Mass Spectrometry Timeline

This timeline is intended to be a record of significant events in the evolution of Mass Spectrometry.

2014

Draft of the Human Proteome

Mass spectrometry has revolutionized proteomics in a manner analogous to the impact of massively parallel DNA sequencing on genomics and transcriptomics. In this study, high-resolution Fourier-transform mass spectrometry was employed to systematically map the human proteome across 30 different histologically normal human tissues/cell types. This resulted in identification of proteins encoded by more than 17,200 genes accounting for approximately 84% of all the known protein coding genes in human. In addition, the study employed a unique proteogenomics strategy to identify about 200 novel protein coding regions in the human genome. This comprehensive human proteome dataset can be accessed through an interactive web-based resource called Human Proteome Map (humanproteomemap.org).

Kim M-S., Pinto S.M., Getnet D....., A draft map of the human proteome, Nature 2014, 509, 575-581

Wilhelm M., Schlegl J., Hahne H...., Mass-spectrometry-based draft of the human proteome, Nature 2014, 509, 582-587

2013

Surgical "intelligent knife" (iKnife)

Balog J., Sasi-Szabo L., Kinross J., Lewis M.R., Muirhead L.J., Veselkov K., Mirnezami R., Dezso B., Damjanovich L., Darzi A., Nicholson J.K., Takatz Z., Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry, Sci Transl Med 2013, 5, 194, 194ra93

2005

Direct Analysis in Real Time (DART)

A new ion source for the direct analysis of molcules from surfaces.

DART is based on the atmospheric pressure interactions of long-lived electronic excitedstate atoms or vibronic excited-state molecules with the sample and atmospheric gases.

A gas (typically helium or nitrogen) flows through a chamber where an electrical discharge produces ions, electrons, and excited-state (metastable) atoms and molecules. Most of the charged particles are removed as the gas passes through perforated lenses or grids and only the neutral gas molecules, including metastable species, remain. A perforated lens or grid at the exit of the DART provides several functions: it prevents ion-ion and ion-electron recombination, it acts as a source of electrons by surface Penning ionization, and it acts as an electrode to promote ion drift toward the orifice of the mass spectrometer?s atmospheric pressure interface. (U.S. Patent # 6,949,741 in 2005)

Cody R.B., Laramee J.A., Durst H.D., Versatile New Ion Source for the Analysis of Materials in Open Air under Ambient Conditions, Anal. Chem. 2005, 77, 8, 2297

2004

Desorption Electrospray Ionization (DESI)

A desorption ionization using electrosprayed droplets.

Takats Z., Wiseman J.M., Gologan B., Cooks R.G., Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization, Science 2004, 306, 5695, 471 | Related

Electron Transfer Dissociation (ETD)

Peptide sequence analysis using electron transfer dissociation (ETD) which occurs via a combination of gas-phase ion ion chemistry and tandem mass spectrometry (MS MS). Singly charged anions transfer an electron to multiply protonated peptides in a radio frequency quadrupole ion trap and induce fragmentation of the peptide backbone along pathways that are analogous to those observed in electron capture dissociation.

Syka J.E.P., Coon J.J., Schroeder M.J., Shabanowitz J., Hunt D.F., Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry, PNAS 2004, 101, 9528

2003

Shotgun Lipidomics

Han X., Gross R.W., Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics, Journal of Lipid Research 2003, 44, 1071-1079

2000

Orbitrap

A new type of mass analyzer which employs trapping in an electrostatic field.

Makarov A., Electrostatic Axially Harmonic Orbital Trapping: A High-Performance Technique of Mass Analysis, Analytical Chemistry 2000, 72, 6, 1156

1999

Nanostructure Desorption/Ionization

A matrix-less approach for laser desorption/ionization on silicon (DIOS).

Wei J., Buriak J., Siuzdak G., Desorption/Ionization Mass Spectrometry on Porous Silicon , Nature 1999, 399, 6733, 243

Quantitative Proteomics and Metabolomics with Isotope Labels

Quantitative analysis of proteins using mass spectrometry and isotope labeling.

Gygi S.P., Rist B., Gerber S.A., Turecek F., Gelb M.H., Aebersold R., Quantitative analysis of complex protein mixtures using isotope-coded affinity tags, Nature Biotechnology 1999, 17, 10, 994

Oda Y., Huang K., Cross F.R., Cowburn D., Chait B.T., Accurate quantitation of protein expression and site-specific phosphorylation, PNAS 1999, 96, 6591

Tong G.C., Want E.J., Smith C.A., Shen Z., Tsao M-L., Meng J., Brandon T., Webb W., Siuzdak G., Motabolite Profiling with Isotopically Encoded Chemical Derivatization, Poster presented at the 53rd ASMS Conference in Mass Spectrometry 2005

1998

Electron Capture Dissociation (ECD)

Electron Capture Dissociation (ECD) was first applied to biomolecules in the McLafferty lab at Cornell. ECD has the useful ability to produce odd-electron, free-radical driven fragmentation of the same type as are generated by EI mass spectrometry. This fragmentation method generates different and often complementary fragmentation patterns when compared with Collisionally Activated Dissociation (CAD), Infrared Multiphoton Dissociation (IRMPD), or other slow, even-electron fragmentation methods.

For proteins, ECD cleaves between the backbone amide and the alpha carbon to form C and Z* fragments. Moreover, the cleavage sites show very little selectivity for particular amino acids with the two exceptions of disulphide bonds (having high radical affinity) and proline (which is cyclic around the amide - alpha carbon and therefore requires breaking 2 bonds).

Additionally, for proteins, labile post-translational modifications such as phosphorylation sites, o-glycosylation sites, n-glycosylation sites, and others remain attached to the backbone during ECD MS/MS experiments allowing determination of the site and identity of post-translational modifications.

Zubarev R.A., Kelleher N.L., McLafferty F.W., Electron Capture Dissociation of Multiply Charged Protein Cations - a Nonergodic Process, J. Am. Chem. Soc. 1998, 120, 13, 3265

1996

Intact Virus Analyses

Demonstration of the viability of a virus after passing through a mass spectrometer and mass measurement of intact viruses (~40 million Daltons).

Siuzdak G., Bothner B., Yeager M., Brugidou C., Fauquet C.M., Hoey K., Chang C.M., Mass Spectrometry and Viral Analysis, Chemistry & Biology 1996, 3, 45

Fuerstenau, Benner, Thomas, Brugidou, Bothner, Siuzdak, Mass spectrometry of an Intact Virus, Angew.Chem.Int.Ed. 2001, 40, 541

1994

MALDI Imaging

The first example of using MALDI-MS to perform imaging experiments.

Spengler B., Hubert M. Kaufmann R., MALDI ion imaging and biological ion imaging with a new scanning UV-laser microprobe, Proc. 42nd Annual Conf. Mass Spectrom. and Allied Topics 1994, 1041

Hubert M., Spengler B., Kaufmann R., Development of a new scanning UV-laser microprobe for ion imaging and confocal microscopy, Proc. 42nd Annual Conf. Mass Spectrom. and Allied Topics 1994, 1044 | Related

1993

Oligonucleotide Ladder Sequencing

A novel approach to small oligonucleotide sequencing with MALDI.

Pieles U., Zurcher W., Sch?r M., Moser H.E., Matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a powerful tool for the mass and sequence analysis of natural and modified oligonucleotides, Nucleic Acids Research 1993, 21, 14, 3191

Protein Mass Mapping

Protein mass mapping for protein identification is turning into one of the most important applications of mass spectrometry.

It has become an indispensible tool in proteomics and its utility is still growing.

Henzel W.J., Billeci T.M., Stults J.T., Wong S.C., Grimley C., Watanabe C., Identifying Proteins From 2-Dimensional Gels By Molecular Mass Searching of Peptide Fragments in Protein Sequence Databases, Proceedings Of The National Academy Of Sciences Of The United States Of America 1993, 90, 11, 5011

Henzel W.J., Watanabe C., Stults J.T., Protein Identification: The Origins of Peptide Mass Fingerprinting, Journal of the American Society for Mass Spectrometry 2003, 14, 931

DXMS

Hydrogen Deuterium Exchange Mass Spectrometry (DXMS) developed for protein structure.

Zhang Z., Smith D.L., Determination of amide hydrogen exchange by mass spectrometry: A new tool for protein structure elucidation, Protein Science 1993, 2, 522-531

1992

Low Level Peptide Analysis

Don Hunt set the standard with these original measurements on peptides.

Hunt D.F., Henderson R.A., Shabanowitz J., Sakaguchi K., Michel H., Sevilir N., Cox A.L., Appella E., Engelhard V.H., Characterization Of Peptides Bound To The Class-I Mhc Molecule Hla-A2.1 By Mass Spectrometry, Science 1992, 255, 5049, 1261

1991

MALDI Post-Source Decay

An interesting approach to gain structural information on peptides using MALDI.

Spengler B., Kirsch D., Kaufmann R., Metastable Decay of Peptides and Proteins in Matrix-Assisted Laser-Desorption Mass Spectrometry, Rapid Communications in Mass Spectrometry 1991, 5, 198

Spengler B., Kirsch D., Kaufmann R., Jaeger E., Peptide Sequencing by Matrix-Assisted Laser-Desorption Mass Spectrometry, Rapid Communications in Mass Spectrometry 1992, 6, 105

Kaufmann R., Spengler B., Lutzenkirchen F., Mass Spectrometric Sequencing of Linear Peptides by Product-Ion Analysis in a Reflectron Time-of-Flight Mass Spectrometer Using Matrix-Assisted Laser Desorption Ionization, Rapid Communications in Mass Spectrometry 1993, 7, 902

Spengler B., Lutzenkirchen F., Kaufmann R., On-Target Deuteration for Peptide Sequencing by Laser Mass Spectrometry, Organic Mass Spectrometry 1993, 28, 1482

Kaufmann R., Kirsch D., Spengler B., Sequencing of Peptides in a Time-of-Flight Mass Spectrometer - Evaluation of Postsource Decay Following Matrix-Assisted Laser Desorption Ionisation (MALDI), International Journal of Mass Spectrometry and Ion Processes 1994, 131, 355

Spengler B., Kirsch D., Kaufmann R., Lemoine J., Structure Analysis of Branched Oligosaccharides Using Post-Source Decay in Matrix-Assisted Laser Desorption Ionization Mass Spectrometry, Organic Mass Spectrometry 1994, 29, 782

Kaufmann R., Chaurand P., Kirsch D., Spengler B., Post-Source Decay and Delayed Extraction in Matrix-Assisted Laser Desorption/Ionization/Reflectron Time-of-Flight Mass Spectrometry - Are There Trade-Offs, Rapid Communications in Mass Spectrometry 1996, 10, 10, 1199

Higher Order Structure

Rockwood AL, Busman M, Smith RD, Coulombic effects in the dissociation of large highly charged ions, International Journal of Mass Spectrometry and Ion Processes 1991, 111, 103-129

Non-covalent Interactions with ESI

An interesting observation about the relative softness of electrospray ionization is that it is possible to conserve noncovalent interactions from solution (such as protein/ligand interactions) into the gas phase.

Ganem B., Li Y.T., Henion J.D., Detection of Noncovalent Receptor Ligand Complexes by Mass Spectrometry, Journal of the American Chemical Society 1991, 113, 16, 6294

Katta V., Chait B.T., Conformational Changes In Proteins Probed By Hydrogen-Exchange Electrospray-Ionization Mass Spectrometry, Rapid Communications In Mass Spectrometry 1991, 5, 4, 214

Katta V., Chait B.T., Observation Of The Heme Globin Complex In Native Myoglobin By Electrospray-Ionization Mass Spectrometry, Journal Of The American Chemical Society 1991, 113, 22, 8534

1990

Protein Conformational Changes with ESI-MS

The utility of electrospray for protein structure information became evident with these studies.

Chowdhury S.K., Katta V., Chait B.T., Probing Conformational Changes in Proteins by Mass Spectrometry, Journal of the American Chemical Society 1990, 112, 24, 9012

Chowdhury S.K., Katta V., Chait B.T., Electrospray ionization mass spectrometric peptide mapping: a rapid, sensitive technique for protein structure analysis, Biochemical and Biophysical Research Communications 1990, 167, 2, 686

Clinical Mass Spectrometry

Origins of the widespread use of mass spectrometry in clinical chemistry.

Millington D.S., Kodo N., Norwood D.L., Roe C.R., Tandem Mass Spectrometry: A New Method for Acylcarnitine Profiling with Potential for Neonatal Screening for Inborn Errors of Metabolism, J. Inher. Metab. Dis. 1990, 13, 321-324

1989

ESI on Biomolecules

The application of ESI to biomolecules was one of the most important discoveries in mass spectrometry in the latter part of the twentieth century.

Fenn J.B., Mann M., Meng C.K., Wong S.F., Whitehouse C.M., Electrospray Ionization for Mass Spectrometry of Large Biomolecules, Science 1989, 246, 4926, 64

Fenn J.B., Review: Electrospray Ionization Mass Spectrometry: How it all began., Journal of Biomolecular Techniques 2002, 13, 3, 101

Monitoring Enzyme Reactions with ESI-MS

Lee E.D., Mueck W., Henion J.D., Covey T.R., Real-time reaction monitoring by continuous-introduction ion-spray tandem mass spectrometry, J. Am. chem. Soc. 1989, 111, 13, 4600

Wu J., Takayama S., Wong C.H., Siuzdak G., Quantitative Electrospray Mass Spectrometry for the Rapid Assay of Enzyme Inhibitors, Chemistry & Biology 1997, 4, 9, 653

1987

Soft Laser Desorption of Proteins

Karas M., Bachmann D., Hillenkamp F., Influence of the Wavelength in High Irradiance Ultraviolet Laser Desorption Mass Spectrometry of Organic Molecules, Anal. Chem. 1985, 57, , 2935-2939

Tanaka K., Ido Y., Akita S., Yoshida Y. Yoshida T., Detection of High Mass Molecules by Laser Desorption Time-Of-Flight Mass Spectrometry, Proceedings of the Second Japan-China Joint Symposium on Mass Spectrometry 1987, 185

Tanaka K., Waki H., Ido Y., Akita S., Yoshida Y., Yoshida T., Protein and polymer analysis up to m/z 100,000 by laser ionization time-of-flight mass spectrometry, Rapid Commun. Mass Spectrom. 1988, 2, 8, 151

1985

Matrix-Assisted Laser Desorption Ionization (MALDI)

MALDI (along with electrospray) was one of the most important discoveries in mass spectrometry in the latter part of the twentieth century.

Karas M., Hillenkamp F., Laser desorption ionization of proteins with molecular mass exceeding 10,000 Daltons, Analytical Chemistry 1988, 60, , 2299

Tanaka K., Ido Y., Akita S., Yoshida Y., Yoshida T., Detection of High Mass Molecules by Laser Desorption Time-Of-Flight Mass Spectrometry, Proceedings of the Second Japan-China Joint Symposium on Mass Spectrometry 1987, 185

Karas M., Bachmann D., Hillenkamp F., Influence of the Wavelength in High Irradiance Ultraviolet Laser Desorption Mass Spectrometry of Organic Molecules, Anal. Chem. 1985, 57, , 2935-2939

Karas M., Hillenkamp F., Laser Desorption Ionization of Proteins with Molecular Masses Exceeding 10,000 Daltons, Anal. Chem. 1988, 60, 20, 2299-2301

1984

Quadrupole/Time-Of-Flight Mass Analyzer

Glish G.L., and Goeringer D.E., Tandem Quadrupole/Time-of-Flight Instrument for Mass Spectrometry/Mass Spectrometry, Anal. Chem. 1984, 56, 2291

1981

Matrix-Assisted Desorption Ionization

The beginnings of the matrix-assisted desorption techniques such as FAB and MALDI.

Barber M., Bordoli R.S., Sedgwick R.D., Tyler, A.N., Fast atom bombardment of solids as an ion source in mass spectroscopy, Nature 1981, 293, 270

Liu L.K., Busch K.L., Cooks R.G., Matrix-assisted secondary ion mass spectra of biological compounds, Analytical Chemistry 1981, 53, 1, 109

1980

Inductively Coupled Plasma MS

A very powerful tool for elemental composition analysis.

Reed T.B., Induction-Coupled Plasma Torch, Journal of Applied Physics 1961, 32, 5, 821

Reed T.B., Growth of Refractory Crystals Using Induction Plasma Torch, Journal of Applied Physics 1961, 32, 12, 2534

Wendt R.H., Fassel V.A., Induction-coupled Plasma Spectrometric Excitation Source, Analytical Chemistry 1965, 37, 7, 920

Greenfield S., Berry C.T., Jones I.L., High-Pressure Plasmas as Spectroscopic Emission Sources, Analyst 1964, 89, 1064, 713

Montaser A., Fassel V.A., Inductively Coupled Plasmas as Atomization Cells for Atomic Fluorescence Spectrometry, Analytical Chemistry 1976, 48, 11, 1490

Houk R.S., Fassel V.A., Flesch G.D., Svec H.J., Gray A.L., Taylor C.E., Inductively Coupled Argon Plasma as an Ion-Source for Mass-Spectrometric Determination of Trace-Elements, Analytical Chemistry 1980, 52, 14, 2283

1978

GC-C-IRMS

First gas chromatograph-combustion-isotope ratio mass spectrometer (GC-C-IRMS) for 13C and 15N at natural abundances.

D.E. Matthews, J.M. Hayes, Isotope-ratio-monitoring gas chromatography-mass spectrometry, Anal. Chem. 1978, 50, 11, 1465

1977

Triple Quadrupole Mass Spectrometer

Yost R.A. and Enke C.G., Selected Ion Fragmentation with a Tandem Quadrupole Mass Spectrometer, Journal of the American Chemical Society 1978, 100, 7, 2274

Morrison J.D., Personal reminiscences of forty years of mass spectrometry in Australia, Organic Mass Spectrometry 1991, 26, 4, 183-194

Enke C.G., Yost R.A., Jim Morrison, Friend and Colleague, American Society for Mass Spectrometry 2013, 24, 1319-1323

Traeger, JC, James Douglas Morrison AO (1924-2013), American Society for Mass Spectrometry 2013, 24, 1326-1327

1976

Californium-252 Plasma Desorption MS

An important technique in its time and a precursor to MALDI as well as DIOS-MS.

Macfarlane R.D., Torgerson D.F., Californium-252 plasma desorption mass spectroscopy, 1976, 191(4230), p.920-5, Science 1976, 191, 4230, 920

The use of the technique in the study of biomolecules is described. Energetic fission fragments from the decay of /sup252/Cf are utilised to volatize and ionize a solid sample.

1975

Atmospheric Pressure Chemical Ionization (APCI)

Carroll D.I., Dzidic I., Stillwell R.N., Haegele K.D., Horning E.C., Atmospheric Pressure Ionization Mass Spectrometry: Corona Discharge Ion Source for Use in Liquid Chromatograph - Mass Spectrometer - Computer Analytical System, Analytical Chemistry 1975, 47, 14, 2369

1974

Fourier Transform Ion Cyclotron Resonance

The application of Fourier transform to ICR mass analysis made FTMS broadly applicable to the biomolecule problems that it is addressing today.

Comisarow M.B., Marshall A.G., Fourier transform ion cyclotron resonance [FT-ICR] spectroscopy, Chem. Phys. Lett. 1974, 25, 2, 282

Henry K.D., Williams E.R., Wang B.H., McLafferty F.W., Shabanowitz J., Hunt D.F., Fourier-Transform Mass Spectrometry of Large Molecules by Electrospray Ionization, Proceedings Of The National Academy Of Sciences Of The United States Of America 1989, 86, 23, 9075

Biemann K., Test results on the Viking gas chromatograph-mass spectrometer experiment, Origins of Life 1974, 5, 3, 417

Hipple J.A., Sommer H., Thomas H.A., A Precise Method of Determining the Faraday by Magnetic Resonance, Phys. Rev. 1949, 76, 12, 1877

Extra-Terrestrial Mass Spectrometry

The beginning of what has yet to be.

1969

Field Desorption-MS of Organic Molecule

An important ionization tool that is still used today.

Beckey H.D., Field ionization mass spectrometry, Research/Development 1969, 20, 11, 26

1968

Electrospray Ionization

The beginning of electrospray ionization, it was almost 20 years before its potential for biomolecules was realized.

Dole M., Mack L.L., Hines R.L., Mobley R.C., Ferguson L.D., Alice M.B., Molecular beams of macroions, Journal of Chemical Physics 1968, 49, 5, 2240

Horning E.C., Carroll D.I., Dzidic I., Haegele K.D., Horning M.D., Stillwell R.N., Atmospheric Pressure Ionization (API) Mass Spectrometry. Solvent-Mediated Ionization of Samples Introduced in Solution and In a Liquid Chromatograph Effluent Stream, Journal of Chromatogr. Sci. 1974, 12, 725

Blakely C.R., Vestal M.L., Thermospray interface for liquid chromatography/mass spectrometry, Anal. Chem. 1983, 55, 4, 750

Yamashita M., Fenn, J.B., Electrospray Ion Source. Another Variation on the free-jet theme, Journal of Physical Chemistry 1984, 88, 20, 4451

Yamashita M., Fenn, J.B., Negative ion production with the electrospray ion source, Journal of Physical Chemistry 1984, 88, 20, 4671

Wilm M.S., Mann M., Electrospray and Taylor-Cone Theory, Doles Beam of Macromolecules at last, International Journal of Mass Spectrometry and Ion Processen 1994, 136, 43864, 167

Fenn J.B., Review: Electrospray Ionization Mass Spectrometry: How it all began., Journal of Biomolecular Techniques 2002, 13, 3, 101

Collision Induced Dissociation

Jennings K.R., Collision-Induced Decompositions of Aromatic Molecular Ions, Int. J. Mass Spec. Ion Physics 1968, 1, 227-235

1966

Chemical Ionization

One of the first soft ionization techniques.

Munson M.S.B., Field F.H., Chemical Ionization Mass Spectrometry I. General introduction, J. Am. Chem. Soc. 1966, 88, 12, 2621-2630

Peptide Sequencing

The beginning of peptide sequencing by mass spectrometry.

Biemann K., Cone C., Webster B.R., Arsenault G.P., Determination of the amino acid sequence in oligopeptides by computer interpretation of their high-resolution mass spectra, J. Am. Chem. Soc. 1966, 88, 23, 5598-606

Tandem Mass Spectrometry

Futrell J.H., Miller C.D., Tandem Mass Spectrometer for the Study of Ion-Molecule Reactions, Review of Scientific Instruments 1966, 37, 1521

Metabolomics

Dalgliesh C.E., Horning E.C., Horning M.G., Knox K.L., Yarger K., A Gas-Liquid-Chromatographic Procedure for Separating a Wide Range of Metabolites occurring in Urine or Tissue Extracts, Biochemical Journal 1966, 101, 792

1962

Mass Spectrometry Imaging

Imaging by mass spectrometry was initially developed at the University of Orsay by Georges Slodzian and Raymond Castaing and was applied to the microanalysis of mineral samples. This "ion microscopy" was first utilized in Biology by Pierre Galle in 1970 (Galle 1970) yet more recently different ion sources have been applied to biological imaging such as SIMS with buckyball, MALDI, DESI and DART.

Castaing R., Slodzian G., Microanalyse par ?mission ionique secondaire (Microanalysis by secondary ion emission), Journal De Microscopie 1962, 1, 395

Galle P., Sur une nouvelle methode d'analyse cellulaire utilisant le phenomene d' << emission ionique secondaire >>, Ann. Phys. Biol. Med. 1970, 42, 83

Colliver T.L., Brummel C.L., Pacholski M.L., Swanek F.D., Ewing A.G., Winograd N., Atomic and Molecular Imaging at the Single-Cell Level with TOF-SIMS, Anal. Chem. 1997, 69, 13, 2225

Stoeckli M., Chaurand P., Hallahan D.E., Caprioli R.M., Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues, Nat Med. 2001, 7, 4, 493

Ostrowski S.G., Van Bell C.T., Winograd N., Ewing A.G., Mass Spectrometric Imaging of Highly Curved Membranes During Tetrahymena Mating, Science 2004, 305, 71

Cody R.B., Laramee J.A., Durst H.D., Versatile New Ion Source for the Analysis of Materials in Open Air under Ambient Conditions, Anal. Chem. 2005, 77, 8, 2297

Cooks R.G., Ouyang Z., Takats Z., Wiseman J.M., Ambient Mass Spectrometry, Science 2006, 311, 5767, 1566

Spengler B., Hubert M., Kaufmann R., MALDI ion imaging and biological ion imaging with a new scanning UV-laser microprobe, Proc. 42nd Annual Conf. Mass Spectrom. and Allied Topics 1994, 1041

1956

Gas Chromatography Mass Spectrometry (GC/MS)

A very powerful tool and still one of the most popular forms of doing mass spectrometry.

Golhke R.S., McLafferty F., Wiley B., Harrington D., First demonstration of GC/MS , Bendix Corporation 1956

Golhke R., Time-of-Flight Mass Spectrometry and Gas-Liquid Partition Chromatography, Analytical Chemistry 1959, 31, 535

Ryhage R., Use of a mass spectrometer as a detector and analyzer for effluents emerging from high temperature GLC columns , Analytical Chemistry 1964, 36, 4, 759

Gohlke R.S., McLafferty F.W., Early gas chromatography/mass spectrometry, Journal of the American Society for Mass Spectrometry 1993, 4, 5, 367

Identifying Organic Compounds with Mass Spectrometry

The beginning of using MS to characterize molecules.

Beynon J.H., The use of the mass spectrometer for the identification of organic compounds, Mikrochim. Acta 1956, 44, 43833, 437

The analysis of an organic compound by mass spectrometry consists in the bombardment of the vapor of a compound at a pressure of 10-5 to 10-6 mm. Of Hg with electrons having energies of 50-100 volts. This is sufficient to break down the molecules in several ways, forming positive, negative, and neutral fragments. It is often possible to identify impurities without any preconcn. Of the impurity. An example of this type of analysis is given. (Hall W.T., Chemical Abstracts, 1956, 50, p.8396)

1953

Reverse Geometry Double-Focusing MS

Double focusing mass analyzers were once the primary means of generating high resolution high accuracy mass measurements.

Quadrupole Analyzers

Paul's invention of the quadrupole and quadrupole ion trap earned him the Nobel Prize in Physics. These mass analyzers are the most widely used today and are still being developed for an even wider range of applicatons. Way to go Wolfgang!

Paul W., Steinwedel H., Ein neues Massenspektrometer ohne Magnetfeld, Z. Naturforschg. 1953, 8a, 448

The instrument described employs a quasi-stationary alternating electric field in place of a magnetic field. (Waldo W.H., Chemical Abstracts, 1953.)

1949

Ion Cyclotron Resonance (ICR)

This represents the beginning of ultra high resolution mass spectrometry offered by FTMS.

Hipple J.A., Sommer H., Thomas H.A., A Precise Method of Determining the Faraday by Magnetic Resonance, Phys. Rev. 1949, 76, 12, 1877

Gal J.F., A historical note on an unrecognized early stage of the development of fast scanning ion cyclotron resonance spectrometers: the resotron, International J. of Mass Spec. and Ion Processes 1996, 157/158, 1

1947

Preparative Mass Spectrometry

In the early 1940s a mass spectrometry-based separation approach to enrich radioactive uranium 235U from the natural isotopic distribution of uranium. This method used Calutron mass spectrometers to separate ions according to their mass-to-charge ratio (m/z), and once separated, the ions were collected. This preparative mass spectrometry approach was used to purify radioactive 235U, which was then used to construct the first nuclear weapon. It was recently demonstrated that viruses as well as other types of molecules could also be separated and collected using electrospray ionization mass spectrometry.

Parkins W.E., The Uranium Bomb, the Calutron, and the Space-Charge Problem, Physics Today 2005, 45,

Siuzdak G., Bothner B., Yeager M., Brugidou C., Fauquet C.M., Hoey K., Chang C.M., Mass Spectrometry and Viral Analysis, Chemistry & Biology 1996, 3, 45

Siuzdak G., Hollenbeck T., Bothner B., Preparative Mass Spectrometry with Electrospray Ionization, Journal of Mass Spectrometry 1999, 34, 1087

Ouyang Z., Takats Z., Blake T.A., Gologan B., Guymon A.J., Wiseman J.M., Oliver J.C., Davisson V.J., Cooks R.G., Preparing protein microarrays by soft-landing of mass-selected ions, Science 2003, 301, 5638, 1351

1946

Time-of-Flight Mass Spectrometry

Stephens is responsible for TOF mass analyzers, the significance of TOF mass analyzers has grown over the last 20 years especially in the biomedical applications of mass spectrometry.

Stephens W., Pulsed Mass Spectrometer with Time Dispersion, Bull. Am. Phys. Soc. 1946, 21, 2, 22

Cameron A.E., Eggers D.F. Jr., An Ion "Velocitron", The Rev. of Sci. Instrum. 1948, 19, 9, 605

Smith L.G., A New Magnetic Period Mass Spectrometer, The Rev. of Sci. Instrum. 1951, 22, 2, 115

Hays E.E., Richards P.I., Goudsmit S.A., Mass Measurements with a Magnetic Time-of-Flight Mass Spectrometer, Phys. Rev. 1951, 84, 824 | Related

Smith L.P., Parkins W.E., Forrester A.T., On the Separation of Isotopes in Quantity by Electromagnetic Means, Phys. Rev. 1947, 72, 11, 989

Wolff M.M., Stephens W.E., A Pulsed Mass Spectrometer with Time Dispersion, The Rev. of Sci. Instrum. 1953, 24, 8, 616

Katzenstein H.S., Friedland W.E., New Time-Of-Flight Mass Spectrometer, The Rev. of Sci. Instrum. 1955, 26, 4, 324

Wiley W.C., McLaren I.H., Time-Of-Flight Mass Spectrometer with Improved Resolution, The Rev. of Sci. Instrum. 1955, 26, 12, 1150

1943

First Mass Spectrometry Advertisement

The Mass Spectrometer: A new electronic method for fast, accurate gas analysis.

The Mass Spectrometer, Westinghouse Electric International Company 1943

1939

Accelerator Mass Spectrometry

An important tool in trace biomolecule detection, still coming into its own.

Bennett C.L., Beukens R.P., Clover M.R., Gove H.E., Liebert R.B., Litherland A.E., Purser K.H., Sondheim W.E., Radiocarbon Dating Using Electrostatic Accelerators: Negative Ions Provide the Key, Science 1977, 198, 4316, 508

Nelson D.E., Korteling R.G., Stott W.R., Carbon-14: Direct Detection at Natural Concentrations, Science 1977, 198, 4316, 507

Vogel J.S., Turteltaub K.W., Biomolecular tracing through accelerator mass spectrometry, Trends in Analytical Chemistry 1992, 11, 4, 142

Turteltaub K.W., Vogel J.S., Franz C.E., Fultz E., Studies on DNA adduction with heterocyclic amines by accelerator mass spectrometry: a new technique for tracing isotope-labelled DNA adduction Postlabelling Methods for Detection of DNA Adducts, Ed. Phillips D.H., Castegnaro M., Bartsch H., Lyon: IARC 1993, 293

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1934

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1919

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1897

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At first there were very few who believed in the existence of these bodies smaller than atoms. I was even told long afterwards by a distinguished physicist who had been present at my [1897] lecture at the Royal Institution that he thought I had been 'pulling their legs.

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