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title: "Galileo and Ulysses Dust Detectors"
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source: "https://en.wikipedia.org/wiki/Galileo_and_Ulysses_Dust_Detectors"
category: "reference"
tags: "science, encyclopedia"
date_saved: "2026-05-05T03:13:38.437042+00:00"
instance: "kb-cron"
---
The Galileo and Ulysses Dust Detectors are almost identical dust instruments on the Galileo and Ulysses missions. The instruments are large-area (0.1 m2 sensitive area) highly reliable impact ionization detectors of sub-micron and micron sized dust particles. With these instruments the interplanetary dust cloud was characterized between Venus and Jupiter's orbits and over the solar poles. A stream of interstellar dust passing through the planetary system was discovered. Close to and inside the Jupiter system streams nanometer sized dust particles that were emitted from volcanoes on Jupiter's moon Io and ejecta clouds around the Galilean moons were discovered and characterized.
== Overview ==
Following the first dust instruments from the Max Planck Institute for Nuclear Physics (MPIK), Heidelberg (Germany) on the HEOS 2 satellite and the Helios spacecraft a new dust instrument was developed by a Team of Scientists and Engineers of Eberhard Grün to detect cosmic dust in the outer planetary system. This instrument had 10 times larger sensitive area (0.1 m2) and employed a multiple coincidence of impact signals in order to cope with the low fluxes of cosmic dust and the hostile environment in the outer planets magnetospheres.
The Galileo and Ulysses dust detectors use impact ionization from hypervelocity impacts of cosmic dust particles onto the hemispherical target. Electrons and ions from the impact plasma are separated by the electric field between the target and the center ion collector. Ions are partly collected by the semi-transparent grid and the center channeltron multiplier. The amplitudes of the impact, the rise-times, and time relations of the charge signals are measured, stored and transmitted to ground. Using this information noise from impacts events were separated and properties (mass and speed) of the impacting dust particles were determined. The center grid of the three grids at the entrance of the detector pick-up the electric charge of the dust particle. Unfortunately, no dust charges were reliably identified by these instruments during their space operation.
The Galileo Dust Detector was developed by the Team of Scientists and Engineers led by Eberhard Grün at the Max Planck Institute for Nuclear Physics (MPIK), Heidelberg (Germany) and was selected in 1977 by NASA to explore the dust environment of Jupiter on board the Galileo Jupiter Orbiter. The Galileo spacecraft was a dual-spin spacecraft with its antenna pointing to Earth. The dust detector was mounted on the spinning section at an angle of 60° with respect to the spin axis. Galileo was launched in 1989 and cruised for 6 years interplanetary space between Venus and Jupiter's orbits before it started in 1995 its 7-year path through the Jovian system with several fly-bys of all Galilean moons. The Galileo dust detector operated during the whole mission.
About a year after Galileo the twin instrument was selected for the out-of-ecliptic Ulysses mission. Ulysses was a spinning spacecraft with the dust detector mounted at 85° to the spin axis. Launch of Ulysses was in 1990 and the spacecraft went on a direct trajectory to Jupiter which it reached in 1992 for a swing-by maneuver which put the spacecraft on a heliocentric orbit of 80 degrees inclination. This orbit had a period of 6.2 years and a perihelion of 1.25 AU and an aphelion of 5.4 AU. Ulysses completed 2.5 orbits until the mission was ended. The Ulysses dust detector operated during the whole mission.
The initial Principal Investigator for both instruments was Eberhard Grün. In 1996 the PI-ship was handed over to Harald Krüger from Max Planck Institute for Solar System Research, Göttingen, Germany.
== Major discoveries ==
Interplanetary dust
Galileo and Ulysses traversed interplanetary space from Venus orbit (0.7 AU) to Jupiters orbit (~5 AU) and about 2 AU above and below the solar poles. During all the time the dust experiments recorded cosmic dust particles that were an important input to a model of interplanetary dust.
Interstellar dust
After Jupiter flyby Ulysses identified a flow of interstellar dust sweeping through the Solar System.
Dust in the Jupiter system
After Jupiter flyby Ulysses detected hyper-velocity streams of nano-dust which are emitted from Jupiter and then couple to the solar magnetic field.
Dust streams from Jupiter, and their interactions with the Jovian satellite Io were detected, as well as ejecta clouds around the Galilean moons.
== References ==

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title: "Harvard Collection of Historical Scientific Instruments"
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source: "https://en.wikipedia.org/wiki/Harvard_Collection_of_Historical_Scientific_Instruments"
category: "reference"
tags: "science, encyclopedia"
date_saved: "2026-05-05T03:13:39.707733+00:00"
instance: "kb-cron"
---
Harvard University's Collection of Historical Scientific Instruments (CHSI), established 1948, is "one of the three largest university collections of its kind in the world". Waywiser, the online catalog of the collection, lists over 60% of the collection's 20,000 objects as of 2014. The collection was originally curated by Mr. David P Wheatland in his office to prevent obsolete equipment from being cannibalized for its component parts and materials.
== Physical facilities ==
A selection of instruments and artifacts from the collection comprise the exhibition Time, Life, & Matter: Science in Cambridge. This permanent display can be found in the Putnam Gallery on the first floor of the Harvard Science Center, which is free and open to the public during regularly scheduled hours, Sunday through Friday. In addition, rotating collaborative exhibitions drawn in part from the collection are shown in the Special Exhibitions Gallery on the second floor, as well as the more modest Foyer Gallery on the third floor.
The physical facilities in the Science Center were expanded in 2004, by replacing a one-story wing of the building with a four-story "townhouse"-style structure with offices, classrooms, and a fully-glazed internal stairway. The new wing houses the Department of the History of Science as well as public display spaces for CHSI. The modifications to the Science Center (originally by Josep Lluís Sert) were designed by Leers Weinzapfel Associates of Boston.
== Collection ==
The CHSI includes a number of scientific instruments and demonstration apparatus purchased circa 1765 under the advice of Benjamin Franklin, to replace original equipment which had been lost in a disastrous fire which also destroyed the university's library in the original Harvard Hall. This display includes apparatus for experimenting with electricity, as well as demonstrating the laws of physics as they were understood in the late 18th century.
Other highlights of the permanent exhibit include a fine assemblage of sundials (part of the largest private collection in North America), a geometrical compass designed by Galileo Galilei, and the control console from the former Harvard Cyclotron Laboratory.
One of the larger items in the collection is the Harvard Mark I, a historic room-sized electromechanical computer commissioned in 1944, which was exhibited next to the central stairwell in the main lobby of the Science Center, and has since been moved to the Harvard John A. Paulson School of Engineering and Applied Sciences.
== Governance ==
The collection continues to be expanded, under the guidance of David P. Wheatland Curator Sara J. Schechner. Originally a part of the Harvard Library system, the CHSI is now presented under the auspices of Harvard's Department of the History of Science, and is one of the four Harvard Museums of Science and Culture.
The CHSI is also affiliated with the American Alliance of Museums.
A strategic plan has been developed to expand the CHSI's missions of preservation, education, research, and display, including expanded educational outreach and higher-profile public exhibitions.
== References ==
== External links ==
Official website

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title: "Helios Dust Instrumentation"
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source: "https://en.wikipedia.org/wiki/Helios_Dust_Instrumentation"
category: "reference"
tags: "science, encyclopedia"
date_saved: "2026-05-05T03:13:40.867741+00:00"
instance: "kb-cron"
---
The Helios 1 and 2 spacecraft each carried two dust instruments to characterize the Zodiacal dust cloud inside the Earths orbit down to spacecraft positions 0.3 AU from the sun. The Zodiacal light instrument measured the brightness of light scattered by interplanetary dust along the line of sight. The in situ Micrometeoroid analyzer recorded impacts of meteoroids onto the sensitive detector surface and characterized their composition. The instruments delivered radial profiles of their measured data. Comet or meteoroid streams, and even interstellar dust were identified in the data.
== Overview ==
The two Helios spacecraft were the result of a joint venture of West Germany's space agency DLR and NASA. The spacecraft were built in Germany and launched from Cape Canaveral Air Force Station, Florida. Helios 1 was launched in December 1974 onto an elliptic orbit between 1 and 0.31 au. Helios 2 followed in January 1976 and reached 0.29 au perihelion distance. The orbital periods were about 6 months. The Helios spacecraft were spinning with the spin axis perpendicular to the ecliptic plane. The Helios 1 spin axis pointed to ecliptic north whereas the Helios 2 orientation was inverted and the spin axis pointed to ecliptic south. The despun high gain antenna beam pointed always to Earth. Because of the orbit the distance between the spacecraft and Earth varied between a few and 300 million km and the data transmission rate varied accordingly. Twice per Helios orbit the spacecraft was in conjunction (in front or behind the Sun) and no data transmission was possible for a few weeks. Helios 1 delivered scientific data for ten years and Helios 2 for five years.
== Zodiacal light instrument ==
The primary goal of the Zodiacal light instrument on Helios was to determine the three-dimensional spatial distribution of interplanetary dust.
To this end, from all along its orbit, Helios performed
precise zodiacal light measurements covering a substantial part of the sky.
These partial sky maps, because of the rotation of Helios, consisted of a band 1° wide at ecliptic latitude ß = 16° with 32 sectors 5.62°, 11.25° and 22.5° long, a similar band 2° wide at ecliptic latitude ß = 31° and a field of 3° diameter at the ecliptic pole. All fields were in the south for Helios 1, in the north for Helios 2. The width of the sectors was chosen to be smallest for the brightest regions of zodiacal light.
This map has been realized by three small (36 mm aperture) photometers, P15, P30, and P90, one for each ecliptic latitude.
A stepping motor changed the observing wavelength with or without polarization to 360±30 nm, 420±40 nm, 540±70 nm (close to the UBV system) or to dark current and calibration measurements.
Each of the 36 resulting different brightness maps represents an average over 512 Helios rotations, leading to a cycle of total length 5.2 hours, which is continually repeated.
The sensors were photomultipliers EMR 541 N operating in photon pulse counting mode.
Throughout their mission the Helios space probes were exposed to full sunlight, which exceed the typical zodiacal light intensity by factor of 1012 to 1013. For accurate (1%) measurements demanding stray light suppression by a factor of 1015 was required, the main design goal to be met. This could be achieved in three steps:
The zodiacal light photometers were fully kept in the shadow of the Helios solar cell cone, giving 3×103 stray light reduction.
The multiple reflection in the stray light suppressing baffle added 4×107.
The coronograph design of the photometers provided the needed additional 3×106 of stray light reduction.
The Zodiacal light instrument was developed at the Max Planck Institute for Astronomy in Heidelberg by Christoph Leinert and colleagues and built by Dornier systems.
== Micrometeoroid analyzer ==
The goal of the Micrometeoroid Analyzer was 1. to determine the spatial distribution of the dust flux in the inner planetary system, and 2. to search for variations of the compositional and physical properties of micrometeoroids.
The instrument consisted of two impact ionization time-of-flight mass spectrometers and was developed by PI Eberhard Grün, Principal Engineer Peter Gammelin, and colleagues at the Max Planck Institute for Nuclear Physics in Heidelberg. Each sensor (Ecliptic sensor and South sensor) was a 1 m long and 0.15 m diameter tube with two grids and a venetian blind type impact target in front, several more grids, a 0.8 m long field-free drift tube and an electron multiplier in the inside. Micrometeoroids hitting the venetian blind type impact target generate an impact plasma. Electrons are collected by the positively biased grid in front of the target while positive ions are drawn inward by a negatively biased grid behind the target. Part of the ions reach the time-lag focusing region from which they fly through the field-free drift tube at 200 V potential. Ions of different masses reach the electron multiplier at different times and generate a mass spectrum at the multiplier output. Impact signals are recorded by charge-sensitive preamplifiers attached to the electron grid in front and the ion grid behind the target. From these signals together with the mass spectrum the mass and energy of the dust particle and the composition of the impact plasma are obtained.

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title: "Helios Dust Instrumentation"
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source: "https://en.wikipedia.org/wiki/Helios_Dust_Instrumentation"
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instance: "kb-cron"
---
The South sensor was shielded by the spacecraft rim from direct sun light, whereas the ecliptic sensor was directly exposed to the intense solar radiation (up to 13 kW/m2). Therefore, the interior of the sensor was protected by a 0.3 μm thick aluminized parylene film which was attached to the first entrance grid. In order to study the effect of micrometeoroids penetrating the film, extensive dust accelerator studies with various materials were performed. It was shown that the penetration limit of the Helios film depends strongly on the density of meteoroids. Impact experiments with a lab version of the Helios micrometeoroid sensor were performed using several materials at the accelerators at the Max Planck Institute for Nuclear Physics in Heidelberg and at the Ames Research Center, ARC, in Moffet Field. The projectile materials included iron (Fe), quartz, glass, aluminium (Al), aluminium oxide (Al2O3), polystyrene, and kaolin. The mass resolution of the mass spectra of the Helios sensors was low
R
=
M
Δ
M
10
{\displaystyle R={\cfrac {M}{\Delta M}}\sim 10}
, i.e. only ions of atomic mass 10 Da could be separated from ions of mass 11 Da.
These mass spectra served as reference for the spectra obtained in space. Spectra were recorded from 10 Da to 70 Da. The mean calibration spectra are presented in a three phase diagram: low masses (10 to 30 Da), medium masses (30 to 50 Da), and high masses (50 to 70 Da).
=== Micrometeoroid data ===
During ten orbits about the sun from 1974 to 1980 the Helios 1 micrometeoroid analyzer transmitted data of 235 dust impacts to Earth. Since the onboard data storage capability was limited and the data transmission rate varied strongly depending on the distance between spacecraft and Earth not all data recorded by the sensors was received on Earth. The effective measuring time ranged from ~30% at perihel to ~75% at 1 au distance. Many noise events caused by solar wind plasma and photo-electrons were recorded by the sensors as well. Only events within a coincidence time of 12 microseconds between positive and negative signals and, mainly, the measurement of a mass spectrum following the initial trigger were considered dust impacts. Quantities determined for each impact are: the time and position, the azimuth of the sensor viewing at the time of impact, the total positive charge of the impact signal, the rise-time of the charge signal (proxy for the impact speed) and a complete mass spectrum. The micrometeoroid instrument on Helios 2 was much noisier and recorded only a handful of impacts that did not provide additional information.
== Results ==
The Zodiacal light carries information on those regions of interplanetary space along the line of sight, which
contribute significantly to its observed brightness. For Helios this covers the range of 0.09 to about 2 astronomical units.
=== Spatial distribution ===
==== Radial dependencies ====
The zodiacal light instrument observed a strong increase of the zodiacal light brightness inward the Earth orbit. The brightness was more than a factor 10 higher at spacecraft position 0.3 au than at 1 au. This brightness increase corresponds to interplanetary dust density increase corresponding to
N
(
r
)
r
1.3
{\displaystyle N(r)\sim r^{-1.3}}
. This strong increase requires that there is a source of interplanetary dust inside the Earths orbit. It was suggested that collisional fragmentation of bigger meteoroids generates the dust observed in the zodiacal light.
The radial flux of micrometeoroids recorded by Helios increased by a factor 5 to 10 depending on the mass from 1017 kg to 1013 kg. This information together with the position and azimuth measurements was used in the first dynamical model of the interplanetary dust cloud; also the zodiacal light intensities observed by the Helios Zodiacal light instrument were included in this model. The Helios data defined the core, the inclined, and the eccentric populations of this model.
==== Plane of symmetry ====
From the difference between the measured zodiacal light
brightness during inbound and outbound parts of the orbit and
between right and left of the Sun the plane of symmetry of the
interplanetary dust cloud was determined. With its ascending node of
87°±5° and inclination of 3.0°±0.3° it lies between the
invariable plane of the Solar System and the plane of the
solar equator.
=== Orbital distribution ===
Of the 235 impacts total 152 were recorded by the South sensor and 83 by the Ecliptic sensor. This excess of impacts on the South sensor had mostly small impact (charge) signals but there was also some excess of big impacts. From thee azimuth values of Ecliptic sensor impacts it was concluded that the micrometeoroids moved on low eccentric orbits, e < 0.4, whereas South sensor impacts moved mostly on higher eccentric orbits. There was even an excess of outward compared to inward trajectories like the beta-meteoroids that were observed earlier by the Pioneer 8 and 9 dust instruments.
=== Optical, physical, and chemical properties ===
The measurements of zodiacal light color essentially constant
along the Helios orbit and of polarization showing a decrease
closer toward the Sun also contain information on properties
on interplanetary dust particles.
On the basis of the penetration studies with the Helios film the excess of impacts on the South sensor was interpreted to be due to low density,
ρ
{\displaystyle \rho }
< 1000 kg/m3, meteoroids that were shielded by the entrance film from entering the Ecliptic sensor.
Helios mass spectra range from those with dominant low masses up to 30 Da that are compatible with silicates to those with dominant high masses between 50 and 60 Da of iron and molecular ion types. The spectra display no clustering of single minerals. The continuous transition from low to high ion masses indicates that individual grains are a mixture of various minerals and carbonaceous compounds.
=== Cometary and interstellar dust streams ===
The Helios zodiacal light measurements show excellent stability.
This allows detecting local brightness excesses if they are crossed
by the Helios field-of-view, like it happened for comet West or for
the Quadrantid meteor shower. Repetition by about 0.2% from
orbit to orbit sufficed to detect the dust ring along the orbit
of Venus.
Inspection of the Helios micrometeoroid data showed a clustering of impacts in the same region of space on different Helios orbits. A search with the Interplanetary Meteoroid Environment for eXploration (IMEX) dust streams in space model identified the trails of comets 45P/HondaMrkosPajdušáková and 72P/DenningFujikawa that Helios traversed multiple times during the first ten orbits around the Sun.
After the discovery of interstellar dust passing through the planetary system by the Ulysses spacecraft interstellar dust particles were also found in the Helios micrometeoroid data. Based on the spacecraft position, the azimuth and impact charge 27 impactors are compatible with an interstellar source. The Helios measurements comprise interstellar dust measurements closest to the Sun.
== References ==

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title: "Holotomography"
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source: "https://en.wikipedia.org/wiki/Holotomography"
category: "reference"
tags: "science, encyclopedia"
date_saved: "2026-05-05T03:13:42.064553+00:00"
instance: "kb-cron"
---
Holotomography (HT) is a laser technique to measure the three-dimensional refractive index (RI) tomogram of a microscopic sample such as biological cells and tissues. Because the RI can serve as an intrinsic imaging contrast for transparent or phase objects, measurements of RI tomograms can provide label-free quantitative imaging of microscopic phase objects. In order to measure 3-D RI tomogram of samples, HT employs the principle of holographic imaging and inverse scattering. Typically, multiple 2D holographic images of a sample are measured at various illumination angles, employing the principle of interferometric imaging. Then, a 3D RI tomogram of the sample is reconstructed from these multiple 2D holographic images by inversely solving light scattering in the sample.
== History ==
The first theoretical proposal was presented by Emil Wolf, and the first experimental demonstration was shown by Fercher et al. From 2000s, HT techniques had been extensively studied and applied to the field of biology and medicine, by several research groups including the MIT spectroscopy laboratory. Both the technical developments and applications of HT have been significantly advanced. In 2012 the first commercial HT company Nanolive was founded, later followed by Tomocube in 2014.
== Principles ==
The principle of HT is very similar to X-ray computed tomography (CT) or CT scan. CT scan measures multiple 2-D X-ray images of a human body at various illumination angles, and a 3-D tomogram (X-ray absorptivity) is then retrieved via the inverse scattering theory. Both the X-ray CT and laser HT shares the same governing equation Helmholtz equation, the wave equation for a monochromatic wavelength. HT is also known as optical diffraction tomography.
== Advantages and limitations ==
HT provides following advantages over conventional 3D microscopic techniques.
Label-free: Cellular membrane and subcellular organelles can clearly be imaged without using exogenous labeling agents. Thus, there are no issues of phototoxicity, photobleaching and photodamaging.
Quantitative imaging capability: HT directly measures cell's 3D RI maps, which is intrinsic optical properties of materials. Because the measured RI can be translated into the mass density of a cell and using this information, mass of a cell can also be retrieved.
Precise and fast measurements: HT provides the spatial resolution down to approximately 100 nm and the temporal resolution of a few to a hundred frames per second, depending on the numerical apertures of used objective lenses and the speed of an image sensor.
However, 3D RI tomography does not provide molecular specificity. Generally, the measured RI information cannot be directly related to information about molecules or proteins, except for notable cases such as gold nanoparticles or lipid droplets that exhibit distinctly high RI values compared to cell cytoplasm.
== Applications ==
The applications of HT include:
=== Cell biology ===
HT provides 3D dynamic images of live cells and thin tissues without using exogenous labeling agents such as fluorescence proteins or dyes. HT enables quantitative live cell imaging, and also provides quantitative information such as cell volume, surface area, protein concentration. The label-free imaging and quantification of chromosomes were presented. The regulatory pathway of proteasome degradation by autophagy in cells were studies using HT.
=== Correlative imaging ===
HT can be used with other imaging modalities for correlative imaging. For example, a combination of HT and fluorescence imaging enables a synergistic analytic approach. HT provides structural information whereas fluorescence signal provides molecular specific imaging, an optical analogous to positron emission tomography (PET) and CT. Various approaches have been reported for correlative imaging approaches using HT.
=== Lipid quantification ===
Intracellular lipid droplets play important roles in energy storage and metabolism, and are also related to various pathologies, including cancer, obesity, and diabetes mellitus. HT enables label-free and quantitative imaging and analysis for free or intracellular lipid droplets. Because lipid droplets have distinctly high RI (n > 1.375) compared to other parts of cytoplasm, the measurements of RI tomograms provide information about the volume, concentration, and dry mass of lipid droplets. Recently, HT was used to evaluate the therapeutic effects of a nanodrug designed to affect the targeted delivery of lobeglitazone by measuring lipid droplets in foam cells.
=== Experimental laboratory ===
HT provide various quantitative imaging capability, providing morphological, biochemical, and mechanical properties of individuals cells. 3D RI tomography directly provides morphological properties including volume, surface area, and sphericity (roundness) of a cell. Local RI value can be translated into biochemical information or cytoplasmic protein concentration, because the RI of a solution is linearly proportional to its concentration. In particular, for the case of red blood cells, RI value can be converted into hemoglobin concentration. Measurements of dynamic cell membrane fluctuation, which can also be obtained with a HT instrument, provides information about cellular deformability. Furthermore, these various quantitative parameters can be obtained at the single cell level, allowing correlative analysis between various cellular parameters. HT has been utilized for the study of red blood cells, white blood cells, blood storage, and diabetes.
=== Infectious diseases ===
The quantitative label-free imaging capability of HT have been exploited for the study of various infectious diseases. In particular, parasites-invaded host cells can be effectively imaged and studied using HT. This is because the staining or labeling of parasites requires complicated preparation process and the staining/labeling is not very effective in several parasites. The invasion of plasmodium falciparum, or malaria inducing parasites, to individual red blood cells were measured using HT. The structural and biophysical alteration to host cells and parasites have been systematically analyzed. The invasion of babesia parasites to red blood cells were also studied. Toxoplasma gondii, an apicomplexan parasite causing toxoplasmosis, can infect nucleated cells. The alterations of 3D morphology and biophysical properties of T. gondii infected cells were studied using HT.
=== Biotechnology ===
The cell volume and dry mass of individual bacteria or micro algae can be effectively quantified using HT. Because it does not require the staining process while providing the precise quantification values, HT can be used for testing the efficacy of engineered stains.
== Scientific community ==
The following are active scientific conferences on HT, as a part of quantitative phase imaging techniques:
Quantitative phase imaging conference, SPIE Photonics West
The HT technique and applications have been included in the following special issues of scientific journals:
Special Issue on Quantitative Phase Imaging for Label-Free Cytometry in Cytometry Part A, 2019
Research Topic on Quantitative Phase Imaging and Its Applications to Biophysics, Biology, and Medicine in Frontiers in Physics
== See also ==
Quantitative phase imaging
Digital holographic microscopy
Holography
== References ==

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title: "Kymograph"
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source: "https://en.wikipedia.org/wiki/Kymograph"
category: "reference"
tags: "science, encyclopedia"
date_saved: "2026-05-05T03:13:43.239711+00:00"
instance: "kb-cron"
---
A kymograph (from Greek κῦμα, swell or wave + γραφή, writing; also called a kymographion) is a type of two-dimensional plot that represents spatial position or signal intensity over time. In its modern usage, a kymograph is typically a spacetime plot used in fields such as microscopy, cell biology, and speech science to track dynamic processes. These plots are generated by extracting intensity values along a predefined path across sequential image frames. The resulting image reduces the dimension to show time on one axis and sequential spatial information on the other. Using this technique allows for the visualization of dynamics within the image sequence, often by measuring the resulting slope of lines or streaks. This allows researchers to quantify velocity and directionality of movement, especially in applications like mitochondrial transport, vesicle trafficking, or vocal fold vibration. Although they reduce spatial information to a one-dimensional line, kymographs offer high temporal resolution and are often used alongside or in place of particle tracking techniques.
== Kymograph device ==
A kymograph is also an analog device that draws a graphical representation of spatial position over time. The graphical representation is a graph in which the y axis shows position and the x axis shows time. A kymograph consists of a revolving drum wrapped in paper on which a stylus draws to record measured changes of phenomena such as motion or pressure.
The kymograph was initially a mechanical and hydraulic device, invented by German physiologist Carl Ludwig in the 1840s, and found its first use as a means to monitor blood pressure. The blood pressure was conveyed by hydraulics and levers to move a stylus that scratched a white trace into soot-covered paper on the revolving drum. Time is represented by the drum's rotation rate, and was recorded by a second stylus driven by a clock or tuning fork. The kymograph almost immediately became the central instrument in physiology and physiology education. Throughout the nineteenth and twentieth centuries, researchers and technicians devised many improvements to the device, plus numerous new sensory components to measure a wide range of physiological phenomena such as breathing, muscle movement, and speech. New detection and registration systems included electrical and electronic methods, and plotted in ink.
Kymographs were also used outside medical science to measure atmospheric pressure, tuning fork vibrations, the functioning of steam engines, animal habits, and the movement of molecules in cells.
== Kymography in Experimental Physiology ==
The kymograph is generally used to study the effects of xenobiotics on tissue preparations. It is a standalone recording apparatus used alongside other apparatuses such as organ baths. Writing levers are used to trace the recording from muscle contractions. Some of the commonly used writing levers are the simple lever, the frontal writing lever and the starling heart lever. These writing levers are connected to a fulcrum which is found on a secondary apparatus.
== Videokymography ==
Videokymography is a high-speed imaging method used to examine vocal fold vibrations. It is a one-dimensional version of high-speed video imaging that captures images from a single transverse line across the glottis. These line images are recorded in rapid succession and displayed in real time with the vertical axis representing time. The resulting kymogram shows mucosal wave motion, glottal opening and closing, periodicity, and symmetry of vocal fold vibration. This method is particularly useful for detecting pathologies that alter vibratory patterns, such as vocal fold nodules or polyps. Modern systems often integrate videokymographs with endoscopic views to allow simultaneous structural and dynamic visualization.
== Depth Kymography ==
Depth kymography extends traditional kymographic analysis into three dimensions by incorporating depth-resolved imaging techniques such as optical coherence tomography. In this method, vertical sections of tissue (commonly vocal folds) are captured over time to create a dynamic depth-resolved kymogram. It allows for simultaneous visualization of surface and sub-surface vibration, offering enhanced diagnostic capability in laryngeal studies. This technology provides a comprehensive view of biomechanical motion within layered tissue structures.
== See also ==
Videokymography
Depth kymography
== References ==

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---
title: "Liulin type instruments"
chunk: 1/1
source: "https://en.wikipedia.org/wiki/Liulin_type_instruments"
category: "reference"
tags: "science, encyclopedia"
date_saved: "2026-05-05T03:13:44.389426+00:00"
instance: "kb-cron"
---
Liulin-type is a class of spectrometry-dosimetry instruments. The instruments are specific types of semiconductor-based ionizing radiation sensors that are capable of measuring the deposited energy of the particle in silicon PIN diode and also the flux of particles. The measured data output is then a time series of spectral intensity. The data about mixed field radiation (usually the secondary cosmic rays) is then used to calculate radiation dose relevant to the specific mission e.g. for a crew or aerospace equipment.
The main advantages of this type of ionizing radiation detector compared to classical setups with scintillators are a significant reduction in weight, and size together with extremely low power consumption.
== History ==
The first Liulin device was developed in 19861988 time period for the scientific program of the second Bulgarian cosmonaut for the flight on MIR space station. After the MIR station deorbit similar experiments with revised versions of detectors continue on ISS.
Since the beginning of 2015, open-source hardware detectors based on the same technology called SPACEDOS have been developed. Then the SPACEDOS instruments in different variants are used on board ISS parallel to Liulin dosimeters.
== Principle of function ==
All Liulin type dosimetric instruments use one or more silicon detectors and measure the deposited energy and number of particles in the period into the detector(s) when especially the charged particles hit the device, the semiconductor material is ionized and the charge is measured allowing to calculate the dose rate and particle flux.
In detail, the signal processing in the original LIULIN instrument was based on a single silicon PIN diode followed by a charge-sensitive shaping amplifier (CSA). The number of pulses at the output of CSA above a given threshold was proportional to the particle flux hitting the detector; the amplitude of the pulses at the output of CSA was proportional to the energy deposited by particles. Further the integral of the energy depositions of the particles accumulated in the detector during the measurement interval allowed calculation of the dose rate.
The original concept has a significant drawback in poor repeatability of original LIULIN instruments because the peak detection threshold was set by a mechanical trimmer, which was sensitive to initial setup and vibrations during usage.
That situation resulted in the design of multiple open-source Liulin-equivalent instruments developed in the Czech Republic called AIRDOS and SPACEDOS, where the given energy threshold is replaced by the invention of a new type of peak detector with analog memory. The improved signal processing circuit improves multiple parameters not only the issue with different energy threshold of different Liulin detector pieces, but at the same time allows to detection of deposited energies down to noise of detector itself.
== Use cases ==
The main usage of the described semiconductor detector type is in cosmic ray dosimetry. There exist multiple variants of Liulin-type detectors which extend its use cases to airliner dosimetry.
For example, there exists a variant of open-source hardware AIRDOS instruments specially designed for multiple types of UAVs.
== References ==

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MEMS testing is one of the processes in the development of a MEMS device. It is a collection of testing methods such as electrical, mechanical and environment tests.
== Motivation ==
When looking at the electronic market it becomes obvious, as there is a need for production output, high system performance, product reliability and long lifecycle, for MEMS to create trust in the eyes of customers. If those conditions would not be met customers would not invest into technologies using MEMS, which justifies the need for testing as a part of a high quality standard.
Testing is also fairly important from an economical point of view. As it is said that the failure cost increase by a factor of ten for each stage before it gets discovered.
Most MEMS producers check their products at two distinct stages(at the wafer level, and the packaging), as well as random sampling on every stage.
If one includes this into cost calculation for a MEMS device the costs for testing amounts to 20-50% of the overall unit costs.
Even when looking at producers that manufacture MEMS, and CMOS devices it is not really possible to reduce the costs by including the economy of scopes effect for testing, as both types of device. This is because even though about 80% of the processing is shared, only 20% of the tests are.
To decrease these costs for U.S. manufactures the National Institute of Standards and Technologies(NIST) conducted several workshops and questionnaires to tackle this issue and increase competitiveness of US companies.
== Testing ==
Due to the wide variety of MEMS it is hard to be very specific as of what is tested the table below shows what is tested in general:
== Different technologies ==
To test MEMS researchers came up with a wide variety of techniques that can display certain values. However, there is no single technology that can cover all; each has strengths as well as weaknesses.
Below is a list with all major and some minor technologies employed in MEMS testing:
Atomic force microscopy (AFM)
Confocal microscopy (CM)
Digital holographic microscopy (DHM)
Laser Doppler vibrometer (LDV)
Optical microscopy (OM)
Scanning electron microscopy (SEM)
Stroboscopic video microscopy (SVM)
White light interferometry (WLI)
Following technologies were experimented with but are no longer considered for MEMS testing:
Beam deflection
Electronic speckle pattern interferometry (ESPI)
Ellipsometry
Light scattering
Spectroscopy
All these technologies have strengths and weaknesses, so in order to maximize the effectiveness of test equipment researchers combined technologies. For instance Christian Rembe, former researcher at UC Berkeley, combined laser doppler vibrometry, white light interferometry and strobe video microscopy into one tool to eliminate each technologies weakness.
== References ==

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Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a mass spectrum, a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used in many different fields and is applied to pure samples as well as complex mixtures.
A mass spectrum is a type of plot of the ion signal as a function of the mass-to-charge ratio. These spectra are used to determine the elemental or isotopic signature of a sample, the masses of particles and of molecules, and to elucidate the chemical identity or structure of molecules and other chemical compounds.
In a typical MS procedure, a sample, which may be solid, liquid, or gaseous, is ionized, for example by bombarding it with a beam of electrons. This may cause some of the sample's molecules to break up into positively charged fragments or simply become positively charged without fragmenting. These ions (fragments) are then separated according to their mass-to-charge ratio, for example by accelerating them and subjecting them to an electric or magnetic field: ions of the same mass-to-charge ratio will undergo the same amount of deflection. The ions are detected by a mechanism capable of detecting charged particles, such as an electron multiplier. Results are displayed as spectra of the signal intensity of detected ions as a function of the mass-to-charge ratio. The atoms or molecules in the sample can be identified by correlating known masses (e.g. an entire molecule) to the identified masses or through a characteristic fragmentation pattern.
== History of the mass spectrometer ==
In 1886, Eugen Goldstein observed rays in gas discharges under low pressure that traveled away from the anode and through channels in a perforated cathode, opposite to the direction of negatively charged cathode rays (which travel from cathode to anode). Goldstein called these positively charged anode rays "Kanalstrahlen"; the standard translation of this term into English is "canal rays". Wilhelm Wien found that strong electric or magnetic fields deflected the canal rays and, in 1899, constructed a device with perpendicular electric and magnetic fields that separated the positive rays according to their charge-to-mass ratio (Q/m). Wien found that the charge-to-mass ratio depended on the nature of the gas in the discharge tube. English scientist J. J. Thomson later improved on the work of Wien by reducing the pressure to create the mass spectrograph.
The word spectrograph had become part of the international scientific vocabulary by 1884. Early spectrometry devices that measured the mass-to-charge ratio of ions were called mass spectrographs which consisted of instruments that recorded a spectrum of mass values on a photographic plate. A mass spectroscope is similar to a mass spectrograph except that the beam of ions is directed onto a phosphor screen. A mass spectroscope configuration was used in early instruments when it was desired that the effects of adjustments be quickly observed. Once the instrument was properly adjusted, a photographic plate was inserted and exposed. The term mass spectroscope continued to be used even though the direct illumination of a phosphor screen was replaced by indirect measurements with an oscilloscope. The use of the term mass spectroscopy is now discouraged due to the possibility of confusion with light spectroscopy. Mass spectrometry is often abbreviated as mass-spec or simply as MS.
Modern techniques of mass spectrometry were devised by Arthur Jeffrey Dempster and F.W. Aston in 1918 and 1919 respectively.
Sector mass spectrometers known as calutrons were developed by Ernest O. Lawrence and used for separating the isotopes of uranium during the Manhattan Project. Calutron mass spectrometers were used for uranium enrichment at the Oak Ridge, Tennessee Y-12 plant established during World War II.
In 1989, half of the Nobel Prize in Physics was awarded to Hans Dehmelt and Wolfgang Paul for the development of the ion trap technique in the 1950s and 1960s.
In 2002, the Nobel Prize in Chemistry was awarded to John Bennett Fenn for the development of electrospray ionization (ESI) and Koichi Tanaka for the development of soft laser desorption (SLD) and their application to the ionization of biological macromolecules, especially proteins.
== Parts of a mass spectrometer ==
A mass spectrometer consists of three components: an ion source, a mass analyzer, and a detector. The ionizer converts a portion of the sample into ions. There is a wide variety of ionization techniques, depending on the phase (solid, liquid, gas) of the sample and the efficiency of various ionization mechanisms for the unknown species. An extraction system removes ions from the sample, which are then targeted through the mass analyzer and into the detector. The differences in masses of the fragments allows the mass analyzer to sort the ions by their mass-to-charge ratio. The detector measures the value of an indicator quantity and thus provides data for calculating the abundances of each ion present. Some detectors also give spatial information, e.g., a multichannel plate.

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=== Theoretical example ===
The following describes the operation of a spectrometer mass analyzer, which is of the sector type. (Other analyzer types are treated below.) Consider a sample of sodium chloride (table salt). In the ion source, the sample is vaporized (turned into gas) and ionized (transformed into electrically charged particles) into sodium (Na+) and chloride (Cl) ions.
Sodium atoms and ions are monoisotopic, with a mass of about 23 daltons (symbol: Da or older symbol: u). Chloride atoms and ions come in two stable isotopes with masses of approximately 35 u (at a natural abundance of about 75 percent) and approximately 37 u (at a natural abundance of about 25 percent).
The analyzer part of the spectrometer contains electric and magnetic fields, which exert forces on ions traveling through these fields. The speed of a charged particle may be increased or decreased while passing through the electric field, and its direction may be altered by the magnetic field.
The magnitude of the deflection of the moving ion's trajectory depends on its mass-to-charge ratio. Lighter ions are deflected by the magnetic force to a greater degree than heavier ions (based on Newton's second law of motion, F = ma).
The streams of magnetically sorted ions pass from the analyzer to the detector, which records the relative abundance of each ion type. This information is used to determine the chemical element composition of the original sample (i.e. that both sodium and chlorine are present in the sample) and the isotopic composition of its constituents (the ratio of 35Cl to 37Cl).
== Creating ions ==
The ion source is the part of the mass spectrometer that ionizes the material under analysis (the analyte).
Techniques for ionization have been key to determining what types of samples can be analyzed by mass spectrometry.
Electron ionization and chemical ionization are used for gases and vapors.
In chemical ionization sources, the analyte is ionized by chemical ion-molecule reactions during collisions in the source. Two techniques often used with liquid and solid biological samples include electrospray ionization (invented by John Fenn) and matrix-assisted laser desorption/ionization (MALDI, initially developed as a similar technique "Soft Laser Desorption (SLD)" by K. Tanaka for which a Nobel Prize was awarded and as MALDI by M. Karas and F. Hillenkamp).
=== Hard ionization and soft ionization ===
In mass spectrometry, ionization refers to the production of gas phase ions suitable for resolution in the mass analyser or mass filter. Ionization occurs in the ion source. There are several ion sources available; each has advantages and disadvantages for particular applications. For example, electron ionization (EI) gives a high degree of fragmentation, yielding highly detailed mass spectra which when skilfully analysed can provide important information for structural elucidation/characterisation and facilitate identification of unknown compounds by comparison to mass spectral libraries obtained under identical operating conditions. However, EI is not suitable for coupling to HPLC, i.e. LC-MS, since at atmospheric pressure, the filaments used to generate electrons burn out rapidly. Thus EI is coupled predominantly with GC, i.e. GC-MS, where the entire system is under high vacuum.
Hard ionization techniques are processes which impart high quantities of residual energy in the subject molecule invoking large degrees of fragmentation (i.e. the systematic rupturing of bonds acts to remove the excess energy, restoring stability to the resulting ion). Resultant ions tend to have m/z lower than the molecular ion (other than in the case of proton transfer and not including isotope peaks). The most common example of hard ionization is electron ionization (EI).
Soft ionization refers to the processes which impart little residual energy onto the subject molecule and as such result in little fragmentation. Examples include fast atom bombardment (FAB), chemical ionization (CI), atmospheric-pressure chemical ionization (APCI), atmospheric-pressure photoionization (APPI), electrospray ionization (ESI), desorption electrospray ionization (DESI), and matrix-assisted laser desorption/ionization (MALDI).
=== Inductively coupled plasma ===
Inductively coupled plasma (ICP) sources are used primarily for cation analysis of a wide array of sample types. In this source, a plasma that is electrically neutral overall, but that has had a substantial fraction of its atoms ionized by high temperature, is used to atomize introduced sample molecules and to further strip the outer electrons from those atoms. The plasma is usually generated from argon gas, since the first ionization energy of argon atoms is higher than the first of any other elements except He, F and Ne, but lower than the second ionization energy of all except the most electropositive metals. The heating is achieved by a radio-frequency current passed through a coil surrounding the plasma.
=== Photoionization mass spectrometry ===
Photoionization can be used in experiments which seek to use mass spectrometry as a means of resolving chemical kinetics mechanisms and isomeric product branching. In such instances a high energy photon, either X-ray or uv, is used to dissociate stable gaseous molecules in a carrier gas of He or Ar. In instances where a synchrotron light source is utilized, a tuneable photon energy can be utilized to acquire a photoionization efficiency curve which can be used in conjunction with the charge ratio m/z to fingerprint molecular and ionic species. More recently atmospheric pressure photoionization (APPI) has been developed to ionize molecules mostly as effluents of LC-MS systems.
=== Ambient ionization ===
Some applications for ambient ionization include environmental applications as well as clinical applications. In these techniques, ions form in an ion source outside the mass spectrometer. Sampling becomes easy as the samples don't need previous separation nor preparation. Some examples of ambient ionization techniques are Direct Analysis in Real Time (DART), DESI, SESI, LAESI, desorption atmospheric-pressure chemical ionization (DAPCI), Soft Ionization by Chemical Reaction in Transfer (SICRT) and desorption atmospheric pressure photoionization DAPPI among others.
=== Other ionization techniques ===
Others include glow discharge, field desorption (FD), fast atom bombardment (FAB), thermospray, desorption/ionization on silicon (DIOS), atmospheric pressure chemical ionization (APCI), secondary ion mass spectrometry (SIMS), spark ionization and thermal ionization (TIMS).

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== Mass selection ==
Mass analyzers separate the ions according to their mass-to-charge ratio. The following two laws govern the dynamics of charged particles in electric and magnetic fields in vacuum:
F
=
Q
(
E
+
v
×
B
)
{\displaystyle \mathbf {F} =Q(\mathbf {E} +\mathbf {v} \times \mathbf {B} )}
(Lorentz force law);
F
=
m
a
{\displaystyle \mathbf {F} =m\mathbf {a} }
(Newton's second law of motion in the non-relativistic case, i.e. valid only at ion velocity much lower than the speed of light).
Here F is the force applied to the ion, m is the mass of the ion, a is the acceleration, Q is the ion charge, E is the electric field, and v × B is the vector cross product of the ion velocity and the magnetic field
Equating the above expressions for the force applied to the ion yields:
(
m
/
Q
)
a
=
E
+
v
×
B
.
{\displaystyle (m/Q)\mathbf {a} =\mathbf {E} +\mathbf {v} \times \mathbf {B} .}
This differential equation is the classic equation of motion for charged particles. Together with the particle's initial conditions, it completely determines the particle's motion in space and time in terms of m/Q. Thus mass spectrometers could be thought of as "mass-to-charge spectrometers". When presenting data, it is common to use the (officially) dimensionless m/z, where z is the number of elementary charges (e) on the ion (z=Q/e). This quantity, although it is informally called the mass-to-charge ratio, more accurately speaking represents the ratio of the mass number and the charge number, z.
There are many types of mass analyzers, using either static or dynamic fields, and magnetic or electric fields, but all operate according to the above differential equation. Each analyzer type has its strengths and weaknesses. Many mass spectrometers use two or more mass analyzers for tandem mass spectrometry (MS/MS). In addition to the more common mass analyzers listed below, there are others designed for special situations.
There are several important analyzer characteristics. The mass resolving power is the measure of the ability to distinguish two peaks of slightly different m/z. The mass accuracy is the ratio of the m/z measurement error to the true m/z. Mass accuracy is usually measured in ppm or milli mass units. The mass range is the range of m/z amenable to analysis by a given analyzer. The linear dynamic range is the range over which ion signal is linear with analyte concentration. Speed refers to the time frame of the experiment and ultimately is used to determine the number of spectra per unit time that can be generated.
=== Sector instruments ===
A sector field mass analyzer uses a static electric and/or magnetic field to affect the path and/or velocity of the charged particles in some way.
As shown above, sector instruments bend the trajectories of the ions as they pass through the mass analyzer, according to their mass-to-charge ratios, deflecting the more charged and faster-moving, lighter ions more. The analyzer can be used to select a narrow range of m/z or to scan through a range of m/z to catalog the ions present.
=== Time-of-flight ===
The time-of-flight (TOF) analyzer uses an electric field to accelerate the ions through the same potential, and then measures the time they take to reach the detector. If the particles all have the same charge, their kinetic energies will be identical, and their velocities will depend only on their masses. For example, ions with a lower mass will travel faster, reaching the detector first. Ions usually are moving prior to being accelerated by the electric field, this causes particles with the same m/z to arrive at different times at the detector. This difference in initial velocities is often not dependent on the mass of the ion, and will turn into a difference in the final velocity. This distribution in velocities broadens the peaks shown on the count vs m/z plot, but will generally not change the central location of the peaks, since the starting velocity of ions is generally centered at zero. To fix this problem, time-lag focusing/delayed extraction has been coupled with TOF-MS.
=== Quadrupole mass filter ===
Quadrupole mass analyzers use oscillating electrical fields to selectively stabilize or destabilize the paths of ions passing through a radio frequency (RF) quadrupole field created between four parallel rods. Only the ions in a certain range of mass/charge ratio are passed through the system at any time, but changes to the potentials on the rods allow a wide range of m/z values to be swept rapidly, either continuously or in a succession of discrete hops. A quadrupole mass analyzer acts as a mass-selective filter and is closely related to the quadrupole ion trap, particularly the linear quadrupole ion trap except that it is designed to pass the untrapped ions rather than collect the trapped ones, and is for that reason referred to as a transmission quadrupole.
A magnetically enhanced quadrupole mass analyzer includes the addition of a magnetic field, either applied axially or transversely. This novel type of instrument leads to an additional performance enhancement in terms of resolution and/or sensitivity depending upon the magnitude and orientation of the applied magnetic field.
A common variation of the transmission quadrupole is the triple quadrupole mass spectrometer. The "triple quad" has three consecutive quadrupole stages, the first acting as a mass filter to transmit a particular incoming ion to the second quadrupole, a collision chamber, wherein that ion can be broken into fragments. The third quadrupole also acts as a mass filter, to transmit a particular fragment ion to the detector. If a quadrupole is made to rapidly and repetitively cycle through a range of mass filter settings, full spectra can be reported. Likewise, a triple quad can be made to perform various scan types characteristic of tandem mass spectrometry.
=== Ion traps ===
==== Three-dimensional quadrupole ion trap ====

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The quadrupole ion trap works on the same physical principles as the quadrupole mass analyzer, but the ions are trapped and sequentially ejected. Ions are trapped in a mainly quadrupole RF field, in a space defined by a ring electrode (usually connected to the main RF potential) between two endcap electrodes (typically connected to DC or auxiliary AC potentials). The sample is ionized either internally (e.g. with an electron or laser beam), or externally, in which case the ions are often introduced through an aperture in an endcap electrode.
There are many mass/charge separation and isolation methods but the most commonly used is the mass instability mode in which the RF potential is ramped so that the orbit of ions with a mass a > b are stable while ions with mass b become unstable and are ejected on the z-axis onto a detector. There are also non-destructive analysis methods.
Ions may also be ejected by the resonance excitation method, whereby a supplemental oscillatory excitation voltage is applied to the endcap electrodes, and the trapping voltage amplitude and/or excitation voltage frequency is varied to bring ions into a resonance condition in order of their mass/charge ratio.
==== Cylindrical ion trap ====
The cylindrical ion trap mass spectrometer (CIT) is a derivative of the quadrupole ion trap where the electrodes are formed from flat rings rather than hyperbolic shaped electrodes. The architecture lends itself well to miniaturization because as the size of a trap is reduced, the shape of the electric field near the center of the trap, the region where the ions are trapped, forms a shape similar to that of a hyperbolic trap.
==== Linear quadrupole ion trap ====
A linear quadrupole ion trap is similar to a quadrupole ion trap, but it traps ions in a two dimensional quadrupole field, instead of a three-dimensional quadrupole field as in a 3D quadrupole ion trap. Thermo Fisher's LTQ ("linear trap quadrupole") is an example of the linear ion trap.
A toroidal ion trap can be visualized as a linear quadrupole curved around and connected at the ends or as a cross-section of a 3D ion trap rotated on edge to form the toroid, donut-shaped trap. The trap can store large volumes of ions by distributing them throughout the ring-like trap structure. This toroidal shaped trap is a configuration that allows the increased miniaturization of an ion trap mass analyzer. Additionally, all ions are stored in the same trapping field and ejected together simplifying detection that can be complicated with array configurations due to variations in detector alignment and machining of the arrays.
As with the toroidal trap, linear traps and 3D quadrupole ion traps are the most commonly miniaturized mass analyzers due to their high sensitivity, tolerance for mTorr pressure, and capabilities for single analyzer tandem mass spectrometry (e.g. product ion scans).
==== Orbitrap ====
Orbitrap instruments are similar to Fourier-transform ion cyclotron resonance mass spectrometers (see text below). Ions are electrostatically trapped in an orbit around a central, spindle shaped electrode. The electrode confines the ions so that they both orbit around the central electrode and oscillate back and forth along the central electrode's long axis. This oscillation generates an image current in the detector plates which is recorded by the instrument. The frequencies of these image currents depend on the mass-to-charge ratios of the ions. Mass spectra are obtained by Fourier transformation of the recorded image currents.
Orbitraps have a high mass accuracy, high sensitivity and a good dynamic range.
=== Fourier-transform ion cyclotron resonance ===
Fourier-transform mass spectrometry (FTMS), or more precisely Fourier-transform ion cyclotron resonance MS, measures mass by detecting the image current produced by ions spiralling in the presence of a magnetic field. Instead of measuring the deflection of ions with a detector such as an electron multiplier, the ions are injected into a Penning trap (a static electric/magnetic ion trap) where they effectively form part of a circuit. Detectors at fixed positions in space measure the electrical signal of ions which pass near them over time, producing a periodic signal. Since the frequency of an ion's cycling is determined by its mass-to-charge ratio, this can be deconvoluted by performing a Fourier transform on the signal. FTMS has the advantage of high sensitivity (since each ion is "counted" more than once) and much higher resolution and thus precision.
Ion cyclotron resonance (ICR) is an older mass analysis technique similar to FTMS except that ions are detected with a traditional detector. Ions trapped in a Penning trap are excited by an RF electric field until they impact the wall of the trap, where the detector is located. Ions of different mass are resolved according to impact time.
== Detectors ==
The final element of the mass spectrometer is the detector. The detector records either the charge induced or the current produced when an ion passes by or hits a surface. In a scanning instrument, the signal produced in the detector during the course of the scan versus where the instrument is in the scan (at what m/Q) will produce a mass spectrum, a record of ions as a function of m/Q.
Typically, some type of electron multiplier is used, though other detectors including Faraday cups and ion-to-photon detectors are also used. Because the number of ions leaving the mass analyzer at a particular instant is typically quite small, considerable amplification is often necessary to get a signal. Microchannel plate detectors are commonly used in modern commercial instruments. In FTMS and Orbitraps, the detector consists of a pair of metal surfaces within the mass analyzer/ion trap region which the ions only pass near as they oscillate. No direct current is produced, only a weak AC image current is produced in a circuit between the electrodes. Other inductive detectors have also been used.
== Tandem mass spectrometry ==

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A tandem mass spectrometer is one capable of multiple rounds of mass spectrometry, usually separated by some form of molecule fragmentation. For example, one mass analyzer can isolate one peptide from many entering a mass spectrometer. A collision cell then stabilizes the peptide ions while they collide with a gas, causing them to fragment by collision-induced dissociation (CID). A further mass analyzer then sorts the fragments produced from the peptides. Tandem MS can also be done in a single mass analyzer over time, as in a quadrupole ion trap. There are various methods for fragmenting molecules for tandem MS, including collision-induced dissociation (CID), electron capture dissociation (ECD), electron transfer dissociation (ETD), infrared multiphoton dissociation (IRMPD), blackbody infrared radiative dissociation (BIRD), electron-detachment dissociation (EDD) and surface-induced dissociation (SID). An important application using tandem mass spectrometry is in protein identification.
Tandem mass spectrometry enables a variety of experimental sequences. Many commercial mass spectrometers are designed to expedite the execution of such routine sequences as selected reaction monitoring (SRM), precursor ion scanning, product ion scanning, and neutral loss scanning.
In SRM, the first analyzer allows only a single mass through and the second analyzer monitors for multiple user-defined fragment ions over longer dwell-times than could be achieved in a full scan. This increases sensitivity.
In product ion scans, the first mass analyzer is fixed to select a particular precursor ion ("parent"), while the second is scanned to find all the fragments ("products", or "daughter ions") to which it can be fragmented in the collision cell.
In precursor ion scans, the second mass analyzer is fixed to select a particular fragment ion ("daughter"), while the first is scanned to find all possible precursor ions that could give rise to this fragment.
In neutral loss scans, the two mass analyzers are scanned in parallel, but separated by the mass of a molecular subunit of interest to the analyst. Ions are detected if they lose that fixed mass during fragmentation. This can be used to look for any chemical that is capable of losing a particular neutral group, for example a sugar residue. Together, neutral loss and precursor ion scans can be used to hunt for chemicals with particular motifs.
Another type of tandem mass spectrometry used for radiocarbon dating is accelerator mass spectrometry (AMS), which uses very high voltages, usually in the mega-volt range, to accelerate negative ions into a type of tandem mass spectrometer.
The METLIN Metabolite and Chemical Entity Database is the largest repository of experimental tandem mass spectrometry data acquired from standards. The tandem mass spectrometry data on over 960,000 molecular standards (as of October 2025) is provided to facilitate the identification of chemical entities from tandem mass spectrometry experiments. In addition to the identification of known molecules it is also useful for identifying unknowns using its similarity searching/analysis. All tandem mass spectrometry data comes from the experimental analysis of standards at multiple collision energies and in both positive and negative ionization modes.
== Common mass spectrometer configurations and techniques ==
When a specific combination of source, analyzer, and detector becomes conventional in practice, a compound acronym may arise to designate it succinctly. One example is MALDI-TOF, which refers to a combination of a matrix-assisted laser desorption/ionization source with a time-of-flight mass analyzer. Other examples include inductively coupled plasma-mass spectrometry (ICP-MS), accelerator mass spectrometry (AMS), thermal ionization-mass spectrometry (TIMS) and spark source mass spectrometry (SSMS).
Certain applications of mass spectrometry have developed monikers that although strictly speaking would seem to refer to a broad application, in practice have come instead to connote a specific or a limited number of instrument configurations. An example of this is isotope-ratio mass spectrometry (IRMS), which refers in practice to the use of a limited number of sector based mass analyzers; this name is used to refer to both the application and the instrument used for the application.
== Separation techniques combined with mass spectrometry ==
An important enhancement to the mass resolving and mass determining capabilities of mass spectrometry is using it in tandem with chromatographic and other separation techniques.
=== Gas chromatography ===
A common combination is gas chromatography-mass spectrometry (GC/MS or GC-MS). In this technique, a gas chromatograph is used to separate different compounds. This stream of separated compounds is fed online into the ion source, a metallic filament to which voltage is applied. This filament emits electrons which ionize the compounds. The ions can then further fragment, yielding predictable patterns. Intact ions and fragments pass into the mass spectrometer's analyzer and are eventually detected. However, the high temperatures (300 °C) used in the GC-MS injection port (and oven) can result in thermal degradation of injected molecules, thus resulting in the measurement of degradation products instead of the actual molecule(s) of interest.
=== Liquid chromatography ===
Similarly to gas chromatography MS (GC-MS), liquid chromatography-mass spectrometry (LC/MS or LC-MS) separates compounds chromatographically before they are introduced to the ion source and mass spectrometer. It differs from GC-MS in that the mobile phase is liquid, usually a mixture of water and organic solvents, instead of gas. Most commonly, an electrospray ionization source is used in LC-MS. Other popular and commercially available LC-MS ion sources are atmospheric pressure chemical ionization and atmospheric pressure photoionization. There are also some newly developed ionization techniques like laser spray.
=== Capillary electrophoresismass spectrometry ===
Capillary electrophoresismass spectrometry (CE-MS) is a technique that combines the liquid separation process of capillary electrophoresis with mass spectrometry. CE-MS is typically coupled to electrospray ionization.
=== Ion mobility ===

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Ion mobility spectrometry-mass spectrometry (IMS/MS or IMMS) is a technique where ions are first separated by drift time through some neutral gas under an applied electrical potential gradient before being introduced into a mass spectrometer. Drift time is a measure of the collisional cross section relative to the charge of the ion. The duty cycle of IMS (the time over which the experiment takes place) is longer than most mass spectrometric techniques, such that the mass spectrometer can sample along the course of the IMS separation. This produces data about the IMS separation and the mass-to-charge ratio of the ions in a manner similar to LC-MS.
The duty cycle of IMS is short relative to liquid chromatography or gas chromatography separations and can thus be coupled to such techniques, producing triple modalities such as LC/IMS/MS.
== Data and analysis ==
=== Data representations ===
Mass spectrometry produces various types of data. The most common data representation is the mass spectrum.
Certain types of mass spectrometry data are best represented as a mass chromatogram. Types of chromatograms include selected ion monitoring (SIM), total ion current (TIC), and selected reaction monitoring (SRM), among many others.
Other types of mass spectrometry data are well represented as a three-dimensional contour map. In this form, the mass-to-charge, m/z is on the x-axis, intensity the y-axis, and an additional experimental parameter, such as time, is recorded on the z-axis.
=== Data analysis ===
Mass spectrometry data analysis is specific to the type of experiment producing the data. General subdivisions of data are fundamental to understanding any data.
Many mass spectrometers work in either negative ion mode or positive ion mode. It is very important to know whether the observed ions are negatively or positively charged. This is often important in determining the neutral mass but it also indicates something about the nature of the molecules.
Different types of ion source result in different arrays of fragments produced from the original molecules. An electron ionization source produces many fragments and mostly single-charged (1-) radicals (odd number of electrons), whereas an electrospray source usually produces non-radical quasimolecular ions that are frequently multiply charged. Tandem mass spectrometry purposely produces fragment ions post-source and can drastically change the sort of data achieved by an experiment.
Knowledge of the origin of a sample can provide insight into the component molecules of the sample and their fragmentations. A sample from a synthesis/manufacturing process will probably contain impurities chemically related to the target component. A crudely prepared biological sample will probably contain a certain amount of salt, which may form adducts with the analyte molecules in certain analyses.
Results can also depend heavily on sample preparation and how it was run/introduced. An important example is the issue of which matrix is used for MALDI spotting, since much of the energetics of the desorption/ionization event is controlled by the matrix rather than the laser power. Sometimes samples are spiked with sodium or another ion-carrying species to produce adducts rather than a protonated species.
Mass spectrometry can measure molar mass, molecular structure, and sample purity. Each of these questions requires a different experimental procedure; therefore, adequate definition of the experimental goal is a prerequisite for collecting the proper data and successfully interpreting it.
==== Interpretation of mass spectra ====
Since the precise structure or peptide sequence of a molecule is deciphered through the set of fragment masses, the interpretation of mass spectra requires combined use of various techniques. Usually the first strategy for identifying an unknown compound is to compare its experimental mass spectrum against a library of mass spectra. If no matches result from the search, then manual interpretation or software assisted interpretation of mass spectra must be performed. Computer simulation of ionization and fragmentation processes occurring in mass spectrometer is the primary tool for assigning structure or peptide sequence to a molecule. An a priori structural information is fragmented in silico and the resulting pattern is compared with observed spectrum. Such simulation is often supported by a fragmentation library that contains published patterns of known decomposition reactions. Software taking advantage of this idea has been developed for both small molecules and proteins.
Analysis of mass spectra can also be spectra with accurate mass. A mass-to-charge ratio value (m/z) with only integer precision can represent an immense number of theoretically possible ion structures; however, more precise mass figures significantly reduce the number of candidate molecular formulas. A computer algorithm called formula generator calculates all molecular formulas that theoretically fit a given mass with specified tolerance.
A recent technique for structure elucidation in mass spectrometry, called precursor ion fingerprinting, identifies individual pieces of structural information by conducting a search of the tandem spectra of the molecule under investigation against a library of the product-ion spectra of structurally characterized precursor ions.
== Applications ==

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Mass spectrometry has both qualitative and quantitative uses. These include identifying unknown compounds, determining the isotopic composition of elements in a molecule, and determining the structure of a compound by observing its fragmentation. Other uses include quantifying the amount of a compound in a sample or studying the fundamentals of gas phase ion chemistry (the chemistry of ions and neutrals in a vacuum). MS is now commonly used in analytical laboratories that study physical, chemical, or biological properties of a great variety of compounds. Quantification can be relative (analyzed relative to a reference sample) or absolute (analyzed using a standard curve method).
As an analytical technique it possesses distinct advantages such as: Increased sensitivity over most other analytical techniques because the analyzer, as a mass-charge filter, reduces background interference, Excellent specificity from characteristic fragmentation patterns to identify unknowns or confirm the presence of suspected compounds, Information about molecular weight, Information about the isotopic abundance of elements, Temporally resolved chemical data.
A few of the disadvantages of the method is that it often fails to distinguish between optical and geometrical isomers and the positions of substituent in o-, m- and p- positions in an aromatic ring. Also, its scope is limited in identifying hydrocarbons that produce similar fragmented ions.
=== Isotope ratio mass spectrometry ===
Mass spectrometry is also used to determine the isotopic composition of elements within a sample. Differences in mass among isotopes of an element are very small, and the less abundant isotopes of an element are typically very rare, so a very sensitive instrument is required. For the measurement of light elements (e.g. H,C,N,O,S), isotope ratio mass spectrometers (IRMS) usually use a single magnet to bend a beam of ionized particles towards a series of Faraday cups which convert particle impacts to electric current. A fast on-line analysis of deuterium content of water can be done using flowing afterglow mass spectrometry, FA-MS. Probably the most sensitive and accurate mass spectrometer for this purpose is the accelerator mass spectrometer (AMS). This is because it provides ultimate sensitivity, capable of measuring individual atoms and measuring nuclides with a dynamic range of ~1015 relative to the major stable isotope. Isotopic signatures can serve as markers of a variety of processes. Some isotope ratios are used to determine the age of materials for example as in carbon dating. Labeling with stable isotopes is also used for protein quantification (see protein characterization below).
==== Membrane-introduction mass spectrometry: measuring gases in solution ====
Membrane-introduction mass spectrometry combines the IRMS with a reaction chamber/cell separated by a gas-permeable membrane. This method allows the study of gases as they evolve in solution. This method has been extensively used for the study of the production of oxygen by Photosystem II.
=== Trace gas analysis ===
Several techniques use ions created in a dedicated ion source injected into a flow tube or a drift tube: selected ion flow tube (SIFT-MS), and proton transfer reaction (PTR-MS), are variants of chemical ionization dedicated for trace gas analysis of air, breath or liquid headspace using well defined reaction time allowing calculations of analyte concentrations from the known reaction kinetics without the need for internal standard or calibration.
Another technique with applications in trace gas analysis field is secondary electrospray ionization (SESI-MS), which is a variant of electrospray ionization. SESI consist of an electrospray plume of pure acidified solvent that interacts with neutral vapors. Vapor molecules get ionized at atmospheric pressure when charge is transferred from the ions formed in the electrospray to the molecules. One advantage of this approach is that it is compatible with most ESI-MS systems.
=== Residual gas analysis ===
=== Atom probe ===
An atom probe is an instrument that combines time-of-flight mass spectrometry and field-evaporation microscopy to map the location of individual atoms.
=== Pharmacokinetics ===
Pharmacokinetics is often studied using mass spectrometry because of the complex nature of the matrix (often blood or urine) and the need for high sensitivity to observe low dose and long time point data. The most common instrumentation used in this application is LC-MS with a triple quadrupole mass spectrometer. Tandem mass spectrometry is usually employed for added specificity. Standard curves and internal standards are used for quantitation of usually a single pharmaceutical in the samples. The samples represent different time points as a pharmaceutical is administered and then metabolized or cleared from the body. Blank or t=0 samples taken before administration are important in determining background and ensuring data integrity with such complex sample matrices. Much attention is paid to the linearity of the standard curve; however it is not uncommon to use curve fitting with more complex functions such as quadratics since the response of most mass spectrometers is less than linear across large concentration ranges.
There is currently considerable interest in the use of very high sensitivity mass spectrometry for microdosing studies, which are seen as a promising alternative to animal experimentation.
Recent studies show that secondary electrospray ionization (SESI) is a powerful technique to monitor drug kinetics via breath analysis. Because breath is naturally produced, several datapoints can be readily collected. This allows for the number of collected data-points to be greatly increased. In animal studies, this approach SESI can reduce animal sacrifice. In humans, SESI-MS non-invasive analysis of breath can help study the kinetics of drugs at a personalized level.
=== Protein characterization ===

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Mass spectrometry is an important method for the characterization and sequencing of proteins. The two primary methods for ionization of whole proteins are electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). In keeping with the performance and mass range of available mass spectrometers, two approaches are used for characterizing proteins. In the first, intact proteins are ionized by either of the two techniques described above, and then introduced to a mass analyzer. This approach is referred to as "top-down" strategy of protein analysis. The top-down approach however is largely limited to low-throughput single-protein studies. In the second, proteins are enzymatically digested into smaller peptides using proteases such as trypsin or pepsin, either in solution or in gel after electrophoretic separation. Other proteolytic agents are also used. The collection of peptide products are often separated by chromatography prior to introduction to the mass analyzer. When the characteristic pattern of peptides is used for the identification of the protein the method is called peptide mass fingerprinting (PMF), if the identification is performed using the sequence data determined in tandem MS analysis it is called de novo peptide sequencing. These procedures of protein analysis are also referred to as the "bottom-up" approach, and have also been used to analyse the distribution and position of post-translational modifications such as phosphorylation on proteins. A third approach is also beginning to be used, this intermediate "middle-down" approach involves analyzing proteolytic peptides that are larger than the typical tryptic peptide.
=== Space exploration ===
As a standard method for analysis, mass spectrometers have reached other planets and moons. Two were taken to Mars by the Viking program. In early 2005 the CassiniHuygens mission delivered a specialized GC-MS instrument aboard the Huygens probe through the atmosphere of Titan, the largest moon of the planet Saturn. This instrument analyzed atmospheric samples along its descent trajectory and was able to vaporize and analyze samples of Titan's frozen, hydrocarbon covered surface once the probe had landed. These measurements compare the abundance of isotope(s) of each particle comparatively to earth's natural abundance. Also on board the CassiniHuygens spacecraft was an ion and neutral mass spectrometer which had been taking measurements of Titan's atmospheric composition as well as the composition of Enceladus' plumes. A Thermal and Evolved Gas Analyzer mass spectrometer was carried by the Mars Phoenix Lander launched in 2007.
Mass spectrometers are also widely used in space missions to measure the composition of plasmas. For example, the Cassini spacecraft carried the Cassini Plasma Spectrometer (CAPS), which measured the mass of ions in Saturn's magnetosphere.
=== Respired gas monitor ===
Mass spectrometers were used in hospitals for respiratory gas analysis beginning around 1975 through the end of the century. Some are probably still in use but none are currently being manufactured.
Found mostly in the operating room, they were a part of a complex system, in which respired gas samples from patients undergoing anesthesia were drawn into the instrument through a valve mechanism designed to sequentially connect up to 32 rooms to the mass spectrometer. A computer directed all operations of the system. The data collected from the mass spectrometer was delivered to the individual rooms for the anesthesiologist to use.
The uniqueness of this magnetic sector mass spectrometer may have been the fact that a plane of detectors, each purposely positioned to collect all of the ion species expected to be in the samples, allowed the instrument to simultaneously report all of the gases respired by the patient. Although the mass range was limited to slightly over 120 u, fragmentation of some of the heavier molecules negated the need for a higher detection limit.
=== Preparative mass spectrometry ===
The primary function of mass spectrometry is as a tool for chemical analyses based on detection and quantification of ions according to their mass-to-charge ratio. However, mass spectrometry also shows promise for material synthesis. Ion soft landing is characterized by deposition of intact species on surfaces at low kinetic energies which precludes the fragmentation of the incident species. The soft landing technique was first reported in 1977 for the reaction of low energy sulfur containing ions on a lead surface.
=== Charge detection mass spectrometry ===
Most mass spectrometers measure the mass-to-charge ratio; the actual mass can be found only if the charge is known. For smaller molecules the charge can be determined from the spacing of isotope peaks, but for very large biomolecules and particles (in the megadalton range) resolution may not be adequate to separate isotope peaks, and thus the mass cannot be determined. In charge detection mass spectrometry (CDMS), the charge of an individual ion/particle is measured directly (alongside its mass-to-charge ratio) and therefore the true mass is known. It is a single-particle technique, but to produce more precise and accurate results, the data from many individually-measured ions can be combined.
== See also ==
== References ==
== Bibliography ==
== External links ==
Interactive tutorial on mass spectra National High Magnetic Field Laboratory
Mass spectrometer simulation An interactive application simulating the console of a mass spectrometer
Realtime Mass Spectra simulation Tool to simulate mass spectra in the browser

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A microscope (from Ancient Greek μικρός (mikrós) 'small' and σκοπέω (skopéō) 'to look (at); examine, inspect') is a 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 electrons through a sample in its optical path, by detecting photon emissions 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 lenses to refract visible light that passed through a 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 microscopes.
== History ==
Although objects resembling lenses date back 4,000 years and there are 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 glasses) dates back to the widespread use of lenses in eyeglasses in the 13th century. The earliest known examples of compound microscopes, which combine an objective lens near the specimen with an eyepiece to view a real image, appeared in Europe around 1620. 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, claims it was invented by their neighbor and rival spectacle maker, Hans Lippershey (who applied for the first telescope patent in 1608), and claims it was invented by expatriate Cornelis Drebbel, who was noted to have a version in London in 1619. 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. Giovanni Faber coined the name microscope for the compound microscope Galileo submitted to the Accademia dei Lincei in 1625 (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.
=== Rise of modern light microscopes ===
The first detailed account of the 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.
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. 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. Then, Van Leeuwenhoek re-discovered red blood cells (after Jan Swammerdam) and spermatozoa, and helped popularise the use of microscopes to view biological ultrastructure. On 9 October 1676, van Leeuwenhoek reported the discovery of micro-organisms.
The performance of a compound light microscope depends on the quality and correct use of the condensor lens system to focus light on the specimen and the objective lens to capture the light from the specimen and form an image. 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 by Frits Zernike in 1953, and differential interference contrast illumination by Georges Nomarski in 1955; both of which allow imaging of unstained, transparent samples.
=== Electron microscopes ===

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In the early 20th century a significant alternative to the light microscope was developed, an instrument that uses a beam of electrons 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. 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. 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 ===
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.
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 ===
The most recent developments in light microscope largely centre on the rise of fluorescence microscopy in biology. During the last decades of the 20th century, particularly in the post-genomic era, many techniques for fluorescent staining of cellular structures were developed. 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. 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 and Christoph Cremer developed the first practical confocal laser scanning microscope and the technique rapidly gained popularity through the 1980s.
=== Super resolution microscopes ===
Much current research (in the early 21st century) on optical microscope techniques is focused on development of superresolution analysis of fluorescently labelled samples. Structured illumination can improve resolution by around two to four times and techniques like stimulated emission depletion (STED) microscopy are approaching the resolution of electron microscopes. 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.
=== X-ray microscopes ===
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. They are often used in tomography (see 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.
== Types ==

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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), electrons (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 (in optical microscopes) or electron beams (in electron microscopes). 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.
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 ===
The most common type of microscope (and the first invented) is the optical microscope. This is an optical instrument containing one or more lenses producing an enlarged image of a sample placed in the focal plane. Optical microscopes have 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 resolution limit of around 0.250 micrometres or 250 nanometres. This limits practical magnification to ~1,500×. Specialized techniques (e.g., 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 nanometre) and isolated nano-objects (down to 2 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 fluoresce, which allows viewing by eye or with specifically sensitive cameras.
Phase-contrast microscopy is an optical microscopic illumination technique in which small phase shifts in the light passing through a transparent specimen are converted into amplitude or contrast changes in the image. 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 eyepieces, 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 digital cameras. It has been demonstrated that a light source providing pairs of 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.
=== Electron microscope ===
The two major types of electron microscopes are transmission electron microscopes (TEMs) and scanning electron microscopes (SEMs). 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 basic optical microscopy. This requires careful sample preparation, since electrons are scattered strongly by most materials. The samples must also be very thin (below 100 nm) in order for the electrons to pass through it. Cross-sections of cells stained with osmium and heavy metals reveal clear organelle membranes and proteins such as ribosomes. With a 0.1 nm level of resolution, detailed views of viruses (20 300 nm) and a strand of DNA (2 nm in width) can be obtained. 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. SEM allows fast surface imaging of samples, possibly in thin water vapor to prevent drying.
=== Scanning probe ===

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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 microscopes (AFM), near-field scanning optical microscopes (NSOM or SNOM, scanning near-field optical microscopy), and scanning tunneling microscopes (STM). 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. 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.
=== Other types ===
Scanning acoustic microscopes 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.
==== 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, are often limited to 40x, and the resolution limits of the camera lens itself.
== See also ==
== References ==
== External links ==
Milestones in Light Microscopy, Nature Publishing
FAQ on Optical Microscopes (archived 4 April 2009)
Nikon MicroscopyU, tutorials from Nikon
Molecular Expressions : Exploring the World of Optics and Microscopy, Florida State University.

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A multi-component gas analyzer system (Multi-GAS) is an instrument package used to take real-time high-resolution measurements of volcanic gases. A Multi-GAS package includes an infrared spectrometer for CO2, two electrochemical sensors for SO2 and H2S, and pressuretemperaturehumidity sensors, all in a weatherproof box. The system can be used for individual surveys or set up as permanent stations connected to radio transmitters for transmission of data from remote locations. The instrument package is portable, and its operation and data analysis are simple enough to be conducted by non-specialists.
Multi-GAS instruments have been used to measure volcanic gases at Mount Etna, Stromboli, Vulcano Italy, Villarrica (volcano) Chile, Masaya Volcano Nicaragua, Mount Yasur, Miyake-jima and Mount Asama Japan, Soufrière Hills Montserrat, with permanent installations at Etna and Stromboli.
The development of this instrument has helped scientists to monitor real-time changes in volcanic gas composition, allowing for more rapid hazard mitigation and an enhanced understanding of volcano processes.
== System mechanics ==
Multi-component gas analyzer systems are used for measuring the major components of volcanic gases. CO2, SO2, H2S, and pressure-temperature-humidity sensors are typically included in a package. Other electrochemical sensors have been successfully incorporated as well, including for H2 and HCl. The instruments are packaged in compact, portable, weather-resistant containers allowing for in situ measurements of various types of outgassing terrains. Gas is pumped into the system at a constant flow rate through a silicone tube placed near the location of interest. A data-logger is used to automatically record and convert the voltage values from the sensors into gas composition values. While the field use of a multi-GAS is simple, postprocessing of the data can be complex. This is due to factors like instrument drift, and atmospheric or environmental conditions. The system can be used for short term or long term studies. Short term usage can include powering the multi-GAS by a lithium battery and moving it around to desired locations or setting up a multi-GAS in a fixed location for a short period of time. Long term studies involve setting up a permanent installment for an extended time. These stations can be set-up with terrestrial (e.g. 3G) or satellite radio transmitters to send data from distant locations.
== Volcano monitoring ==
Monitoring changes in gas composition allows for an understanding of changes occurring in the associated volcanic system. Multi-GAS measurements of real-time CO2/SO2 ratios can allow detection of the pre-eruptive degassing of rising magmas, improving the prediction of volcanic activity. As magma rises beneath the surface CO2 solubility decreases and the gas readily exsolves, leading to an increase in the CO2/SO2 ratio. A new input of CO2-rich magma into a previously degassed system would also cause the CO2/SO2 ratio to rise, indicating changes in volcanic activity. During a two year study at Mount Etna quiescent periods had CO2/SO2 ratios <1, but during the lead up to an eruption values as high as 25 were seen. Magmatic or hydrothermal input can be monitored by the temporal variations in H2S/SO2 ratios, advancing the understanding of future eruptive behavior. CO2/H2S ratios are used to define the characteristic gas composition of the sampled area. The ratio can be a tool for understanding how the magmatic gas may have been scrubbed. Other molar ratios and gas species measured by a multi-GAS can provide information for further analysis of volcanic conditions.
== Case studies ==
Multi-GAS stations have been employed at many volcanoes all around the world and due to its simple design it can be employed by many groups, like scientists, for academic purposes, or government agencies like the USGS, that can use data for public safety reasons. In Europe and Asia volcanoes like Stromboli and Vulcano, Mount Yasur, Miyake-jima and Mount Asama are well monitored with stations. In the Americas, Villarrica, Masaya Volcano, Mount St. Helens, and Soufrière Hills are also observed with instruments for changes in volcanic gas output.
=== Mount Etna, Italy ===
A permanent multi-GAS installment was placed by Mount Etna's summit crater to collect real-time measurements of H2O, CO2, and SO2 over a 2-year period. Data was used to correlate increasing CO2/SO2 ratios with rising magma beneath the edifice and associated volcanic eruptions.
=== Krýsuvík, Iceland ===
A multi-GAS was emplaced in the Krýsuvík geothermal system to collect real-time time-series data of H2O, CO2, SO2, and H2S. Molar ratios were compared with local seismic data; increased gas ratio values followed episodes of increased seismicity. Degassing activity increases after ground movement due to the opening of new paths (e.g. fractures) in the crust for the gas to flow.
=== Yellowstone, United States ===
To help understand caldera dynamics a multi-GAS was used to measure temporal variations in volcanic gases at Yellowstone. Temporal variations coincided with atmospheric and environmental fluctuations. Molar ratios fell within a binary mixing trend.
=== Nyiragongo, Democratic Republic of the Congo ===
CO2/SO2 molar ratios from multi-GAS measurements confirmed a previous observation that an increase in lava lake levels correlates with an increase in the CO2/SO2 ratio.
=== Deep Earth Carbon Degassing Project (DECADE) ===
The DECADE project supported initiatives to set up and expand the use of permanent instrumentation for continuous CO2, and SO2 measurements from volcanoes. Multi-GAS systems have been set up at volcanoes such as Villarrica, Chile and Turrialba, Costa Rica.
== See also ==
Prediction of volcanic activity
Fourier-transform infrared spectroscopy
Differential optical absorption spectroscopy
Ultravioletvisible spectroscopy
== References ==
== External links ==
USGS Volcano Hazards Program: Monitoring Gas & Water Methods