Editing Bioreactor

{{Short description|System that supports a biologically active environment}}
{{More citations needed|date=October 2010}}A '''bioreactor''' is any manufactured device or system that supports a biologically active environment.<ref>{{GoldBookRef|title=bioreactor|file=B00662}}</ref> In one case, a bioreactor is a vessel in which a [[chemical reaction|chemical process]] is carried out which involves [[organism]]s or [[biochemistry|biochemically]] active [[chemical substance|substance]]s derived from such organisms. This process can either be [[Aerobic organism|aerobic]] or [[Anaerobic organism|anaerobic]]. These bioreactors are commonly cylindrical, ranging in size from litres to cubic metres, and are often made of [[stainless steel]].{{citation needed|date=October 2019}}

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.{{citation needed|date=October 2019}}[[File:Bioreactor principle.svg|thumb|210px|General structure of a continuous stirred-tank type bioreactor]]

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]].{{citation needed|date=October 2019}}

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.<ref>{{cite journal |last1=López |first1=Asunción |last2=Lázaro |first2=Nuria |last3=Marqués |first3=Ana M. |title=The interphase technique: a simple method of cell immobilization in gel-beads |journal=Journal of Microbiological Methods |date=September 1997 |volume=30 |issue=3 |pages=231–234 |doi=10.1016/S0167-7012(97)00071-7 }}</ref> It can be applied to basically all types of
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]] (MBBR)
*[[packed bed]]
*[[fibrous bed]]
*[[Membrane bioreactor|membrane]]

==Design==
[[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.{{citation needed|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.{{citation needed|date=October 2019}}

[[Scale-down bioreactor|Scale-down bioreactors]] play an important rule in process development as they allow for parameters to be fine-tuned without substantial materials or consumables investments.<ref>{{Cite journal |last1=Tozer |first1=Stephanie |last2=Krishnan |first2=Raj |last3=Rausch |first3=Steve |last4=Smiley |first4=Dave |last5=Rathore |first5=Anurag |date=2005-03-01 |title=Scaling Down of Biopharmaceutical Unit Operations — Part 1: Fermentation |url=https://www.biopharminternational.com/view/scaling-down-biopharmaceutical-unit-operations-part-1-fermentation |journal=BioPharm International |series=BioPharm International-03-01-2005 |language=en |volume=18 |issue=3}}</ref>

==Types==

===Photobioreactor===
[[File:Bioreaktor quer2.jpg|thumb|upright|[[Moss bioreactor|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 [[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.{{citation needed|date=October 2019}}

===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 [[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|date=October 2019}}

===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.{{citation needed|date=October 2019}}

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.

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|date=October 2019}}

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|date=October 2019}}

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.<ref>{{cite web |title=An introduction to modeling of bioreactors |first1=Bengt |last1=Carlsson |date=March 24, 2009 |url=https://www.it.uu.se/edu/course/homepage/modynsyst/vt11/Lecture/DynSystBior2009.pdf }}</ref>

=== Operational stages in a bio-process ===
A bioprocess is composed mainly of three stages&mdash;upstream processing, bioreaction, and downstream processing&mdash;to convert raw material to finished product.<ref>{{Citation|last1=Rosser|first1=J.|title=10 - Bioreactor processes for maturation of 3D bioprinted tissue|date=2018-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780081011034000107|work=3D Bioprinting for Reconstructive Surgery|pages=191–215|editor-last=Thomas|editor-first=Daniel J.|publisher=Woodhead Publishing|language=en|isbn=978-0-08-101103-4|access-date=2020-12-14|last2=Thomas|first2=D. J.|editor2-last=Jessop|editor2-first=Zita M.|editor3-last=Whitaker|editor3-first=Iain S.}}</ref>

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|date=October 2019}}

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|date=October 2019}}

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}}{{page needed|date=October 2019}}</ref>

=== 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.<ref>{{Cite web|url=http://iitd.vlab.co.in/?sub=63&brch=177&sim=647&cnt=1|title=Bioreactor- Basics}}</ref>

==See also==
{{Portal|Biology|Technology}}
{{div col|colwidth=20em}}
* [[ATP test]]
* [[Biochemical engineering]]
* [[Biofuel from algae]]
* [[Biological hydrogen production (algae)]]
* [[Bioprocessor]]
* [[Bioreactor landfill]]
* [[Biotechnology]]
* [[Cell culture]]
* [[Chemostat]]
* [[Anaerobic digestion|Digester]]
* [[Electro-biochemical reactor]] (EBR)
* [[Hairy root culture]]
* [[History of biotechnology]]
* [[Hollow fiber bioreactor]]
* [[Immobilized enzyme]]
* [[Industrial biotechnology]]
* [[Moving bed biofilm reactor]]
* [[Septic tank]]
* [[Single-use bioreactor]]
* [[Tissue engineering]]
{{div col end}}
{{commons category|Bioreactors}}

== References ==
<references/>

==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 ==
* [https://web.archive.org/web/20090411214045/http://inventgeek.com/Projects/photo-bio-reactor/overview.aspx Photo-bioreactor].

{{Biotechnology}}
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[[Category:Biotechnology]]
[[Category:Biological engineering]]
[[Category:Bioreactors| ]]
[[Category:Biochemical engineering]]