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== Types == === Optical biosensors === Many optical biosensors are based on the phenomenon of [[surface plasmon resonance]] (SPR) techniques.<ref>{{cite journal|author=S.Zeng|title=Nanomaterials enhanced surface plasmon resonance for biological and chemical sensing applications|journal=Chemical Society Reviews|volume=43|pages=3426–3452|year=2014|doi=10.1039/C3CS60479A|last2=Baillargeat|first2=Dominique|last3=Ho|first3=Ho-Pui|last4=Yong|first4=Ken-Tye|pmid=24549396|issue=10|hdl=10356/102043|display-authors=etal|url=http://dr.ntu.edu.sg/bitstream/handle/10220/18851/Nanomaterials%20enhanced%20surface%20plasmon%20resonance%20for%20biological%20and%20chemical%20sensing%20applications.pdf?sequence=3|access-date=14 September 2015|archive-url=https://web.archive.org/web/20160106172212/https://dr.ntu.edu.sg/bitstream/handle/10220/18851/Nanomaterials%20enhanced%20surface%20plasmon%20resonance%20for%20biological%20and%20chemical%20sensing%20applications.pdf?sequence=3|archive-date=6 January 2016}}</ref><ref>{{cite journal|author=Krupin, O. |author2=Wang, C. |author3=Berini, P.|title=Optical plasmonic biosensor for leukemia detection|journal=SPIE Newsroom|issue=22 January 2016|doi=10.1117/2.1201512.006268|year=2016 }}</ref> This utilises a property of gold and other materials (metals);<ref>{{Cite journal |last1=Damborský |first1=Pavel |last2=Švitel |first2=Juraj |last3=Katrlík |first3=Jaroslav |date=2016-06-30 |title=Optical biosensors |journal=Essays in Biochemistry |volume=60 |issue=1 |pages=91–100 |doi=10.1042/EBC20150010 |issn=0071-1365 |pmc=4986466 |pmid=27365039}}</ref> specifically that a thin layer of gold on a high refractive index glass surface can absorb laser light, producing electron waves (surface plasmons) on the gold surface. This occurs only at a specific angle and wavelength of incident light and is highly dependent on the surface of the gold, such that binding of a target [[analyte]] to a receptor on the gold surface produces a measurable signal. Surface plasmon resonance sensors operate using a sensor chip consisting of a plastic cassette supporting a glass plate, one side of which is coated with a microscopic layer of gold. This side contacts the optical detection apparatus of the instrument. The opposite side is then contacted with a microfluidic flow system. The contact with the flow system creates channels across which reagents can be passed in solution. This side of the glass sensor chip can be modified in a number of ways, to allow easy attachment of molecules of interest. Normally it is coated in carboxymethyl [[dextran]] or similar compound. The refractive index at the flow side of the chip surface has a direct influence on the behavior of the light reflected off the gold side. Binding to the flow side of the chip has an effect on the [[refractive]] index and in this way biological interactions can be measured to a high degree of sensitivity with some sort of energy. The refractive index of the medium near the surface changes when biomolecules attach to the surface, and the SPR angle varies as a function of this change. Light of a fixed wavelength is reflected off the gold side of the chip at the angle of total internal reflection, and detected inside the instrument. The angle of incident light is varied in order to match the evanescent wave propagation rate with the propagation rate of the surface plasmon polaritons.<ref>{{cite journal |author=Homola J |title= Present and future of surface plasmon resonance biosensors |journal= Anal. Bioanal. Chem. |volume=377 |issue=3 |pages=528–539 |year=2003 |doi=10.1007/s00216-003-2101-0|pmid= 12879189 |s2cid= 14370505 }}</ref> This induces the evanescent wave to penetrate through the glass plate and some distance into the liquid flowing over the surface. Other optical biosensors are mainly based on changes in absorbance or fluorescence of an appropriate indicator compound and do not need a total internal reflection geometry. For example, a fully operational prototype device detecting casein in milk has been fabricated. The device is based on detecting changes in absorption of a gold layer.<ref>{{cite journal | last1 = Hiep | first1 = H. M. | display-authors = etal | year = 2007 | title = A localized surface plasmon resonance based immunosensor for the detection of casein in milk | doi = 10.1016/j.stam.2006.12.010 | journal = Sci. Technol. Adv. Mater. | volume = 8 | issue = 4| pages = 331–338 |bibcode = 2007STAdM...8..331M | doi-access = free }}</ref> A widely used research tool, the micro-array, can also be considered a biosensor. === Biological biosensors === Biological biosensors, also known as [[Optogenetic methods to record cellular activity|optogenetic sensors]], often incorporate a genetically modified form of a native protein or enzyme. The protein is configured to detect a specific analyte and the ensuing signal is read by a detection instrument such as a fluorometer or luminometer. An example of a recently developed biosensor is one for detecting [[cytosol]]ic concentration of the analyte cAMP (cyclic adenosine monophosphate), a second messenger involved in cellular signaling triggered by ligands interacting with receptors on the cell membrane.<ref>{{cite journal | last1 = Fan | first1 = F. | display-authors = etal | year = 2008 | title = Novel Genetically Encoded Biosensors Using Firefly Luciferase | journal = ACS Chem. Biol. | volume = 3 | issue = 6| pages = 346–51 | doi=10.1021/cb8000414| pmid = 18570354 }}</ref> Similar systems have been created to study cellular responses to native ligands or xenobiotics (toxins or small molecule inhibitors). Such "assays" are commonly used in drug discovery development by pharmaceutical and biotechnology companies. Most cAMP assays in current use require lysis of the cells prior to measurement of cAMP. A live-cell biosensor for cAMP can be used in non-lysed cells with the additional advantage of multiple reads to study the kinetics of receptor response. Nanobiosensors use an immobilized bioreceptor probe that is selective for target analyte molecules. Nanomaterials are exquisitely sensitive chemical and biological sensors. Nanoscale materials demonstrate unique properties. Their large surface area to volume ratio can achieve rapid and low cost reactions, using a variety of designs.<ref>{{cite journal | last1 = Urban | first1 = Gerald A | year = 2009 | title = Micro- and nanobiosensors—state of the art and trends| journal = Meas. Sci. Technol. | volume = 20 | issue = 1| page = 012001 | doi = 10.1088/0957-0233/20/1/012001 |bibcode = 2009MeScT..20a2001U | s2cid = 116936804 }}</ref> <!--=== Evanescent wave-based biosensors ===--> Other evanescent wave biosensors have been commercialised using waveguides where the propagation constant through the waveguide is changed by the absorption of molecules to the waveguide surface. One such example, [[dual polarisation interferometry]] uses a buried waveguide as a reference against which the change in propagation constant is measured. Other configurations such as the [[Mach–Zehnder]] have reference arms lithographically defined on a substrate. Higher levels of integration can be achieved using resonator geometries where the resonant frequency of a ring resonator changes when molecules are absorbed.<ref>{{cite journal | last1 = Iqbal | first1 = M. | last2 = Gleeson | first2 = M. A. | last3 = Spaugh | first3 = B. | last4 = Tybor | first4 = F. | last5 = Gunn | first5 = W. G. | last6 = Hochberg | first6 = M. | last7 = Baehr-Jones | first7 = T. | last8 = Bailey | first8 = R. C. | last9 = Gunn | first9 = L. C. | year = 2010 | title = Label-Free Biosensor Arrays Based on Silicon Ring Resonators and High-Speed Optical Scanning Instrumentation | journal = IEEE Journal of Selected Topics in Quantum Electronics | volume = 16 | issue = 3| pages = 654–661 | doi=10.1109/jstqe.2009.2032510| bibcode = 2010IJSTQ..16..654I | s2cid = 41944216 }}</ref><ref>{{cite journal|author1=J. Witzens |author2=M. Hochberg |title=Optical detection of target molecule induced aggregation of nanoparticles by means of high-Q resonators|journal=Opt. Express|volume=19|issue=8 |pages=7034–7061|year=2011|url = http://www.opticsinfobase.org/oe/fulltext.cfm?uri=oe-19-8-7034&id=211400|doi=10.1364/oe.19.007034|pmid=21503017 |bibcode = 2011OExpr..19.7034W |doi-access=free}}</ref> === Electronic nose devices === {{See also|Machine olfaction}} Recently, arrays of many different detector molecules have been applied in so called [[electronic nose]] devices, where the pattern of response from the detectors is used to fingerprint a substance.<ref>{{cite web|title=UCSB sensor sniffs explosives through microfluidics, might replace Rover at the airport (video) |url=http://www.microfluidicsolutions.com/apps/blog/show/20808263-ucsb-sensor-sniffs-explosives-through-microfluidics-might-replace-rover-at-the-airport-video- |publisher=Microfluidic Solutions |date=8 December 2012 |archive-url=https://web.archive.org/web/20140704002927/http://www.microfluidicsolutions.com/apps/blog/show/20808263-ucsb-sensor-sniffs-explosives-through-microfluidics-might-replace-rover-at-the-airport-video- |archive-date=4 July 2014}}</ref> In the [[Wasp Hound]] odor-detector, the mechanical element is a video camera and the biological element is five parasitic wasps who have been conditioned to swarm in response to the presence of a specific chemical.<ref name=scicentr>{{cite web|title=Wasp Hound |url=http://www.sciencentral.com/articles/view.php3?article_id=218392717 |publisher=Science Central |access-date=23 February 2011 |archive-url=https://web.archive.org/web/20110716014856/http://www.sciencentral.com/articles/view.php3?article_id=218392717 |archive-date=16 July 2011 }}</ref> Current commercial electronic noses, however, do not use biological elements. ===DNA biosensors=== DNA can be the analyte of a biosensor, being detected through specific means, but it can also be used as part of a biosensor or, theoretically, even as a whole biosensor. Many techniques exist to detect DNA, which is usually a means to detect organisms that have that particular DNA. DNA sequences can also be used as described above. But more forward-looking approaches exist, where DNA can be synthesized to hold enzymes in a biological, stable gel.<ref>{{Cite journal|last1=Huang|first1=Yishun|last2=Xu|first2=Wanlin|last3=Liu|first3=Guoyuan|last4=Tian|first4=Leilei|date=2017|title=A pure DNA hydrogel with stable catalytic ability produced by one-step rolling circle amplification|url=http://xlink.rsc.org/?DOI=C7CC00636E|journal=Chemical Communications|language=en|volume=53|issue=21|pages=3038–3041|doi=10.1039/C7CC00636E|pmid=28239729|issn=1359-7345|url-access=subscription}}</ref> Other applications are the design of aptamers, sequences of DNA that have a specific shape to bind a desired molecule. The most innovative processes use [[DNA origami]] for this, creating sequences that fold in a predictable structure that is useful for detection.<ref>{{Cite journal|last1=Tinnefeld|first1=Philip|last2=Acuna|first2=Guillermo P.|last3=Wei|first3=Qingshan|last4=Ozcan|first4=Aydogan|last5=Ozcan|first5=Aydogan|last6=Ozcan|first6=Aydogan|last7=Vietz|first7=Carolin|last8=Lalkens|first8=Birka|last9=Trofymchuk|first9=Kateryna|last10=Close|first10=Cindy M.|last11=Inan|first11=Hakan|date=2019-04-15|title=DNA origami nanotools for single-molecule biosensing and superresolution microscopy|url=https://www.osapublishing.org/abstract.cfm?uri=OMA-2019-AW5E.5|journal=Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP) (2019), Paper AW5E.5|language=EN|publisher=Optical Society of America|pages=AW5E.5|doi=10.1364/OMA.2019.AW5E.5|isbn=978-1-943580-54-5|s2cid=210753045|url-access=subscription}}</ref><ref>{{Cite journal|last1=Selnihhin|first1=Denis|last2=Sparvath|first2=Steffen Møller|last3=Preus|first3=Søren|last4=Birkedal|first4=Victoria|last5=Andersen|first5=Ebbe Sloth|date=26 June 2018|title=Multifluorophore DNA Origami Beacon as a Biosensing Platform|journal=ACS Nano|volume=12|issue=6|pages=5699–5708|doi=10.1021/acsnano.8b01510|issn=1936-086X|pmid=29763544|s2cid=206719944 }}</ref> Scientists have built prototype sensors to detect DNA of animals from sucked in air, "airborne eDNA".<ref>{{cite news |title=Scientists vacuumed animal DNA out of thin air for the first time |url=https://www.sciencenews.org/article/animal-dna-air-scientist-vacuum-first-time-zoo |access-date=29 January 2022 |work=Science News |date=18 January 2022}}</ref> "Nanoantennas" made out of DNA – a novel type of nano-scale [[optical antenna]]<!-- reported in 2021--> – can be attached to [[protein]]s and produce a signal via [[fluorescence]] when these perform their biological functions, in particular for distinct [[conformational change]]s.<ref>{{cite news |title=Chemists use DNA to build the world's tiniest antenna |url=https://phys.org/news/2022-01-chemists-dna-world-tiniest-antenna.html |access-date=19 January 2022 |work=University of Montreal |language=en}}</ref><ref>{{cite journal |last1=Harroun |first1=Scott G. |last2=Lauzon |first2=Dominic |last3=Ebert |first3=Maximilian C. C. J. C. |last4=Desrosiers |first4=Arnaud |last5=Wang |first5=Xiaomeng |last6=Vallée-Bélisle |first6=Alexis |title=Monitoring protein conformational changes using fluorescent nanoantennas |journal=Nature Methods |date=January 2022 |volume=19 |issue=1 |pages=71–80 |doi=10.1038/s41592-021-01355-5 |pmid=34969985 |s2cid=245593311 |language=en |issn=1548-7105|doi-access=free }}</ref> === Graphene-based biosensor === [[Graphene]] is a two-dimensional carbon-based substance with superior optical, electrical, mechanical, thermal, and mechanical properties. The ability to absorb and immobilize a variety of proteins, particularly some with carbon ring structures, has proven graphene to be an excellent candidate as a biosensor transducer. As a result, various graphene-based biosensors have been explored and developed in recent times.<ref name="High-performance graphene-based bio"/> <ref>{{cite journal |last1=Khayamian |first1=Mohammad Ali |last2=Parizi |first2=Mohammad Salemizadeh |last3=Ghaderinia |first3=Mohammadreza |last4=Abadijoo |first4=Hamed |last5=Vanaei |first5=Shohreh |last6=Simaee |first6=Hossein |last7=Abdolhosseini |first7=Saeed |last8=Shalileh |first8=Shahriar |last9=Faramarzpour |first9=Mahsa |last10=Naeini |first10=Vahid Fadaei |last11=Hoseinpour |first11=Parisa |last12=Shojaeian |first12=Fatemeh |last13=Abbasvandi |first13=Fereshteh |last14=Abdolahad |first14=Mohammad |title=A label-free graphene-based impedimetric biosensor for real-time tracing of the cytokine storm in blood serum; suitable for screening COVID-19 patients |journal=RSC Advances |date=2021 |volume=11 |issue=55 |pages=34503–34515 |doi=10.1039/D1RA04298J|pmid=35494759 |pmc=9042719 |bibcode=2021RSCAd..1134503K }}</ref> Graphene has been employed as a biosensor in various formats especially electrochemical sensors and field effect transistors. Amongst them graphene field effect transistors (GFETs) especially have shown excellent performance as rapid point of care (PoC) diagnostics as observed through a surge in number of research articles reporting COVID-19 diagnostics using GFETs. They have been reported to have some of the lowest limit of detection whilst also having a rapid turn around time of a few seconds along with multiplexing abilities.<ref>{{Cite journal |last1=Kumar |first1=Neelotpala |last2=Towers |first2=Dalton |last3=Myers |first3=Samantha |last4=Galvin |first4=Cooper |last5=Kireev |first5=Dmitry |last6=Ellington |first6=Andrew D. |last7=Akinwande |first7=Deji |date=2023-09-13 |title=Graphene Field Effect Biosensor for Concurrent and Specific Detection of SARS-CoV-2 and Influenza |url=https://pubs.acs.org/doi/10.1021/acsnano.3c07707 |journal=ACS Nano |volume=17 |issue=18 |pages=18629–18640 |language=en |doi=10.1021/acsnano.3c07707 |pmid=37703454 |issn=1936-0851}}</ref> These capabilities allow for immediate disease detection especially in cases with overlapping symptoms which are hard to distinguish at the outset, thus allowing for better patient outcomes especially in resource strained medical settings.
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