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{{Short description|System that supports a biologically active environment}}
{{More citations needed|date=October 2010}}A '''bioreactor'''
It may also refer to a device or system designed to grow [[Cell (biology)|cells]] or [[Biological tissue|tissues]] in the context of [[cell culture]].<ref>{{cite web |url=http://www.eolss.net/Sample-Chapters/C17/E6-58-04-15.pdf|title=Bioreactoes and Cultivation Systems for Cell and Tissue Culture|website=eolss.net|access-date=12 August 2023}}</ref> These devices are being developed for use in [[tissue engineering]] or [[biochemical engineering|biochemical]]/[[bioprocess engineering|bioprocess]] engineering.{{
On the basis of mode of operation, a bioreactor may be classified as [[batch reactor|batch]], [[fed-batch|fed batch]] or [[continuous reactor|continuous]] (e.g. a [[continuous stirred-tank reactor model]]). An example of a continuous bioreactor is the [[chemostat]].{{
Organisms or biochemically active substances growing in bioreactors may be submerged in liquid medium or may be
biocatalysis including enzymes, cellular organelles, animal and plant cells and organs.<ref>{{Cite journal |last1=Kowalczyk |first1=Tomasz |last2=Sitarek |first2=Przemysław |last3=Toma |first3=Monika |last4=Rijo |first4=Patricia |last5=Domínguez‐Martín |first5=Eva |last6=Falcó |first6=Irene |last7=Sánchez |first7=Gloria |last8=Śliwiński |first8=Tomasz |date=August 2021 |title=Enhanced Accumulation of Betulinic Acid in Transgenic Hairy Roots of Senna obtusifolia Growing in the Sprinkle Bioreactor and Evaluation of Their Biological Properties in Various Biological Models |url=https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202100455 |journal=Chemistry & Biodiversity |language=en |volume=18 |issue=8 |pages=e2100455 |doi=10.1002/cbdv.202100455 |pmid=34185351 |hdl=10261/247635 |s2cid=235672736 |issn=1612-1872|hdl-access=free }}</ref><ref>{{cite journal |last1=Peinado |first1=Rafael A. |last2=Moreno |first2=Juan J. |last3=Villalba |first3=Jose M. |last4=González-Reyes |first4=Jose A. |last5=Ortega |first5=Jose M. |last6=Mauricio |first6=Juan C. |title=Yeast biocapsules: A new immobilization method and their applications |journal=Enzyme and Microbial Technology |date=December 2006 |volume=40 |issue=1 |pages=79–84 |doi=10.1016/j.enzmictec.2005.10.040 }}</ref> 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:
*moving media, also known as [[moving bed biofilm reactor
*[[packed bed]]
*[[fibrous bed]]
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[[Image:Pg166 bioreactor.jpg|thumb|right|192x192px|A closed bioreactor used in cellulosic ethanol research]]
Bioreactor design is a relatively complex engineering task, which is studied in the discipline of [[biochemical engineering|biochemical]]/[[bioprocess engineering|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 "[[air stripping|strips]]" out waste gases, such as carbon dioxide. In practice, bioreactors are often pressurized; this increases the [[Henry's law|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. [[Mixing (process engineering)#Liquid–gas mixing|Gas dispersing agitators]] are used to break up air bubbles and circulate them throughout the vessel.{{
''[[Fouling]]'' can harm the overall efficiency of the bioreactor, especially the [[heat exchanger]]s. 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.{{fact|date=October 2019}}▼
▲''[[Fouling]]'' can harm the overall efficiency of the bioreactor, especially the [[heat exchanger]]s. 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.{{
==Types==
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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 [[phototroph]]ic organisms such as [[cyanobacteria]], [[alga]]e, or [[moss]] plants.<ref>{{cite journal |last1=Decker |first1=Eva L. |last2=Reski |first2=Ralf |title=Current achievements in the production of complex biopharmaceuticals with moss bioreactors |journal=Bioprocess and Biosystems Engineering |date=14 August 2007 |volume=31 |issue=1 |pages=3–9 |doi=10.1007/s00449-007-0151-y |pmid=17701058 |s2cid=4673669 }}</ref> These organisms use light through [[photosynthesis]] as their [[energy]] source and do not require [[sugar]]s or [[lipid]]s as energy
source. Consequently, risk of [[contamination]] with other organisms like [[bacterium|bacteria]] or [[fungus|fungi]] is lower in photobioreactors when compared to bioreactors for [[heterotroph]] organisms.{{
===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 [[Water aeration#Aeration methods|aerator]]s 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 [[
===Bioreactors for specialized tissues===
[[File:Loading bioreactor.jpg|thumb|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 [[Auxotrophy|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.{{
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,<ref>{{cite journal |last1=Bursac |first1=N. |last2=Papadaki |first2=M. |last3=Cohen |first3=R. J. |last4=Schoen |first4=F. J. |last5=Eisenberg |first5=S. R. |last6=Carrier |first6=R. |last7=Vunjak-Novakovic |first7=G. |last8=Freed |first8=L. E. |title=Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies |journal=American Journal of Physiology. Heart and Circulatory Physiology |date=1 August 1999 |volume=277 |issue=2 |pages=H433–H444 |doi=10.1152/ajpheart.1999.277.2.h433 |pmid=10444466 }}</ref><ref>{{cite journal |last1=Carrier |first1=Rebecca L. |last2=Papadaki |first2=Maria |last3=Rupnick |first3=Maria |last4=Schoen |first4=Frederick J. |last5=Bursac |first5=Nenad |last6=Langer |first6=Robert |last7=Freed |first7=Lisa E. |last8=Vunjak-Novakovic |first8=Gordana |title=Cardiac tissue engineering: Cell seeding, cultivation parameters, and tissue construct characterization |journal=Biotechnology and Bioengineering |date=5 September 1999 |volume=64 |issue=5 |pages=580–589 |doi=10.1002/(SICI)1097-0290(19990905)64:5<580::AID-BIT8>3.0.CO;2-X |pmid=10404238 }}</ref> skeletal muscle tissue,<ref>{{cite journal |last1=Heher |first1=Philipp |last2=Maleiner |first2=Babette |last3=Prüller |first3=Johanna |last4=Teuschl |first4=Andreas Herbert |last5=Kollmitzer |first5=Josef |last6=Monforte |first6=Xavier |last7=Wolbank |first7=Susanne |last8=Redl |first8=Heinz |last9=Rünzler |first9=Dominik |last10=Fuchs |first10=Christiane |title=A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain |journal=Acta Biomaterialia |date=September 2015 |volume=24 |pages=251–265 |doi=10.1016/j.actbio.2015.06.033 |pmid=26141153 }}</ref> 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.
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== 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.{{
Bioreactors are generally used in those industries which are concerned with food, beverages and pharmaceuticals. The emergence of ''[[
Until now, the industries associated with biotechnology have lagged behind other industries in implementing control over the process and optimization strategies
=== Operational stages in a bio-process ===
A bioprocess is composed mainly of three stages
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.{{
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.{{
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|liquid-liquid extraction]], [[distillation]], [[drying]] etc.<ref name=":0">{{Cite book|title=CHEMICAL PROCESS MODELLING AND COMPUTER SIMULATION|last=Jana|first=AMIYA K.|publisher=PHI Learning Pvt. Ltd.|year=2011}}{{
=== Specifications ===
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==Further reading==
* Pauline M Doran, ''Bio-process Engineering Principles,'' Elsevier, 2nd ed., 2013 {{ISBN|978-0-12-220851-5}}
* [https://nationalpost.com/news/canada/canadas-medicago-begins-human-trials-of-plant-based-covid-19-vaccine Biotechnology company
== External links ==
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