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| [[Image:Chemostat shematic.svg|thumb|Stirred bioreactor operated as a chemostat, with a continuous inflow (the feed) and outflow (the effluent). The rate of medium flow is controlled to keep the culture volume constant.]] | | [http://www.dailyroads.com/profile_info.php?ID=2363798 over the counter std test] writer is called Irwin. Years ago we moved to North Dakota. Bookkeeping is what I do. To collect coins is what her family and her appreciate. |
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| A '''chemostat''' (from '''Chem'''ical environment is '''stat'''ic) is a [[bioreactor]] to which fresh medium is continuously added, while culture liquid is continuously removed to keep the culture volume constant.<ref name=Novick_1950>{{cite journal |author=Novick A, Szilard L |title=Description of the Chemostat |journal=Science |volume=112 |issue=2920 |pages=715–6 |year=1950 |pmid=14787503 |doi=10.1126/science.112.2920.715}}</ref><ref name=James_1961>{{cite journal |author=James TW |title=Continuous Culture of Microorganisms |journal=Annual Review of Microbiology |volume=15 |pages=27–46 |year=1961 |doi=10.1146/annurev.mi.15.100161.000331}}</ref> By changing the rate with which medium is added to the bioreactor the [[Population growth rate|growth rate]] of the [[microorganism]] can be easily controlled.
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| == Operation ==
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| === Steady state ===
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| One of the most important features of chemostats is that micro-organisms can be grown in a physiological steady state. In steady state, growth occurs at a constant rate and all culture parameters remain constant (culture volume, dissolved oxygen concentration, nutrient and product concentrations, pH, cell density, etc.). In addition environmental conditions can be controlled by the experimenter.<ref name="Herbert1956">{{cite journal |author=D Herbert, R Elsworth Telling RC|title=The continuous culture of bacteria;a Theoretical and Experimental study|journal=J. Gen. Microbiol |volume=14 |issue=3 |pages=601–622 |year=1956|doi=10.1099/00221287-14-3-601 |pmid=13346021}}</ref> Micro-organisms grown in chemostats naturally strive to steady state: if a low amount of cells are present in the bioreactor, the cells can grow at growth rates higher than the dilution rate, as growth isn't limited by the addition of the [[limiting nutrient]]. The limiting nutrient is a nutrient essential for growth, present in the media at a limiting concentration (all other nutrients are usually supplied in surplus). However, if the cell concentration becomes too high, the amount of cells that are removed from the reactor cannot be replenished by growth as the addition of the [[limiting nutrient]] is insufficient. This results in a steady state.
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| === Dilution rate ===
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| At steady state the [[specific growth rate]] (μ) of the micro-organism is equal to the dilution rate (D). The dilution rate is defined as the rate of flow of medium over the volume of culture in the bioreactor
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| <math>D = \dfrac{\mbox{Medium flow rate}}{\mbox{Culture volume}} = \dfrac{\mbox{F}}{\mbox{V}}</math>
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| === Maximal growth rate ===
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| Each microorganism growing on a particular substrate has a maximum specific growth rate (μ<sub>max</sub>) (the rate of growth observed if none of the nutrients are limiting). If a dilution rate is chosen that is higher than μ<sub>max</sub>, the culture will not be able to sustain itself in the bioreactor, and will wash out. Even though maximum rates can be obtained, the reactors may become very large. This is especially true in E. coli fatty acid production in a glucose medium.
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| == Applications ==
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| === Research ===
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| Chemostats in research are used for investigations in cell biology, as a source for large volumes of uniform cells or protein. The chemostat is often used to gather steady state data about an organism in order to generate a mathematical model relating to its metabolic processes. Chemostats are also used as [[Microcosm: Model / experimental ecosystem|microcosms]] in ecology<ref name=becks1>{{cite journal |author=Becks L, Hilker FM, Malchow H, Jürgens K, Arndt H |title=Experimental demonstration of chaos in a microbial food web |journal=Nature |volume=435 |issue=7046 |pages=1226–9 |year=2005 |pmid=15988524 |doi=10.1038/nature03627}}</ref><ref name=Pavlou1>{{cite journal |author=Pavlou S, Kevrekidis IG |title=Microbial predation in a periodically operated chemostat: a global study of the interaction between natural and externally imposed frequencies |journal=Math Biosci |volume=108 |issue=1 |pages=1–55 |year=1992 |pmid=1550993 |doi=10.1016/0025-5564(92)90002-E}}</ref> and evolutionary biology.<ref name=Wichman1>{{cite journal |author=Wichman HA, Millstein J, Bull JJ |title=Adaptive Molecular Evolution for 13,000 Phage Generations: A Possible Arms Race |journal=Genetics |volume=170 |issue=1 |pages=19–31 |year=2005 |pmid=15687276 |doi=10.1534/genetics.104.034488 |pmc=1449705}}</ref><ref name=dykhuizen1>{{cite journal |author=Dykhuizen DE, Dean AM |title=Evolution of specialists in an experimental microcosm |journal=Genetics |volume=167 |issue=4 |pages=2015–26 |year=2004 |pmid=15342537 |doi=10.1534/genetics.103.025205 |pmc=1470984}}</ref><ref name=Wick1>{{cite journal |author=Wick LM, Weilenmann H, Egli T |title=The apparent clock-like evolution of Escherichia coli in glucose-limited chemostats is reproducible at large but not at small population sizes and can be explained with Monod kinetics |journal=Microbiology (Reading, Engl.) |volume=148 |issue=Pt 9 |pages=2889–902 |year=2002 |pmid=12213934 |doi=}}</ref><ref name=Jones1>{{cite journal |author=Jones LE, Ellner SP |title=Effects of rapid prey evolution on predator-prey cycles |journal=J Math Biol |volume=55 |issue=4 |pages=541–73 |year=2007 |pmid=17483952 |doi=10.1007/s00285-007-0094-6}}</ref> In the one case, mutation/selection is a nuisance, in the other case, it is the desired process under study. Chemostats can also be used to [[Enrichment culture|enrich]] for specific types of bacterial mutants in culture such as [[auxotroph]]s or those that are resistant to [[antibiotic]]s or [[bacteriophage]]s for further scientific study.<ref>{{cite journal |author=Schlegel HG, Jannasch HW |title=Enrichment cultures |journal=Annu. Rev. Microbiol. |volume=21 |issue= |pages=49–70 |year=1967 |pmid=4860267 |doi=10.1146/annurev.mi.21.100167.000405 |url=}}</ref>
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| Competition for single and multiple resources, the evolution of resource acquisition and utilization pathways, cross-feeding/symbiosis,<ref name=daughton1>{{cite journal |author=Daughton CG, Hsieh DP |title=Parathion utilization by bacterial symbionts in a chemostat |journal=Appl. Environ. Microbiol. |volume=34 |issue=2 |pages=175–84 |year=1977 |pmid=410368 |doi= |pmc=242618}}</ref><ref name=Pfeiffer>{{cite journal |author=Pfeiffer T, Bonhoeffer S |title=Evolution of cross-feeding in microbial populations |journal=Am. Nat. |volume=163 |issue=6 |pages=E126–35 |year=2004 |pmid=15266392 |doi=10.1086/383593}}</ref> antagonism, predation, and competition among predators have all been studied in [[ecology]] and [[evolutionary biology]] using chemostats.<ref>{{cite journal |author=G. J. Butler and G. S. K. Wolkowicz. |title=Predator-mediated competition in the chemostat |journal=J Math Biol. |volume=24 |issue=2 |pages=67–191 |date=july 1986 |pmid= |doi= 10.1007/BF00275997|url=http://www.springerlink.com/content/nwg1r43026l47q45/fulltext.pdf|format=PDF}}</ref><ref>{{cite journal |author=Dykhuizen DE, Hartl DL |title=Selection in chemostats |journal=Microbiol. Rev. |volume=47 |issue=2 |pages=150–68 |date=June 1983 |pmid=6308409 |doi= |url=http://mmbr.asm.org/cgi/pmidlookup?view=long&pmid=6308409 |pmc=281569}}</ref><ref>{{cite journal |author=Dykhuizen DE, Hartl DL |title=Evolution of Competitive Ability in Escherichia coli |journal=Evolution |volume=35 |issue=3 |pages=581–94 |date=May 1981 |pmid= |doi= 10.2307/2408204 |publisher=Evolution, Vol. 35, No. 3 |jstor=2408204}}</ref>
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| === Industry ===
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| Chemostats are frequently used in the industrial manufacturing of [[ethanol]]. In this case, several chemostats are used in series, each maintained at decreasing sugar concentrations.{{Citation needed|date=April 2008}}
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| == Concerns ==
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| * Foaming results in overflow with the volume of liquid not exactly constant.
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| * Some very fragile cells are ruptured during [[agitation (action)|agitation]] and [[aeration]].
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| * Cells may grow on the walls or adhere to other surfaces,<ref name=Bonomi1>{{cite journal |author=Bonomi A, Fredrickson AG |title=Protozoan feeding and bacterial wall growth |journal=[[Biotechnol. Bioeng.]] |volume=18 |issue=2 |pages=239–52 |year=1976 |pmid=1267931 |doi=10.1002/bit.260180209}}</ref> which is easily overcome by treating the glass walls of the vessel with a [[silane]] to render them hydrophobic.
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| * Mixing may not truly be uniform, upsetting the "static" property of the chemostat.
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| * Dripping the media into the chamber actually results in small pulses of nutrients and thus oscillations in concentrations, again upsetting the "static" property of the chemostat.
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| * Bacteria travel upstream quite easily. They will reach the reservoir of sterile medium quickly unless the liquid path is interrupted by an air break in which the medium falls in drops through air.
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| Continuous efforts to remedy each defect lead to variations on the basic chemostat quite regularly. Examples in the literature are numerous.
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| * Antifoaming agents are used to suppress foaming.
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| * Agitation and aeration can be done gently.
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| * Many approaches have been taken to reduce wall growth<ref name=deCrecy>{{cite journal |author=de Crécy E, Metzgar D, Allen C, Pénicaud M, Lyons B, Hansen CJ, de Crécy-Lagard V |title=Development of a novel continuous culture device for experimental evolution of bacterial populations |journal=[[Appl. Microbiol. Biotechnol.]] |volume=77 |issue=2 |pages=489–96 |year=2007 |pmid=17896105 |doi=10.1007/s00253-007-1168-5}}</ref><ref name=ZhangZ1>{{cite journal |author=Zhang Z, Boccazzi P, Choi HG, Perozziello G, Sinskey AJ, Jensen KF |title=Microchemostat-microbial continuous culture in a polymer-based, instrumented microbioreactor |journal=Lab Chip |volume=6 |issue=7 |pages=906–13 |year=2006 |pmid=16804595 |doi=10.1039/b518396k}}</ref>
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| * Various applications use paddles, bubbling, or other mechanisms for mixing<ref name=vanhulle1 >{{cite journal |author=Van Hulle SW, Van Den Broeck S, Maertens J, Villez K, Schelstraete G, Volcke EI, Vanrolleghem PA |title=Practical experiences with start-up and operation of a continuously aerated lab-scale SHARON reactor |journal=[[Commun. Agric. Appl. Biol. Sci.]] |volume=68 |issue=2 Pt A |pages=77–84 |year=2003 |pmid=15296140 |doi= }}</ref>
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| * Dripping can be made less drastic with smaller droplets and larger vessel volumes
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| * Many improvements target the threat of contamination
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| == Variations ==
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| Fermentation setups closely related to the chemostats are the [[turbidostat]], the [[auxostat]] and the [[retentostat]]. In retentostats culture liquid is also removed from the bioreactor, but a filter retains the biomass. In this case, the biomass concentration increases until the nutrient requirement for biomass maintenance has become equal to the amount of limiting nutrient that can be consumed.
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| == See also ==
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| *[[Bacterial growth]]
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| *[[Biochemical engineering]]
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| *[[Continuous stirred-tank reactor model|Continuous stirred-tank reactor (CSTR)]]
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| *[[E. coli long-term evolution experiment]]
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| *[[Fed-batch]]
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| Batch culture
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| == References ==
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| {{Reflist}}
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| ==External links==
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| # [http://www.midgard.liu.se/~b00perst/chemostat.pdf http://www.midgard.liu.se/~b00perst/chemostat.pdf]
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| # [http://www.rpi.edu/dept/chem-eng/Biotech-Environ/Contin/chemosta.htm http://www.rpi.edu/dept/chem-eng/Biotech-Environ/Contin/chemosta.htm]
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| # [http://pererikstrandberg.se/examensarbete/strandberg_tillampad_matematik_bioreaktorer.pdf A final thesis including mathematical models of the chemostat and other bioreactors]
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| # [http://openwetware.org/wiki/Endy:Chemostat A page about one laboratory chemostat design]
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| {{Laboratory equipment}}
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| [[Category:Bioreactors]]
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over the counter std test writer is called Irwin. Years ago we moved to North Dakota. Bookkeeping is what I do. To collect coins is what her family and her appreciate.