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Chromatography

In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the mobile phase, which carries it through a system (a column, a capillary tube, a plate, or a sheet) on which a material called the stationary phase is fixed. Because the different constituents of the mixture tend to have different affinities for the stationary phase and are retained for different lengths of time depending on their interactions with its surface sites, the constituents travel at different apparent velocities in the mobile fluid, causing them to separate. The separation is based on the differential partitioning between the mobile and the stationary phases. Subtle differences in a compound's partition coefficient result in differential retention on the stationary phase and thus affect the separation.

Chromatography may be preparative or analytical. The purpose of preparative chromatography is to separate the components of a mixture for later use, and is thus a form of purification. This process is associated with higher costs due to its mode of production. Analytical chromatography is done normally with smaller amounts of material and is for establishing the presence or measuring the relative proportions of analytes in a mixture. The two types are not mutually exclusive.

Etymology and pronunciation
Chromatography, pronounced, is derived from Greek χρῶμα chroma, which means "color", and γράφειν graphein, which means "to write". The combination of these two terms was directly inherited from the invention of the technique first used to separate biological pigments.

History
Chromatography was first devised at the University of Kazan by the Italian-born Russian scientist Mikhail Tsvet in 1900. He developed the technique and coined the term chromatography in the first decade of the 20th century, primarily for the separation of plant pigments such as chlorophyll, carotenes, and xanthophylls. Since these components separate in bands of different colors (green, orange, and yellow, respectively) they directly inspired the name of the technique. New types of chromatography developed during the 1930s and 1940s made the technique useful for many separation processes.

Chromatography technique developed substantially as a result of the work of Archer John Porter Martin and Richard Laurence Millington Synge during the 1940s and 1950s, for which they won the 1952 Nobel Prize in Chemistry. They established the principles and basic techniques of partition chromatography, and their work encouraged the rapid development of several chromatographic methods: paper chromatography, gas chromatography, and what would become known as high-performance liquid chromatography. Since then, the technology has advanced rapidly. Researchers found that the main principles of Tsvet's chromatography could be applied in many different ways, resulting in the different varieties of chromatography described below. Advances are continually improving the technical performance of chromatography, allowing the separation of increasingly similar molecules.

Terms
Chromatography is based on the concept of partition coefficient. Any solute partitions between two immiscible solvents. When one make one solvent immobile (by adsorption on a solid support matrix) and another mobile it results in most common applications of chromatography. If the matrix support, or stationary phase, is polar (e.g, cellulose, silica etc.) it is forward phase chromatography. Otherwise this technique is known as reversed phase, where a non-polar stationary phase (e.g, non-polar derivative of C-18) is used.
 * Analyte – the substance to be separated during chromatography. It is also normally what is needed from the mixture.
 * Analytical chromatography – the use of chromatography to determine the existence and possibly also the concentration of analyte(s) in a sample.
 * Bonded phase – a stationary phase that is covalently bonded to the support particles or to the inside wall of the column tubing.
 * Chromatogram – the visual output of the chromatograph. In the case of an optimal separation, different peaks or patterns on the chromatogram correspond to different components of the separated mixture.Rt 5 9.png Rt 5 12.pnged on the x-axis is the retention time and plotted on the y-axis a signal (for example obtained by a spectrophotometer, mass spectrometer or a variety of other detectors) corresponding to the response created by the analytes exiting the system. In the case of an optimal system the signal is proportional to the concentration of the specific analyte separated.
 * Chromatograph – an instrument that enables a sophisticated separation, e.g. gas chromatographic or liquid chromatographic separation.
 * Chromatography – a physical method of separation that distributes components to separate between two phases, one stationary (stationary phase), the other (the mobile phase) moving in a definite direction.
 * Eluent (sometimes spelled eluant) – the solvent or solvent fixure used in elution chromatography and is synonymous with mobile phase.
 * Eluate – the mixture of solute (see Eluite) and solvent (see Eluent) exiting the column.
 * Effluent – the stream flowing out of a chromatographic column. In practise, it is used synonymously with eluate, but the term more precisely refers to the stream independent of separation taking place.
 * Eluite – a more precise term for solute or analyte. It is a sample component leaving the chromatographic column.
 * Eluotropic series – a list of solvents ranked according to their eluting power.
 * Immobilized phase – a stationary phase that is immobilized on the support particles, or on the inner wall of the column tubing.
 * Mobile phase – the phase that moves in a definite direction. It may be a liquid (LC and capillary electrochromatography, CEC), a gas (GC), or a supercritical fluid (supercritical-fluid chromatography, SFC). The mobile phase consists of the sample being separated/analyzed and the solvent that moves the sample through the column. In the case of HPLC the mobile phase consists of a non-polar solvent(s) such as hexane in normal phase or a polar solvent such as methanol in reverse phase chromatography and the sample being separated. The mobile phase moves through the chromatography column (the stationary phase) where the sample interacts with the stationary phase and is separated.
 * Preparative chromatography – the use of chromatography to purify sufficient quantities of a substance for further use, rather than analysis.
 * Retention time – the characteristic time it takes for a particular analyte to pass through the system (from the column inlet to the detector) under set conditions. See also: Kovats' retention index
 * Sample – the matter analyzed in chromatography. It may consist of a single component or it may be a mixture of components. When the sample is treated in the course of an analysis, the phase or the phases containing the analytes of interest is/are referred to as the sample whereas everything out of interest separated from the sample before or in the course of the analysis is referred to as waste.
 * Solute – the sample components in partition chromatography.
 * Solvent – any substance capable of solubilizing another substance, and especially the liquid mobile phase in liquid chromatography.
 * Stationary phase – the substance fixed in place for the chromatography procedure. Examples include the silica layer in thin-layer chromatography
 * Detector – the instrument used for qualitative and quantitative detection of analytes after separation.

Column chromatography

Column chromatography is a separation technique in which the stationary bed is within a tube. The particles of the solid stationary phase or the support coated with a liquid stationary phase may fill the whole inside volume of the tube (packed column) or be concentrated on or along the inside tube wall leaving an open, unrestricted path for the mobile phase in the middle part of the tube (open tubular column). Differences in rates of movement through the medium are calculated to different retention times of the sample. In 1978, W. Clark Still introduced a modified version of column chromatography called flash column chromatography (flash). The technique is very similar to the traditional column chromatography, except that the solvent is driven through the column by applying positive pressure. This allowed most separations to be performed in less than 20 minutes, with improved separations compared to the old method. Modern flash chromatography systems are sold as pre-packed plastic cartridges, and the solvent is pumped through the cartridge. Systems may also be linked with detectors and fraction collectors providing automation. The introduction of gradient pumps resulted in quicker separations and less solvent usage.

In expanded bed adsorption, a fluidized bed is used, rather than a solid phase made by a packed bed. This allows omission of initial clearing steps such as centrifugation and filtration, for culture broths or slurries of broken cells.

Phosphocellulose chromatography utilizes the binding affinity of many DNA-binding proteins for phosphocellulose. The stronger a protein's interaction with DNA, the higher the salt concentration needed to elute that protein.

Planar chromatography
Planar chromatography is a separation technique in which the stationary phase is present as or on a plane. The plane can be a paper, serving as such or impregnated by a substance as the stationary bed (paper chromatography) or a layer of solid particles spread on a support such as a glass plate (thin-layer chromatography). Different compounds in the sample mixture travel different distances according to how strongly they interact with the stationary phase as compared to the mobile phase. The specific Retention factor (Rf) of each chemical can be used to aid in the identification of an unknown substance.

Paper chromatography

Paper chromatography is a technique that involves placing a small dot or line of sample solution onto a strip of chromatography paper. The paper is placed in a container with a shallow layer of solvent and sealed. As the solvent rises through the paper, it meets the sample mixture, which starts to travel up the paper with the solvent. This paper is made of cellulose, a polar substance, and the compounds within the mixture travel further if they are less polar. More polar substances bond with the cellulose paper more quickly, and therefore do not travel as far.

Thin-layer chromatography (TLC)
Thin-layer chromatography (TLC) is a widely employed laboratory technique used to separate different biochemicals on the basis of their relative attractions to the stationary and mobile phases. It is similar to paper chromatography. However, instead of using a stationary phase of paper, it involves a stationary phase of a thin layer of adsorbent like silica gel, alumina, or cellulose on a flat, inert substrate. TLC is very versatile; multiple samples can be separated simultaneously on the same layer, making it very useful for screening applications such as testing drug levels and water purity.

Possibility of cross-contamination is low since each separation is performed on a new layer. Compared to paper, it has the advantage of faster runs, better separations, better quantitative analysis, and the choice between different adsorbents. For even better resolution and faster separation that utilizes less solvent, high-performance TLC can be used. An older popular use had been to differentiate chromosomes by observing distance in gel (separation of was a separate step).

Displacement chromatography
The basic principle of displacement chromatography is: A molecule with a high affinity for the chromatography matrix (the displacer) competes effectively for binding sites, and thus displaces all molecules with lesser affinities. There are distinct differences between displacement and elution chromatography. In elution mode, substances typically emerge from a column in narrow, Gaussian peaks. Wide separation of peaks, preferably to baseline, is desired for maximum purification. The speed at which any component of a mixture travels down the column in elution mode depends on many factors. But for two substances to travel at different speeds, and thereby be resolved, there must be substantial differences in some interaction between the biomolecules and the chromatography matrix. Operating parameters are adjusted to maximize the effect of this difference. In many cases, baseline separation of the peaks can be achieved only with gradient elution and low column loadings. Thus, two drawbacks to elution mode chromatography, especially at the preparative scale, are operational complexity, due to gradient solvent pumping, and low throughput, due to low column loadings. Displacement chromatography has advantages over elution chromatography in that components are resolved into consecutive zones of pure substances rather than "peaks". Because the process takes advantage of the nonlinearity of the isotherms, a larger column feed can be separated on a given column with the purified components recovered at significantly higher concentrations.

Gas chromatography
Gas chromatography (GC), also sometimes known as gas-liquid chromatography, (GLC), is a separation technique in which the mobile phase is a gas. Gas chromatographic separation is always carried out in a column, which is typically "packed" or "capillary". Packed columns are the routine work horses of gas chromatography, being cheaper and easier to use and often giving adequate performance. Capillary columns generally give far superior resolution and although more expensive are becoming widely used, especially for complex mixtures. Further, capillary columns can be split into three classes: porous layer open tubular (PLOT), wall-coated open tubular (WCOT) and support-coated open tubular (SCOT) columns. PLOT columns are unique in a way that the stationary phase is adsorbed to the column walls, while WCOT columns have a stationary phase that is chemically bonded to the walls. SCOT columns are in a way the combination of the two types mentioned in a way that they have support particles adhered to column walls, but those particles have liquid phase chemically bonded onto them. Both types of column are made from non-adsorbent and chemically inert materials. Stainless steel and glass are the usual materials for packed columns and quartz or fused silica for capillary columns.

Gas chromatography is based on a partition equilibrium of analyte between a solid or viscous liquid stationary phase (often a liquid silicone-based material) and a mobile gas (most often helium). The stationary phase is adhered to the inside of a small-diameter (commonly 0.53 – 0.18mm inside diameter) glass or fused-silica tube (a capillary column) or a solid matrix inside a larger metal tube (a packed column). It is widely used in analytical chemistry; though the high temperatures used in GC make it unsuitable for high molecular weight biopolymers or proteins (heat denatures them), frequently encountered in biochemistry, it is well suited for use in the petrochemical, environmental monitoring and remediation, and industrial chemical fields. It is also used extensively in chemistry research.

Liquid chromatography
Liquid chromatography (LC) is a separation technique in which the mobile phase is a liquid. It can be carried out either in a column or a plane. Present day liquid chromatography that generally utilizes very small packing particles and a relatively high pressure is referred to as high-performance liquid chromatography.

In HPLC the sample is forced by a liquid at high pressure (the mobile phase) through a column that is packed with a stationary phase composed of irregularly or spherically shaped particles, a porous monolithic layer, or a porous membrane. Monoliths are "sponge-like chromatographic media" and are made up of an unending block of organic or inorganic parts. HPLC is historically divided into two different sub-classes based on the polarity of the mobile and stationary phases. Methods in which the stationary phase is more polar than the mobile phase (e.g., toluene as the mobile phase, silica as the stationary phase) are termed normal phase liquid chromatography (NPLC) and the opposite (e.g., water-methanol mixture as the mobile phase and C18 as the stationary phase) is termed reversed phase liquid chromatography (RPLC).

Supercritical fluid chromatography
Supercritical fluid chromatography is a separation technique in which the mobile phase is a fluid above and relatively close to its critical temperature and pressure.

Specific techniques under this broad heading are listed below.

Affinity chromatography
Affinity chromatography is based on selective non-covalent interaction between an analyte and specific molecules. It is very specific, but not very robust. It is often used in biochemistry in the purification of proteins bound to tags. These fusion proteins are labeled with compounds such as His-tags, biotin or antigens, which bind to the stationary phase specifically. After purification, these tags are usually removed and the pure protein is obtained.

Affinity chromatography often utilizes a biomolecule's affinity for the cations of a metal (Zn, Cu, Fe, etc.). Columns are often manually prepared and could be designed specifically for the proteins of interest. Traditional affinity columns are used as a preparative step to flush out unwanted biomolecules, or as a primary step in analyzing a protein with unknown physical properties.

However, liquid chromatography techniques exist that do utilize affinity chromatography properties. Immobilized metal affinity chromatography (IMAC) is useful to separate the aforementioned molecules based on the relative affinity for the metal. Often these columns can be loaded with different metals to create a column with a targeted affinity.

Ion exchange chromatography
Ion exchange chromatography (usually referred to as ion chromatography) uses an ion exchange mechanism to separate analytes based on their respective charges. It is usually performed in columns but can also be useful in planar mode. Ion exchange chromatography uses a charged stationary phase to separate charged compounds including anions, cations, amino acids, peptides, and proteins. In conventional methods the stationary phase is an ion-exchange resin that carries charged functional groups that interact with oppositely charged groups of the compound to retain. There are two types of ion exchange chromatography: Cation-Exchange and Anion-Exchange. In the Cation-Exchange Chromatography the stationary phase has negative charge and the exchangeable ion is a cation, whereas, in the Anion-Exchange Chromatography the stationary phase has positive charge and the exchangeable ion is an anion. Ion exchange chromatography is commonly used to purify proteins using FPLC.

Size-exclusion chromatography
Size-exclusion chromatography (SEC) is also known as gel permeation chromatography (GPC) or gel filtration chromatography and separates molecules according to their size (or more accurately according to their hydrodynamic diameter or hydrodynamic volume). Smaller molecules are able to enter the pores of the media and, therefore, molecules are trapped and removed from the flow of the mobile phase. The average residence time in the pores depends upon the effective size of the analyte molecules. However, molecules that are larger than the average pore size of the packing are excluded and thus suffer essentially no retention; such species are the first to be eluted. It is generally a low-resolution chromatography technique and thus it is often reserved for the final, "polishing" step of a purification. It is also useful for determining the tertiary structure and quaternary structure of purified proteins, especially since it can be carried out under native solution conditions.

Expanded bed adsorption chromatographic separation
An expanded bed chromatographic adsorption (EBA) column for a biochemical separation process comprises a pressure equalization liquid distributor having a self-cleaning function below a porous blocking sieve plate at the bottom of the expanded bed, an upper part nozzle assembly having a backflush cleaning function at the top of the expanded bed, a better distribution of the feedstock liquor added into the expanded bed ensuring that the fluid passed through the expanded bed layer displays a state of piston flow. The expanded bed layer displays a state of piston flow. The expanded bed chromatographic separation column has advantages of increasing the separation efficiency of the expanded bed.

Expanded-bed adsorption (EBA) chromatography is a convenient and effective technique for the capture of proteins directly from unclarified crude sample. In EBA chromatography, the settled bed is first expanded by upward flow of equilibration buffer. The crude feed, which is a mixture of soluble proteins, contaminants, cells, and cell debris, is then passed upward through the expanded bed. Target proteins are captured on the adsorbent, while particulates and contaminants pass through. A change to elution buffer while maintaining upward flow results in desorption of the target protein in expanded-bed mode. Alternatively, if the flow is reversed, the adsorbed particles will quickly settle and the proteins can be desorbed by an elution buffer. The mode used for elution (expanded-bed versus settled-bed) depends on the characteristics of the feed. After elution, the adsorbent is cleaned with a predefined cleaning-in-place (CIP) solution, with cleaning followed by either column regeneration (for further use) or storage.

Reversed-phase chromatography
Reversed-phase chromatography (RPC) is any liquid chromatography procedure in which the mobile phase is significantly more polar than the stationary phase. It is so named because in normal-phase liquid chromatography, the mobile phase is significantly less polar than the stationary phase. Hydrophobic molecules in the mobile phase tend to adsorb to the relatively hydrophobic stationary phase. Hydrophilic molecules in the mobile phase will tend to elute first. Separating columns typically comprise a C8 or C18 carbon-chain bonded to a silica particle substrate.

Hydrophobic interaction chromatography
Hydrophobic Interaction Chromatography (HIC) is a purification and analytical technique that separates analytes, such as proteins, based on hydrophobic interactions between that analyte and the chromatographic matrix. It can provide a non-denaturing orthogonal approach to reversed phase separation, preserving native structures and potentially protein activity. In hydrophobic interaction chromatography, the matrix material is lightly substituted with hydrophobic groups. These groups can range from methyl, ethyl, propyl, butyl, octyl, or phenyl groups. At high salt concentrations, non-polar sidechains on the surface on proteins "interact" with the hydrophobic groups; that is, both types of groups are excluded by the polar solvent (hydrophobic effects are augmented by increased ionic strength). Thus, the sample is applied to the column in a buffer which is highly polar, which drives an association of hydrophobic patches on the analyte with the stationary phase. The eluent is typically an aqueous buffer with decreasing salt concentrations, increasing concentrations of detergent (which disrupts hydrophobic interactions), or changes in pH. Of critical importance is the type of salt used, with more kosmotropic salts as defined by the Hofmeister series providing the most water structuring around the molecule and resulting hydrophobic pressure. Ammonium sulfate is frequently used for this purpose. The addition of organic solvents or other less polar constituents may assist in improving resolution.

In general, Hydrophobic Interaction Chromatography (HIC) is advantageous if the sample is sensitive to pH change or harsh solvents typically used in other types of chromatography but not high salt concentrations. Commonly, it is the amount of salt in the buffer which is varied. In 2012, Müller and Franzreb described the effects of temperature on HIC using Bovine Serum Albumin (BSA) with four different types of hydrophobic resin. The study altered temperature as to effect the binding affinity of BSA onto the matrix. It was concluded that cycling temperature from 50 to 10 degrees would not be adequate to effectively wash all BSA from the matrix but could be very effective if the column would only be used a few times. Using temperature to effect change allows labs to cut costs on buying salt and saves money.

If high salt concentrations along with temperature fluctuations want to be avoided one can use a more hydrophobic to compete with one's sample to elute it. This so-called salt independent method of HIC showed a direct isolation of Human Immunoglobulin G (IgG) from serum with satisfactory yield and used β-cyclodextrin as a competitor to displace IgG from the matrix. This largely opens up the possibility of using HIC with samples which are salt sensitive as we know high salt concentrations precipitate proteins.

Hydrodynamic chromatography
Hydrodynamic chromatography (HDC) is derived from the observed phenomenon that large droplets move faster than small ones. In a column, this happens because the center of mass of larger droplets is prevented from being as close to the sides of the column as smaller droplets because of their larger overall size. Larger droplets will elute first from the middle of the column while smaller droplets stick to the sides of the column and elute last. This form of chromatography is useful for separating analytes by molar mass (or molecular mass), size, shape, and structure when used in conjunction with light scattering detectors, viscometers, and refractometers. The two main types of HDC are open tube and packed column. Open tube offers rapid separation times for small particles, whereas packed column HDC can increase resolution and is better suited for particles with an average molecular mass larger than $$10^5$$ daltons. HDC differs from other types of chromatography because the separation only takes place in the interstitial volume, which is the volume surrounding and in between particles in a packed column.

HDC shares the same order of elution as Size Exclusion Chromatography (SEC) but the two processes still vary in many ways. In a study comparing the two types of separation, Isenberg, Brewer, Côté, and Striegel use both methods for polysaccharide characterization and conclude that HDC coupled with multiangle light scattering (MALS) achieves more accurate molar mass distribution when compared to off-line MALS than SEC in significantly less time. This is largely due to SEC being a more destructive technique because of the pores in the column degrading the analyte during separation, which tends to impact the mass distribution. However, the main disadvantage of HDC is low resolution of analyte peaks, which makes SEC a more viable option when used with chemicals that are not easily degradable and where rapid elution is not important.

HDC plays an especially important role in the field of microfluidics. The first successful apparatus for HDC-on-a-chip system was proposed by Chmela, et al. in 2002. Their design was able to achieve separations using an 80 mm long channel on the timescale of 3 minutes for particles with diameters ranging from 26 to 110 nm, but the authors expressed a need to improve the retention and dispersion parameters. In a 2010 publication by Jellema, Markesteijn, Westerweel, and Verpoorte, implementing HDC with a recirculating bidirectional flow resulted in high resolution, size based separation with only a 3 mm long channel. Having such a short channel and high resolution was viewed as especially impressive considering that previous studies used channels that were 80 mm in length. For a biological application, in 2007, Huh, et al. proposed a microfluidic sorting device based on HDC and gravity, which was useful for preventing potentially dangerous particles with diameter larger than 6 microns from entering the bloodstream when injecting contrast agents in ultrasounds. This study also made advances for environmental sustainability in microfluidics due to the lack of outside electronics driving the flow, which came as an advantage of using a gravity based device.

Two-dimensional chromatography
In some cases, the selectivity provided by the use of one column can be insufficient to provide resolution of analytes in complex samples. Two-dimensional chromatography aims to increase the resolution of these peaks by using a second column with different physico-chemical (chemical classification) properties. Since the mechanism of retention on this new solid support is different from the first dimensional separation, it can be possible to separate compounds by two-dimensional chromatography that are indistinguishable by one-dimensional chromatography. Furthermore, the separation on the second dimension occurs faster than the first dimension. An example of a two-dimensional TLC separation is where the sample is spotted at one corner of a square plate, developed, air-dried, then rotated by 90° and usually redeveloped in a second solvent system. Two-dimensional chromatography can be applied to GC or LC separations. This separation method can also be used in a heart-cutting approach, where specific regions of interest on the first dimension are selected for separation by the second dimension, or in a comprehensive approach, where all the analytes from the first dimension undergo the second dimension separation.

Simulated moving-bed chromatography
The simulated moving bed (SMB) technique is a variant of high performance liquid chromatography; it is used to separate particles and/or chemical compounds that would be difficult or impossible to resolve otherwise. This increased separation is brought about by a valve-and-column arrangement that is used to lengthen the stationary phase indefinitely. In the moving bed technique of preparative chromatography the feed entry and the analyte recovery are simultaneous and continuous, but because of practical difficulties with a continuously moving bed, simulated moving bed technique was proposed. In the simulated moving bed technique instead of moving the bed, the sample inlet and the analyte exit positions are moved continuously, giving the impression of a moving bed. True moving bed chromatography (TMBC) is only a theoretical concept. Its simulation, SMBC is achieved by the use of a multiplicity of columns in series and a complex valve arrangement. This valve arrangement provides for sample and solvent feed and analyte and waste takeoff at appropriate locations of any column, whereby it allows switching at regular intervals the sample entry in one direction, the solvent entry in the opposite direction, whilst changing the analyte and waste takeoff positions appropriately as well.

Pyrolysis gas chromatography
Pyrolysis–gas chromatography–mass spectrometry is a method of chemical analysis in which the sample is heated to decomposition to produce smaller molecules that are separated by gas chromatography and detected using mass spectrometry.

Pyrolysis is the thermal decomposition of materials in an inert atmosphere or a vacuum. The sample is put into direct contact with a platinum wire, or placed in a quartz sample tube, and rapidly heated to 600–1000 °C. Depending on the application even higher temperatures are used. Three different heating techniques are used in actual pyrolyzers: Isothermal furnace, inductive heating (Curie point filament), and resistive heating using platinum filaments. Large molecules cleave at their weakest points and produce smaller, more volatile fragments. These fragments can be separated by gas chromatography. Pyrolysis GC chromatograms are typically complex because a wide range of different decomposition products is formed. The data can either be used as fingerprints to prove material identity or the GC/MS data is used to identify individual fragments to obtain structural information. To increase the volatility of polar fragments, various methylating reagents can be added to a sample before pyrolysis.

Besides the usage of dedicated pyrolyzers, pyrolysis GC of solid and liquid samples can be performed directly inside Programmable Temperature Vaporizer (PTV) injectors that provide quick heating (up to 30 °C/s) and high maximum temperatures of 600–650 °C. This is sufficient for some pyrolysis applications. The main advantage is that no dedicated instrument has to be purchased and pyrolysis can be performed as part of routine GC analysis. In this case, quartz GC inlet liners have to be used. Quantitative data can be acquired, and good results of derivatization inside the PTV injector are published as well.

Fast protein liquid chromatography
Fast protein liquid chromatography (FPLC), is a form of liquid chromatography that is often used to analyze or purify mixtures of proteins. As in other forms of chromatography, separation is possible because the different components of a mixture have different affinities for two materials, a moving fluid (the "mobile phase") and a porous solid (the stationary phase). In FPLC the mobile phase is an aqueous solution, or "buffer". The buffer flow rate is controlled by a positive-displacement pump and is normally kept constant, while the composition of the buffer can be varied by drawing fluids in different proportions from two or more external reservoirs. The stationary phase is a resin composed of beads, usually of cross-linked agarose, packed into a cylindrical glass or plastic column. FPLC resins are available in a wide range of bead sizes and surface ligands depending on the application.

Countercurrent chromatography
Countercurrent chromatography (CCC) is a type of liquid-liquid chromatography, where both the stationary and mobile phases are liquids and the liquid stationary phase is held stagnant by a strong centrifugal force.

Hydrodynamic countercurrent chromatography (CCC)
The operating principle of CCC instrument requires a column consisting of an open tube coiled around a bobbin. The bobbin is rotated in a double-axis gyratory motion (a cardioid), which causes a variable gravity (G) field to act on the column during each rotation. This motion causes the column to see one partitioning step per revolution and components of the sample separate in the column due to their partitioning coefficient between the two immiscible liquid phases used. There are many types of CCC available today. These include HSCCC (High Speed CCC) and HPCCC (High Performance CCC). HPCCC is the latest and best-performing version of the instrumentation available currently.

Centrifugal partition chromatography (CPC)
In the CPC (centrifugal partition chromatography or hydrostatic countercurrent chromatography) instrument, the column consists of a series of cells interconnected by ducts attached to a rotor. This rotor rotates on its central axis creating the centrifugal field necessary to hold the stationary phase in place. The separation process in CPC is governed solely by the partitioning of solutes between the stationary and mobile phases, which mechanism can be easily described using the partition coefficients (KD) of solutes. CPC instruments are commercially available for laboratory, pilot, and industrial-scale separations with different sizes of columns ranging from some 10 milliliters to 10 liters in volume.

Periodic counter-current chromatography
In contrast to Counter current chromatography (see above), periodic counter-current chromatography (PCC) uses a solid stationary phase and only a liquid mobile phase. It thus is much more similar to conventional affinity chromatography than to counter current chromatography. PCC uses multiple columns, which during the loading phase are connected in line. This mode allows for overloading the first column in this series without losing product, which already breaks through the column before the resin is fully saturated. The breakthrough product is captured on the subsequent column(s). In a next step the columns are disconnected from one another. The first column is washed and eluted, while the other column(s) are still being loaded. Once the (initially) first column is re-equilibrated, it is re-introduced to the loading stream, but as last column. The process then continues in a cyclic fashion.

Chiral chromatography
Chiral chromatography involves the separation of stereoisomers. In the case of enantiomers, these have no chemical or physical differences apart from being three-dimensional mirror images. To enable chiral separations to take place, either the mobile phase or the stationary phase must themselves be made chiral, giving differing affinities between the analytes. Chiral chromatography HPLC columns (with a chiral stationary phase) in both normal and reversed phase are commercially available.

Conventional chromatography are incapable of separating racemic mixtures of enantiomers. However, in some cases nonracemic mixtures of enantiomers may be separated unexpectedly by conventional liquid chromatography (e.g. HPLC without chiral mobile phase or stationary phase ).

Aqueous normal-phase chromatography
Aqueous normal-phase (ANP) chromatography is characterized by the elution behavior of classical normal phase mode (i.e. where the mobile phase is significantly less polar than the stationary phase) in which water is one of the mobile phase solvent system components. It is distinguished from hydrophilic interaction liquid chromatography (HILIC) in that the retention mechanism is due to adsorption rather than partitioning.

Applications
Chromatography is used in many fields including the pharmaceutical industry, the food and beverage industry, the chemical industry, forensic science, environment analysis, and hospitals.

title: Chromatography


text:
Clement Martyn Doke

Clement Martyn Doke (16 May 1893 in Bristol, United Kingdom – 24 February 1980 in East London, South Africa) was a South African linguist working mainly on African languages. Realizing that the grammatical structures of Bantu languages are quite different from those of European languages, he was one of the first African linguists of his time to abandon the Euro-centric approach to language description for a more locally grounded one. A most prolific writer, he published a string of grammars, several dictionaries, comparative work, and a history of Bantu linguistics.

Early life and career
The Doke family had been engaged in missionary activity for the Baptist Church for some generations. His father, Reverend Joseph J. Doke, left England and travelled to South Africa in 1882, where he met and married Agnes Biggs. They returned to England, where Clement was born as the third of four children. The family moved to New Zealand and eventually returned to South Africa in 1903, where it later settled in Johannesburg.

At the age of 18, Clement received a bachelor's degree from Transvaal University College in Pretoria (now the University of Pretoria). He decided to devote his life to missionary activity. In 1913, he accompanied his father on a tour of north-western Rhodesia, to an area called Lambaland, now known as Ilamba. It is at the watershed of the Congo and Zambesi rivers. Part of the district lay in Northern Rhodesia and part of the Belgian Congo. The Cape-Cairo Railway threaded through its eastern portion; otherwise, most travel had to be on foot.

The Reverend William Arthur Phillips of the Nyasa Industrial Mission in Blantyre had established a Baptist mission there in 1905; it served an area of 25000 sqmi and 50,000 souls. The Dokes were supposed to investigate whether the mission in Lambaland could be taken over by the Baptist Union of South Africa. It was on that trip that Doke's father contracted enteric fever and died soon afterwards. Mahatma Gandhi attended the memorial service and addressed the congregation. Clement assumed his father's role.

The South African Baptists decided to take over Kafulafuta Mission, and its founder, Reverend Phillips, remained as superintendent. Clement Doke returned to Kafulafuta as missionary in 1914, followed by his sister Olive two years later.

Study of Lamba
At first, Clement Doke was frustrated by his inability to communicate with the Lamba. The only written material available at the time was a translation of Jonah and a collection of 47 hymns. Soon, however, he mastered the language and published his first book, Ifintu Fyakwe Lesa ("The Things of God, a Primer of Scripture Knowledge") in 1917. He enrolled in Johannesburg as the extension of Transvaal University College for an MA degree. His thesis was published as The Grammar of the Lamba language. The book is couched in traditional grammatical terms, as Doke had not yet established his innovative method to analyse and describe the Bantu languages. His later Textbook of Lamba Grammar is far superior in that respect.

Doke was also interested in ethnology. In 1931 he compiled The Lambas of Northern Rhodesia, which remains one of the outstanding ethnographic descriptions of the peoples of Central Africa. For Doke, literacy was part of evangelisation since it was required so that people to appreciate the Bible's message, but it was only after his retirement that he completed the translation of the Bible into Lamba. It was published under the title of Amasiwi AwaLesa ("The Words of God") in 1959.

University of the Witwatersrand
In 1919, Doke married Hilda Lehmann, who accompanied him back to Lambaland. Both contracted malaria during their work, and she was forbidden to return to Lambaland. Clement Doke also realised that his field work could not continue much longer, and he left in 1921. He was recruited by the newly-founded University of the Witwatersrand. So that he could secure a qualification as a lecturer, the family moved to England, where he registered at the School of Oriental and African Studies. His major languages were Lamba and Luba, but as no suitable examiner was available, he eventually had to change his language to Zulu.

Doke took up his appointment in the new Department of Bantu Studies at the University of Witwatersrand in 1923. In 1925 he received his D. Litt. for his doctoral thesis The Phonetics of the Zulu Language and was promoted to Senior Lecturer. In 1931 he was appointed to the Chair of Bantu Studies and thus headed the Department of Bantu Studies. The Department acted as a catalyst for the admission of Africans to the university. As early as 1925 a limited number were admitted to the vacation course in African Studies. Doke supported the appointment of Benedict Wallet Vilakazi as member of the staff, as he believed a native speaker was essential for acquiring a language. That provoked a storm of criticism and controversy from the public. Both of them collaborated on the Zulu-English Dictionary. First published in 1948, it is still one of the best examples of lexicography for any Bantu language.

At the request of the government of Southern Rhodesia, Doke investigated the range of dialect diversity among the languages of the country and made recommendations for Unified Shona, which formed the basis for Standard Shona. He devised a unified orthography based on the Zezuru, Karanga and Manyika dialects. However, Doke's orthography was never fully accepted, and the South African government introduced an alternative, which left Shona with two competing orthographies between 1935 and 1955.

During his tenure, Doke developed and promoted a method of linguistic analysis and description of the Bantu languages that was based upon the structure of these languages. The "Dokean model" continues to be one of the dominant models of linguistic description in Southern and Central Africa. His classification of the Bantu languages was for many years the dominant view of the interrelations among the African languages. He was also an early describer of Khoisan and Bantu click consonants, devising phonetic symbols for a number of them.

Doke served the University of the Witwatersrand until his retirement in 1953. He was awarded the honorary degree of Doctor of Letters by Rhodes University and the honorary degree of Doctor of Laws by the University of the Witwatersrand in 1972.

The former missionary always remained devoted to the Baptist Church. He was elected President of the South African Baptist Union in 1949 and spent a year visiting churches and mission stations. He used his presidential address in condemning the recently established apartheid policy: I solemnly warn the Government that the spirit behind their apartheid legislation, and the way in which they are introducing discriminatory measures of all types today, will bring disaster upon this fair land of ours.

Selected publications

 * Ifintu Fyakwe Lesa (The Things of God, a Primer of Scripture Knowledge in Lamba), 1917.
 * An outline of the phonetics of the language of the ʗhũ̬꞉ Bushman of the North-West Kalahari. Bantu Studies. 2: 129–166, 1925.
 * The phonetics of the Zulu language. University of the Witwatersrand Press, 1969 [1926].
 * The Lambas of Northern Rhodesia: A Study of their Customs and Beliefs. London: George G. Harrap, 1931.
 * Report on the Unification of the Shona Dialects. Government of Southern Rhodesia: Government Blue Book, 1931.
 * Bantu linguistic terminology. London; New York Longmans, Green, 1935.
 * Textbook of Lamba Grammar. Johannesburg: Witwatersrand University Press, 1938.
 * Outline grammar of Bantu. Johannesburg: University of the Witwatersrand, 1943.
 * Zulu–English Dictionary. Johannesburg: Witwatersrand University Press, 1948. (with Benedict Wallet Vilakazi)
 * The Southern Bantu languages. London; New York: Oxford University Press, 1954.
 * Amasiwi AwaLesa (The Words of God in Lamba), 1959.
 * Contributions to the history of Bantu linguistics. Johannesburg: Witwatersrand University Press, 1961 (with D. T. Cole).
 * Trekking in South Central Africa 1913–1919. Johannesburg: Witwatersrand University Press, 1993.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Clement Martyn Doke


text:
Carl Meinhof

Carl Friedrich Michael Meinhof (23 July 1857 – 11 February 1944) was a German linguist and one of the first linguists to study African languages.

Early years and career
Meinhof was born in Barzwitz near Rügenwalde in the Province of Pomerania, Kingdom of Prussia. He studied at the University of Tübingen and at the University of Greifswald. In 1905 he became professor at the School of Oriental Studies in Berlin. On 5 May 1933 he became a member of the Nazi Party.

Works
His most notable work was developing comparative grammar studies of the Bantu languages, building on the pioneering work of Wilhelm Bleek. In his work, Meinhof looked at the common Bantu languages such as Swahili and Zulu to determine similarities and differences.

In his work, Meinhof looked at noun classes with all Bantu languages having at least 10 classes and with 22 classes of nouns existing throughout the Bantu languages, though his definition of noun class differs slightly from the accepted one, considering the plural form of a word as belonging to a different class from the singular form (thus leading, for example, to consider a language like French as having four classes instead of two). While no language has all 22 (later: 23) classes active, Venda has 20, Lozi has 18, and Ganda has 16 or 17 (depending on whether the locative class 23 e- is included). All Bantu languages have a noun class specifically for humans (sometimes including other animate beings).

Meinhof also examined other African languages, including groups classified at the time as Kordofanian, Bushman, Khoikhoi, and Hamitic.

Meinhof developed a comprehensive classification scheme for African languages. His classification was the standard one for many years (Greenberg 1955:3). It was replaced by those of Joseph Greenberg in 1955 and in 1963.

In 1902, Meinhof made recordings of East African music. These are among the first recordings made of traditional African music.

Controversial views
In 1912, Carl Meinhof published Die Sprachen der Hamiten (The Languages of the Hamites). He used the term Hamitic. Meinhof's system of classification of the Hamitic languages was based on a belief that "speakers of Hamitic became largely coterminous with cattle herding peoples with essentially Caucasian origins, intrinsically different from and superior to the 'Negroes of Africa'." However, in the case of the so-called Nilo-Hamitic languages (a concept he introduced), it was based on the typological feature of gender and a "fallacious theory of language mixture." Meinhof did this in spite of earlier work by scholars such as Lepsius and Johnston demonstrating that the languages which he would later dub "Nilo-Hamitic" were in fact Nilotic languages with numerous similarities in vocabulary with other Nilotic languages.

Family
Carl Meinhof was the great-uncle (the brother of the grandfather) of Ulrike Meinhof, a founding member of the German Red Army Faction (RAF), a left-wing militant group, which operated in West Germany in the 1970s and 1980s.

title: Carl Meinhof


text:
Cucurbitaceae

The Cucurbitaceae, also called cucurbits or the gourd family, are a plant family consisting of about 965 species in 101 genera. Those most important to humans are the following:
 * Cucurbita – squash, pumpkin, zucchini or courgette, some gourds
 * Lagenaria – calabash, and others that are inedible
 * Citrullus – watermelon (C. lanatus, C. colocynthis) and others
 * Cucumis – cucumber (C. sativus), various melons and vines
 * Momordica – bitter melon
 * Luffa – the common name is also luffa, sometimes spelled loofah (when fully ripened, two species of this fibrous fruit are the source of the loofah scrubbing sponge)
 * Cyclanthera – Caigua

The plants in this family are grown around the tropics and in temperate areas, where those with edible fruits were among the earliest cultivated plants in both the Old and New Worlds. The family Cucurbitaceae ranks among the highest of plant families for number and percentage of species used as human food. The name Cucurbitaceae comes to international scientific vocabulary from Neo-Latin, from Cucurbita, the type genus, + -aceae, a standardized suffix for plant family names in modern taxonomy. The genus name comes from the Classical Latin word , meaning "gourd".

Description
Most of the plants in this family are annual vines, but some are woody lianas, thorny shrubs, or trees (Dendrosicyos). Many species have large, yellow or white flowers. The stems are hairy and pentangular. Tendrils are present at 90° to the leaf petioles at nodes. Leaves are exstipulate, alternate, simple palmately lobed or palmately compound. The flowers are unisexual, with male and female flowers on different plants (dioecious) or on the same plant (monoecious). The female flowers have inferior ovaries. The fruit is often a kind of modified berry called a pepo.

Fossil history
One of the oldest fossil cucurbits so far is †Cucurbitaciphyllum lobatum from the Paleocene epoch, found at Shirley Canal, Montana. It was described for the first time in 1924 by the paleobotanist Frank Hall Knowlton. The fossil leaf is palmate, trilobed with rounded lobal sinuses and an entire or serrate margin. It has a leaf pattern similar to the members of the genera Kedrostis, Melothria and Zehneria.

Tribal classification
The most recent classification of Cucurbitaceae delineates 15 tribes:

 * Tribe Gomphogyneae Benth. & Hook.f.
 * Alsomitra (Blume) Spach (1 sp.)
 * Bayabusua (1 sp.)
 * Gomphogyne Griff. (2 spp.)
 * Gynostemma Blume (10 spp.)
 * Hemsleya Cogn. ex F.B.Forbes & Hemsl. (30 spp.)
 * Neoalsomitra Hutch. (12 spp.)
 * Tribe Triceratieae A.Rich.
 * Cyclantheropsis Harms (3 spp.)
 * Fevillea L. (8 spp.)
 * Pteropepon (Cogn.) Cogn. (5 spp.)
 * Sicydium Schltdl. (9 spp.)
 * Tribe Zanonieae Benth. & Hook.f.
 * Gerrardanthus Harvey in Hook.f. (3–5 spp.)
 * Siolmatra Baill. (1 sp.)
 * Xerosicyos Humbert (5 spp.)
 * Zanonia L. (1 sp.)
 * Tribe Actinostemmateae H.Schaef. & S.S.Renner
 * Actinostemma Griff. (3 spp.)
 * Bolbostemma Franquet (2 spp.)
 * Tribe Indofevilleeae H.Schaef. & S.S.Renner
 * Indofevillea Chatterjee (2 sp.)
 * Tribe Thladiantheae H.Schaef. & S.S.Renner
 * Baijiania A.M.Lu & J.Q.Li (30 spp.)
 * Sinobaijiania C.Jeffrey & W.J.de Wilde (5 spp.)
 * Thladiantha Bunge 1833 (5 spp.)
 * Tribe Siraitieae H. Schaef. & S.S. Renner
 * Siraitia Merr. (3–4 spp.)
 * Tribe Momordiceae H.Schaef. & S.S.Renner
 * Momordica L. (60 spp.)
 * Tribe Joliffieae Schrad.
 * Ampelosicyos Thouars (5 spp.)
 * Cogniauxia Baill. (2 spp.)
 * Telfairia Hook. (3 spp.)
 * Tribe Bryonieae Dumort.
 * Austrobryonia H.Schaef. (4 spp.)
 * Bryonia L. (10 spp.)
 * Ecballium A.Rich. (1 sp.)
 * Tribe Schizopeponeae C.Jeffrey
 * Herpetospermum Wall. ex Hook.f. (3 spp.)
 * Schizopepon Maxim. (6–8 spp.)
 * Tribe Sicyoeae Schrad.
 * Brandegea Cogn. (1 sp.)
 * Cyclanthera Schrad. (40 spp.)
 * Echinocystis Torr. & A.Gray (1 sp.)
 * Echinopepon Naudin (19 spp.)
 * Hanburia Seem. (7 spp.)
 * Hodgsonia Hook.f. & Thomson (2 spp.)
 * Linnaeosicyos H.Schaef. & Kocyan (1 sp.)
 * Luffa Mill. (5–7 spp.)
 * Marah Kellogg (7 spp.)
 * Microsechium Naudin (4 spp.)
 * Nothoalsomitra Hutch. (1 sp.)
 * Parasicyos Dieterle (2 sp.)
 * Sechiopsis Naudin (5 spp.)
 * Sicyocaulis Wiggins (1 sp.)
 * Sicyos L. (64 spp., including Frantzia Pittier and Sechium P.Browne )
 * Sicyosperma A.Gray (1 sp.)
 * Trichosanthes L. (≤100 spp.)
 * Tribe Coniandreae Endl.
 * Apodanthera Arn. (16 spp.)
 * Bambekea Cogn. (1 sp.)
 * Ceratosanthes Adans. (4 spp.)
 * Corallocarpus Welw. ex Benth. & Hook.f. (17 spp.)
 * Cucurbitella Walp. (1 sp.)
 * Dendrosicyos Balf.f. (1 sp.)
 * Doyerea Grosourdy (1 sp.)
 * Eureiandra Hook.f. (8 spp.)
 * Gurania (Schltdl.) Cogn. (37 spp.)
 * Halosicyos Mart.Crov (1 sp.)
 * Helmontia Cogn. (2–4 spp.)
 * Ibervillea Greene (8 spp.)
 * Kedrostis Medik. (28 spp.)
 * Psiguria Neck. ex Arn. (6–12 spp.)
 * Seyrigia Keraudren (6 spp.)
 * Trochomeriopsis Cogn. (1 sp.)
 * Wilbrandia Silva Manso (5 spp.)
 * Tribe Benincaseae Ser.
 * Acanthosicyos Welw. ex Hook.f. (1 sp.)
 * Benincasa Savi (2 spp., including Praecitrullus Pangalo )
 * Blastania Kotschy & Peyr. (3 spp., including Ctenolepis Hook.f. )
 * Borneosicyos (1–2 spp.)
 * Cephalopentandra Chiov. (1 sp.)
 * Citrullus Schrad. (4 spp.)
 * Coccinia Wight & Arn. (30 spp.)
 * Cucumis L. (65 spp.)
 * Dactyliandra Hook.f. (2 spp.)
 * Diplocyclos (Endl.) T.Post & Kuntze (4 spp.)
 * Indomelothria (2 spp.)
 * Khmeriosicyos (1 sp.)
 * Lagenaria Ser. (6 spp.)
 * Lemurosicyos Keraudren (1 sp.)
 * Melothria L. (12 spp., including M. scabra)
 * Muellerargia Cogn. (2 sp.)
 * Oreosyce Hook.f. (1 sp.)
 * Papuasicyos (8 spp.)
 * Peponium Engl. (20 spp.)
 * Raphidiocystis Hook.f. (5 spp.)
 * Ruthalicia C.Jeffrey (2 spp.)
 * Scopellaria W.J.de Wilde & Duyfjes (2 spp.)
 * Solena Lour. (3 spp.)
 * Trochomeria Hook.f. (8 spp.)
 * Zehneria Endl. (ca. 60 spp.)
 * Tribe Cucurbiteae Ser.
 * Abobra Naudin (1 sp.)
 * Calycophysum H.Karst. & Triana (5 spp.)
 * Cayaponia Silva Manso (74 spp.)
 * Cionosicys Griseb. (4–5 spp.)
 * Cucurbita L. (15 spp.)
 * Penelopeia Urb. (2 spp.)
 * Peponopsis Naudin (1 sp.)
 * Polyclathra Bertol. (6 spp.)
 * Schizocarpum Schrad. (11 spp.)
 * Selysia Cogn. (4 spp.)
 * Sicana Naudin (4 spp.)
 * Tecunumania Standl. & Steyerm. (1 sp.)

Systematics
Modern molecular phylogenetics suggest the following relationships:

Pests and diseases
Sweet potato whitefly is the vector of a number of cucurbit viruses that cause yellowing symptoms throughout the southern United States.

title: Cucurbitaceae


text:
Chorded keyboard

A keyset or chorded keyboard (also called a chorded keyset, chord keyboard or chording keyboard) is a computer input device that allows the user to enter characters or commands formed by pressing several keys together, like playing a "chord" on a piano. The large number of combinations available from a small number of keys allows text or commands to be entered with one hand, leaving the other hand free. A secondary advantage is that it can be built into a device (such as a pocket-sized computer or a bicycle handlebar) that is too small to contain a normal-sized keyboard.

A chorded keyboard minus the board, typically designed to be used while held in the hand, is called a keyer. Douglas Engelbart introduced the chorded keyset as a computer interface in 1968 at what is often called "The Mother of All Demos".

Principles of operation
Each key is mapped to a number and then can be mapped to a corresponding letter or command. By pressing two or more keys together the user can generate many combinations. In Engelbart's original mapping, he used five keys: 1, 2, 4, 8, 16. The keys were mapped as follows: a = 1, b = 2, c = 3, d = 4, and so on. If the user pressed keys 1 and 2 simultaneously, and then released the keys, 1 and 2 would be added to 3, and since C is the 3rd letter of the alphabet, and the letter "c" appeared. Unlike pressing a chord on a piano, the chord is recognized only after all the keys or mouse buttons are released. Since Engelbart introduced the keyset, several different designs have been developed based on similar concepts.

As a crude example, each finger might control one key which corresponds to one bit in a byte, so that using seven keys and seven fingers, one could enter any character in the ASCII set—if the user could remember the binary codes. Due to the small number of keys required, chording is easily adapted from a desktop to mobile environment.

Practical devices generally use simpler chords for common characters (e.g., Baudot), or may have ways to make it easier to remember the chords (e.g., Microwriter ), but the same principles apply. These portable devices first became popular with the wearable computer movement in the 1980s.

Thad Starner from Georgia Institute of Technology and others published numerous studies  showing that two-handed chorded text entry was faster and yielded fewer errors than on a QWERTY keyboard. Currently stenotype machines hold the record for fastest word entry. Many stenotype users can reach 300 words per minute. However, stenographers typically train for three years before reaching professional levels of speed and accuracy.

History
The earliest known chord keyboard was part of the "five-needle" telegraph operator station, designed by Wheatstone and Cooke in 1836, in which any two of the five needles could point left or right to indicate letters on a grid. It was designed to be used by untrained operators (who would determine which keys to press by looking at the grid), and was not used where trained telegraph operators were available. The first widespread use of a chord keyboard was in the stenotype machine used by court reporters, which was invented in 1868 and is still in use. The output of the stenotype was originally a phonetic code that had to be transcribed later (usually by the same operator who produced the original output), rather than arbitrary text—automatic conversion software is now commonplace.

In 1874, the five-bit Baudot telegraph code and a matching 5-key chord keyboard was designed to be used with the operator forming the codes manually. The code is optimized for speed and low wear: chords were chosen so that the most common characters used the simplest chords. But telegraph operators were already using typewriters with QWERTY keyboards to "copy" received messages, and at the time it made more sense to build a typewriter that could generate the codes automatically, rather than making them learn to use a new input device.

Some early keypunch machines used a keyboard with 12 labeled keys to punch the correct holes in paper cards. The numbers 0 through 9 were represented by one punch; 26 letters were represented by combinations of two punches, and symbols were represented by combinations of two or three punches. Braille (a writing system for the blind) uses either 6 or 8 tactile 'points' from which all letters and numbers are formed. When Louis Braille invented it, it was produced with a needle holing successively all needed points in a cardboard sheet. In 1892, Frank Haven Hall, superintendent of the Illinois Institute for the Education of the Blind, created the Hall Braille Writer, which was like a typewriter with 6 keys, one for each dot in a braille cell. The Perkins Brailler, first manufactured in 1951, uses a 6-key chord keyboard (plus a spacebar) to produce braille output, and has been very successful as a mass market affordable product. Braille, like Baudot, uses a number symbol and a shift symbol, which may be repeated for shift lock, to fit numbers and upper case into the 63 codes that 6 bits offer.

After World War II, with the arrival of electronics for reading chords and looking in tables of "codes", the postal sorting offices started to research chordic solutions to be able to employ people other than trained and expensive typists. In 1954, an important concept was discovered: chordic production is easier to master when the production is done at the release of the keys instead of when they are pressed.

Researchers at IBM investigated chord keyboards for both typewriters and computer data entry as early as 1959, with the idea that it might be faster than touch-typing if some chords were used to enter whole words or parts of words. A 1975 design by IBM Fellow Nat Rochester had 14 keys that were dimpled on the edges as well as the top, so one finger could press two adjacent keys for additional combinations. Their results were inconclusive, but research continued until at least 1978.

Doug Engelbart began experimenting with keysets to use with the mouse in the mid 1960s. In a famous 1968 demonstration, Engelbart introduced a computer human interface that included the QWERTY keyboard, a three button mouse, and a five key keyset. Engelbart used the keyset with his left hand and the mouse with his right to type text and enter commands. The mouse buttons marked selections and confirmed or aborted commands.

Users in Engelbart's Augmentation Research Center at SRI became proficient with the mouse and keyset. In the 1970s the funding Engelbart's group received from the Advanced Research Projects Agency (ARPA) was cut and many key members of Engelbart's team went to work for Xerox PARC where they continued to experiment with the mouse and keyset. Keychord sets were used at Xerox PARC in the early 1980s, along with mice, GUIs, on the Xerox Star and Alto workstations. A one-button version of the mouse was incorporated into the Apple Macintosh but Steve Jobs decided against incorporating the chorded keyset.

In the early 1980s, Philips Research labs at Redhill, Surrey did a brief study into small, cheap keyboards for entering text on a telephone. One solution used a grid of hexagonal keys with symbols inscribed into dimples in the keys that were either in the center of a key, across the boundary of two keys, or at the joining of three keys. Pressing down on one of the dimples would cause either one, two or three of the hexagonal buttons to be depressed at the same time, forming a chord that would be unique to that symbol. With this arrangement, a nine button keyboard with three rows of three hexagonal buttons could be fitted onto a telephone and could produce up to 33 different symbols. By choosing widely separated keys, one could employ one dimple as a 'shift' key to allow both letters and numbers to be produced. With eleven keys in a 3/4/4 arrangement, 43 symbols could be arranged allowing for lowercase text, numbers and a modest number of punctuation symbols to be represented along with a 'shift' function for accessing uppercase letters. While this had the advantage of being usable by untrained users via 'hunt and peck' typing and requiring one less key switch than a conventional 12 button keypad, it had the disadvantage that some symbols required three times as much force to depress them as others which made it hard to achieve any speed with the device. That solution is still alive and proposed by Fastap and Unitap among others, and a commercial phone has been produced and promoted in Canada during 2006.

Standards
Historically, the baudot and braille keyboards were standardized to some extent, but they are unable to replicate the full character set of a modern keyboard. Braille comes closest, as it has been extended to eight bits.

The only proposed modern standard, GKOS (or Global Keyboard Open Standard) can support most characters and functions found on a computer keyboard but has had little commercial development. There is, however, a GKOS keyboard application available for iPhone since May 8, 2010, for Android since October 3, 2010 and for MeeGo Harmattan since October 27, 2011.

Stenography
Stenotype machines, sometimes used by court reporters, use a chording keyboard to represent sounds: on the standard keyboard, the U represents the sound and word, 'you', and the three-key trigraph KAT represents the sound and word 'cat'. The stenotype keyboard is explicitly ordered: in KAT, K , on the left, is the starting sound. P, S , and T , which are common starting sounds and also common ending sounds, are available on both sides of the keyboard: POP is a 3-key chord, using both P keys. .

Open-source designs
Multiple open-source keyer/keyset designs are available, such as the pickey, a PS/2 device based on the PIC microcontroller; the spiffchorder, a USB device based on the Atmel AVR family of microcontrollers; the FeatherChorder, a BLE chorder based on the Adafruit Feather, an all-in-one board incorporating an Arduino-compatible microcontroller; and the GKOS keypad driver for Linux as well as the Gkos library for the Atmel/Arduino open-source board.

Plover is a free, open-source, cross-platform program intended to bring real-time stenographic technology not just to stenographers, but also to hobbyists using anything from professional Stenotype machines to low-cost NKRO gaming keyboards. It is available for Linux, Windows, and macOS.

Joy2chord is a chorded keyboard driver for Linux. With a configuration file, any joystick or gamepad can be turned into a chorded keyboard. This design philosophy was decided on to lower the cost of building devices, and in turn lower the entry barrier to becoming familiar with chorded keyboards. Macro keys, and multiple modes are also easily implemented with a user space driver.

Commercial devices
One minimal chordic keyboard example is Edgar Matias' Half-Qwerty keyboard described in patent  circa 1992 that produces the letters of the missing half when the user simultaneously presses the space bar along with the mirror key. INTERCHI '93 published a study by Matias, MacKenzie and Buxton showing that people who have already learned to touch-type can quickly recover 50 to 70% of their two-handed typing speed. The loss contributes to the speed discussion above. It is implemented on two popular mobile phones, each provided with software disambiguation, which allows users to avoid using the space-bar.

"Multiambic" keyers for use with wearable computers were invented in Canada in the 1970s. Multiambic keyers are similar to chording keyboards but without the board, in that the keys are grouped in a cluster for being handheld, rather than for sitting on a flat surface.

Chording keyboards are also used as portable but two handed input devices for the visually impaired (either combined with a refreshable braille display or vocal synthesis). Such keyboards use a minimum of seven keys, where each key corresponds to an individual braille point, except one key which is used as a spacebar. In some applications, the spacebar is used to produce additional chords which enable the user to issue editing commands, such as moving the cursor, or deleting words. Note that the number of points used in braille computing is not 6, but 8, as this allows the user, among other things, to distinguish between small and capital letters, as well as identify the position of the cursor. As a result, most newer chorded keyboards for braille input include at least nine keys.

Touch screen chordic keyboards are available to smartphone users as an optional way of entering text. As the number of keys is low, the button areas can be made bigger and easier to hit on the small screen. The most common letters do not necessarily require chording as is the case with the GKOS keyboard optimised layouts (Android app) where the twelve most frequent characters only require single keys.

The company CharaChorder commerially sells chorded entry devices. Their first commercially available device is the CharaChorder One, which features a split design with each having access to 9 switches that can be moved in five directions (up, down, left, right, and pressed) in contrast to typical keyboards. This device allows for both chorded entry as well as traditional character entry. The set of words that can be chorded can be dynamically changed by the user in real time, but by default includes the 300 most common words in the English language. This chorded entry feature allows for potentially extremely fast typing speeds, so much so the founder of the company has been banned from online typing competitions. Additionally, they create the Charachorder Lite with a more traditional keyboard design. The manufacturer claimed that users of the Charachorder One can reach speeds of 300 words per minute, while users of the Charachorder Lite can reach 250 words per minute.

Historical
The WriteHander, a 12-key chord keyboard from NewO Company, appeared in 1978 issues of ROM Magazine, an early microcomputer applications magazine.

Another early commercial model was the six-button Microwriter, designed by Cy Endfield and Chris Rainey, and first sold in 1980. Microwriting is the system of chord keying and is based on a set of mnemonics. It was designed only for right-handed use.

In 1982 the Octima 8 keys cord keyboard was presented by Ergoplic Kebords Ltd an Israeli Startup that was founded by Israeli researcher with intensive experience in Man Machine Interface design. The keyboard had 8 keys one for each finger and additional 3 keys that enabled the production of numbers, punctuations and control functions. The keyboard was fully compatible with the IBM PC and AT keyboards and had an Apple IIe version as well. Its key combinations were based on a mnemonic system that enabled fast and easy touch type learning. Within a few hours the user could achieve a typing speed similar to hand writing speed. The unique design also gave a relief from hand stress (Carpal Tunnel Syndrome) and allowed longer typing sessions than traditional keyboards. It was multi-lingual supporting English, German, French and Hebrew.

The BAT is a 7-key hand-sized device from Infogrip, and has been sold since 1985. It provides one key for each finger and three for the thumb. It is proposed for the hand which does not hold the mouse, in an exact continuation of Engelbart's vision.

title: Chorded keyboard


text:
Carolyn Beug

Carolyn Ann Mayer-Beug (December 11, 1952 – September 11, 2001) was a filmmaker and video producer from Santa Monica, California. She died in the September 11 attacks as a passenger of the American Airlines Flight 11.

Career
In addition to her work as video producer, Beug also directed three music videos for country singer Dwight Yoakam: "Ain't That Lonely Yet", "A Thousand Miles from Nowhere" and "Fast as You." Beug co-directed the former two videos with Yoakam and was the sole director of the latter video. She won an MTV Video Music award for the Van Halen music video of the song "Right Now", which she produced. She also served as senior vice president of Walt Disney Records.

Personal life
Beug lived in a Tudor-style home in the North 25th Street neighborhood. She hosted an annual backyard barbecue for the Santa Monica High School cross country and track team, which her daughters captained. Beug was a Latter-day Saint.

Death and legacy
Beug was killed at the age of 48 in the crash of American Airlines Flight 11 in the September 11, 2001 attacks. At the time of her death, Carolyn Beug was working on a children's book about Noah's Ark which was to be told from Noah's wife's point of view. On the plane with her was her mother, Mary Alice Wahlstrom. Beug was survived by her twin eighteen-year-old daughters Lauren and Lindsey Mayer-Beug, her 13-year-old son, Nick, and her husband, John Beug, a senior vice president in charge of filmed production for Warner Brothers' record division. She was returning home from taking her daughters to college at the Rhode Island School of Design.

At the National 9/11 Memorial, Beug is memorialized at the North Pool, on Panel N-1.

title: Carolyn Beug