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97-406: The PR-7820 is the only player ever sold to either the industrial or consumer market that was entirely designed and engineered by the technicians at MCA Disco-Vision and contained all of their preferred design approaches, such as playing the disc with the laser on top (instead of underneath) and moving the disc radially to provide tracking instead of moving the laser radially. MCA engineers designed

194-509: A USB port . MinION decodes DNA directly as the molecule is drawn at the rate of 450 bases/second through a nanopore suspended in a membrane. Changes in electric current indicate which base is present. Initially, the device was 60 to 85 percent accurate, compared with 99.9 percent in conventional machines. Even inaccurate results may prove useful because it produces long read lengths. In early 2021, researchers from University of British Columbia has used special molecular tags and able to reduce

291-519: A gain medium , a mechanism to energize it, and something to provide optical feedback . The gain medium is a material with properties that allow it to amplify light by way of stimulated emission. Light of a specific wavelength that passes through the gain medium is amplified (power increases). Feedback enables stimulated emission to amplify predominantly the optical frequency at the peak of the gain-frequency curve. As stimulated emission grows, eventually one frequency dominates over all others, meaning that

388-471: A lens system, as is always included, for instance, in a laser pointer whose light originates from a laser diode . That is possible due to the light being of a single spatial mode. This unique property of laser light, spatial coherence , cannot be replicated using standard light sources (except by discarding most of the light) as can be appreciated by comparing the beam from a flashlight (torch) or spotlight to that of almost any laser. A laser beam profiler

485-464: A broad spectrum of light or emit different wavelengths of light simultaneously. Certain lasers are not single spatial mode and have light beams that diverge more than is required by the diffraction limit . All such devices are classified as "lasers" based on the method of producing light by stimulated emission. Lasers are employed where light of the required spatial or temporal coherence can not be produced using simpler technologies. A laser consists of

582-504: A chain reaction. The materials chosen for lasers are the ones that have metastable states , which stay excited for a relatively long time. In laser physics , such a material is called an active laser medium . Combined with an energy source that continues to "pump" energy into the material, it is possible to have enough atoms or molecules in an excited state for a chain reaction to develop. Lasers are distinguished from other light sources by their coherence . Spatial (or transverse) coherence

679-436: A coherent beam has been formed. The process of stimulated emission is analogous to that of an audio oscillator with positive feedback which can occur, for example, when the speaker in a public-address system is placed in proximity to the microphone. The screech one hears is audio oscillation at the peak of the gain-frequency curve for the amplifier. For the gain medium to amplify light, it needs to be supplied with energy in

776-419: A device lacks the spatial and temporal coherence achievable with lasers. Such a device cannot be described as an oscillator but rather as a high-gain optical amplifier that amplifies its spontaneous emission. The same mechanism describes so-called astrophysical masers /lasers. The optical resonator is sometimes referred to as an "optical cavity", but this is a misnomer: lasers use open resonators as opposed to

873-508: A gain medium must have a gain bandwidth sufficiently broad to amplify those frequencies. An example of a suitable material is titanium -doped, artificially grown sapphire ( Ti:sapphire ), which has a very wide gain bandwidth and can thus produce pulses of only a few femtoseconds duration. Such mode-locked lasers are a most versatile tool for researching processes occurring on extremely short time scales (known as femtosecond physics, femtosecond chemistry and ultrafast science ), for maximizing

970-480: A given pulse energy, this requires creating pulses of the shortest possible duration utilizing techniques such as Q-switching . The optical bandwidth of a pulse cannot be narrower than the reciprocal of the pulse width. In the case of extremely short pulses, that implies lasing over a considerable bandwidth, quite contrary to the very narrow bandwidths typical of CW lasers. The lasing medium in some dye lasers and vibronic solid-state lasers produces optical gain over

1067-399: A higher energy level with energy difference ΔE, it will not stay that way forever. Eventually, a photon will be spontaneously created from the vacuum having energy ΔE. Conserving energy, the electron transitions to a lower energy level that is not occupied, with transitions to different levels having different time constants. This process is called spontaneous emission . Spontaneous emission is

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1164-476: A laser beam, it is highly collimated : the wavefronts are planar, normal to the direction of propagation, with no beam divergence at that point. However, due to diffraction , that can only remain true well within the Rayleigh range . The beam of a single transverse mode (gaussian beam) laser eventually diverges at an angle that varies inversely with the beam diameter, as required by diffraction theory. Thus,

1261-471: A laser is normally a material of controlled purity, size, concentration, and shape, which amplifies the beam by the process of stimulated emission described above. This material can be of any state : gas, liquid, solid, or plasma . The gain medium absorbs pump energy, which raises some electrons into higher energy (" excited ") quantum states . Particles can interact with light by either absorbing or emitting photons. Emission can be spontaneous or stimulated. In

1358-418: A multi-level system as a method for obtaining the population inversion, later a main method of laser pumping. Townes reports that several eminent physicists—among them Niels Bohr , John von Neumann , and Llewellyn Thomas —argued the maser violated Heisenberg's uncertainty principle and hence could not work. Others such as Isidor Rabi and Polykarp Kusch expected that it would be impractical and not worth

1455-601: A number of software tools which are optimised for the analysis of 454 sequencing data. Such as, Illumina produces a number of next-generation sequencing machines using technology acquired from Manteia Predictive Medicine and developed by Solexa. Illumina makes a number of next generation sequencing machines using this technology including the HiSeq, Genome Analyzer IIx, MiSeq and the HiScanSQ, which can also process microarrays . The technology leading to these DNA sequencers

1552-441: A process called pumping . The energy is typically supplied as an electric current or as light at a different wavelength. Pump light may be provided by a flash lamp or by another laser. The most common type of laser uses feedback from an optical cavity —a pair of mirrors on either end of the gain medium. Light bounces back and forth between the mirrors, passing through the gain medium and being amplified each time. Typically one of

1649-414: A proprietary DNBSEQ technology. It is based upon DNA nanoball sequencing and combinatorial probe anchor synthesis technologies, in which DNA nanoballs (DNBs) are loaded onto a patterned array chip via the fluidic system, and later a sequencing primer is added to the adaptor region of DNBs for hybridization . DNBSEQ-T7 can generate short reads at a very large scale—up to 60 human genomes per day. DNBSEQ-T7

1746-468: A quantum-mechanical effect and a direct physical manifestation of the Heisenberg uncertainty principle . The emitted photon has a random direction, but its wavelength matches the absorption wavelength of the transition. This is the mechanism of fluorescence and thermal emission . A photon with the correct wavelength to be absorbed by a transition can also cause an electron to drop from the higher to

1843-427: A sample of DNA , a DNA sequencer is used to determine the order of the four bases: G ( guanine ), C ( cytosine ), A ( adenine ) and T ( thymine ). This is then reported as a text string , called a read. Some DNA sequencers can be also considered optical instruments as they analyze light signals originating from fluorochromes attached to nucleotides . The first automated DNA sequencer, invented by Lloyd M. Smith ,

1940-432: A seminar on this idea, and Charles H. Townes asked him for a copy of the paper. In 1953, Charles H. Townes and graduate students James P. Gordon and Herbert J. Zeiger produced the first microwave amplifier, a device operating on similar principles to the laser, but amplifying microwave radiation rather than infrared or visible radiation. Townes's maser was incapable of continuous output. Meanwhile, in

2037-431: A small volume of material at the surface of a workpiece can be evaporated if it is heated in a very short time, while supplying the energy gradually would allow for the heat to be absorbed into the bulk of the piece, never attaining a sufficiently high temperature at a particular point. Other applications rely on the peak pulse power (rather than the energy in the pulse), especially to obtain nonlinear optical effects. For

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2134-600: A steel chassis, weight is a shipping problem. Laser A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation . The word laser is an anacronym that originated as an acronym for light amplification by stimulated emission of radiation . The first laser was built in 1960 by Theodore Maiman at Hughes Research Laboratories , based on theoretical work by Charles H. Townes and Arthur Leonard Schawlow . A laser differs from other sources of light in that it emits light that

2231-646: A very narrow frequency spectrum . Temporal coherence can also be used to produce ultrashort pulses of light with a broad spectrum but durations as short as an attosecond . Lasers are used in optical disc drives , laser printers , barcode scanners , DNA sequencing instruments , fiber-optic and free-space optical communications, semiconductor chip manufacturing ( photolithography , etching ), laser surgery and skin treatments, cutting and welding materials, military and law enforcement devices for marking targets and measuring range and speed, and in laser lighting displays for entertainment. Semiconductor lasers in

2328-430: A wide bandwidth, making a laser possible that can thus generate pulses of light as short as a few femtoseconds (10 s). In a Q-switched laser, the population inversion is allowed to build up by introducing loss inside the resonator which exceeds the gain of the medium; this can also be described as a reduction of the quality factor or 'Q' of the cavity. Then, after the pump energy stored in the laser medium has approached

2425-492: A wide range of technologies addressing many different motivations. Some lasers are pulsed simply because they cannot be run in continuous mode. In other cases, the application requires the production of pulses having as large an energy as possible. Since the pulse energy is equal to the average power divided by the repetition rate, this goal can sometimes be satisfied by lowering the rate of pulses so that more energy can be built up between pulses. In laser ablation , for example,

2522-445: Is coherent . Spatial coherence allows a laser to be focused to a tight spot, enabling applications such as optical communication, laser cutting , and lithography . It also allows a laser beam to stay narrow over great distances ( collimation ), a feature used in applications such as laser pointers , lidar , and free-space optical communication . Lasers can also have high temporal coherence , which permits them to emit light with

2619-404: Is a transition between energy levels that match the energy carried by the photon or phonon. For light, this means that any given transition will only absorb one particular wavelength of light. Photons with the correct wavelength can cause an electron to jump from the lower to the higher energy level. The photon is consumed in this process. When an electron is excited from one state to that at

2716-480: Is also required for three-level lasers in which the lower energy level rapidly becomes highly populated, preventing further lasing until those atoms relax to the ground state. These lasers, such as the excimer laser and the copper vapor laser, can never be operated in CW mode. In 1917, Albert Einstein established the theoretical foundations for the laser and the maser in the paper " Zur Quantentheorie der Strahlung " ("On

2813-410: Is another company developing third-generation sequencers using electronic systems based on nanopore sensing technologies. DNA sequencers have been developed, manufactured, and sold by the following companies, among others. The 454 DNA sequencer was the first next-generation sequencer to become commercially successful. It was developed by 454 Life Sciences and purchased by Roche in 2007. 454 utilizes

2910-413: Is called an optical amplifier . When an optical amplifier is placed inside a resonant optical cavity, one obtains a laser. For lasing media with extremely high gain, so-called superluminescence , light can be sufficiently amplified in a single pass through the gain medium without requiring a resonator. Although often referred to as a laser (see, for example, nitrogen laser ), the light output from such

3007-462: Is emitted by stimulated emission is identical to the photon that triggered its emission, and both photons can go on to trigger stimulated emission in other atoms, creating the possibility of a chain reaction . For this to happen, many of the atoms or molecules must be in the proper excited state so that the photons can trigger them. In most materials, atoms or molecules drop out of excited states fairly rapidly, making it difficult or impossible to produce

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3104-421: Is formed by single-frequency quantum photon states distributed according to a Poisson distribution . As a result, the arrival rate of photons in a laser beam is described by Poisson statistics. Many lasers produce a beam that can be approximated as a Gaussian beam ; such beams have the minimum divergence possible for a given beam diameter. Some lasers, particularly high-power ones, produce multimode beams, with

3201-443: Is frequently used in the field, meaning "to give off coherent light," especially about the gain medium of a laser; when a laser is operating, it is said to be " lasing ". The terms laser and maser are also used for naturally occurring coherent emissions, as in astrophysical maser and atom laser . A laser that produces light by itself is technically an optical oscillator rather than an optical amplifier as suggested by

3298-421: Is impossible. In some other lasers, it would require pumping the laser at a very high continuous power level, which would be impractical, or destroying the laser by producing excessive heat. Such lasers cannot be run in CW mode. The pulsed operation of lasers refers to any laser not classified as a continuous wave so that the optical power appears in pulses of some duration at some repetition rate. This encompasses

3395-517: Is less vital such as resequencing and transcriptome analysis and more recently ChIP-Seq and methylation experiments. The DNA sample preparation time for SOLiD systems has become much quicker with the automation of sequencing library preparations such as the Tecan system. The colour space data produced by the SOLiD platform can be decoded into DNA bases for further analysis, however software that considers

3492-405: Is not the result of random thermal processes. Instead, the release of a photon is triggered by the nearby passage of another photon. This is called stimulated emission . For this process to work, the passing photon must be similar in energy, and thus wavelength, to the one that could be released by the atom or molecule, and the atom or molecule must be in the suitable excited state. The photon that

3589-489: Is to heat an object; some of the thermal energy being applied to the object will cause the molecules and electrons within the object to gain energy, which is then lost through thermal radiation , that we see as light. This is the process that causes a candle flame to give off light. Thermal radiation is a random process, and thus the photons emitted have a range of different wavelengths , travel in different directions, and are released at different times. The energy within

3686-504: Is to pump the laser material with a source that is itself pulsed, either through electronic charging in the case of flash lamps, or another laser that is already pulsed. Pulsed pumping was historically used with dye lasers where the inverted population lifetime of a dye molecule was so short that a high-energy, fast pump was needed. The way to overcome this problem was to charge up large capacitors which are then switched to discharge through flashlamps, producing an intense flash. Pulsed pumping

3783-441: Is typically expressed through the output being a narrow beam, which is diffraction-limited . Laser beams can be focused to very tiny spots, achieving a very high irradiance , or they can have a very low divergence to concentrate their power at a great distance. Temporal (or longitudinal) coherence implies a polarized wave at a single frequency, whose phase is correlated over a relatively great distance (the coherence length ) along

3880-430: Is used to measure the intensity profile, width, and divergence of laser beams. Diffuse reflection of a laser beam from a matte surface produces a speckle pattern with interesting properties. The mechanism of producing radiation in a laser relies on stimulated emission , where energy is extracted from a transition in an atom or molecule. This is a quantum phenomenon that was predicted by Albert Einstein , who derived

3977-444: The genotyping of genetic markers where only the length of a DNA fragment(s) needs to be determined (e.g. microsatellites , AFLPs ). The Human Genome Project spurred the development of cheaper, high throughput and more accurate platforms known as Next Generation Sequencers (NGS) to sequence the human genome . These include the 454, SOLiD and Illumina DNA sequencing platforms. Next generation sequencing machines have increased

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4074-410: The phase of the emitted light is 90 degrees in lead of the stimulating light. This, combined with the filtering effect of the optical resonator gives laser light its characteristic coherence, and may give it uniform polarization and monochromaticity, depending on the resonator's design. The fundamental laser linewidth of light emitted from the lasing resonator can be orders of magnitude narrower than

4171-421: The transverse modes often approximated using Hermite – Gaussian or Laguerre -Gaussian functions. Some high-power lasers use a flat-topped profile known as a " tophat beam ". Unstable laser resonators (not used in most lasers) produce fractal-shaped beams. Specialized optical systems can produce more complex beam geometries, such as Bessel beams and optical vortexes . Near the "waist" (or focal region ) of

4268-505: The "pencil beam" directly generated by a common helium–neon laser would spread out to a size of perhaps 500 kilometers when shone on the Moon (from the distance of the Earth). On the other hand, the light from a semiconductor laser typically exits the tiny crystal with a large divergence: up to 50°. However even such a divergent beam can be transformed into a similarly collimated beam employing

4365-590: The 3500 Genetic Analyzer. Under the Ion Torrent brand, Applied Biosystems produces four next-generation sequencers: the Ion PGM System, Ion Proton System, Ion S5 and Ion S5xl systems. The company is also believed to be developing their new capillary DNA sequencer called SeqStudio that will be released early 2018. SOLiD systems was acquired by Applied Biosystems in 2006. SOLiD applies sequencing by ligation and dual base encoding . The first SOLiD system

4462-577: The 454 GS FLX Titanium system was released in 2008, achieving an output of 0.7G of data per run, with 99.9% accuracy after quality filter, and a read length of up to 700bp. In 2009, Roche launched the GS Junior, a bench top version of the 454 sequencer with read length up to 400bp, and simplified library preparation and data processing. One of the advantages of 454 systems is their running speed. Manpower can be reduced with automation of library preparation and semi-automation of emulsion PCR. A disadvantage of

4559-539: The 454 sequencer, followed by Solexa Genome Analyzer and SOLiD (Supported Oligo Ligation Detection) by Agencourt in 2006. Applied Biosystems acquired Agencourt in 2006, and in 2007, Roche bought 454 Life Sciences, while Illumina purchased Solexa. Ion Torrent entered the market in 2010 and was acquired by Life Technologies (now Thermo Fisher Scientific ). And BGI started manufacturing sequencers in China after acquiring Complete Genomics under their MGI arm. These are still

4656-554: The 454 system is that it is prone to errors when estimating the number of bases in a long string of identical nucleotides. This is referred to as a homopolymer error and occurs when there are 6 or more identical bases in row. Another disadvantage is that the price of reagents is relatively more expensive compared with other next-generation sequencers. In 2013 Roche announced that they would be shutting down development of 454 technology and phasing out 454 machines completely in 2016 when its technology became noncompetitive. Roche produces

4753-747: The CEQ 8000. The company now produces the GeXP Genetic Analysis System, which uses dye terminator sequencing . This method uses a thermocycler in much the same way as PCR to denature, anneal, and extend DNA fragments, amplifying the sequenced fragments. Pacific Biosciences produces the PacBio RS and Sequel sequencing systems using a single molecule real time sequencing , or SMRT, method. This system can produce read lengths of multiple thousands of base pairs. Higher raw read errors are corrected using either circular consensus - where

4850-568: The HiSeq 2000 provided one of the cheapest sequencing platforms at $ 0.02 per million bases as costed by the Beijing Genomics Institute . In 2011 Illumina released a benchtop sequencer called the MiSeq. At its release the MiSeq could generate 1.5G per run with paired end 150bp reads. A sequencing run can be performed in 10 hours when using automated DNA sample preparation. The Illumina HiSeq uses two software tools to calculate

4947-677: The Quantum Theory of Radiation") via a re-derivation of Max Planck 's law of radiation, conceptually based upon probability coefficients ( Einstein coefficients ) for the absorption, spontaneous emission, and stimulated emission of electromagnetic radiation. In 1928, Rudolf W. Ladenburg confirmed the existence of the phenomena of stimulated emission and negative absorption. In 1939, Valentin A. Fabrikant predicted using stimulated emission to amplify "short" waves. In 1947, Willis E. Lamb and R.   C.   Retherford found apparent stimulated emission in hydrogen spectra and effected

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5044-509: The Soviet Union, Nikolay Basov and Aleksandr Prokhorov were independently working on the quantum oscillator and solved the problem of continuous-output systems by using more than two energy levels. These gain media could release stimulated emissions between an excited state and a lower excited state, not the ground state, facilitating the maintenance of a population inversion . In 1955, Prokhorov and Basov suggested optical pumping of

5141-614: The acronym. It has been humorously noted that the acronym LOSER, for "light oscillation by stimulated emission of radiation", would have been more correct. With the widespread use of the original acronym as a common noun, optical amplifiers have come to be referred to as laser amplifiers . Modern physics describes light and other forms of electromagnetic radiation as the group behavior of fundamental particles known as photons . Photons are released and absorbed through electromagnetic interactions with other fundamental particles that carry electric charge . A common way to release photons

5238-443: The addition of nucleotides in the complementary strand in real time. Two companies introduced different approaches in their third-generation sequencers. Pacific Biosciences sequencers utilize a method called Single-molecule real-time (SMRT), where sequencing data is produced by light (captured by a camera) emitted when a nucleotide is added to the complementary strand by enzymes containing fluorescent dyes. Oxford Nanopore Technologies

5335-476: The beam. A beam produced by a thermal or other incoherent light source has an instantaneous amplitude and phase that vary randomly with respect to time and position, thus having a short coherence length. Lasers are characterized according to their wavelength in a vacuum . Most "single wavelength" lasers produce radiation in several modes with slightly different wavelengths. Although temporal coherence implies some degree of monochromaticity , some lasers emit

5432-425: The blue to near-UV have also been used in place of light-emitting diodes (LEDs) to excite fluorescence as a white light source; this permits a much smaller emitting area due to the much greater radiance of a laser and avoids the droop suffered by LEDs; such devices are already used in some car headlamps . The first device using amplification by stimulated emission operated at microwave frequencies, and

5529-475: The consumer player, the Magnavox VH-8000, could not cope with. In 1980, Discovision Associates released a factory update ( it could also be retrofitted to existing PR-7820s ) that reduced disc search times to less than 3 seconds, and added the ability to jump up to 99 tracks during vertical blanking, giving essentially "instant" searches. An external computer interface box was also made available at

5626-571: The detection of pyrophosphate released by the DNA polymerase reaction when adding a nucleotide to the template strain. Roche currently manufactures two systems based on their pyrosequencing technology: the GS FLX+ and the GS Junior System. The GS FLX+ System promises read lengths of approximately 1000 base pairs while the GS Junior System promises 400 base pair reads. A predecessor to GS FLX+,

5723-561: The effect of nonlinearity in optical materials (e.g. in second-harmonic generation , parametric down-conversion , optical parametric oscillators and the like). Unlike the giant pulse of a Q-switched laser, consecutive pulses from a mode-locked laser are phase-coherent; that is, the pulses (and not just their envelopes ) are identical and perfectly periodic. For this reason, and the extremely large peak powers attained by such short pulses, such lasers are invaluable in certain areas of research. Another method of achieving pulsed laser operation

5820-564: The effort. In 1964, Charles H. Townes, Nikolay Basov, and Aleksandr Prokhorov shared the Nobel Prize in Physics , "for fundamental work in the field of quantum electronics, which has led to the construction of oscillators and amplifiers based on the maser–laser principle". DNA sequencer A DNA sequencer is a scientific instrument used to automate the DNA sequencing process. Given

5917-455: The experiment objectives and available budget. The first DNA sequencing methods were developed by Gilbert (1973) and Sanger (1975). Gilbert introduced a sequencing method based on chemical modification of DNA followed by cleavage at specific bases whereas Sanger's technique is based on dideoxynucleotide chain termination. The Sanger method became popular due to its increased efficiency and low radioactivity. The first automated DNA sequencer

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6014-436: The final data that is generated. Therefore, comparing data quality and cost across different technologies can be a daunting task. Each manufacturer provides their own ways to inform sequencing errors and scores. However, errors and scores between different platforms cannot always be compared directly. Since these systems rely on different DNA sequencing approaches, choosing the best DNA sequencer and method will typically depend on

6111-603: The first demonstration of stimulated emission. In 1950, Alfred Kastler (Nobel Prize for Physics 1966) proposed the method of optical pumping , which was experimentally demonstrated two years later by Brossel, Kastler, and Winter. In 1951, Joseph Weber submitted a paper on using stimulated emissions to make a microwave amplifier to the June 1952 Institute of Radio Engineers Vacuum Tube Research Conference in Ottawa , Ontario, Canada. After this presentation, RCA asked Weber to give

6208-702: The five-to-15 per cent error rate of the device to less than 0.005 per cent even when sequencing many long stretches of DNA at a time. There are two more product iterations based on MinION; the first one is the GridION which is a slightly larger sequencer that processes up to five MinION flow cells at once. And, the second one is the PromethION which uses as many as 100,000 pores in parallel, more suitable for high volume sequencing. MGI produces high-throughput sequencers for scientific research and clinical applications such as DNBSEQ-G50, DNBSEQ-G400, and DNBSEQ-T7, under

6305-422: The laser power inside the cavity; this equilibrium determines the operating point of the laser. If the applied pump power is too small, the gain will never be sufficient to overcome the cavity losses, and laser light will not be produced. The minimum pump power needed to begin laser action is called the lasing threshold . The gain medium will amplify any photons passing through it, regardless of direction; but only

6402-501: The lasing medium or pumping mechanism, then it is still classified as a "modulated" or "pulsed" continuous wave laser. Most laser diodes used in communication systems fall into that category. Some applications of lasers depend on a beam whose output power is constant over time. Such a laser is known as a continuous-wave ( CW ) laser. Many types of lasers can be made to operate in continuous-wave mode to satisfy such an application. Many of these lasers lase in several longitudinal modes at

6499-414: The latter case, the photon is emitted in the same direction as the light that is passing by. When the number of particles in one excited state exceeds the number of particles in some lower-energy state, population inversion is achieved. In this state, the rate of stimulated emission is larger than the rate of absorption of light in the medium, and therefore the light is amplified. A system with this property

6596-450: The linewidth of light emitted from the passive resonator. Some lasers use a separate injection seeder to start the process off with a beam that is already highly coherent. This can produce beams with a narrower spectrum than would otherwise be possible. In 1963, Roy J. Glauber showed that coherent states are formed from combinations of photon number states, for which he was awarded the Nobel Prize in physics . A coherent beam of light

6693-402: The literal cavity that would be employed at microwave frequencies in a maser . The resonator typically consists of two mirrors between which a coherent beam of light travels in both directions, reflecting on itself so that an average photon will pass through the gain medium repeatedly before it is emitted from the output aperture or lost to diffraction or absorption. If the gain (amplification) in

6790-522: The lower level, emitting a new photon. The emitted photon exactly matches the original photon in wavelength, phase, and direction. This process is called stimulated emission. The gain medium is put into an excited state by an external source of energy. In most lasers, this medium consists of a population of atoms that have been excited into such a state using an outside light source, or an electrical field that supplies energy for atoms to absorb and be transformed into their excited states. The gain medium of

6887-412: The maximum possible level, the introduced loss mechanism (often an electro- or acousto-optical element) is rapidly removed (or that occurs by itself in a passive device), allowing lasing to begin which rapidly obtains the stored energy in the gain medium. This results in a short pulse incorporating that energy, and thus a high peak power. A mode-locked laser is capable of emitting extremely short pulses on

6984-498: The medium is larger than the resonator losses, then the power of the recirculating light can rise exponentially . But each stimulated emission event returns an atom from its excited state to the ground state, reducing the gain of the medium. With increasing beam power, the net gain (gain minus loss) reduces to unity and the gain medium is said to be saturated. In a continuous wave (CW) laser, the balance of pump power against gain saturation and cavity losses produces an equilibrium value of

7081-422: The most common NGS systems due to their competitive cost, accuracy, and performance. More recently, a third generation of DNA sequencers was introduced. The sequencing methods applied by these sequencers do not require DNA amplification (polymerase chain reaction – PCR), which speeds up the sample preparation before sequencing and reduces errors. In addition, sequencing data is collected from the reactions caused by

7178-525: The number and position of DNA clusters to assess the sequencing quality: the HiSeq control system and the real-time analyzer. These methods help to assess if nearby clusters are interfering with each other. Life Technologies (now Thermo Fisher Scientific ) produces DNA sequencers under the Applied Biosystems and Ion Torrent brands. Applied Biosystems makes the SOLiD next-generation sequencing platform, and Sanger-based DNA sequencers such as

7275-404: The object is not random, however: it is stored by atoms and molecules in " excited states ", which release photons with distinct wavelengths. This gives rise to the science of spectroscopy , which allows materials to be determined through the specific wavelengths that they emit. The underlying physical process creating photons in a laser is the same as in thermal radiation, but the actual emission

7372-456: The order of tens of picoseconds down to less than 10  femtoseconds . These pulses repeat at the round-trip time, that is, the time that it takes light to complete one round trip between the mirrors comprising the resonator. Due to the Fourier limit (also known as energy–time uncertainty ), a pulse of such short temporal length has a spectrum spread over a considerable bandwidth. Thus such

7469-479: The original colour space information can give more accurate results. Life Technologies has released BioScope, a data analysis package for resequencing, ChiP-Seq and transcriptome analysis. It uses the MaxMapper algorithm to map the colour space reads. Beckman Coulter (now Danaher ) has previously manufactured chain termination and capillary electrophoresis-based DNA sequencers under the model name CEQ, including

7566-418: The photons in a spatial mode supported by the resonator will pass more than once through the medium and receive substantial amplification. In most lasers, lasing begins with spontaneous emission into the lasing mode. This initial light is then amplified by stimulated emission in the gain medium. Stimulated emission produces light that matches the input signal in direction, wavelength, and polarization, whereas

7663-672: The player at the DiscoVision labs in Torrance, California and Universal-Pioneer mass-produced it in Japan . The PR-7820 was such a high-quality player that MCA themselves used it at their DiscoVision disc pressing plant in Carson, California for quality control checks of both master discs and finished sets. Unfortunately, this caused problems because the PR-7820 could easily play discs that

7760-409: The power output is essentially continuous over time or whether its output takes the form of pulses of light on one or another time scale. Of course, even a laser whose output is normally continuous can be intentionally turned on and off at some rate to create pulses of light. When the modulation rate is on time scales much slower than the cavity lifetime and the period over which energy can be stored in

7857-662: The properties of the emitted light, such as the polarization, wavelength, and shape of the beam. Electrons and how they interact with electromagnetic fields are important in our understanding of chemistry and physics . In the classical view , the energy of an electron orbiting an atomic nucleus is larger for orbits further from the nucleus of an atom . However, quantum mechanical effects force electrons to take on discrete positions in orbitals . Thus, electrons are found in specific energy levels of an atom, two of which are shown below: An electron in an atom can absorb energy from light ( photons ) or heat ( phonons ) only if there

7954-512: The rate of DNA sequencing substantially, as compared with the previous Sanger methods. DNA samples can be prepared automatically in as little as 90 mins, while a human genome can be sequenced at 15 times coverage in a matter of days. More recent, third-generation DNA sequencers such as PacBio SMRT and Oxford Nanopore offer the possibility of sequencing long molecules, compared to short-read technologies such as Illumina SBS or MGI Tech's DNBSEQ. Because of limitations in DNA sequencer technology,

8051-464: The reads of many of these technologies are short, compared to the length of a genome therefore the reads must be assembled into longer contigs . The data may also contain errors, caused by limitations in the DNA sequencing technique or by errors during PCR amplification . DNA sequencer manufacturers use a number of different methods to detect which DNA bases are present. The specific protocols applied in different sequencing platforms have an impact in

8148-457: The relationship between the A coefficient , describing spontaneous emission, and the B coefficient which applies to absorption and stimulated emission. In the case of the free electron laser , atomic energy levels are not involved; it appears that the operation of this rather exotic device can be explained without reference to quantum mechanics . A laser can be classified as operating in either continuous or pulsed mode, depending on whether

8245-425: The same strand is read over and over again - or using optimized assembly strategies. Scientists have reported 99.9999% accuracy with these strategies. The Sequel system was launched in 2015 with an increased capacity and a lower price. Oxford Nanopore Technologies ' MinION sequencer is based on evolving nanopore sequencing technology to nucleic acid analyses. The device is four inches long and gets power from

8342-445: The same time which contained additional memory that increased the total size of a disc-based computer program the PR-7820 could store and execute to 256k. The PR-7820 was the first LD player to use solid-state tangential tracking — instead of a tangential tracking mirror, the PR-7820 used an electronic CCD delay line to provide tangential tracking corrections, giving the player superb color quality. It wasn't until 1985/6 that

8439-410: The same time, and beats between the slightly different optical frequencies of those oscillations will produce amplitude variations on time scales shorter than the round-trip time (the reciprocal of the frequency spacing between modes), typically a few nanoseconds or less. In most cases, these lasers are still termed "continuous-wave" as their output power is steady when averaged over longer periods, with

8536-486: The tangential mirror began to be replaced by electronic correction, first by Yamaha in their first consumer LD player, and eventually, by Pioneer themselves. MCA DiscoVision had no suggested retail price for the PR-7820. Depending on the number purchased, it varied from $ 3,500 to $ 2,200 per unit if more than 1000 were bought at once. Fully functional PR-7820s are not easily available on eBay and are nearly impossible to find in fully functional condition. Because they have

8633-425: The two mirrors, the output coupler , is partially transparent. Some of the light escapes through this mirror. Depending on the design of the cavity (whether the mirrors are flat or curved ), the light coming out of the laser may spread out or form a narrow beam . In analogy to electronic oscillators , this device is sometimes called a laser oscillator . Most practical lasers contain additional elements that affect

8730-410: The very high-frequency power variations having little or no impact on the intended application. (However, the term is not applied to mode-locked lasers, where the intention is to create very short pulses at the rate of the round-trip time.) For continuous-wave operation, the population inversion of the gain medium needs to be continually replenished by a steady pump source. In some lasing media, this

8827-598: Was called a maser , for "microwave amplification by stimulated emission of radiation". When similar optical devices were developed they were first called optical masers , until "microwave" was replaced by "light" in the acronym, to become laser . Today, all such devices operating at frequencies higher than microwaves (approximately above 300 GHz ) are called lasers (e.g. infrared lasers , ultraviolet lasers , X-ray lasers , gamma-ray lasers ), whereas devices operating at microwave or lower radio frequencies are called masers. The back-formed verb " to lase "

8924-592: Was first released by Solexa in 2006 as the Genome Analyzer. Illumina purchased Solexa in 2007. The Genome Analyzer uses a sequencing by synthesis method. The first model produced 1G per run. During the year 2009 the output was increased from 20G per run in August to 50G per run in December. In 2010 Illumina released the HiSeq 2000 with an output of 200 and then 600G per run which would take 8 days. At its release

9021-482: Was introduced by Applied Biosystems in 1987. It used the Sanger sequencing method, a technology which formed the basis of the "first generation" of DNA sequencers and enabled the completion of the human genome project in 2001. This first generation of DNA sequencers are essentially automated electrophoresis systems that detect the migration of labelled DNA fragments. Therefore, these sequencers can also be used in

9118-411: Was launched in 2007, generating reading lengths of 35bp and 3G data per run. After five upgrades, the 5500xl sequencing system was released in 2010, considerably increasing read length to 85bp, improving accuracy up to 99.99% and producing 30G per 7-day run. The limited read length of the SOLiD has remained a significant shortcoming and has to some extent limited its use to experiments where read length

9215-467: Was the AB370A, introduced in 1986 by Applied Biosystems . The AB370A was able to sequence 96 samples simultaneously, 500 kilobases per day, and reaching read lengths up to 600 bases. This was the beginning of the "first generation" of DNA sequencers, which implemented Sanger sequencing, fluorescent dideoxy nucleotides and polyacrylamide gel sandwiched between glass plates - slab gels. The next major advance

9312-482: Was the release in 1995 of the AB310 which utilized a linear polymer in a capillary in place of the slab gel for DNA strand separation by electrophoresis. These techniques formed the base for the completion of the human genome project in 2001. The human genome project spurred the development of cheaper, high throughput and more accurate platforms known as Next Generation Sequencers (NGS). In 2005, 454 Life Sciences released

9409-406: Was used to generate 150 bp paired-end reads, sequencing 30X, to sequence the genome of SARS-CoV-2 or COVID-19 to identify the genetic variants predisposition in severe COVID-19 illness. Using a novel technique the researchers from China National GeneBank sequenced PCR -free libraries on MGI's PCR-free DNBSEQ arrays to obtain for the first time a true PCR-free whole genome sequencing . MGISEQ-2000

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