ability to rapidly set up processes in smaller footprints compared to stainless steel vessels. New configurations like hollow fiber membrane biological reactor aim to achieve high cell densities while separating cells from the culture broth.
Scaling Up Bioreactors
A key application of biological reactor is to enable efficient scale-up of industrial bioprocesses from laboratory scale work to commercial production levels. Achieving consistent scale-up is challenging due to changes in mass transfer and culture hydrodynamics at different scales. Fundamental parameters like kLa, power input per unit volume and shear stress need characterization at different scales.
Systematic scale-up strategies involve characterizing these parameters through dimensionless numbers and mathematical modeling to facilitate rational scale-up. Methods like matched partial viscosity scaling and constant tip speed scaling are common approaches used. With advances in computational fluid dynamics, numerical simulation aids in bioreactor design scale-up. Single-use biological reactor have made autoclavable stainless steel vessels less critical at production scales below 10,000 liters.
Newer Applications in Tissue Engineering
Beyond traditional applications in pharmaceutical manufacturing, biological reactor are finding increasing roles in advanced areas like tissue engineering and regenerative medicine. Dynamic culture conditions mimicking the in vivo microenvironment are essential for growth of 3D tissues requiring elaborate mass transfer.
Biological reactor designed with perfusion mechanisms enable nutrient delivery and waste removal critical for formation of vascularized tissues. Specialized bioreactor designs integrate elements like mechanical stimulation to aid development of cartilage, bone and other mechanically loaded tissues. Other emerging applications are in developing disease models for toxicity testing and drug screening using 3D tissue constructs grown in biological reactor.
Advancing the Field through Continuous Innovation
Going forward, further innovation will be crucial to leverage the potential of biological reactor across diverse industrial and medical fields. Development of modular, multi-functional bioreactor platforms can enhance process design flexibility. Integrating novel sensing technologies can provide real-time, localized assessment of microenvironment variables influencing cell behavior.
continuous bioprocesses are an attractive avenue to enhance productivity but require new bioreactor configurations and control strategies. Advances in process analytical technologies, mechanobiology understanding and “digital biomanufacturing” through platforms like computer aided bioreactor engineering will be pivotal in addressing emerging challenges. Sustaining growth will demand new strategic public-private partnerships that nurture cross-disciplinary research and translation. With continued innovation, biological reactor are certain to transform diverse domains from bulk chemicals to regenerative therapies.
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