Bioreactor

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A bioreactor refers to any manufactured device or system that supports a biologically active environment. [1] In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. This process can either be aerobic or anaerobic. These bioreactors are commonly cylindrical, ranging in size from litres to cubic metres, and are often made of stainless steel.[ citation needed ] It may also refer to a device or system designed to grow cells or tissues in the context of cell culture. [2] These devices are being developed for use in tissue engineering or biochemical/bioprocess engineering.[ citation needed ]

Contents

General structure of a continuous stirred-tank type bioreactor Bioreactor principle.svg
General structure of a continuous stirred-tank type bioreactor

On the basis of mode of operation, a bioreactor may be classified as batch, fed batch or continuous (e.g. a continuous stirred-tank reactor model). An example of a continuous bioreactor is the chemostat.[ citation needed ]

Organisms or biochemically active substances growing in bioreactors may be submerged in liquid medium or may be anchored to the surface of a solid medium. Submerged cultures may be suspended or immobilized. Suspension bioreactors may support a wider variety of organisms, since special attachment surfaces are not needed, and can operate at a much larger scale than immobilized cultures. However, in a continuously operated process the organisms will be removed from the reactor with the effluent. Immobilization is a general term describing a wide variety of methods for cell or particle attachment or entrapment. [3] It can be applied to basically all types of biocatalysis including enzymes, cellular organelles, animal and plant cells and organs. [4] [5] Immobilization is useful for continuously operated processes, since the organisms will not be removed with the reactor effluent, but is limited in scale because the microbes are only present on the surfaces of the vessel.

Large scale immobilized cell bioreactors are:

Design

Benchtop bioreactor for cultivation of micro-organisms Bioreacteur CiYOU.png
Benchtop bioreactor for cultivation of micro-organisms
A closed bioreactor used in cellulosic ethanol research Pg166 bioreactor.jpg
A closed bioreactor used in cellulosic ethanol research

Bioreactor design is a relatively complex engineering task, which is studied in the discipline of biochemical/bioprocess engineering. Under optimum conditions, the microorganisms or cells are able to perform their desired function with limited production of impurities. The environmental conditions inside the bioreactor, such as temperature, nutrient concentrations, pH, and dissolved gases (especially oxygen for aerobic fermentations) affect the growth and productivity of the organisms. The temperature of the fermentation medium is maintained by a cooling jacket, coils, or both. Particularly exothermic fermentations may require the use of external heat exchangers. Nutrients may be continuously added to the fermenter, as in a fed-batch system, or may be charged into the reactor at the beginning of fermentation. The pH of the medium is measured and adjusted with small amounts of acid or base, depending upon the fermentation. For aerobic (and some anaerobic) fermentations, reactant gases (especially oxygen) must be added to the fermentation. Since oxygen is relatively insoluble in water (the basis of nearly all fermentation media), air (or purified oxygen) must be added continuously. The action of the rising bubbles helps mix the fermentation medium and also "strips" out waste gases, such as carbon dioxide. In practice, bioreactors are often pressurized; this increases the solubility of oxygen in water. In an aerobic process, optimal oxygen transfer is sometimes the rate limiting step. Oxygen is poorly soluble in water—even less in warm fermentation broths—and is relatively scarce in air (20.95%). Oxygen transfer is usually helped by agitation, which is also needed to mix nutrients and to keep the fermentation homogeneous. Gas dispersing agitators are used to break up air bubbles and circulate them throughout the vessel.[ citation needed ]

Fouling can harm the overall efficiency of the bioreactor, especially the heat exchangers. To avoid it, the bioreactor must be easily cleaned. Interior surfaces are typically made of stainless steel for easy cleaning and sanitation. Typically bioreactors are cleaned between batches, or are designed to reduce fouling as much as possible when operated continuously. Heat transfer is an important part of bioreactor design; small vessels can be cooled with a cooling jacket, but larger vessels may require coils or an external heat exchanger.[ citation needed ]

Types

Photobioreactor

Moss photobioreactor with Physcomitrella patens Bioreaktor quer2.jpg
Moss photobioreactor with Physcomitrella patens

A photobioreactor (PBR) is a bioreactor which incorporates some type of light source (that may be natural sunlight or artificial illumination). Virtually any translucent container could be called a PBR, however the term is more commonly used to define a closed system, as opposed to an open storage tank or pond. Photobioreactors are used to grow small phototrophic organisms such as cyanobacteria, algae, or moss plants. [6] These organisms use light through photosynthesis as their energy source and do not require sugars or lipids as energy source. Consequently, risk of contamination with other organisms like bacteria or fungi is lower in photobioreactors when compared to bioreactors for heterotroph organisms.[ citation needed ]

Sewage treatment

Conventional sewage treatment utilises bioreactors to undertake the main purification processes. In some of these systems, a chemically inert medium with very high surface area is provided as a substrate for the growth of biological film. Separation of excess biological film takes place in settling tanks or cyclones. In other systems aerators supply oxygen to the sewage and biota to create activated sludge in which the biological component is freely mixed in the liquor in "flocs". In these processes, the liquid's biochemical oxygen demand (BOD) is reduced sufficiently to render the contaminated water fit for reuse. The biosolids can be collected for further processing, or dried and used as fertilizer. An extremely simple version of a sewage bioreactor is a septic tank whereby the sewage is left in situ, with or without additional media to house bacteria. In this instance, the biosludge itself is the primary host for the bacteria.[ citation needed ]

Bioreactors for specialized tissues

A bioreactor used to ferment ethanol from corncob waste being loaded with yeast Loading bioreactor.jpg
A bioreactor used to ferment ethanol from corncob waste being loaded with yeast

Many cells and tissues, especially mammalian ones, must have a surface or other structural support in order to grow, and agitated environments are often destructive to these cell types and tissues. Higher organisms, being auxotrophic, also require highly specialized growth media. This poses a challenge when the goal is to culture larger quantities of cells for therapeutic production purposes, and a significantly different design is needed compared to industrial bioreactors used for growing protein expression systems such as yeast and bacteria.[ citation needed ]

Many research groups have developed novel bioreactors for growing specialized tissues and cells on a structural scaffold, in attempt to recreate organ-like tissue structures in-vitro. Among these include tissue bioreactors that can grow heart tissue, [7] [8] skeletal muscle tissue, [9] ligaments, cancer tissue models, and others. Currently, scaling production of these specialized bioreactors for industrial use remains challenging and is an active area of research.

For more information on artificial tissue culture, see tissue engineering.

Modelling

Mathematical models act as an important tool in various bio-reactor applications including wastewater treatment. These models are useful for planning efficient process control strategies and predicting the future plant performance. Moreover, these models are beneficial in education and research areas.[ citation needed ]

Bioreactors are generally used in those industries which are concerned with food, beverages and pharmaceuticals. The emergence of biochemical engineering is of recent origin. Processing of biological materials using biological agents such as cells, enzymes or antibodies are the major pillars of biochemical engineering. Applications of biochemical engineering cover major fields of civilization such as agriculture, food and healthcare, resource recovery and fine chemicals.[ citation needed ]

Until now, the industries associated with biotechnology have lagged behind other industries in implementing control over the process and optimization strategies. A main drawback in biotechnological process control is the problem of measuring key physical and biochemical parameters. [10]

Operational stages in a bio-process

A bioprocess is composed mainly of three stagesupstream processing, bioreaction, and downstream processingto convert raw material to finished product. [11]

The raw material can be of biological or non-biological origin. It is first converted to a more suitable form for processing. This is done in an upstream processing step which involves chemical hydrolysis, preparation of liquid medium, separation of particulate, air purification and many other preparatory operations.[ citation needed ]

After the upstream processing step, the resulting feed is transferred to one or more bioreaction stages. The biochemical reactors or bioreactors form the base of the bioreaction step. This step mainly consists of three operations, namely, production of biomass, metabolite biosynthesis and biotransformation.[ citation needed ]

Finally, the material produced in the bioreactor must be further processed in the downstream section to convert it into a more useful form. The downstream process mainly consists of physical separation operations which include solid liquid separation, adsorption, liquid-liquid extraction, distillation, drying etc. [12]

Specifications

A typical bioreactor consists of following parts:

Agitator – Used for the mixing of the contents of the reactor which keeps the cells in the perfect homogenous condition for better transport of nutrients and oxygen to the desired product(s).

Baffle – Used to break the vortex formation in the vessel, which is usually highly undesirable as it changes the center of gravity of the system and consumes additional power.

Sparger – In aerobic cultivation process, the purpose of the sparger is to supply adequate oxygen to the growing cells.

Jacket – The jacket provides the annular area for circulation of constant temperature of water which keeps the temperature of the bioreactor at a constant value. [13]

See also

Related Research Articles

<span class="mw-page-title-main">Tissue engineering</span> Biomedical engineering discipline

Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials, having grown in scope and importance it can be considered as a field of its own.

<span class="mw-page-title-main">Biochemical engineering</span> Manufacturing by chemical reactions of biological organisms

Biochemical engineering, also known as bioprocess engineering, is a field of study with roots stemming from chemical engineering and biological engineering. It mainly deals with the design, construction, and advancement of unit processes that involve biological organisms or organic molecules and has various applications in areas of interest such as biofuels, food, pharmaceuticals, biotechnology, and water treatment processes. The role of a biochemical engineer is to take findings developed by biologists and chemists in a laboratory and translate that to a large-scale manufacturing process.

A bioprocess is a specific process that uses complete living cells or their components to obtain desired products.

Industrial fermentation is the intentional use of fermentation in manufacturing processes. In addition to the mass production of fermented foods and drinks, industrial fermentation has widespread applications in chemical industry. Commodity chemicals, such as acetic acid, citric acid, and ethanol are made by fermentation. Moreover, nearly all commercially produced industrial enzymes, such as lipase, invertase and rennet, are made by fermentation with genetically modified microbes. In some cases, production of biomass itself is the objective, as is the case for single-cell proteins, baker's yeast, and starter cultures for lactic acid bacteria used in cheesemaking.

<span class="mw-page-title-main">Chemostat</span>

A chemostat is a bioreactor to which fresh medium is continuously added, while culture liquid containing left over nutrients, metabolic end products and microorganisms is continuously removed at the same rate to keep the culture volume constant. By changing the rate with which medium is added to the bioreactor the specific growth rate of the microorganism can be easily controlled within limits.

<span class="mw-page-title-main">Secondary treatment</span> Biological treatment process for wastewater or sewage

Secondary treatment is the removal of biodegradable organic matter from sewage or similar kinds of wastewater. The aim is to achieve a certain degree of effluent quality in a sewage treatment plant suitable for the intended disposal or reuse option. A "primary treatment" step often precedes secondary treatment, whereby physical phase separation is used to remove settleable solids. During secondary treatment, biological processes are used to remove dissolved and suspended organic matter measured as biochemical oxygen demand (BOD). These processes are performed by microorganisms in a managed aerobic or anaerobic process depending on the treatment technology. Bacteria and protozoa consume biodegradable soluble organic contaminants while reproducing to form cells of biological solids. Secondary treatment is widely used in sewage treatment and is also applicable to many agricultural and industrial wastewaters.

<span class="mw-page-title-main">Fermentation</span> Metabolic process

Fermentation is a metabolic process that produces chemical changes in organic substances through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food production, it may more broadly refer to any process in which the activity of microorganisms brings about a desirable change to a foodstuff or beverage. The science of fermentation is known as zymology.

<span class="mw-page-title-main">Photobioreactor</span> Bioreactor with a light source to grow photosynthetic microorganisms

A photobioreactor (PBR) refers to any cultivation system designed for growing photoautotrophic organisms using artificial light sources or solar light to facilitate photosynthesis. PBRs are typically used to cultivate microalgae, cyanobacteria, and some mosses. PBRs can be open systems, such as raceway ponds, which rely upon natural sources of light and carbon dioxide. Closed PBRs are flexible systems that can be controlled to the physiological requirements of the cultured organism, resulting in optimal growth rates and purity levels. PBRs are typically used for the cultivation of bioactive compounds for biofuels, pharmaceuticals, and other industrial uses.

Fed-batch culture is, in the broadest sense, defined as an operational technique in biotechnological processes where one or more nutrients (substrates) are fed (supplied) to the bioreactor during cultivation and in which the product(s) remain in the bioreactor until the end of the run. An alternative description of the method is that of a culture in which "a base medium supports initial cell culture and a feed medium is added to prevent nutrient depletion". It is also a type of semi-batch culture. In some cases, all the nutrients are fed into the bioreactor. The advantage of the fed-batch culture is that one can control concentration of fed-substrate in the culture liquid at arbitrarily desired levels.

Biomolecular engineering is the application of engineering principles and practices to the purposeful manipulation of molecules of biological origin. Biomolecular engineers integrate knowledge of biological processes with the core knowledge of chemical engineering in order to focus on molecular level solutions to issues and problems in the life sciences related to the environment, agriculture, energy, industry, food production, biotechnology and medicine.

Product inhibition is a type of enzyme inhibition where the product of an enzyme reaction inhibits its production. Cells utilize product inhibition to regulate of metabolism as a form of negative feedback controlling metabolic pathways. Product inhibition is also an important topic in biotechnology, as overcoming this effect can increase the yield of a product, such as an antibiotic. Product inhibition can be Competitive, non-competitive or uncompetitive.

<span class="mw-page-title-main">Sartorius AG</span> German pharmaceutical company

Sartorius AG is an international pharmaceutical and laboratory equipment supplier, covering the segments of Bioprocess Solutions and Lab Products & Services.

<span class="mw-page-title-main">Microcarrier</span>

A microcarrier is a support matrix that allows for the growth of adherent cells in bioreactors. Instead of on a flat surface, cells are cultured on the surface of spherical microcarriers so that each particle carries several hundred cells, and therefore expansion capacity can be multiplied several times over. It provides a straightforward way to scale up culture systems for industrial production of cell or protein-based therapies, or for research purposes.

A single-use bioreactor or disposable bioreactor is a bioreactor with a disposable bag instead of a culture vessel. Typically, this refers to a bioreactor in which the lining in contact with the cell culture will be plastic, and this lining is encased within a more permanent structure. Commercial single-use bioreactors have been available since the end of the 1990s and are now made by several well-known producers.

<span class="mw-page-title-main">Moss bioreactor</span>

A moss bioreactor is a photobioreactor used for the cultivation and propagation of mosses. It is usually used in molecular farming for the production of recombinant protein using transgenic moss. In environmental science moss bioreactors are used to multiply peat mosses e.g. by the Mossclone consortium to monitor air pollution.

<span class="mw-page-title-main">Culture of microalgae in hatcheries</span>

Microalgae or microscopic algae grow in either marine or freshwater systems. They are primary producers in the oceans that convert water and carbon dioxide to biomass and oxygen in the presence of sunlight.

Solid state fermentation (SSF) is a biomolecule manufacturing process used in the food, pharmaceutical, cosmetic, fuel and textile industries. These biomolecules are mostly metabolites generated by microorganisms grown on a solid support selected for this purpose. This technology for the culture of microorganisms is an alternative to liquid or submerged fermentation, used predominantly for industrial purposes.

<span class="mw-page-title-main">Oscillatory baffled reactor</span>

A Continuous Oscillatory Baffled Reactor (COBR) is a specially designed chemical reactor to achieve plug flow under laminar flow conditions. Achieving plug flow has previously been limited to either a large number of continuous stir tank reactors (CSTR) in series or conditions with high turbulent flow. The technology incorporates annular baffles to a tubular reactor framework to create eddies when liquid is pushed up through the tube. Likewise, when liquid is on a downstroke through the tube, eddies are created on the other side of the baffles. Eddy generation on both sides of the baffles creates very effective mixing while still maintaining plug flow. By using COBR, potentially higher yields of product can be made with greater control and reduced waste.

Substrate inhibition in bioreactors occurs when the concentration of substrate exceeds the optimal parameters and reduces the growth rate of the cells within the bioreactor. This is often confused with substrate limitation, which describes environments in which cell growth is limited due to of low substrate. Limited conditions can be modeled with the Monod equation; however, the Monod equation is no longer suitable in substrate inhibiting conditions. A Monod deviation, such as the Haldane (Andrew) equation, is more suitable for substrate inhibiting conditions. These cell growth models are analogous to equations that describe enzyme kinetics, although, unlike enzyme kinetics parameters, cell growth parameters are generally empirically estimated.

References

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Further reading