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== Invention and development == The history of X-ray microscopy can be traced back to the early 20th century. After the German physicist [[Wilhelm Röntgen|Röntgen]] discovered X-rays in 1895, scientists soon illuminated an object using an X-ray point source and captured the shadow images of the object with a resolution of several micrometers.<ref>{{Cite journal |last=Malsch |first=Friedrich |date=1939-12-01 |title=Erzeugung stark vergrößerter Röntgen-Schattenbilder (Generation of highly enlarged X-ray shadow images)|journal=Naturwissenschaften |language=de |volume=27 |issue=51 |pages=854–855 |doi=10.1007/BF01489432 |bibcode=1939NW.....27..854M |s2cid=34980746 |issn=1432-1904}}</ref> In 1918, Einstein pointed out that the [[refractive index]] for X-rays in most mediums should be just slightly greater than 1,<ref>{{Citation |last=Senn |first=E. |chapter=Grundsätzliche Überlegungen zur physikalischen Diagnostik und Therapie von Muskelschmerzen (Basic considerations for the physical diagnosis and therapy of muscle pain)|lang=de |date=1989 |pages=668–674 |publisher=Springer Berlin Heidelberg |isbn=9783540514374 |doi=10.1007/978-3-642-83864-4_129 |title=Verhandlungen der Deutschen Gesellschaft für Innere Medizin |volume=95}}</ref> which means that refractive optical parts would be difficult to use for X-ray applications. Early X-ray microscopes by [[Paul Kirkpatrick]] and [[Albert Baez]] used [[angle of incidence (optics)|grazing-incidence]] reflective [[X-ray optics]] to focus the X-rays, which grazed X-rays off [[parabolic reflector|parabolic]] curved mirrors at a very high [[angle of incidence (optics)|angle of incidence]]. An alternative method of focusing X-rays is to use a tiny [[Fresnel]] [[zone plate]] of concentric gold or nickel rings on a [[silicon dioxide]] substrate. Sir [[Lawrence Bragg]] produced some of the first usable X-ray images with his apparatus in the late 1940s. [[File:Hohlraum irradiation on NOVA laser.jpg|thumb|right|Indirect-drive laser [[inertial confinement fusion]] uses a "hohlraum" irradiated with laser beam cones from either side on its inner surface to bathe a fusion microcapsule inside with smooth high-intensity X-rays. The highest-energy X-rays that penetrate the hohlraum can be visualized using an X-ray microscope such as here, where X-radiation is represented in orange/red.]] In the 1950s [[Sterling Newberry]] produced a shadow X-ray microscope, which placed the specimen between the source and a target plate, this became the basis for the first commercial X-ray microscopes from the [[General Electric Company]]. After a silent period in the 1960s, X-ray microscopy regained people's attention in the 1970s. In 1972, [[Paul Horowitz|Horowitz]] and Howell built the first synchrotron-based X-ray microscope at the Cambridge Electron Accelerator.<ref>{{Cite journal |last1=Horowitz |first1=P. |last2=Howell |first2=J. A. |date=1972-11-10 |title=A Scanning X-Ray Microscope Using Synchrotron Radiation |journal=Science |volume=178 |issue=4061 |pages=608–611 |doi=10.1126/science.178.4061.608 |pmid=5086391 |issn=0036-8075 |bibcode=1972Sci...178..608H|s2cid=36311578 }}</ref> This microscope scanned samples using synchrotron radiation from a tiny pinhole and showed the abilities of both transmission and fluorescence microscopy. Other developments in this period include the first holographic demonstration by [[Sadao Aoki]] and [[Seishi Kikuta]] in Japan,<ref>{{Cite journal |last1=Aoki |first1=Sadao |last2=Kikuta |first2=Seishi |date=1974 |title=X-Ray Holographic Microscopy |journal=Japanese Journal of Applied Physics |volume=13 |issue=9 |pages=1385–1392 |doi=10.1143/jjap.13.1385 |issn=0021-4922 |bibcode=1974JaJAP..13.1385A|s2cid=121234705 }}</ref> the first TXMs using zone plates by Schmahl et al.,<ref>{{Cite journal |last1=Niemann |first1=B. |last2=Rudolph |first2=D. |last3=Schmahl |first3=G. |date=1974 |title=Soft X-ray imaging zone plates with large zone numbers for microscopic and spectroscopic applications |journal=Optics Communications |volume=12 |issue=2 |pages=160–163 |doi=10.1016/0030-4018(74)90381-2 |issn=0030-4018 |bibcode=1974OptCo..12..160N}}</ref> and Stony Brook's experiments in [[Scanning transmission X-ray microscopy|STXM]].<ref>{{Cite journal |last1=Rarback |first1=H. |last2=Cinotti |first2=F. |last3=Jacobsen |first3=C. |last4=Kenney |first4=J. M. |last5=Kirz |first5=J. |last6=Rosser |first6=R. |date=1987 |title=Elemental analysis using differential absorption techniques |journal=Biological Trace Element Research |volume=13 |issue=1 |pages=103–113 |doi=10.1007/bf02796625 |pmid=24254669 |s2cid=2773029 |issn=0163-4984}}</ref><ref>{{Citation |last1=Rarback |first1=H. |title=The Stony Brook/NSLS Scanning Microscope |date=1988 |pages=194–200 |publisher=Springer Berlin Heidelberg |isbn=9783662144909 |last2=Shu |first2=D. |last3=Feng |first3=Su Cheng |last4=Ade |first4=H. |last5=Jacobsen |first5=C. |last6=Kirz |first6=J. |last7=McNulty |first7=I. |last8=Vladimirsky |first8=Y. |last9=Kern |first9=D. |series=Springer Series in Optical Sciences |volume=56 |doi=10.1007/978-3-540-39246-0_35}}</ref> The uses of synchrotron light sources brought new possibilities for X-ray microscopy in the 1980s. However, as new synchrotron-source-based microscopes were built in many groups, people realized that it was difficult to perform such experiments due to insufficient technological capabilities at that time, such as poor coherent illuminations, poor-quality x-ray optical elements, and user-unfriendly light sources.<ref name=":1">{{Cite journal |last1=Kirz |first1=J. |last2=Jacobsen |first2=C. |date=2009-09-01 |title=The history and future of X-ray microscopy |journal=Journal of Physics: Conference Series |volume=186 |issue=1 |pages=012001 |doi=10.1088/1742-6596/186/1/012001 |issn=1742-6596 |bibcode=2009JPhCS.186a2001K |doi-access=free}}</ref> Entering the 1990s, new instruments and new light sources greatly fueled the improvement of X-ray microscopy. Microscopy methods including tomography, cryo-, and cryo-tomography were successfully demonstrated. With rapid development, X-ray microscopy found new applications in soil science, geochemistry, polymer sciences, and magnetism. The hardware was also miniaturized, so that researchers could perform experiments in their own laboratories.<ref name=":1" /> Extremely high-intensity sources of 9.25 keV X-rays for X-ray phase-contrast microscopy, from a focal spot about 10 μm × 10 μm, may be obtained with a non-synchrotron X-ray source that uses a focused electron beam and a liquid-metal anode. This was demonstrated in 2003 and in 2017 was used to image mouse brain at a voxel size of about one cubic micrometer (see below).<ref name="doi.org">{{cite journal |title=Liquid-metal-jet anode electron-impact x-ray source |author=O. Hemberg |author2=M. Otendal |author3=H. M. Hertz |journal=Appl. Phys. Lett. |volume=83 |page=1483 |year=2003 |issue=7 |doi=10.1063/1.1602157|bibcode=2003ApPhL..83.1483H }}</ref> With the applications continuing to grow, X-ray microscopy has become a routine, proven technique used in environmental and soil sciences, geo- and cosmo-chemistry, polymer sciences, biology, magnetism, material sciences. With this increasing demand for X-ray microscopy in these fields, microscopes based on synchrotron, liquid-metal anode, and other laboratory light sources are being built around the world. X-ray optics and components are also being commercialized rapidly.<ref name=":1" />
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