Editing Microscope (section)

==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" />