Editing Microscope

{{short description|Scientific instrument}}
{{about|microscopes, the instruments, in general|light microscopes|Optical microscope|other uses}}
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{{More science citations needed|date=April 2017}}
{{Use Canadian English|date=September 2016}}
{{Infobox laboratory equipment
|name   = Microscope
|image  = Ukrainian microscope (cropped).jpg
|uses   = Small sample observation
|notable_experiments = Discovery of [[Cell (biology)|cells]]
|inventor =
|related = [[Optical microscope]], [[electron microscope]]
}}

A '''microscope''' ({{etymology|grc|''{{wikt-lang|grc|μικρός}}'' ({{grc-transl|μικρός}})|small||''{{wikt-lang|grc|σκοπέω}}'' ({{grc-transl|σκοπέω}})|to look (at); examine, inspect}}) is a [[laboratory equipment|laboratory instrument]] used to examine objects that are too small to be seen by the [[naked eye]]. [[Microscopy]] is the [[science]] of investigating small objects and structures using a microscope. [[Microscopic]] means being invisible to the eye unless aided by a microscope.

There are many types of microscopes, and they may be grouped in different ways. One way is to describe the method an instrument uses to interact with a sample and produce images, either by sending a beam of [[light]] or [[electron]]s through a sample in its [[optical path]], by detecting [[fluorescence|photon emission]]s from a sample, or by scanning across and a short distance from the surface of a sample using a probe. The most common microscope (and the first to be invented) is the [[optical microscope]], which uses [[lens]]es to [[refract]] [[visible light]] that passed through a [[microtome|thinly sectioned]] sample to produce an observable image. Other major types of microscopes are the [[fluorescence microscope]], [[electron microscope]] (both the [[transmission electron microscope]] and the [[scanning electron microscope]]) and various types of [[scanning probe microscope]]s.<ref name="CAP">{{cite book|title=Characterization and Analysis of Polymers|date=2008|publisher=Wiley-Interscience|location=Hoboken, NJ|isbn=978-0-470-23300-9}}</ref>

==History==
{{Further|Timeline of microscope technology|Optical microscope#History}}
[[File:Old-microscopes.jpg|thumb|right|200px|18th-century microscopes from the [[Musée des Arts et Métiers]], [[Paris]]]]

Although objects resembling lenses date back 4,000 years and there are [[Greeks|Greek]] accounts of the optical properties of water-filled spheres (5th century BC) followed by many centuries of writings on optics, the earliest known use of simple microscopes ([[magnifying glass]]es) dates back to the widespread use of lenses in [[eyeglasses]] in the 13th century.<ref name="Bardell2004">{{cite journal|last1=Bardell|first1=David|title=The Invention of the Microscope|journal=BIOS|date=May 2004|volume=75|issue=2|pages=78–84|jstor=4608700|doi=10.1893/0005-3155(2004)75<78:tiotm>2.0.co;2|s2cid=96668398 }}</ref><ref>''The history of the telescope'' by Henry C. King, Harold Spencer Jones Publisher Courier Dover Publications, 2003, pp. 25–27 {{ISBN|0-486-43265-3|978-0-486-43265-6}}</ref><ref>Atti Della Fondazione Giorgio Ronchi E Contributi Dell'Istituto Nazionale Di Ottica, Volume 30, La Fondazione-1975, p. 554</ref> The earliest known examples of compound microscopes, which combine an [[Objective (optics)|objective lens]] near the specimen with an [[eyepiece]] to view a [[real image]], appeared in Europe around 1620.<ref name="Murphy">{{cite book|last1=Murphy|first1=Douglas B.|last2=Davidson|first2=Michael W.|title=Fundamentals of light microscopy and electronic imaging|date=2011|publisher=Wiley-Blackwell|location=Oxford|isbn=978-0-471-69214-0|edition=2nd}}</ref> The inventor is unknown, even though many claims have been made over the years. Several revolve around the spectacle-making centers in the [[Netherlands]], including claims it was invented in 1590 by [[Zacharias Janssen]] (claim made by his son) or Zacharias' father, Hans Martens, or both,<ref>{{cite book|author=Sir Norman Lockyer|title=Nature Volume 14|url=https://books.google.com/books?id=yaNFAAAAYAAJ&q=Zacharias+Janssen+Inventor&pg=PA54|year=1876}}</ref><ref>{{cite book|author1=Albert Van Helden|author2=Sven Dupré|author3=Rob van Gent|title=The Origins of the Telescope|url=https://books.google.com/books?id=XguxYlYd-9EC&pg=PA36|year=2010|publisher=Amsterdam University Press|isbn=978-90-6984-615-6|pages=32–36, 43}}</ref> claims it was invented by their neighbor and rival spectacle maker, [[Hans Lippershey]] (who applied for the first [[telescope]] patent in 1608),<ref>{{cite web|url=http://www.livescience.com/39649-who-invented-the-microscope.html|title=Who Invented the Microscope? |website=[[Live Science]] |date=14 September 2013 |access-date=31 March 2017}}</ref> and claims it was invented by [[expatriate]] [[Cornelis Drebbel]], who was noted to have a version in London in 1619.<ref>{{cite book|author1=Eric Jorink|title=Reading the Book of Nature in the Dutch Golden Age, 1575-1715|url=https://books.google.com/books?id=XAiEMHlll9QC&q=compound+microscope+Cornelis+Drebbel&pg=PA4|isbn=978-90-04-18671-2|date=2010-10-25|publisher=BRILL }}</ref><ref>William Rosenthal, Spectacles and Other Vision Aids: A History and Guide to Collecting, Norman Publishing, 1996, pp. 391–92</ref> [[Galileo Galilei]] (also sometimes cited as compound microscope inventor) seems to have found after 1610 that he could close focus his telescope to view small objects and, after seeing a compound microscope built by Drebbel exhibited in Rome in 1624, built his own improved version.<ref>Raymond J. Seeger, Men of Physics: Galileo Galilei, His Life and His Works, Elsevier – 2016, p. 24</ref><ref>J. William Rosenthal, Spectacles and Other Vision Aids: A History and Guide to Collecting, Norman Publishing, 1996, page 391</ref><ref>[http://abyss.uoregon.edu/~js/glossary/galileo.html uoregon.edu, Galileo Galilei (Excerpt from the Encyclopedia Britannica)]</ref> [[Giovanni Faber]] coined the name ''microscope'' for the compound microscope Galileo submitted to the {{lang|it|[[Accademia dei Lincei]]|italic=no}} in 1625<ref>{{cite book |author=Gould, Stephen Jay |title=The Lying Stones of Marrakech: Penultimate Reflections in Natural History |url=https://archive.org/details/isbn_9780095031417 |url-access=registration | chapter = Chapter 2: The Sharp-Eyed Lynx, Outfoxed by Nature |publisher=Harmony |location=New York |year=2000 |isbn=978-0-224-05044-9}}</ref> (Galileo had called it the ''occhiolino'' 'little eye'). [[René Descartes]] (''Dioptrique'', 1637) describes microscopes wherein a concave mirror, with its concavity towards the object, is used, in conjunction with a lens, for illuminating the object, which is mounted on a point fixing it at the focus of the mirror.<ref name=EB1911>{{cite EB1911 |wstitle=Microscope |volume=18 |page=392 |first=Otto |last=Henker}}</ref>

===Rise of modern light microscopes===
[[File:Gutteridge Microscope HAGAM.jpg|thumb|286x286px|A stand microscope created by [[Joseph Gutteridge]] in the 1860s, held in the collection of the [[Herbert Art Gallery and Museum]]]]
The first detailed account of the [[histology|microscopic anatomy]] of organic tissue based on the use of a microscope did not appear until 1644, in Giambattista Odierna's ''L'occhio della mosca'', or ''The Fly's Eye''.<ref name="Wootton">{{cite book |author=Wootton, David |title=Bad medicine: doctors doing harm since Hippocrates |publisher=Oxford University Press |location=Oxford [Oxfordshire] |year=2006 |page=110|isbn=978-0-19-280355-9 }}{{page needed|date=November 2013}}</ref>

The microscope was still largely a novelty until the 1660s and 1670s when naturalists in Italy, the Netherlands and England began using them to study biology. Italian scientist [[Marcello Malpighi]], called the father of [[histology]] by some historians of biology, began his analysis of biological structures with the lungs. The publication in 1665 of [[Robert Hooke]]'s ''[[Micrographia]]'' had a huge impact, largely because of its impressive illustrations. Hooke created tiny lenses of small glass globules made by fusing the ends of threads of spun glass.<ref name="EB1911" /> A significant contribution came from [[Antonie van Leeuwenhoek]] who achieved up to 300 times magnification using a simple single lens microscope. He sandwiched a very small glass [[ball lens]] between the holes in two metal plates riveted together, and with an adjustable-by-screws needle attached to mount the specimen.<ref>{{cite web|url=http://www.smithsonianmag.com/science-nature/early-microscopes-revealed-new-world-tiny-living-things-180958912|title=Early Microscopes Revealed a New World of Tiny Living Things|author=Liz Logan|publisher=Smithsonian.com|date=27 April 2016|access-date=3 June 2016}}</ref> Then, Van Leeuwenhoek re-discovered [[red blood cell]]s (after [[Jan Swammerdam]]) and [[spermatozoon|spermatozoa]], and helped popularise the use of microscopes to view biological ultrastructure. On 9 October 1676, van Leeuwenhoek reported the discovery of micro-organisms.<ref name="Wootton" />

[[File:Binocular compound microscope, Carl Zeiss Jena, 1914 (6779276516).jpg|thumb|Carl Zeiss binocular compound microscope, 1914|upright]]

The performance of a compound light microscope depends on the quality and correct use of the [[Condenser (optics)|condensor]] lens system to focus light on the specimen and the objective lens to capture the light from the specimen and form an image.<ref name="Murphy" /> Early instruments were limited until this principle was fully appreciated and developed from the late 19th to very early 20th century, and until electric lamps were available as light sources. In 1893 [[August Köhler]] developed a key principle of sample illumination, [[Köhler illumination]], which is central to achieving the theoretical limits of resolution for the light microscope. This method of sample illumination produces even lighting and overcomes the limited contrast and resolution imposed by early techniques of sample illumination. Further developments in sample illumination came from the discovery of [[Phase-contrast microscopy|phase contrast]] by [[Frits Zernike]] in 1953, and [[Differential interference contrast microscopy|differential interference contrast]] illumination by [[Georges Nomarski]] in 1955; both of which allow imaging of unstained, transparent samples.

===Electron microscopes===
{{See also|electron microscope}}
[[File:Ernst Ruska Electron Microscope - Deutsches Museum - Munich-edit.jpg|thumb|Electron microscope constructed by [[Ernst Ruska]] in 1933]]
In the early 20th century a significant alternative to the light microscope was developed, an instrument that uses a beam of [[electron]]s rather than [[light]] to generate an image. The German physicist, [[Ernst Ruska]], working with electrical engineer [[Max Knoll]], developed the first prototype electron microscope in 1931, a [[transmission electron microscope]] (TEM). The transmission electron microscope works on similar principles to an optical microscope but uses electrons in the place of light and electromagnets in the place of glass lenses. Use of electrons, instead of light, allows for much higher resolution.

Development of the transmission electron microscope was quickly followed in 1935 by the development of the [[scanning electron microscope]] by [[Max Knoll]].<ref name="knoll">{{cite journal |last=Knoll |first=Max|year=1935 |title=Aufladepotentiel und Sekundäremission elektronenbestrahlter Körper |journal=Zeitschrift für Technische Physik |volume=16|pages=467–475}}</ref> Although TEMs were being used for research before WWII, and became popular afterwards, the SEM was not commercially available until 1965.

Transmission electron microscopes became popular following the [[Second World War]]. Ernst Ruska, working at [[Siemens]], developed the first commercial transmission electron microscope and, in the 1950s, major scientific conferences on electron microscopy started being held. In 1965, the first commercial scanning electron microscope was developed by Professor Sir [[Charles Oatley]] and his postgraduate student Gary Stewart, and marketed by the [[Cambridge Instrument Company]] as the "Stereoscan".

One of the latest discoveries made about using an electron microscope is the ability to identify a virus.<ref>{{Cite journal|last1=Goldsmith|first1=Cynthia S.|last2=Miller|first2=Sara E.|date=2009-10-01|title=Modern Uses of Electron Microscopy for Detection of Viruses|journal=Clinical Microbiology Reviews|language=en|volume=22|issue=4|pages=552–563|doi=10.1128/cmr.00027-09|issn=0893-8512|pmid=19822888|pmc=2772359}}</ref> Since this microscope produces a visible, clear image of small organelles, in an electron microscope there is no need for reagents to see the virus or harmful cells, resulting in a more efficient way to detect pathogens.

===Scanning probe microscopes===
{{See also|scanning probe microscope}}
[[File:Atomic Force Microscope Science Museum London.jpg|thumb|First atomic force microscope]]
From 1981 to 1983 [[Gerd Binnig]] and [[Heinrich Rohrer]] worked at [[IBM]] in [[Zürich]], Switzerland to study the [[quantum tunnelling]] phenomenon. They created a practical instrument, a [[scanning probe microscope]] from quantum tunnelling theory, that read very small forces exchanged between a probe and the surface of a sample. The probe approaches the surface so closely that electrons can flow continuously between probe and sample, making a current from surface to probe. The microscope was not initially well received due to the complex nature of the underlying theoretical explanations. In 1984 [[Jerry Tersoff]] and D.R. Hamann, while at AT&T's Bell Laboratories in [[Murray Hill, New Jersey]] began publishing articles that tied theory to the experimental results obtained by the instrument. This was closely followed in 1985 with functioning commercial instruments, and in 1986 with Gerd Binnig, Quate, and Gerber's invention of the [[atomic force microscope]], then Binnig's and Rohrer's Nobel Prize in Physics for the SPM.<ref name="Morita">{{cite book|last1=Morita|first1=Seizo|title=Roadmap of Scanning Probe Microscopy|date=2007|publisher=Springer-Verlag Berlin Heidelberg|location=Berlin, Heidelberg|isbn=978-3-540-34315-8}}</ref>

New types of scanning probe microscope have continued to be developed as the ability to machine ultra-fine probes and tips has advanced.

===Fluorescence microscopes===

{{See also|fluorescence microscope|immunofluorescence|confocal microscope}}

[[File:Olympus-BX61-fluorescence microscope.jpg|thumb|upright|Fluorescence microscope with the filter cube turret above the objective lenses, coupled with a camera]]

The most recent developments in light microscope largely centre on the rise of [[fluorescence microscope|fluorescence microscopy]] in [[biology]].<ref name=":0" /> During the last decades of the 20th century, particularly in the post-[[genome|genomic]] era, many techniques for fluorescent [[staining]] of [[cell (biology)|cellular]] structures were developed.<ref name=":0" /> The main groups of techniques involve targeted chemical staining of particular cell structures, for example, the chemical compound [[DAPI]] to label [[DNA]], use of antibodies conjugated to fluorescent reporters, see
[[immunofluorescence]], and fluorescent proteins, such as [[green fluorescent protein]].<ref name=":1" /> These techniques use these different fluorophores for analysis of cell structure at a molecular level in both live and fixed samples.

The rise of fluorescence microscopy drove the development of a major modern microscope design, the [[confocal microscope]]. The principle was patented in 1957 by [[Marvin Minsky]], although [[laser]] technology limited practical application of the technique. It was not until 1978 when [[Thomas Cremer|Thomas]] and [[Christoph Cremer]] developed the first practical [[confocal laser scanning microscope]] and the technique rapidly gained popularity through the 1980s.

===Super resolution microscopes===
{{Main|Super-resolution microscopy|Microscopy#Sub-diffraction techniques}}
Much current research (in the early 21st century) on optical microscope techniques is focused on development of [[superresolution]] analysis of fluorescently labelled samples. [[Microscopy#Structured illumination|Structured illumination]] can improve resolution by around two to four times and techniques like [[stimulated Emission Depletion microscopy|stimulated emission depletion (STED) microscopy]] are approaching the resolution of electron microscopes.<ref>{{Cite web |title=The Nobel Prize in Chemistry 2014 – Scientific Background |url=https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2014/advanced-chemistryprize2014.pdf |archive-url=https://web.archive.org/web/20180320230951/https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2014/advanced-chemistryprize2014.pdf |archive-date=2018-03-20 |access-date=2018-03-20 |website=www.nobelprize.org}}</ref> This occurs because the diffraction limit is occurred from light or excitation, which makes the resolution must be doubled to become super saturated. Stefan Hell was awarded the 2014 Nobel Prize in Chemistry for the development of the STED technique, along with Eric Betzig and William Moerner who adapted fluorescence microscopy for single-molecule visualization.<ref>{{Cite web|url=https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2014/press.html|title=The Nobel Prize in Chemistry 2014|website=www.nobelprize.org|access-date=2018-03-20}}</ref>

===X-ray microscopes===
{{main|X-ray microscope}}
X-ray microscopes are instruments that use electromagnetic radiation usually in the soft X-ray band to image objects. Technological advances in X-ray lens optics in the early 1970s made the instrument a viable imaging choice.<ref name="Erko">{{cite book|last1=Erko|first1=A.|title=Modern developments in X-ray and neutron optics|date=2008|publisher=Springer|location=Berlin|isbn=978-3-540-74561-7}}</ref> They are often used in tomography (see [[X-ray microtomography|micro-computed tomography]]) to produce three dimensional images of objects, including biological materials that have not been chemically fixed. Currently research is being done to improve optics for hard X-rays which have greater penetrating power.<ref name="Erko" />

==Types==
[[Image:MicroscopesOverview.svg|thumb|right|300px|Types of microscopes illustrated by the principles of their beam paths]]
[[File:MicroscopyResolution.png|thumb|300px|Evolution of spatial resolution achieved with optical, transmission (TEM) and aberration-corrected electron microscopes (ACTEM)<ref>{{cite journal|doi=10.1557/mrs2006.4|url=http://web.pdx.edu/~pmoeck/pennycooks%20aberration%20corrected%20microscopes.pdf|title=Materials Advances through Aberration-Corrected Electron Microscopy|journal=MRS Bulletin|volume=31|pages=36–43|year=2011|last1=Pennycook|first1=S.J.|last2=Varela|first2=M.|last3=Hetherington|first3=C.J.D.|last4=Kirkland|first4=A.I.|s2cid=41889433 }}</ref>]]

Microscopes can be separated into several different classes. One grouping is based on what interacts with the sample to generate the image, i.e., [[light]] or [[photons]] (optical microscopes), [[electron]]s (electron microscopes) or a probe (scanning probe microscopes). Alternatively, microscopes can be classified based on whether they analyze the sample via a scanning point (confocal optical microscopes, scanning electron microscopes and scanning probe microscopes) or analyze the sample all at once (wide field optical microscopes and transmission electron microscopes).

Wide field optical microscopes and transmission electron microscopes both use the theory of lenses ([[optics]] for light microscopes and [[electromagnet]] lenses for electron microscopes) in order to magnify the image generated by the passage of a [[wave]] transmitted through the sample, or reflected by the sample. The waves used are [[electromagnetic waves|electromagnetic]] (in [[optical microscope]]s) or [[electron]] beams (in [[electron microscopes]]). [[Optical resolution|Resolution]] in these microscopes is limited by the [[wavelength]] of the radiation used to image the sample, where shorter wavelengths allow for a higher resolution.<ref name=":0">{{Cite journal|last1=Lodish|first1=Harvey|last2=Berk|first2=Arnold|last3=Zipursky|first3=S. Lawrence|last4=Matsudaira|first4=Paul|last5=Baltimore|first5=David|last6=Darnell|first6=James|date=2000|title=Microscopy and Cell Architecture|url=https://www.ncbi.nlm.nih.gov/books/NBK21629/|journal=Molecular Cell Biology. 4th Edition|language=en}}</ref>

Scanning optical and electron microscopes, like the confocal microscope and scanning electron microscope, use lenses to focus a spot of light or electrons onto the sample then analyze the signals generated by the beam interacting with the sample. The point is then scanned over the sample to analyze a rectangular region. Magnification of the image is achieved by displaying the data from scanning a physically small sample area on a relatively large screen. These microscopes have the same resolution limit as wide field optical, probe, and electron microscopes.

Scanning probe microscopes also analyze a single point in the sample and then scan the probe over a rectangular sample region to build up an image. As these microscopes do not use electromagnetic or electron radiation for imaging they are not subject to the same resolution limit as the optical and electron microscopes described above.

===Optical microscope===
{{main|Optical microscope|Digital microscope|USB microscope}}
The most common type of microscope (and the first invented) is the [[optical microscope]]. This is an [[optics|optical]] [[measuring instrument|instrument]] containing one or more [[Lens (optics)|lenses]] producing an enlarged image of a sample placed in the focal plane. Optical microscopes have [[refraction|refractive]] glass (occasionally plastic or [[quartz]]), to focus light on the eye or on to another light detector. Mirror-based optical microscopes operate in the same manner. Typical magnification of a light microscope, assuming visible range light, is up to 1,250× with a theoretical [[Diffraction-limited system|resolution limit]] of around 0.250&nbsp;[[micrometre]]s or 250&nbsp;[[nanometre]]s.<ref name=":0"/> This limits practical magnification to ~1,500×. Specialized techniques (e.g., [[Confocal laser scanning microscopy|scanning confocal microscopy]], [[Vertico SMI]]) may exceed this magnification but the resolution is [[diffraction]] limited. The use of shorter wavelengths of light, such as ultraviolet, is one way to improve the spatial resolution of the optical microscope, as are devices such as the [[near-field scanning optical microscope]].

[[Sarfus]] is a recent optical technique that increases the sensitivity of a standard optical microscope to a point where it is possible to directly visualize nanometric films (down to 0.3&nbsp;nanometre) and isolated nano-objects (down to 2&nbsp;nm-diameter). The technique is based on the use of non-reflecting substrates for cross-polarized reflected light microscopy.

[[Ultraviolet]] light enables the resolution of microscopic features as well as the imaging of samples that are transparent to the eye. [[Near infrared]] light can be used to visualize circuitry embedded in bonded silicon devices, since silicon is transparent in this region of wavelengths.

In [[fluorescence microscopy]] many wavelengths of light ranging from the ultraviolet to the visible can be used to cause samples to [[fluorescence|fluoresce]], which allows viewing by eye or with specifically sensitive cameras.[[File:Brightfield phase contrast cell image.jpg|thumb|Unstained cells viewed by typical brightfield (left) compared to phase-contrast microscopy (right)]]

[[Phase-contrast microscopy]] is an [[optical microscope|optical microscopic]] illumination technique in which small [[phase shifts]] in the light passing through a transparent specimen are converted into [[amplitude]] or [[contrast (vision)|contrast]] changes in the image.<ref name=":0"/> The use of phase contrast does not require [[staining]] to view the slide. This microscope technique made it possible to study the [[cell cycle]] in live cells.

The traditional optical microscope has more recently evolved into the [[digital microscope]]. In addition to, or instead of, directly viewing the object through the [[eyepiece]]s, a type of sensor similar to those used in a [[digital camera]] is used to obtain an image, which is then displayed on a computer monitor. These sensors may use [[CMOS]] or [[charge-coupled device]] (CCD) technology, depending on the application.

Digital microscopy with very low light levels to avoid damage to vulnerable biological samples is available using sensitive [[photon counting|photon-counting]] digital cameras. It has been demonstrated that a light source providing pairs of [[Photon entanglement|entangled photons]] may minimize the risk of damage to the most light-sensitive samples. In this application of [[ghost imaging]] to photon-sparse microscopy, the sample is illuminated with infrared photons, each of which is spatially correlated with an entangled partner in the visible band for efficient imaging by a photon-counting camera.<ref name="AspdenGemmell2015">{{cite journal|last1=Aspden|first1=Reuben S. |last2=Gemmell|first2=Nathan R. |last3=Morris|first3=Peter A. |last4=Tasca|first4=Daniel S. |last5=Mertens|first5=Lena |last6=Tanner|first6=Michael G. |last7=Kirkwood|first7=Robert A. |last8=Ruggeri|first8=Alessandro |last9=Tosi|first9=Alberto |last10=Boyd|first10=Robert W. |last11=Buller|first11=Gerald S. |last12=Hadfield |first12=Robert H. |last13=Padgett |first13=Miles J. |title=Photon-sparse microscopy: visible light imaging using infrared illumination |journal=Optica |volume=2 |issue=12 |year=2015 |pages=1049 |issn=2334-2536 |doi=10.1364/OPTICA.2.001049|bibcode=2015Optic...2.1049A |url=http://eprints.gla.ac.uk/112219/1/112219.pdf |doi-access=free }}</ref>
[[File:Electron Microscope.jpg|thumb|upright|Modern transmission electron microscope]]

===Electron microscope===

[[File:Cytokinesis-electron-micrograph.jpg|thumb|Transmission electron micrograph of a dividing cell undergoing cytokinesis]]{{main|Electron microscope}}
The two major types of electron microscopes are [[transmission electron microscope]]s (TEMs) and [[scanning electron microscope]]s (SEMs).<ref name=":0" /><ref name=":1">{{Cite journal|last1=Alberts|first1=Bruce|last2=Johnson|first2=Alexander|last3=Lewis|first3=Julian|last4=Raff|first4=Martin|last5=Roberts|first5=Keith|last6=Walter|first6=Peter|date=2002|title=Looking at the Structure of Cells in the Microscope|url=https://www.ncbi.nlm.nih.gov/books/NBK26880/|journal=Molecular Biology of the Cell. 4th Edition|language=en}}</ref> They both have series of electromagnetic and electrostatic lenses to focus a high energy beam of electrons on a sample. In a TEM the electrons pass through the sample, analogous to [[bright field microscopy|basic optical microscopy]].<ref name=":0"/> This requires careful sample preparation, since electrons are scattered strongly by most materials.<ref name=":1"/> The samples must also be very thin (below 100&nbsp;nm) in order for the electrons to pass through it.<ref name=":0"/><ref name=":1"/> Cross-sections of cells stained with osmium and heavy metals reveal clear organelle membranes and proteins such as ribosomes.<ref name=":1"/> With a 0.1&nbsp;nm level of resolution, detailed views of viruses (20 – 300&nbsp;nm) and a strand of DNA (2&nbsp;nm in width) can be obtained.<ref name=":1"/> In contrast, the SEM has raster coils to scan the surface of bulk objects with a fine electron beam. Therefore, the specimen do not necessarily need to be sectioned, but coating with a nanometric metal or carbon layer may be needed for nonconductive samples.<ref name=":0"/> SEM allows fast surface imaging of samples, possibly in thin water vapor to prevent drying.<ref name=":0"/><ref name=":1"/>

===Scanning probe===
{{main|Scanning probe microscopy}}

The different types of scanning probe microscopes arise from the many different types of interactions that occur when a small probe is scanned over and interacts with a specimen. These interactions or modes can be recorded or mapped as function of location on the surface to form a characterization map. The three most common types of scanning probe microscopes are [[atomic force microscopy|atomic force microscopes]] (AFM), [[near-field scanning optical microscopy|near-field scanning optical microscopes]] (NSOM or SNOM, scanning near-field optical microscopy), and [[scanning tunneling microscopy|scanning tunneling microscopes]] (STM).<ref name="Bhushan">{{cite book|editor1-last=Bhushan|editor1-first=Bharat|title=Springer handbook of nanotechnology|date=2010|publisher=Springer|location=Berlin|isbn=978-3-642-02525-9|page=620|edition=3rd rev. & extended}}</ref> An atomic force microscope has a fine probe, usually of silicon or silicon nitride, attached to a cantilever; the probe is scanned over the surface of the sample, and the forces that cause an interaction between the probe and the surface of the sample are measured and mapped. A near-field scanning optical microscope is similar to an AFM but its probe consists of a light source in an optical fiber covered with a tip that has usually an aperture for the light to pass through. The microscope can capture either transmitted or reflected light to measure very localized optical properties of the surface, commonly of a biological specimen. Scanning tunneling microscopes have a metal tip with a single apical atom; the tip is attached to a tube through which a current flows.<ref name="Sakurai">{{cite book|editor1-last=Sakurai|editor1-first=T.|editor2-last=Watanabe|editor2-first=Y.|title=Advances in scanning probe microscopy|date=2000|publisher=Springer|location=Berlin|isbn=978-3-642-56949-4}}</ref> The tip is scanned over the surface of a conductive sample until a tunneling current flows; the current is kept constant by computer movement of the tip and an image is formed by the recorded movements of the tip.<ref name="Bhushan"/>
[[File:Leaf epidermis.jpg|thumb|Leaf surface viewed by a scanning electron microscope]]

=== Other types ===
[[Scanning acoustic microscope]]s use sound waves to measure variations in acoustic impedance. Similar to [[Sonar]] in principle, they are used for such jobs as detecting defects in the subsurfaces of materials including those found in integrated circuits. On February 4, 2013, Australian engineers built a "quantum microscope" which provides unparalleled precision.<ref>{{cite web|url=https://www.sciencedaily.com/releases/2013/02/130204163442.htm|title=Quantum Microscope for Living Biology|website=Science Daily|date=4 February 2013|access-date=5 February 2013}}</ref>

====Mobile apps====
[[Mobile app]] microscopes can optionally be used as [[optical microscope]] when the flashlight is activated. However, mobile app microscopes are harder to use due to visual [[Noise (video)|noise]], are often limited to 40x, and the resolution limits of the [[camera lens]] itself.

==See also==
{{div col|colwidth=30em}}
* [[Fluorescence interference contrast microscopy]]
* [[Laser capture microdissection]]
* [[Microscope image processing]]
* [[Microscope slide]]
* [[Multifocal plane microscopy]]
* [[Royal Microscopical Society]]
{{div col end}}

==References==
{{Reflist}}

==External links==
{{commons category|Microscopes}}
* [http://www.nature.com/milestones/milelight/index.html Milestones in Light Microscopy], ''Nature Publishing''
* [https://web.archive.org/web/20090404024608/http://www.micro.magnet.fsu.edu/primer/faq.html FAQ on Optical Microscopes] (archived 4 April 2009)
* [http://www.microscopyu.com Nikon MicroscopyU, tutorials from Nikon]
* [http://micro.magnet.fsu.edu/index.html Molecular Expressions : ''Exploring the World of Optics and Microscopy'', Florida State University.]

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{{Analytical chemistry}}
{{Optical microscopy}}
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[[Category:Microbiology equipment]]
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[[Category:Microscopy]]
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