History of Mass Spectrometry - Content
"Instruments of Science: An Historical Encyclopedia."
Robert Bud and Deborah Jean Warner, editors. 1998.
New York & London: The Science Museum, London, and The National Museum of American History,
Smithsonian Institution, in association with Garland Publishing, Inc. Pages 552-56.
Contributed on November 15, 1999
Mass spectrometers constitute a large, very diverse, and widely employed and produced class or family of instruments. It is likely that no other type of complex instrument has been as important for so many fields of science in the twentieth century. The defining characteristics of this vast range of devices are operational (or functional) and hypothetical in nature, more than material or structural. As Cooks, Busch, and Glish stated in 1983; "Instruments that go by the name of mass spectrometer are appearing in ever-increasing variety with an astonishing range of applications." A mass spectrometer is whatever operates by process that could be used to produce a mass spectrum, no matter how different its design and processes may be from those of any other mass spectrometer. The mass spectrum of any substance or mixture is a record of the distribution of materials of different masses that can be found when a sample is ionized. The instruments were first created as experiments early in the twentieth century, and proliferated most dramatically both in terms of new types developed and number of machines in use during the last third of the century.
The heart of any mass spectrometer is its analyzer. This is a region of high vacuum through which ions extracted from sample substances are made to move by some kind or kinds of static or oscillating electromagnetic field. Ions of different mass, velocity, and charge are moved differently by the field(s). Taking account of velocity and charge effects, ions of specific masses can be separately collected if the field is carefully controlled, and their numbers and masses precisely determined. Mass spectrometers accordingly must have vacuum systems and arrangements to produce, control, and vary the analyzing field(s), as well as ways to introduce samples, to create ions from the sample and get them into the analyzer, to collect analyzed ions, and to display or record the results. Within these shared requirements, different types, arrangements, and uses of analyzers, different sources of samples, and different modes of ionization have resulted in a remarkably extensive set of different types of mass spectrometers, each of which could warrant its own entry.
"Mass spectrometry," (MS) refers to these machines, to information about them, and to development of techniques of employing them in the several branches of natural science and industry; it labels as well a range of research areas in various fields of chemistry that have been intensively developed with these devices. Some significant instruments earlier in the century that used photographic plates to collect ions were called mass "spectrographs," as distinct from "spectrometers," while "mass spectroscope" and "mass spectroscopy" served as inclusive labels, but that distinction and terminology have become uncommon except in reference works.
The origin of all mass spectrometers was the turn-of-the-century research on kanalstrahlen, the streams of positive ions formed from residual gases in cathode ray tubs, initially found coming through channels cut in the cathode plate. Local magnetic and electrostatic fields differentially deflected these positive rays depending on their mass; they made diverging traces on a photographic plate. J. J. Thomson was the crucial experimenter, and the first evidence for the existence of stable (nonradioactive) isotopes was the most dramatic result. Since World War I, a rough cycle of five recurrent, overlapping processes, phases, or stages of development of mass spectrometers is discernible. These can conveniently be called demonstration, familiarization, routinization, radiation, and diversification. In the first, a mass spectrometer was the experiment; instead of an integrated unit, an instrument used to do work defined in other terms, it was the arrangement of equipment composing essentially the whole experiment. Successful experiments provided particular results, but also demonstrated that apparatus of this design could be made to work. An experimental arrangement that was successfully copied for use in further research (and named) made more scientists familiar with its potentials. When a design was standardized and treated as a reliable entity by more people in more contexts, it became a routine instrument. The instruments were spread in wider areas of applications where their basic viability was not at issue. Inevitable limitations spurred trials of alternative components and designs, generating diverse types of equipment that in turn needed demonstration of viability, founding new lines of instrument development.
The clear demonstration of mass spectrometry came at the end of World War I by Francis W. Aston (who has helped design Thomson's equipment and make it work) and Arthur J. Dempster, in Cambridge and Chicago, respectively. Dempster used a magnetic analyzer that focused ions into an electrical collector, while Aston used both electrostatic and magnetic fields to focus ions on a photographic plate. Their continued work, along with that of Joseph H. E. Mattauch, R. F. K. Herzog, Kenneth T. Bainbridge, and Alfred O. C. Nier, among others, produced major results in atomic and nuclear physics, including discovery of the existence, and measurement of the abundance and masses, of numerous isotopes and the determination of their nuclear stabilities and energies. Such work led to Aston's Nobel Prize (in chemistry) and created some familiarity with such equipment in the 1930s.
Stabilizing the esoteric and "touchy" experimental apparatus into routine instruments and applying them to new kinds of tasks required extensive effort. Most influential in the first cycle were the papers, devices, and students of Alfred Nier (often cooperating with various others) from the end of the 1930s to the early 1950s. Nier incorporated recent developments in vacuum technologies and electronics for power supplies, ion detection, and so on, while providing the foundation for determining the age of the earth. His work significantly improved magnetic focusing instruments, establishing that good results could be obtained with ions being sent merely through a comparatively modest wedge-shaped sector magnetic field rather than having as their entire path a semicircle within an analyzer completely confined between the poles of a massive magnet (prior standard practice). A more practical electron-bombardment ion sources, along with several other crucial aspects of construction and technique, also brought improvements in performance, convenience, and costs. Double-focusing machines, attaining greater precision by adding an electrostatic analyzer, were also greatly refined. During these years machines and expertise spread outward from a few physics laboratories, founding precise geochronology and cosmochronology, facilitating isotopic tracer studies, providing the analytic and vacuum controls that made the Manhattan Project's uranium enrichment facilities workable, and making the instruments common in the petroleum industry. Commercial production of mass spectrometers began in the 1940s.
By 1953, convenient handbooks of design and practice had appeared in the United States, the U. K., Germany, and Russia, and annual conferences of mass spectrometrists began. Instrument designs created for isotopic analysis soon were applied to analysis of complex organic molecules. Meanwhile, the demonstration of quite different instrument types was well underway. Analyzers based on the different times of flight over a set path for different accelerated ions, and others using various types and combinations of fields had some success. In 1953 Wolfgang Paul and his colleagues initiated development of what became the most common type of those mass spectrometers having no magnetic field, the quadrupole mass analyzer (and ion trap), using crossed radio-frequency and electrostatic fields. This eventuated in Paul's Nobel Prize (in physics). The middle and later 1950s saw the first wave of effort to concatenate mass spectrometer with other significant types of instruments, in this case creating various types of gas chromatograph mass spectrometers, which have become the most widely sold of all mass spectrometer instrumentation.
Despite the growing familiarity of these and other types, the great majority of mass spectrometers in service well into the 1960s were magnetic sector or double-focusing machines, mostly producing ions by electron bombardment. A score of companies marketed the standard models, costing thousands and tens of thousands of dollars. The spread of mass spectrometers from physics into geology, chemistry, physiology, and other industries continued. They performed gas analysis in venues as disparate as hospital operating rooms and rockets in the upper atmosphere. From the perspective of earlier decades, their numbers and impact seemed to be growing quite rapidly, but by comparison with later decades, the expansion of numbers, uses, and types had hardly started.
Since then a host of workers have transformed mass spectrometers, and founded an array of new families of machines of vastly enhanced scope and precision, based particularly on different approaches to ion production but also on other modes of analysis. Cooks, Busch, and Glish rightly noted that "latitude in methodology, and characteristics of the hardware which demand interaction with the equipment, have made mass spectroscopists likely to modify instrumentation or to develop entirely new instruments." Each new type has grown (despite the substantial cost of the machines), being commercialized in turn and approaching or surpassing the total growth of the 1950s; three score companies were in the market early in the 1990s.
In the 1960s, chemical ionization mass spectrometry (or CIMS) and field desorption MS (FDMS) emerged, and several mass spectrometry journals began publication. In the 1970s, secondary ionization MS, Fourier transform MS, plasma desorption MS, electrohydrodynamic MS, laser desorption MS, thermal desorption MS, spark source MS, and glow discharge MS were invented or developed significantly, and additional journals were started. At the same time, the scale of the machines went to opposite extremes, with the quest for high performance and the development of tandem MS (in which machines are combined, one serving as a source for the next) leading to large "grand scale" instruments, with particle accelerators being used as new forms of mass spectrometer, with instruments being shrunk for portable medical uses, and others miniaturized for missions to Mars, Venus, Halley's comet, and beyond.
Clearly identifiable developments of the 1980s, beyond still
more new journals, included laser resonance ionization MS,
matrix-assisted laser desorption MS, fast atom bombardment MS and
its continuous flow transformation, the astonishingly sudden
development of ion trap MS, a dramatic advance in electrospray
MS, as well as a considerable development of liquid
chromatography MS. These lists are hardly complete, nor do they
include combinations. One review found over ten new types of
machine per year appearing in the literature
at the start of the 1990s. Yet earlier designs have not been dropped; what are called "Nier-machines" and quadrupoles remain very numerous and productive. And in a crucial sense all these diversified instruments still compose a single class, sharing their fundamental functional characteristic; they all sort ions by mass. Although the inferences drawn from their data vary enormously, they are many different ways of producing the same basic kind of information.
Originally designed to work with atomic isotopes or comparatively light gases, mass spectrometers now deal with a range of substances that is almost unlimited. By the early 1960s the ever-increasing precision in measurement of isotopic masses and abundances drove physicists and chemists to new international standards for atomic mass and weight. Capable of precision to a part in a billion in dealing with the mass of an atom, the instruments also provide extremely precise measurements when dealing with ever larger molecules, along with a flood of structural information, all on the basis of minuscule samples. In the early 1980s it seemed amazing that mass spectrometers could handle ions even with a molecular weight of over 10,000, yet by the 1990s the proven range extended to several hundred thousand, and no material seemed so involatile or unstable as to be beyond the capabilities of all the techniques.
Several applications of mass spectrometers have been mentioned above. To be comprehensive about the uses to which these instruments have been put and the results achieved, at even the most superficial level, requires little less than a survey of the full range of natural scientific endeavor in the twentieth century and some account as well of a wide range of medical, industrial, and governmental concerns. A partial list is all that is suitable here.
Analyses by mass spectrometers are crucial for astronomical studies of the components of our solar system, for all geochronology (including the histories of climates and of life's evolution), for isotope archaeology, and for much else in geophysics and geochemistry as well. No less than the geological fields, chemistry is "awash" in mass spectrometers, for their use constitutes both one of the most precise modes of experimentation and most powerful methods of chemical analysis. The same can be said increasingly of their biological, biochemical, and medical uses. Mass spectrometry is employed in the identification of complex natural products and of metabolic pathways. The capabilities of detecting and identifying mere trace presences in tiny samples have led to use of mass spectrometers in toxicology, drug abuse diagnosis, environmental pollution monitoring, and elsewhere. These instruments have long played a significant role in materials analysis and process monitoring in the petroleum, chemical, and pharmaceutical industries, and they are being used in food processing and electronics industries. Mass spectrometers are the key to non-invasive (thus politically viable) international monitoring of nuclear facilities. They are even returning to some prominence in physics, where they had become less central since determining the masses of stable and unstable nuclides. They are becoming important tools in studies of surface phenomena, and of the solid state several atoms deep, which may well lead to further industrial applications. Finally, mass spectrometers are the key to coping with next to nothing at all, as leak detectors and as the most sensitive gauges for the most extreme vacua we can produce.
Despite this importance, mass spectrometers have received hardly any attention from historians of science and technology, and remain almost totally unknown among the generally educated public. A notable chronicle literature exists, but the history remains largely unexplored. Even in as laudatory a work as Claude Allègre's survey From Stone to Star, in which almost all the growth of our understanding of how the solar system, the earth, the atmosphere, and the biosphere all developed is ascribed to accurate mass spectrometry, the instruments themselves are left highly praised yet essentially undiscussed and invisible.
Cooks, R. Graham, Kenneth L. Busch, and G. L. Glish.
"Mass Spectrometry: Analytical Capabilities and Potentials."
Science 222 (1983): 273-91.
"Mass Spectrometric Analysis of Inorganic Solids-- The Historical Background."
In Inorganic Mass Spectrometry, edited by F. Adams, R. Gijbels, and R. Van
Grieken, 1-15. New York: Wiley, 1988.
"J. J. Thomson's Work on Positive Rays, 1906-1914."
Historical Studies in the Physical and Biological Sciences 18 (1988): 265-310.
"Zur Entwicklung der Massenspektroskopie von den Anfängen bis zur
Strukturaufklärung organischer Verbindungen."
NTM~Schriftenreihe Geschichte der Naturwissenschaft, Technik, und Medizin 24
Svec, Harry J.
"Mass Spectroscopy--Ways and Means: A Historical Prospectus."
International Journal of Mass Spectrometry and Ion Processes 66 (1985): 3-29.
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Senior Editor, Chemical & Engineering News
Contributed on May 26, 1998
Since its beginnings about 100 years ago, mass spectrometry (MS) has become a virtually ubiquitous research tool. Scientific breakthroughs made possible by MS have included the discovery of isotopes, the exact determination of atomic weights, the characterization of new elements, quantitative gas analysis, stable isotope labeling, fast identification of trace pollutants and drugs, and the characterization of molecular structure, says chemistry professor Fred W. McLafferty of Cornell University. This article covers key developments in MS techniques and instrumentation.
The history of MS began with Sir J. J. Thomson of the Cavendish Laboratory of the University of Cambridge, whose studies on electrical discharges in gases led to the discovery of the electron in 1897. In the first decade of the 20th century, Thomson went on to construct the first mass spectrometer (then called a parabola spectrograph) for the determination of mass-to-charge ratios of ions. In this instrument, ions generated in discharge tubes were passed into electric and magnetic fields, which made the ions move through parabolic trajectories. The rays were then detected on a fluorescent screen or photographic plate. Thomson received the 1906 Nobel Prize in Physics in recognition of the great merits of his theoretical and experimental investigations on the conduction of electricity by gases.
Thomson's protégé, Francis W. Aston of the University of Cambridge, designed a mass spectrometer in which ions were dispersed by mass and focused by velocity--which improved MS resolving power by an order of magnitude over the resolution Thomson had been able to achieve. Aston received the 1922 Nobel Prize in Chemistry for isotope studies carried out with this type of instrument.
Around 1920, professor of physics A. J. Dempster of the University of Chicago developed a magnetic deflection instrument with direction focusing--a format later adopted commercially and still in use today. Dempster also developed the first electron impact source, which ionizes volatilized molecules with a beam of electrons from a hot wire filament. Electron impact ion sources are still very widely used in modern mass spectrometers.
In the 1940s the dominant commercial instrument in the U.S. was the Model 21-101 analytical mass spectrometer, manufactured by Consolidated Engineering Corporation (Pasadena, Calif.). The 21-101, which was based on Dempster?s single-focusing design, was used in the petroleum industry during World War II for quantitative analysis of organic gas mixtures.
The magnetic sector type instrument was also very important in the early 1940s, says McLafferty. This instrument was developed by Professor Alfred O. C. Nier [of the department of physics at the University of Minnesota] during World War II to do isotopic analysis, with separation of uranium-235 from uranium-238 obviously of special importance. Nier isolated by MS the first sample of plutonium (10-9 g), for its first actual characterization. The Calutron, a three-story-high version of Nier's sector instrument, separated uranium-235 for the first atomic bomb. The gaseous diffusion plant at Oak Ridge, Tenn., supplied uranium-235 for the subsequent explosions.
Mass spectrometers were manufactured during or just after World War II by several companies: Metropolitan Vickers in England (later Associated Electrical Industries, then VG and Micromass); Westinghouse and General Electric in the U.S. (in addition to Consolidated Engineering, mentioned above); and Atlas-Werke (later MAT [Mess und Analysentechnik]) in Germany.
High mass-resolution double-focusing instruments, in which ions are focused for both direction and velocity, were developed for the purpose of accurately determining the exact atomic weights of the elements and their isotopes, says chemistry professor Klaus Biemann of the Massachusetts Institute of Technology. One type of double-focusing instrument was developed in the 1930s by professor Josef Mattauch and his student Richard F. K. Herzog of the physics department of the University of Vienna, Austria, and another design was developed by Nier and physicist E. G. Johnson of the University of Minnesota.
By the 1950s it became clear that the high resolving power of the Mattauch-Herzog and Nier-Johnson geometries would be very useful for the identification of organic compounds. says Biemann. John Beynon of Imperial Chemical Industries (later chemistry professor at University College Swansea, Wales) made major contributions in this area.
Magnetic deflection instruments--both single-focusing (of the Dempster design) and double-focusing (of the Mattauch-Herzog design but especially of the Nier-Johnson design)--dominated high performance mass spectrometry well into the 1990s, says Biemann. The cheaper time-of-flight (TOF), quadrupole, and ion trap mass spectrometers evolved in parallel to the preponderant and more expensive magnetic deflection instruments.
The concept of TOF MS was proposed in 1946 by William E. Stephens of the University of Pennsylvania. In a TOF analyzer, ions are separated by differences in their velocities as they move in a straight path toward a collector in order of increasing mass-to-charge ratio. TOF MS is fast, it is applicable to chromatographic detection, and it is now used for the determination of large biomolecules, among other applications.
TOF instruments were first designed and constructed in the
late 1940s and mid-1950s. Key advances were made by William C.
Wiley and I. H. McLaren of Bendix Corp., Detroit, Mich.--the
first company to commercialize TOF mass spectrometers. According
to pharmacology professor Robert J. Cotter of Johns Hopkins
University School of Medicine, Wiley and McLaren devised a
focusing scheme that improved mass resolution by simultaneously correcting for the initial spatial and kinetic energy distributions of the ions. Mass resolution was also greatly improved by the 1974 invention by Boris A. Mamyrin [of the Physical-Technical Institute, Leningrad, Soviet Union] of the reflectron, which corrects for the effects of the kinetic energy distribution of the ions.
When commerical TOF instruments first came out their performance in resolution was so poor that they never lived up to even single-focusing magnetic instruments, says Biemann. However, he adds, this analyzer has been greatly improved recently...to almost match the most sophisticated, and very expensive, double-focusing mass spectrometers.
Ion cyclotron resonance MS (ICR MS) is a technique in which ions are subjected to a simultaneous radiofrequency electric field and a uniform magnetic field, causing them to follow spiral paths in an analyzer chamber. By scanning the radiofrequency or magnetic field, the ions can be detected sequentially.
ICR MS was brought to the attention of chemists in the middle to late ?60s through the work of electrical and computer engineering professor Darold C. Wobschall of the State University of New York at Buffalo, Peter M. Llewellyn of Varian Associates (Palo Alto, Calif.), and chemistry professor John D. Baldeschwieler at Stanford University (now at California Institute of Technology). The technique is particularly applicable to the characterization of ion-molecule reactions.
In 1974, Melvin B. Comisarow and Alan G. Marshall of the department of chemistry at the University of British Columbia, Vancouver, Canada (Marshall is now a chemistry professor at Florida State University, Tallahassee) revolutionized ICR by developing Fourier transform ICR mass spectrometry (FT-ICR MS). The major advantage of FT-ICR MS is that it allows many different ions to be determined at once, instead of one at a time. The technique is also known for its mass resolution, which is higher than that of any other type of mass spectrometer.
The direct coupling of gas chromatography (GC) and TOF MS was achieved in the mid-1950s by Roland S. Gohlke and McLafferty of Dow Chemical Co., Midland, Mich., in collaboration with Wiley, McLaren, and Dan Harrington at Bendix. At about the same time, GC was coupled to a magnetic sector instrument by Joseph C. Holmes and Frank A. Morrell of Phillip Morris, Richmond, Va., among others.
The great utility of modern GC-MS was made possible by the advent in the 1960s of carrier gas separators that removed the GC carrier gas prior to introduction of a sample into the high-vacuum mass spectrometer. Separators were developed independently by Einar Stenhagen (then at Uppsala University, later at Göteborg University, Sweden); Ragnar Ryhage of the Karolinska Institute, Stockholm; and Biemann.
The use of mass spectrometers as GC and liquid chromatography (LC) detectors is very widespread today. Applications of modern GC- and LC-MS include environmental analysis, forensics, drug testing, and pharmacological studies.
One type of instrument that proved to be ideal for coupling to a GC was the quadrupole mass filter, which was first reported in the mid-1950s by the group of physics professor Wolfgang Paul of the University of Bonn, who shared the 1989 Nobel Prize in Physics for his work on ion trapping. In a quadrupole device, a quadrupolar electrical field (comprising radiofrequency and direct-current components) is used to separate ions.
Although quadrupole mass spectrometers are not as accurate and precise as double-focusing instruments, they are fast, which is important for GC detection. But quadrupole instruments have also become very popular as standalone spectrometers. Certainly, the number of quadrupoles sold and in use today far exceeds the total of all other types of mass spectrometers, says McLafferty.
Another instrument that Paul originated was the quadrupole ion trap, which can trap and mass-analyze ions using a three-dimensional quadrupolar radiofrequency electric field. An ion trap system was first introduced commercially in 1983 by Finnigan MAT (San Jose, Calif.), originally as a GC detector. Its design was based on technology developed by Finnigan research scientist George C. Stafford and coworkers. In this instrument, ions of increasing mass-to-charge ratio successively become unstable as the radiofrequency voltage is scanned. Stafford's ?mass-selective instability? scanning...converted quadrupole traps from a curiosity to a useful mass spectrometer, says Comisarow. Today, ion trap instruments serve not only as GC detectors but also as LC-MS detectors and standalone mass spectrometers.
Novel ionization techniques have extended the capabilities of MS beyond those available with the electron impact source. Field ionization, in which a sample is ionized in a strong electric field gradient, was first observed in 1953 by Erwin W. Müller of the department of physics at Pennsylvania State University, University Park. A variation, field desorption--put into practice by Hans D. Beckey of the Institute of Physical Chemistry at the University of Bonn, Germany, in 1959--widened the range of MS by making it possible to study compounds that were involatile or thermally unstable. Field desorption really opened the door for biological MS by demonstrating feasibility, says chemistry professor Ronald D. Macfarlane of Texas A&M University, College Station.
Chemical ionization, a process in which ionization occurs as a result of ion-molecule reactions, was first observed in 1913 by Thomson in hydrogen gas, but he didn?t understand the phenomenon at that time and didn?t call it chemical ionization. Chemical ionization MS was first extensively described, characterized, and patented in the mid-1960s by Frank H. Field and Burnaby Munson, then at Esso Research Laboratories. Field is now professor emeritus at Rockefeller University, New York City, and Munson is a professor of chemistry at the University of Delaware. Chemical ionization MS is a soft ionization technique in which volatilized molecules are ionized by reaction with reagent gas ions. This process is gentler than electron impact ionization and generates fewer fragment ions.
In tandem MS (MS-MS), a precursor ion is mass-selected and typically fragmented by collision-induced dissociation (also called collisionally activated dissociation), followed by mass analysis of the resulting product ions. The technique requires two mass analyzers in series (or a single mass analyzer that can be used sequentially) to analyze the precursor and product ions. Tandem MS provides structural information by establishing relationships between precursor ions and their fragmentation products. The collision-induced dissociation procedure was introduced in 1968 by chemistry professors Keith R. Jennings of the University of Warwick, England, and McLafferty, who was then at Purdue University.
The combination of the newer soft ionization methods with collision-induced dissociation is what gives tandem MS its power in the analysis of mixtures--a feature first recognized by chemistry professor R. Graham Cooks of Purdue University, West Lafayette, Ind.
One of the most popular types of tandem MS instrument is the
triple quadrupole mass spectrometer, invented at Michigan State
University by Richard A. Yost (now a chemistry professor at the
University of Florida, Gainesville) and chemistry professor
Christie G. Enke (now at the University of New Mexico,
Albuquerque). James D. Morrison of Latrobe University, Melbourne,
helped Yost and Enke reduce the technique to practice. Tandem MS was really popularized by triple-stage quadrupoles introduced first by Finnigan and Sciex (in 1980), followed by Extranuclear and Nermag, and some time later by VG, says Michael S. Story of ThermoQuest Corp., San Jose, Calif.
A variety of desorption MS techniques have greatly advanced the capabilities of MS. The first of these was secondary ion MS (SIMS), a technique in which a beam of ions is used to ionize molecules on a surface. Richard E. Honig of RCA Laboratories, Princeton, N.J., was the main driving force in the development of SIMS as an analytical method in the 1950s, says Cooks.
Dempster first demonstrated the potential value of spark-source MS (SSMS), but that technique did not come of age until the 1950s, when N. B. Hannay described an SSMS instrument for semiconductor analysis. In SSMS, electrical discharges (sparks) are used to desorb ions from samples. The technique was widely used for trace analysis of a wide range of sample types.
In the 1960s, Georges Slodzian of the University of Paris developed the ion microscope, a SIMS instrument that combined spatial and depth resolution along with isotopic analysis, making it possible to obtain high-resolution chemical images. And physics professor Alfred Benninghoven and coworkers at the University of Cologne, Germany (now at the University of Münster, Germany), developed SIMS techniques for analyzing organic compounds.
Other desorption techniques include plasma desorption MS (PDMS) and laser desorption MS (LDMS). PDMS uses very high-energy ions to desorb and ionize molecules in solid-film samples. It was developed in the 1970s by Macfarlane and coworkers. According to Macfarlane, PDMS was the first MS method to demonstrate feasibility for studying high molecular weight proteins and complex antibiotics. In LDMS, a photon beam is used to desorb sample molecules. LDMS was developed in the late 1970s by Maarten A. Posthumus, Piet G. Kistemaker, and Henk L. C. Meuzelaar of the FOM Institute for Atomic and Molecular Physics, Amsterdam, the Netherlands.
In 1981 chemistry professor Michael Barber and coworkers at the University of Manchester Institute of Science & Technology, England, developed fast atom bombardment MS (FAB MS), or liquid SIMS. In FAB MS, beams of neutral atoms are used to ionize compounds gently from the surface of a liquid matrix, making it possible to obtain spectra of large, involatile organic molecules.
Two recently developed MS techniques have had a major impact on the ability to use MS for the study of large biomolecules: electrospray ionization MS (ESI MS) and matrix-assisted laser desorption/ionization MS (MALDI MS).
In ESI MS, highly charged droplets dispersed from a capillary in an electric field are evaporated, and the resulting ions are drawn into an MS inlet. The technique was first conceived in the 1960s by chemistry professor Malcolm Dole of Northwestern University, Evanston, but it was put into practice in the early 1980s by molecular beam researcher John B. Fenn of Yale University (now at the department of chemistry of Virginia Commonwealth University, Richmond).
MALDI MS, a form of laser desorption MS, was developed in 1985 at the University of Frankfurt, Germany, by professor of biophysics Franz Hillenkamp (now at the University of Münster, Germany) and Michael Karas (now professor of analytical instrumentation at J. W. Goethe University, Frankfurt), and independently by research scientist Koichi Tanaka and coworkers at Shimadzu Corp., Kyoto, Japan. In MALDI, sample molecules are laser-desorbed from a solid or liquid matrix containing a highly UV-absorbing substance.
ESI MS and MALDI MS have made MS increasingly useful for sophisticated biomedical analysis. Applications include: the sequencing and analysis of peptides and proteins (using techniques pioneered by Biemann); studies of noncovalent complexes and immunological molecules; DNA sequencing; and the analysis of intact viruses.
ESI and MALDI have made it possible for large biomolecules to
be analyzed by low-cost instruments such as quadrupole, ion trap,
and TOF mass spectrometers. This has democratized biomedical MS,
making it available to hundreds of researchers who lack access to
magnetic sector machines, which are much more expensive. MALDI
and ESI now promise a greatly expanded future with molecular
characterization of proteins, DNA, and other large molecules, using instruments providing high sensitivity, specificity, and speed at lower cost, says McLafferty.
A condensed version of this history appeared originally as part of a larger article,
Chemistry Crystallizes Into Modern Science (Chemical & Engineering News,
12 January 1998, pp. 39-75, or <http://pubs.acs.org/hotartcl/cenear/980112/crystal2.html>).
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