- History of mass spectrometry
The history of mass spectrometry dates back more than one hundred years and has its roots in physical and chemical studies regarding the nature of matter. The study of
gas discharges in the mid 19th century led to the discovery of anode and cathode rays, which turned out to be positive ions and electrons. Improved capabilities in the separation of these positive ions enabled the discovery of stable isotopes of the elements. The first such discovery was with the atom neon, which was shown by mass spectrometryto have at least two stable isotopes: neon-20 with 10 protons and 10 neutrons and neon-22 with 10 protons and 12 neutrons. Mass spectrometers were used in the Manhattan Projectfor the separation of isotopes of uranium necessary to create the atomic bomb.
Prout's hypothesiswas an early 19th century attempt to explain the properties of the chemical elements using the internal structure of the atom. In 1815, the English chemist William Proutobserved that the atomic weights that had been measured were integermultiples of the atomic weight of hydrogen. [William Prout (1815). On the relation between the specific gravities of bodies in their gaseous state and the weights of their atoms. "Annals of Philosophy", 6: 321–330. [http://web.lemoyne.edu/~giunta/PROUT.HTML Online reprint] ] [William Prout (1816). Correction of a mistake in the essay on the relation between the specific gravities of bodies in their gaseous state and the weights of their atoms. "Annals of Philosophy", 7: 111–13. [http://web.lemoyne.edu/~giunta/PROUT.HTML#prout2 Online reprint] ] Prout's hypothesis remained influential in chemistry throughout the 1820s. However, more careful measurements of the atomic weights, such as those compiled by Jöns Jakob Berzeliusin 1828 or Edward Turnerin 1832, appeared to disprove it. In particular the atomic weight of chlorine, which is 35.45 times that of hydrogen, could not at the time be explained in terms of Prout's hypothesis. It would take the better part of a century for this problem to be resolved.
In the mid-nineteenth century,
Julius Plückerinvestigated the light emitted in discharge tubesand the influence of magnetic fields on the glow. Later, in 1869, Johann Wilhelm Hittorfstudied discharge tubes with energy rays extending from a negative electrode, the cathode. These rays produced a fluorescencewhen they hit a tube's glass walls, and when interrupted by a solid object they cast a shadow.
Canal rays, also called
Anode rays, were observed by Eugen Goldstein, in 1886. Goldstein used a gas discharge tube which had a perforated cathode. The rays are produced in the holes (canals) in the cathode and travels in a direction opposite to the " cathode rays," which are streams of electrons. Goldstein called these positive rays "Kanalstrahlen" - canal rays. In 1907a study of how this "ray" was deflected in a magnetic field, revealed that the particles making up the ray were not all the same mass
Discovery of isotopes
In 1913, as part of his exploration into the composition of
canal rays, J. J. Thomsonchanneled a stream of ionized neon through a magnetic and an electric field and measured its deflection by placing a photographic plate in its path. Thomson observed two patches of light on the photographic plate (see image on right), which suggested two different parabolas of deflection. Thomson concluded that the neon gas was composed of atoms of two different atomic masses (neon-20 and neon-22). [JJ Thomson (1913), [http://web.lemoyne.edu/~giunta/canal.html "Rays of positive electricity"] , "Proceedings of the Royal Society", A 89, 1-20 — Discovery of neon isotopes]
Francis William Astoncontinued the research at the Trinity College, building the first full functional mass spectrometer in 1919. He was able to identify the isotopes of chlorinewith 35 an 37, bromine79 and 78, kryptonwith 78, 80, 82, 83, 84 and 86, giving a proof of that the natural occurring elements are comprised of a combination of isotopes. The use of electromagnetic focusing in mass spectrograph which rapidly allowed him to identify no fewer than 212 of the 287 naturally occurring isotopes. In 1921 F. W. Aston became a fellow of the famous Royal Society.
His work on isotopes also led to his formulation of the
Whole Number Rulewhich states that "the mass of the oxygen isotope being defined, all the other isotopes have masses that are very nearly whole numbers," a rule that was used extensively in the development of nuclear energy. The exact mass of many isotopes was measured leading to the result that hydrogen has a 1% higher mass than expected by the average mass of the other elements. Aston speculated about the subatomic energy and the use of it in 1936.
1918, Arthur Jeffrey Dempsterdeveloped the first modern mass spectrometer, which was over 100 times more accurate than previous versions, and established the basic theory and design of mass spectrometers that is still used to this day. Dempster's research over his career centered around the mass spectrometer and its applications, leading in 1935to his discovery of the uranium isotope 235U. This isotope's ability to cause a rapidly expanding fission nuclear chain reactionallowed the development of the atom bomband nuclear power.
Kenneth Bainbridgedeveloped a mass spectrometer with a resolving power of 600 and a relative precision of one part in 10,000. cite journal|title=The history of nuclidic masses and of their evaluation|journal=International Journal of Mass Spectrometry |date=2006/4/1|first=Georges|last=Audi|coauthors=|volume=251|issue=2-3|pages=85–94|doi= 10.1016/j.ijms.2006.01.048|url=http://www.sciencedirect.com/science/article/B6VND-4JKRWJX-2/2/628018a7bf50a32b4cdba32b77f181c8|format=|accessdate=2008-04-11] He used this instrument to verify the equivalence of mass and energy, E = mc2. [ cite journal|title= The Equivalence of Mass and Energy|journal=Phys. Rev.|date=July 1933|first=Kenneth T.|last=Bainbridge|coauthors=|volume=44|issue=2|pages=123|doi= 10.1103/PhysRev.44.123.2|url=|format=|accessdate=2008-04-11]
Calutronis a sector mass spectrometer that was used for separating the isotopesof uraniumdeveloped by Ernest O. Lawrence[ cite web|url=http://www.lbl.gov/Science-Articles/Research-Review/Magazine/1981/81fepi2.htm |title=Lawrence and His Laborator |accessdate=2007-09-03 |date=1981 |work=LBL Newsmagazine |publisher=Lawrence Berkeley Lab ] during the Manhattan Projectand was similar to the Cyclotroninvented by Lawrence. Its name is a concatenationof Cal. U.-tron, in tribute to the University of California, Lawrence's institution and the contractor of the Los Alamos laboratory. cite journal|title=The Uranium Bomb, the Calutron, and the Space-Charge Problem|journal=Physics Today|date=2005 May 01|first=William E.|last=Parkins|coauthors=|volume=58|issue=5|pages=45–51|doi= 10.1063/1.1995747|url=http://masspec.scripps.edu/MSHistory/timelines/time_pdf/1947_ParkinsWE.pdf|format=PDF|accessdate=2007-09-01] They were implemented for industrial scale uranium enrichmentat the Oak Ridge, Tennessee Y-12plant established during the war and provided much of the uranium used for the " Little Boy" nuclear weapon, which was dropped onto Hiroshimain 1945.
Development of gas chromatography-mass spectrometry
The use of a mass spectrometer as the detector in gas chromatography was developed during the 1950s by Roland Gohlke and Fred McLafferty. [Gohlke, R. S., [http://masspec.scripps.edu/MSHistory/timelines/time_pdf/1956_Gohlke.pdf Time-of-flight mass spectrometry and gas-liquid partition chromatography] . "Anal. Chem." 1959, "31", 535-41] [Gohlke, R. S.; McLafferty, F. W., [http://dx.doi.org/10.1016/1044-0305(93)85001-E Early gas chromatography/mass spectrometry.] " J. Am. Soc. Mass Spectrom." 1993, "4", (5), 367-371.] The development of affordable and
miniaturized computers has helped in the simplification of the use of this instrument, as well as allowed great improvements in the amount of time it takes to analyse a sample.
Fourier transform mass spectrometry
Fourier transform ion cyclotron resonancemass spectrometry was developed by Alan G. Marshalland Melvin B. Comisarowat the University of British Columbiain 1974. [ [http://dx.doi.org/10.1016/0009-2614(74)89137-2 M.B. Comisarow and A.G. Marshall, "Chem. Phys. Lett." 25, 282 (1974)] ] The inspiration was earlier developments in conventional ICR and Fourier Transform Nuclear Magnetic Resonance (FT-NMR) spectroscopy.
oft ionization methods
Field desorption ionization was first reported by Beckey in 1969. [Beckey H.D. "Field ionization mass spectrometry." Research/Development, "1969", 20(11), 26] In field ionization, a high-potential electric field is applied to an "emitter" with a sharp surface, such as a razor blade, or more commonly, a filament from which tiny "whiskers" have been grown. This produces a very high electric field in which electron tunneling can result in ionization of gaseous analyte molecules. FI produces mass spectra with little or no fragmentation, dominated by molecular radical cations M+. and occasionally protonated molecules .
Chemical ionization was developed in the 1960s. [Munson, M.S.B.; Field, F.H. "J. Am. Chem. Soc." 1966, "88", 2621-2630. [http://dx.doi.org/10.1021/ja00964a001 Chemical Ionization Mass Spectrometry. I. General Introduction] .] cite journal |author=Fales HM, Milne GW, Pisano JJ, Brewer HB, Blum MS, MacConnell JG, Brand J, Law N |title=Biological applications of electron ionization and chemical ionization mass spectrometry |journal=Recent Prog. Horm. Res. |volume=28 |issue= |pages=591–626 |year=1972 |pmid=4569234 |doi=] cite journal |author=Dougherty RC |title=Negative chemical ionization mass spectrometry: applications in environmental analytical chemistry |journal=Biomed. Mass Spectrom. |volume=8 |issue=7 |pages=283–92 |year=1981 |pmid=7025931 |doi=] Ionization of sample (analyte) is achieved by interaction of its molecules with reagent ions. The analyte is ionized by ion-molecule reactions during collisions in the source. The process may involve transfer of an electron, a proton or other charged species between the reactants. This is a less energetic procedure than
electron ionizationand the ions produced are, for example, protonated molecules: [M + H] +. These ions are often relatively stable, tending not to fragment as readily as ions produced by electron ionization. Matrix-assisted laser desorption/ionization(MALDI) is a soft ionizationtechnique used in mass spectrometry, allowing the analysis of biomolecules ( biopolymers such as proteins, peptidesand sugars) and large organic molecules(such as polymers, dendrimersand other macromolecules), which tend to be fragile and fragment when ionized by more conventional ionization methods. It is most similar in character to electrospray ionizationboth in relative softness and the ions produced (although it causes much fewer multiply charged ions). The term was first used in 1985 by Franz Hillenkamp, Michael Karasand their colleagues. [cite journal |author=Karas, M.; Bachmann, D.; Hillenkamp, F. |title=Influence of the Wavelength in High-Irradiance Ultraviolet Laser Desorption Mass Spectrometry of Organic Molecules |journal=Anal. Chem. |volume=57 |issue= |pages=2935–9 |year=1985 |pmid= |issn= |doi=10.1021/ac00291a042] These researchers found that the amino acid alaninecould be ionized more easily if it was mixed with the amino acid tryptophanand irradiated with a pulsed 266 nm laser. The tryptophan was absorbing the laser energy and helping to ionize the non-absorbing alanine. Peptides up to the 2843 Da peptide melittincould be ionized when mixed with this kind of “matrix”. [cite journal |author=Karas, M.; Bachman, D.; Bahr, U.; Hillenkamp, F. |title=Matrix-Assisted Ultraviolet Laser Desorption of Non-Volatile Compounds |journal=Int J Mass Spectrom Ion Proc |volume=78 |issue= |pages=53–68 |year=1987 |pmid= |issn= |doi=10.1016/0168-1176(87)87041-6] The breakthrough for large molecule laser desorption ionization came in 1987 when Koichi Tanakaof Shimadzu Corp. and his co-workers used what they called the “ultra fine metal plus liquid matrix method” that combined 30 nm cobaltparticles in glycerolwith a 337 nm nitrogen laserfor ionization. [cite journal |author=Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshida, T. |title=Protein and Polymer Analyses up to m/z 100 000 by Laser Ionization Time-of flight Mass Spectrometry |journal=Rapid Commun Mass Spectrom |volume=2 |issue=20 |pages=151–3 |year=1988 |pmid= |issn= |doi=10.1002/rcm.1290020802] Using this laser and matrix combination, Tanaka was able to ionize biomolecules as large as the 34,472 Da protein carboxypeptidase-A. Tanaka received one-quarter of the 2002 Nobel Prize in Chemistryfor demonstrating that, with the proper combination of laser wavelength and matrix, a protein can be ionized. [cite web | last =Markides | first =K | authorlink = | coauthors =Gräslund, A | title =Advanced information on the Nobel Prize in Chemistry 2002 | work = | publisher = | date = | url =http://nobelprize.org/chemistry/laureates/2002/chemadv02.pdf | format =PDF | doi = | accessdate = ] Karas and Hillenkamp were subsequently able to ionize the 67 kDa protein albumin using a nicotinic acid matrix and a 266 nm laser. [cite journal |author=Karas M, Hillenkamp F |title=Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons |journal=Anal. Chem. |volume=60 |issue=20 |pages=2299–301 |year=1988 |pmid=3239801 |issn= |doi=10.1021/ac00171a028] Further improvements were realized through the use of a 355 nm laser and the cinnamic acidderivatives ferulic acid, caffeic acidand sinapinic acidas the matrix. [cite journal |author=Beavis RC, Chait BT |title=Matrix-assisted laser-desorption mass spectrometry using 355 nm radiation |journal=Rapid Commun. Mass Spectrom. |volume=3 |issue=12 |pages=436–9 |year=1989 |pmid=2520224 |issn= |doi=10.1002/rcm.1290031208] The availability of small and relatively inexpensive nitrogen lasers operating at 337 nm wavelength and the first commercial instruments introduced in the early 1990s brought MALDI to an increasing number of researchers. [cite journal |author=Karas, M.; Bahr, U. |title=Laser Desorption Ionization Mass Spectrometry of Large Biomolecules |journal=Trends Anal. Chem. |volume=9 |issue= |pages=321–5 |year=1990 |pmid= |issn= |doi=10.1016/0165-9936(90)85065-F] Today, mostly organic matrices are used for MALDI mass spectrometry.
Eugen Goldsteinobserves canal rays.
Wilhelm Wiendemonstrates that canal rays can be deflected using strong electric and magnetic fields. He shows that the mass-to-charge ratioof the particles have opposite polarity and is much larger compared to the electron. He also realizes that the particle mass is similar to the one of hydrogen particle.
J. J. Thomsonmeasures the mass-to-charge ratioof electrons.
:1901::Walter Kaufmann uses a mass spectrometer to measure the relativistic mass increase of electrons.
J. J. Thomsonbegins his study of positive rays.
:1906::Thomson is awarded the Nobel Prize in Physics "in recognition of the great merits of his theoretical and experimental investigations on the conduction of electricity by gases"
:1913::Thomson is able to separate particles of different
mass-to-charge ratios. He separates the Ne20 and the Ne22 isotopes, and he correctly identifies the m/q = 11 Th signal as a doubly charged Ne22 particle. [http://web.lemoyne.edu/~giunta/canal.html]
Francis Astonconstructs the first velocity focusing mass spectrograph with mass resolving power of 130.
:1922::Aston is awarded the Nobel Prize in chemistry "for his discovery, by means of his mass spectrograph, of isotopes, in a large number of non-radioactive elements, and for his enunciation of the whole-number rule."
Ernest O. Lawrenceinvents the cyclotron.
Josef Mattauchand Richard Herzogdevelop the double-focusing mass spectrograph.
Arthur J. Dempsterdevelops the spark ionizationsource.
:1937::Aston constructs a mass spectrograph with resolving power of 2000.
:1939::Lawrence receives the Nobel Prize in Physics for the cyclotron.
:1942::Lawrence develops the
Calutronfor uranium isotope separation.
:1946::William Stephens presents the concept of a
:1956::Fred McLafferty proposes a hydrogen transfer reaction that will come to be known as the
Dow Chemicalinterface a gas chromatographto a mass spectrometer.
:1966::F. H. Field and M. S. B. Munson develop
Malcolm Doledevelops electrospray ionization.
:1969::H. D. Beckey develops
:1974::Comisarow and Marshall develop
Fourier Transform Ion Cyclotron ResonanceMass Spectrometry
:1976::Ronald MacFarlane and co-workers develop
plasma desorption mass spectrometry.
John Fennand co-workers use electrosprayto ionize biomolecules.
:1985::Franz Hillenkamp, Michael Karas and co-workers describe and coin the term
matrix-assisted laser desorption ionization(MALDI).
Koichi Tanakauses the “ultra fine metal plus liquid matrix method” to ionize intact proteins.
Wolfgang Paulreceives the Nobel Prize in Physics "for the development of the ion trap technique"
:1999::Alexander Makarov presents the
Orbitrapmass spectrometer [http://www.asms.org/asms99pdf/095.pdf]
John Fennand Koichi Tanakaare awarded one-quarter of the Nobel Prize in chemistry each "for the development of soft desorption ionisation methods ... for mass spectrometric analyses of biological macromolecules."
History of chemistry
History of physics
*Measuring Mass: From Positive Rays to Proteins by Michael A. Grayson (Editor) (ISBN 0-941901-31-9)
* [http://www.chm.bris.ac.uk/ms/history.html Bristol History of Mass Spectrometry]
* [http://masspec.scripps.edu/MSHistory/mshisto.php Scripps History of Mass Spectrometry]
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