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Interferometry
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===Biology and medicine=== Optical interferometry, applied to biology and medicine, provides sensitive metrology capabilities for the measurement of biomolecules, subcellular components, cells and tissues.<ref name=Nolte2>{{cite book|last=Nolte|first=David D.|title=Optical Interferometry for Biology and Medicine |date=2012 |publisher=Springer |isbn=978-1-4614-0889-5|bibcode=2012oibm.book.....N}}</ref> Many forms of label-free biosensors rely on interferometry because the direct interaction of electromagnetic fields with local molecular polarizability eliminates the need for fluorescent tags or [[nanoparticle]] markers. At a larger scale, cellular interferometry shares aspects with phase-contrast microscopy, but comprises a much larger class of phase-sensitive optical configurations that rely on optical interference among cellular constituents through refraction and diffraction. At the tissue scale, partially-coherent forward-scattered light propagation through the micro aberrations and heterogeneity of tissue structure provides opportunities to use phase-sensitive gating (optical coherence tomography) as well as phase-sensitive fluctuation spectroscopy to image subtle structural and dynamical properties. {| cellspacing="0" border="0" style="margin:1em auto;" |- |[[File:OCT B-Scan Setup-en.svg|border|350px]]<br/><span style="font-size:87%; line-height: 1.3em;">Figure 22. Typical optical setup of single point OCT</span> | |[[File:Central serous retinopathy.jpg|border|300px]]<br/><span style="font-size:87%; line-height: 1.3em;">Figure 23. [[Central serous retinopathy]],imaged using<br/>optical coherence tomography</span> |} [[Optical coherence tomography]] (OCT) is a medical imaging technique using low-coherence interferometry to provide tomographic visualization of internal tissue microstructures. As seen in Fig. 22, the core of a typical OCT system is a Michelson interferometer. One interferometer arm is focused onto the tissue sample and scans the sample in an X-Y longitudinal raster pattern. The other interferometer arm is bounced off a reference mirror. Reflected light from the tissue sample is combined with reflected light from the reference. Because of the low coherence of the light source, interferometric signal is observed only over a limited depth of sample. X-Y scanning therefore records one thin optical slice of the sample at a time. By performing multiple scans, moving the reference mirror between each scan, an entire three-dimensional image of the tissue can be reconstructed.<ref name=Huang1991>{{cite journal|last=Huang|first=D.|author2=Swanson, E.A. |author3=Lin, C.P. |author4=Schuman, J.S. |author5=Stinson, W.G. |author6=Chang, W. |author7=Hee, M.R. |author8=Flotte, T.|author9=Gregory, K. |author10=Puliafito, C.A.|author11=Fujimoto, J.G. |title=Optical Coherence Tomography |journal=Science |date=1991 |volume=254 |issue=5035 |doi=10.1126/science.1957169 |url=http://stuff.mit.edu:8001/afs/athena/course/2/2.717/OldFiles/www/oct_fujimoto_91.pdf |access-date=10 April 2012 |pmid=1957169|bibcode = 1991Sci...254.1178H |pages=1178–81 |pmc=4638169}}</ref><ref name=Fercher1996>{{cite journal |last=Fercher |first=A.F. |title=Optical Coherence Tomography |journal=Journal of Biomedical Optics |date=1996 |volume=1 |issue=2 |pages=157–173 |url=http://otg.downstate.edu/downloads/2008/spring08/refsbmi/oct/fercher.pdf |access-date=10 April 2012 |bibcode=1996JBO.....1..157F |doi=10.1117/12.231361 |pmid=23014682 |archive-date=25 September 2018 |archive-url=https://web.archive.org/web/20180925131609/http://otg.downstate.edu/downloads/2008/spring08/refsbmi/oct/fercher.pdf |url-status=dead }}</ref> Recent advances have striven to combine the nanometer phase retrieval of coherent interferometry with the ranging capability of low-coherence interferometry.<ref name=Olszak/> <gallery mode="packed" heights="190"> File:Spirogyra cell.jpg|Figure 24. Spyrogira cell (detached from algal filament) under phase contrast File:T. gondii unsporulated oocyst, differential interference contrast (DIC), 100×..jpg|Figure 25. ''Toxoplasma gondii'' unsporulated oocyst, differential interference contrast File:Phase-contrast x-ray image of spider.jpg|Figure 26. High resolution phase-contrast x-ray image of a spider </gallery> [[Phase contrast microscopy|Phase contrast]] and [[Differential interference contrast microscopy|differential interference contrast]] (DIC) microscopy are important tools in biology and medicine. Most animal cells and single-celled organisms have very little color, and their intracellular organelles are almost totally invisible under simple [[Bright field microscopy|bright field illumination]]. These structures can be made visible by [[staining]] the specimens, but staining procedures are time-consuming and kill the cells. As seen in Figs. 24 and 25, phase contrast and DIC microscopes allow unstained, living cells to be studied.<ref name=Lang1971>{{cite web |last=Lang |first=Walter |title=Nomarski Differential Interference-Contrast Microscopy |url=http://zeiss-campus.magnet.fsu.edu/referencelibrary/pdfs/Lang_Zeiss_Information_76_69-76_1971.pdf |publisher=Carl Zeiss, Oberkochen |access-date=10 April 2012}}</ref> DIC also has non-biological applications, for example in the [[Differential interference contrast microscopy#Advantages and disadvantages|analysis of planar silicon semiconductor processing]]. [[Angle-resolved low-coherence interferometry]] (a/LCI) uses scattered light to measure the sizes of subcellular objects, including [[Cell (biology)|cell]] nuclei. This allows interferometry depth measurements to be combined with density measurements. Various correlations have been found between the state of tissue health and the measurements of subcellular objects. For example, it has been found that as tissue changes from normal to cancerous, the average cell nuclei size increases.<ref name=Wax>{{Cite journal | last1 = Wax | first1 = A. | last2 = Pyhtila | first2 = J. W. | last3 = Graf | first3 = R. N. | last4 = Nines | first4 = R. | last5 = Boone | first5 = C. W. | last6 = Dasari | first6 = R. R. | last7 = Feld | first7 = M. S. | last8 = Steele | first8 = V. E. | last9 = Stoner | first9 = G. D. | doi = 10.1117/1.2102767 | title = Prospective grading of neoplastic change in rat esophagus epithelium using angle-resolved low-coherence interferometry | journal = Journal of Biomedical Optics | volume = 10 | issue = 5 | pages = 051604 | year = 2005 | pmid = 16292952|bibcode = 2005JBO....10e1604W | hdl = 1721.1/87657 | hdl-access = free }}</ref><ref name=Pyhtila>{{Cite journal | last1 = Pyhtila | first1 = J. W. | last2 = Chalut | first2 = K. J. | last3 = Boyer | first3 = J. D. | last4 = Keener | first4 = J. | last5 = d'Amico | first5 = T. | last6 = Gottfried | first6 = M. | last7 = Gress | first7 = F. | last8 = Wax | first8 = A. | doi = 10.1016/j.gie.2006.10.016 | title = In situ detection of nuclear atypia in Barrett's esophagus by using angle-resolved low-coherence interferometry | journal = Gastrointestinal Endoscopy | volume = 65 | issue = 3 | pages = 487–491 | year = 2007 | pmid = 17321252 }}</ref> Phase-contrast X-ray imaging (Fig. 26) refers to a variety of techniques that use phase information of a coherent x-ray beam to image soft tissues. (For an elementary discussion, see [[Phase-contrast imaging#X-ray imaging|Phase-contrast x-ray imaging (introduction)]]. For a more in-depth review, see [[Phase-contrast X-ray imaging]].) It has become an important method for visualizing cellular and histological structures in a wide range of biological and medical studies. There are several technologies being used for x-ray phase-contrast imaging, all utilizing different principles to convert phase variations in the x-rays emerging from an object into intensity variations.<ref>{{cite journal | last=Fitzgerald | first=Richard | title=Phase-sensitive x-ray imaging | date=2000 | journal=Physics Today | volume=53 | issue=7 | pages=23–26 | doi=10.1063/1.1292471|bibcode = 2000PhT....53g..23F | s2cid=121322301 | doi-access=free }}</ref><ref name=David>{{cite journal | author=David, C | author2=Nohammer, B | author3=Solak, H H | author4=Ziegler E | name-list-style=amp | title=Differential x-ray phase contrast imaging using a shearing interferometer | journal=Applied Physics Letters | date=2002 | volume=81 | issue=17 | pages=3287–3289 | doi=10.1063/1.1516611|bibcode = 2002ApPhL..81.3287D | doi-access=free }}</ref> These include propagation-based phase contrast,<ref>{{cite journal | author = Wilkins, S W | author2 = Gureyev, T E | author3 = Gao, D | author4 = Pogany, A | author5 = Stevenson, A W | name-list-style = amp | date = 1996 | title = Phase-contrast imaging using polychromatic hard X-rays | journal = Nature | volume = 384 | pages = 335–338 | doi = 10.1038/384335a0|bibcode = 1996Natur.384..335W | issue=6607| s2cid = 4273199 }}</ref> [[Talbot effect|Talbot]] interferometry,<ref name=David/> [[Moiré pattern|Moiré]]-based far-field interferometry,<ref>{{Cite journal|last1=Miao|first1=Houxun|last2=Panna|first2=Alireza|last3=Gomella|first3=Andrew A.|last4=Bennett|first4=Eric E.|last5=Znati|first5=Sami|last6=Chen|first6=Lei|last7=Wen|first7=Han|title=A universal moiré effect and application in X-ray phase-contrast imaging|journal=Nature Physics|doi=10.1038/nphys3734|pmid=27746823|volume=12|issue=9|pages=830–834|bibcode=2016NatPh..12..830M|year=2016|pmc=5063246}}</ref> refraction-enhanced imaging,<ref>{{cite journal | author = Davis, T J | author2 = Gao, D | author3 = Gureyev, T E | author4 = Stevenson, A W | author5 = Wilkins, S W | name-list-style = amp | date = 1995 | title = Phase-contrast imaging of weakly absorbing materials using hard X-rays | journal = Nature | volume = 373 | pages = 595–598 | doi = 10.1038/373595a0|bibcode = 1995Natur.373..595D | issue=6515| s2cid = 4287341 }}</ref> and x-ray interferometry.<ref>{{cite journal | author= Momose, A | author2= Takeda, T | author3= Itai, Y | author4= Hirano, K | name-list-style= amp | date= 1996 | title = Phase-contrast X-ray computed tomography for observing biological soft tissues | journal = Nature Medicine | volume = 2 | pages = 473–475 | doi = 10.1038/nm0496-473 | issue=4 | pmid=8597962| s2cid= 23523144 }}</ref> These methods provide higher contrast compared to normal absorption-contrast x-ray imaging, making it possible to see smaller details. A disadvantage is that these methods require more sophisticated equipment, such as [[synchrotron]] or [[X-ray tube#Microfocus X-ray tube|microfocus]] x-ray sources, [[x-ray optics]], or high resolution x-ray detectors.
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