Glossary and Bibliography

Instruments and Techniques

Calutron is a type of mass spectrometer used in the Manhattan Project. It was developed by Ernest Lawrence to separate uranium isotopes via magnets. Calutron magnetic separation was effective but was later replaced with the gaseous-diffusion method, which was more efficient.

CEC 21-101 is one of the earliest commercial mass spectrometers. First introduced in December 1942 and installed in the Atlantic Refining Company in Philadelphia in early 1943, the 21-101 allowed chemists, engineers, and physicists to measure up to mass 72 and up to a five-carbon-atom chain. Remarkably these spectra took only 20 minutes to obtain. Subsequent CEC instruments (21-102 and 21-103, for example) corrected many of the original problems with the 21-101 and made the complex mathematical analyses simpler. Many of these improvements were made at the suggestion of users via the CEC User’s Group Meetings held in Pasadena, California, and through correspondence with CEC mathematician Sibyl Rock.  

Chemical ionization is a type of ionization that happens as the direct result of a chemical reaction between an ionized gas and a neutral compound. Burnaby Munson and Frank Field developed these techniques in the 1960s.

Cyclotron is a particle accelerator that works by using the magnetic force on a moving charge to bend those charges into a semicircular path between accelerations by an applied electric field. Electrons are accelerated between the “dees” (D-shaped regions) of the magnetic field region. The field is reversed to accelerated electrons back across the gap. While many were working on cyclotron-like technology at the time, Ernest Lawrence is credited with inventing, improving, and manufacturing the cyclotron, beginning in 1929. The cyclotron was the first particle accelerator to achieve high-energy beams and was used for decades as the source of those beams for nuclear physics experiments.

Electron ionization is a type of ionization wherein the gaseous compound to be analyzed is bombarded with electrons.

Electrospray ionization is an ionization process that works by spraying a sample solution through a conducting capillary tube at high potential and into a chamber. This sprayed solution creates droplets that carry a charge, and those droplets gradually get smaller. Because the droplets maintain their charge, an instability occurs that leads to the expulsion of highly charged ions of the sample molecules.

FTMS (Fourier transform mass spectrometry) is a mathematical operation that converts mass spectral data into easier-to-read mass-to-charge ratios sine waves; m/z is determined via the cyclotron frequency of the ions.

GC-MS (gas chromatography–mass spectrometry) is done via a hybrid instrument, a gas chromatograph attached to a mass spectrometer. The gaseous current that comes from a gas chromatograph is introduced directly into a mass spectrometer’s ion source.

LC-MS (Liquid chromatography–mass spectrometry) joins the physical separation of a liquid chromatograph to the analysis of a mass spectrometer. LC-MS is commonly used in proteomics, bioanalysis, and drug testing.

Leak detector, or helium mass spectrometer, was developed by Alfred Nier during the Manhattan Project to detect leaks in uranium-enrichment plants using the gas-diffusion process. Helium, the tracer, which penetrates small leaks rapidly, is separated from other gases in a vacuum chamber; the rate of the leak is detected via a mass spectrometer.

MALDI (Matrix-assisted laser desorption/ionization) is a method of mass-spectrometry ionization. Desorption is caused by ultraviolet lasers, followed by ionization within a matrix of crystallized molecules. MALDI was introduced by Franz Hillenkamp and Michael Karas at the University of Münster in the mid-1980s. Koichi Tanaka’s later breakthroughs in large biomolecule mass-spec analysis using MALDI earned him the 2002 Nobel Prize in chemistry. MALDI is often combined with time of flight (ToF).

Mass spectrometer is an instrument that is employed to produce ions from atoms or molecules, separate them according to their mass-to-charge ratio (m/z), and detect those ions from a sample.

MS-MS (Tandem mass spectrometry) involves two stages of mass spectrometry and is aimed at selectively analyzing fragmentation of specific ions in a sample. The first stage of MS-MS consists of isolating ions of a desired m/z; these isolated ions are then induced to undergo a chemical reaction. This chemical reaction will change these ions’ mass or charge, and the ions will thus become “product ions”; those product ions are analyzed by the second stage of MS-MS.

Nier instruments are mass spectrometers employing the Nier-Johnson geometry: 90-degree electric field and 60-degree magnet sector. This type of instrument is a double-focusing mass spectrometer. During World War II many of the mass spectrometers used were Nier instruments, built either by Nier himself or by his students.

Quadrupole mass spectrometer is an instrument that applies a combination of dc (direct current) and rf (radio frequency) voltages to four parallel metal rods to create a filter through which only ions of any one m/z can be transmitted. Any changes in voltage will change the m/z value of ions passed through the transmitter.

ToF (Time of flight) is a method of accelerating ions with a mass spectrometer via a pulse potential instead of an electric field in a vacuum tube. Ion separation occurs via the mass-to-charge ratio based on velocity. ToF mass spectrometers were commercially introduced by Bendix in the 1950s. W. C. Wiley and I. H. MacLaren first published about ToF in 1955 (Wiley and MacLaren, The Review of Scientific Instruments 26 [1955], 1,150). TOF is often combined with MALDI.


Key Terms

Atomic mass number is the total number of protons and neutrons found within the nucleus of an atom. For example, carbon has a mass number of 12 because it contains 6 protons and 6 neutrons. However, many atoms have naturally occurring isotopes in which there are a set number of protons but different numbers of neutrons. The weighted average provides the relative atomic mass (or atomic weight), which can be a decimal.

Atomic number is the number of protons in an atom. This number is the primary way in which atoms can be identified, as each element’s atomic number is unique.

Cathode rays are rays of streaming electrons in a vacuum tube. They form a negative electrode within the vacuum tube toward the positively charged anode. In 1897 J. J. Thomson employed cathode rays in his discovery of electrons, the negatively charged component of the atom.

Fragment ion is an electrically charged, dissociated product of an ionic fragmentation. Ionic fragmentation plays a significant role in mass-spectrometry techniques, such as tandem mass spectrometry (MS-MS).

Ion is the name for an atom that no longer has its native number of electrons. If more electrons have been added, the resulting ion has an overall negative charge; and if electrons have been lost, the resulting ion has an overall positive charge.

Isotopes are atoms that have the same atomic number—the same number of protons—but different numbers of neutrons and therefore different masses. Many atoms have naturally occurring isotopes. For example, carbon occurs naturally as carbon-12, carbon-13, and carbon-14.

Nuclear fission is an energy-releasing process wherein a heavy atom is split after being hit by a neutron. For example, when U-235 is hit by and absorbs a neutron, the resulting instability causes the nucleus to split, releasing two daughter atoms, lone neutrons (which can bombard other U-235 atoms causing additional fission events), and energy. After the discovery of the neutron by James Chadwick in 1932, it was an easy step for nuclear chemists to bombard atoms with neutrons as they had been doing with protons. The resulting daughter atoms were proven to be lighter than the parent atom, not heavier, as expected. In 1939 Otto Hahn, Fritz Strassman, Lise Meitner, and Otto Frisch were able to demonstrate and mathematically explain how fission occurs.

Definitions section of Sibyl Rock's Computation Manual, 1946. CHF Collections. 

Mass spectrum is the data output generated by a mass spectrometer. It provides information about the relative abundances of the ions produced. The y-axis is numbered to 100, representing relative abundance, and the x-axis is the mass-to-charge ratio of the ions generated. The most abundant ion produced in the spectrometer measures 100. If there is a molecular ion present, that is the most abundant ion. For example, if methane (CH4) is being analyzed, the molecular ion is CH4+. Different types of mass spectrometers will generate slightly different-looking outputs. A mass spectrum is a single output, whereas mass spectra are plural.

Petroleum distillation is the process by which crude oil is heated and different component parts of the crude oil are able to be separated. The different carbon chains that compose crude oil weigh more the bigger they are, and in turn they are less volatile—they boil more slowly upon heating. The lightest carbon chains vaporize first and can therefore be separated from the heavier ones, which vaporize slower at higher temperatures. The purified oils collected at different boiling points are called distillation fractions.

U-235 is one of three uranium isotopes. U-238 is the most abundant, composing over 99% of uranium, whereas U-235 makes up only 0.7%. There is also a very slight amount of naturally occurring U-234. While all three uranium isotopes have 92 protons, they have different numbers of neutrons; U-235 has 143 neutrons. Uranium is a radioactive element, meaning its nucleus breaks down. U-235 will undergo fission if bombarded by a neutron and yield significant amounts of energy. Enriching uranium means that the amount of fissionable U-235 present is more concentrated than that which naturally occurs. Power plants require uranium enriched to 3% to 4%, whereas atomic weapons require enrichment at over 90 percent U-235. Alfred Nier’s work during the Manhattan Project helped prove U-235 was the fissionable isotope of uranium and later helped make enrichment possible.


ASMS, or the American Society for Mass Spectrometry, was formed in 1969 and sponsors an annual conference and various meetings and courses aimed at promoting knowledge of the field. Currently ASMS has 7,500 scientists as members from academic, industrial, and government laboratories.

ASTM Committee E-14 was the American Society for Testing and Materials Committee specifically for mass spectrometry in 1952. It was the basis for the formation of the American Society for Mass Spectrometry.

CEC, Consolidated Engineering Corporation, was operational from 1937 to 1960. It was a chemical instrument manufacturer and was a leader in the manufacture of commercial mass spectrometers, including its 21-103C. Seymour Meyerson, Sibyl Rock, and other prominent leaders in mass spectrometry were all part of CEC’s mass-spectrometry operations. CEC was dissolved in 1960 when it became part of Bell and Howell Corporation.

EPA, the U.S. Environmental Protection Agency, sets out to protect human health and the environment. It has used mass spectrometry, especially GC-MS, in various ways, including in testing drinking water and air quality, and for the presence of various pollutants in water, soil, and other materials.

Humble Oil and Refining Company, later a subsidiary of Standard Oil of New Jersey and ExxonMobil, was an oil company founded in Texas in 1911. An affiliate of Standard Oil beginning in 1919, Humble enjoyed relative autonomy until 1959 when Standard Oil took complete control of the company. Humble was one of the early petrochemical companies interested in using mass spectrometry. As head of the mass-spectrometry group, Joe L. Franklin led a team that did both basic mass-spectrometry research and the analytical work the refinery required on a day-to-day basis.

Manhattan Project is the name for the secret scientific undertaking in the United States to develop an atomic bomb. The name derives from the Manhattan Engineer District in New York City where the Army Corps of Engineers, North Atlantic Division, was headquartered.

Metropolitan Vickers introduced their first commercial mass spectrometer, the MS-2, in England in 1950.

National Bureau of Standards, now known as the National Institute of Standards and Technology (NIST), is a measurement standards laboratory. The organization’s mission has traditionally been to promote American innovation and industry. Within the mass-spectrometry community the NIST has been a hub for research with its analytical mass-spectrometry group.

Pittcon, or the Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, is a large technical conference and trade show held annually since 1950. Pittcon serves two audiences: the companies selling research instrumentation and the research scientists who use that instrumentation. Many of CHF’s oral history interviewees discuss their experiences at Pittcon over the years in their oral history interviews.

Rockefeller University is a private institution dedicated solely to biomedical research. In the 1970s and 1980s mass-spectrometry research as it related to biomedical applications flourished there. Frank Fields arrived at Rockefeller in the 1970s to pursue mass-spectrometry work related to biomedicine, and his postdoc, Brian Chait, worked to build the program at Rockefeller. Chait built a MALDI instrument at Fields’s insistence. Today, Chait runs the Laboratory of Mass Spectrometry and Gaseous Ion Chemistry.

Standard Oil of Indiana, later Amoco, was the Midwestern offshoot of the Standard Oil breakup. Seymour Meyerson and other Standard Oil of Indiana chemists, based in Whiting, Indiana, were early adopters of mass spectrometry.

Standard Oil of New Jersey, later ExxonMobil, was the offshoot  of the Standard Oil breakup that encompassed much of the eastern United States.

Westinghouse Electric and Manufacturing Company was one of the first companies to manufacture mass spectrometers commercially, as well as being a rival of CEC. Its first instrument, a portable magnetic sector, was commercially introduced in 1941. Westinghouse withdrew from the instrument business in the late 1940s.

Oral History Interviewees

John H. Beynon (1923– ) is a mass spectrometrist principally working in Wales. Beynon was a longtime Imperial Chemical Industries employee who was charged with building a mass spectrometer in his first year there—in 1947—with no working knowledge of the instrumentation. After that time Beynon would become an integral part of the new field. Beynon went on to Swansea University, where he founded the Mass Spectrometry Unit. Beynon also was a founding member of the British Mass Spectrometry Society and the American Society for Mass Spectrometry.

Klaus Biemann (1926– ) is a chemist and is often called the father of organic mass spectrometry. In the late 1950s Biemann set out to use the instrument to determine the structure of natural products—a rarity in a field then dominated by petroleum research. Biemann’s work at the Massachusetts Institute of Technology in determining the structure and sequencing of peptides laid the groundwork for future biochemical mass spectrometry.

Vincent J. Coates (1925– ) is an engineer and noted instrument developer. Coates began his career at Perkin Elmer and founded Nanometrics Incorporated in 1975, which became an important metrology and process control company.

Mildred Cohn (1913–2009) was a biochemist and early adopter of mass spectrometry for biological-related problems. Cohn received her Ph.D. under Harold Urey and built her own instrument in Carl Cori’s lab at Washington University in St. Louis. In her career Cohn was a woman of many scientist “firsts,” including becoming the first female president of the American Society for Biochemistry and Molecular Biology and the first female career investigator of the American Heart Association.

Frank H. Field (1922– ) is a chemist and a pioneer of the mass-spectrometry field. Field began his career at Humble Oil and, together with Joe Franklin, furthered the field of gaseous-ion chemistry and wrote a book on the subject. With Burnaby Munson, Field developed chemical ionization. Field moved on from Humble and joined Rockefeller University in 1970, where he directed mass-spectrometry research until his retirement in 1989.

Robert E. Finnigan (1927– ) is an electrical engineer noted for his work in building and improving instrumentation and process control, starting with the development of a computer-controlled quadrupole mass spectrometer. He founded his company, Finnigan Corporation, in 1967 and continued manufacturing instrumentation. His company’s instrumentation began with the prototype quadrupole GC-MS and continued on to establish itself as a leader in GC-MS systems.

David M. Hercules (1932– ) is an analytical chemist who has served on the faculty at various universities, including Lehigh Univeristy, the Massachusetts Institute of Technology, and Vanderbilt University. Hercules completed early research on fluorescence and chemiluminescence and became fully immersed in mass spectrometry later, working in surface science and solid-state mass spectrometry. Hercules’s later research involved developing new instrumental analytical techniques and characterizing proteins with mass spectrometry.

Richard E. Honig (1917–2001) was a scientist and leader of the mass-spectrometry community—he became president of the ASMS in 1970—known for his identification of vapor pressures of many chemical elements and the reference table for those results. Honig worked with secondary-ion mass spectrometry first at R.C.A. Laboratories (now Sarnoff Laboratories) and expanded the applications of mass spectrometry to semiconductor materials.

Keith R. Jennings (1932– ) is a chemist and mass spectrometrist in Great Britain. Jennings has spent his research career in academia, first at the University of Sheffield and later the University of Warwick. Jennings has pursued mass-spectrometry research related to gas kinetics, fluorine compounds, and metastable transitions; he has also completed significant research on ion cyclotron resonance, time-dependent ion fragmentation, and gas-phase ion chemistry.

Henry Earl Lumpkin (1920– ) is a chemist who spent a significant portion of his career at Humble Oil and later retired from Exxon Research and Engineering Company. Lumpkin was a leader in the mass-spectrometry community and served as the chairman of the ASTM E-14 Committee.

Fred W. McLafferty (1923– ) is a chemist and mass-spectrometry pioneer noted for the McLafferty rearrangement, a reaction observed in mass spectrometry. McLafferty described this reaction in 1959: the ionic rearrangement involves a keto-group and a g-hydrogen. McLafferty also pioneered the technique of GC-MS with Roland Gohlke. McLafferty began his career in industry at The Dow Chemical Company, and then moved on to Purdue University and later Cornell University.

Seymour Meyerson (1916– ) is a chemist and mass spectrometrist who encountered his first mass spectrometer during World War II. Meyerson was a longtime Standard Oil of Indiana researcher. He worked on both basic research and instrumentation and was a frequent collaborator with various other mass spectrometrists.

Foil Miller (1916– ) is a chemist and retired professor at the University of Pittsburgh. Miller formerly directed the spectroscopy lab there and dedicated his research primarily to Ramen and infrared spectroscopy.

Burnaby Munson (1933– ) is a physical chemist who first worked in industry for Esso and later moved on to academia at the University of Delaware. While at Esso, Munson and Frank Field developed chemical ionization.

Alfred O. C. Nier (1911–1994) was a physicist and one of the earliest mass-spectrometry pioneers. Nier was the primary developer of mass spectrometers and the “go-to” expert for early adopters of the technology in the prewar and World War II eras. Nier’s expertise was far-reaching, and his research on isotopes led to a request to prepare a pure sample of U-235 so that John Dunning could demonstrate it was the isotope responsible for nuclear fission. Nier continued work in the Manhattan Project, leading instrument development at Kellex Corporation and developing a helium leak detector for gaseous-diffusion plants. After the war Nier focused on such topics as geochronology and space science, and designed the mass spectrometers that traveled on the Viking mission.

Marvin Vestal (1934– ) is a scientist who has used mass spectrometry both in industry and in academia. Vestal spent time at the University of Houston and various industry labs, and founded his own companies, Vestac, Virgin Instruments, and SimulTOF, among others, each dedicated to mass-spectrometry instrumentation. Vestal invented the thermospray method of ionization, the most commonly used LC-MS interface before John Fenn’s electrospray ionization. Vestal also developed the first MALDI-ToF mass spectrometers and commercialized ToF-ToF instrumentation.

Harland G. Wood (1907–1991) was a biochemist who spent a significant portion of his career at Case Western Reserve University, where he was the first director of the Department of Biochemistry. Wood set up a mass spectrometer early in his research career at Case Western and used isotopes for his metabolic research. Wood proved that bacteria, animals, and humans alike all used carbon dioxide.


Francis William Aston (1877–1945) was a chemist and physicist who worked under J. J. Thomson at Cavendish Laboratory in Cambridge, United Kingdom. Aston, building on the work of Thomson, constructed the first fully functional mass spectrometer in 1919, for which he won a Nobel Prize in Chemistry in 1922. He continued isotope work, and identified isotopes of chlorine, bromine, and krypton, in the process proving that these elements were composed of a combination of isotopes. Alfred Nier considered Aston's greatest achievement the determination that atomic masses were not whole numbers.

Arthur Jeffrey Dempster (1886–1950) was a physicist and peer of Aston who worked in Canada. In 1918 Dempster developed the first modern mass spectrometer, which was 100 times more accurate than previous versions of the instrument, such as Thomson’s. Dempster's breakthrough was achieved without the use of photographic plates, favoring electrical detection methods.  Dempster also discovered the uranium isotope U-235 in 1935, which paved the way for fission research.

Henry M. Fales (1927-2010) was a mass spectrometrist and organic chemist, noted for his pioneering work in bioanalytical mass spectrometry. Fales spent his career at the National Heart, Lung, and Blood Institute at the National Institutes of Health and co-authored over 350 publications.

John B. Fenn (1917–2010) was an analytical chemist and inventor of the electrospray ionization technique, which garnered him a Nobel Prize in Chemistry in 2002, which he shared with Koichi Tanaka. Fenn began his career in industry, spent time at Monsanto and other labs, and moved on to academia, at Princeton, Virginia Commonwealth, and Yale universities.

Joe L. Franklin (1906–1982) was a chemist and central figure in developing the field of mass spectrometry. The early part of his career was spent at Humble Oil, where he headed the company’s mass-spectrometry group, which included people like Frank Field, Burnaby Munson, and Earl Lumpkin. Franklin created a Humble Lecture Series and placed emphasis on basic research, which led to various breakthroughs in gaseous-ion chemistry. Franklin became the first president of the ASMS in 1969 and authored approximately 200 papers and numerous books dedicated to mass spectrometry. Franklin left Humble for Rice University in 1963.

Ernest O. Lawrence (1901–1958) was a physicist, primarily based at the University of California, Berkeley, who invented, improved, and used the cyclotron and played a significant role in the Manhattan Project’s uranium isotope research. Lawrence ran the radiation lab and later manufactured calutrons for uranium enrichment during the Manhattan Project. Lawrence received a Nobel Prize in Physics in 1939 for his work with the cyclotron; element 103 is named lawrencium in his honor.

Wolfgang Paul (1913–1993) was a German physicist and winner of the 1989 Nobel Prize in Physics, which he shared with Hans Georg Demelt. Paul is best known for his codiscovery of the nonmagnetic quadrupole mass filter; this filter laid the groundwork for the ion trap.

Sibyl Rock (unknown-1981) was a mathematician who worked for Consolidated Engineering Corporation during the beginnings of its development of mass spectrometers. She joined the company, at that time United Geophysical Company, in 1938. Rock’s notable tasks included establishing mathematical techniques to analyze mass-spectrometer data, writing computing manuals, assisting customers, and serving as the intermediary between the engineers who developed the instrumentation and the customers who used the product. Rock also, along with Clifford Berry, helped develop an analog computer to assist with the complicated calculations mass-spectrometry data required.

Koichi Tanaka (1959– ) is a Japanese engineer who developed soft laser desorption, for which he won a Nobel Prize in Chemistry in 2002 (shared with John Fenn). Tanaka proved soft laser desorption could be used to ionize large biological molecules like proteins without fragmentation.

J. J. Thomson (1856–1940) was a physicist known for the discovery of the electron and of isotopes, as well as for the development of the mass spectrograph (via his separation of neon isotopes). Thomson’s methods and instrumentation were furthered by Francis W. Aston, his student, and Arthur J. Dempster. Thomson received the Nobel Prize in Physics in 1906.

Harold C. Urey (1893–1981) was a physical chemist noted for his pioneering work in isotopes as well as mass spectrometry. He won a Nobel Prize in Chemistry in 1934 for his discovery of deuterium. Urey was the Ph.D. adviser of Mildred Cohn, who under his guidance studied various methods of separating isotopes of carbon and oxygen-18 exchange reactions. Urey was a prominent figure in the Manhattan Project, as his lab developed the gaseous-diffusion method for uranium enrichment. After the war Urey focused on developing the field of cosmochemistry.


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