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Mass spectrometry glossary
 Evolving Terminology for Emerging Technologies
Comments? Questions? Revisions? mchitty@healthtech.com
Last revised December 27, 2001 

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The sensitivity and speed of analysis available from mass spectrometry, as well as its versatility, makes this technology attractive for a growing range of applications in pharmaceutical research. Instrument miniaturization, coupling mass spectrometry with other analytical techniques, and improvements in software are among the key technology advances taking place.  Shifts in instrument design and automated sample handling have been very important for opening opportunities to apply mass spectrometry for high throughput analysis.  Such speed is critical for newer applications such as genotyping or other genetic analysis, as well as quality control for large combinatorial libraries.  Other advances have contributed to growing use of mass spectrometry for biomolecular, pharmacokinetic and clinical studies.

Related glossaries include Chromatography & electrophoresis, Protein Structure, Proteomics. Structural genomics.

affinity mass spectrometry: The coupling of solid- phase affinity methods with direct analysis by MALDI- TOF MS, an approach loosely referred to as "affinity mass spectrometry", has greatly increased the speed and scope of MALDI- TOF MS analysis. [Smith, Lloyd et al, Nature Biotechnology 15: 1368 Dec 1997]

2-D CE-IMLS 2D Capillary Electrophoresis with Inverted Mass Ladder Sequencing:  Combination of capillary electrophoresis and mass spectrometry Fluorescence using LIF (Laser Induced Fluorescence) detection to quantify the amount of protein in the sample. Each LIF peak is then subjected to ESI- TOF MS. [CHI Proteomics]

biomolecular interaction analysis mass spectrometry: A two- dimensional, chip- based, analytical technique for rapid and sensitive analysis of biomolecules. ... represents a synergy of two individual technologies: surface plasmon resonance (SPR) sensing and matrix- assisted laser desorption/ ionization time-of- flight (MALDI-TOF) mass spectrometry. [D Nedelkov and RW Nelson "Biomolecular Interaction Analysis Mass Spectrometry: A multiplexed proteomics approach" Biopharm 28-33, Aug. 2001] 

CE-MS Capillary Electrophoresis Mass Spectrometry. Separation is achieved through channels etched on the surface of the capillary (connected to an external high- voltage power supply) which delivers sample to ESI-MS. Automatable approach, with great sensitivity. [CHI Proteomics]

CIEF Capillary electrophoresis IsoElectric Focusing: Sample is "focused" in the capillary tube, both separating and concentrating the protein or peptide at its isoelectric point. Then the entire mixture is delivered to the mass spectrometer. Using this technique the researchers have been able to record the molecular weight of all the proteins under study. Can be used to separate proteins from microorganisms. [CHI Proteomics]

Collision Induced Dissociation CID: Introduced in 1968 by chemistry professors, Keith R. Jennings of the University of Warwick, England and [Fred] 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. [S Borman, "A brief history of mass spectrometry instrumentation" May 1998 http://masspec.scripps.edu/Hist-ms-htm]

daughter ions:

detector: Related terms ionization source, mass analyzer

detection limit: See Assays, labels, signaling & detection ultrasensitive

double quadrupole time of flight ESI-Qq-TOF mass spectrometry:

ESI ElectroSpray Ionization: ESI, in conjunction with high- performance liquid chromatography (HPLC) also capable of high molecular weight analysis, is rapidly replacing GCMS techniques for small molecules, including those of interest in metabolic profiling. Robert Cotter "New Mass Spectrometric Techniques for the Analysis of Biological Molecules"  Metabolic Profiling Dec. 3-4, 2001 Chapel Hill, NC    

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 1960’s by chemistry professor Malcolm Dole of Northwestern University, Evanston, but it was put into practice in the early 1980’s by molecular beam researcher John B. Fenn of Yale University (now at the department of chemistry of Virginia Commonwealth University, Richmond). [S Borman, "A brief history of mass spectrometry instrumentation" May 1998 http://masspec.scripps.edu/Hist-ms-htm] Narrower term nanoelectrospray

ESI-MS/MS ElectroSpray tandem Mass Spectrometry: Provides better certainty of protein identification, especially when used in combination with MALDI-TOF, because it generates peptide sequence information as well as mass and predictable fragmentation patterns. Can also be used with mixtures of proteins. Fully automated. Identification is achieved by correlating these data with information in sequence databases. [CHI Proteomics]

ESI-TOF ElectroSpray Ionization-Time of Flight: Companies such as Sensar, Micromass, and PerSeptive have concluded that conventional ESI can be modified for compatibility with the short pulse requirements of TOF. Orthogonal acceleration ESI- TOF is one promising approach. In this technique, a continuous flow of ions (either from a static source or from a flowing system such as capillary electrophoresis) is gently accelerated in one direction, resulting in a densely packed but slowly moving analyte ion stream. A second acceleration mechanism that pulses at right angles to this ion stream pushes a well-defined packet of ions toward a detector, which can be almost any kind of mass analyzer, including TOF. [Bob Sinclair " MALDI- TOF Goes Mainstream" Scientist 13 (12): 18 June 7 1999] http://www.the-scientist.com/yr1999/june/profile2_990607.html

Fourier Transform- Ion Cyclotron Resonance mass spectrometry FT- ICR:

hybrid mass spectrometry: See under tandem mass spectrometry. 

hyphenated techniques: Include EST- MS/MS, ESI- TOF, LC/MS, others?

ion trap glossary: See under quadrupole ion trap.

ion trap mass spectrometry: Arrangement in which ions with a desired range of quotients mass/charge are first made to describe stable paths under the effect of a high- frequency electric quadrupole field, and are then separated and presented to a detector by adjusting the field so as to selectively induce path instability according to their respective mass/charge ratios. [IUPAC MS] Narrower term quadrupole ion trap

ionization source: Related terms detector, mass analyzer

ionization techniques:Include electron ionization (oldest and most widely used), atomospheric pressure ionization API, electrospray ESI, Atmospheric pressure chemical ionization APCI. [Waters Corp.  "Ionization Techniques" 2001 ] http://www.waters.com/Waters_Website/Applications/lcms/lcms_itq.htm

Narrower term: soft ionization techniques

Liquid Chromatography/ Mass Spectrometry LC/MS: Has become an indispensable tool for problem solving in virtually all analytical fields requiring "information rich" chemical analysis.  In the next decade, the LC/MS instrument market is projected to grow at more than twice the rate of the broader instrument market and will likely surpass GC/MS as the leader of the so-called hyphenated techniques. [LC/MS Home page, Chem- Space Associates] http://www.lcms.com/lcms_top.htm

Used for drug screening, pharmacology studies, environmental analyses and forensics.

LIF Laser Induced Fluorescence: Assays, labeling, signaling & detection glossary

MALDI Matrix Assisted Laser Desorption Ionization: A mass spectrometric technique that is used for the analysis of large biomolecules. Analyte molecules are embedded in an excess matrix of small organic molecules that show a high resonant absorption at the laser wavelength used. The matrix absorbs the laser energy, thus inducing a soft disintegration of the sample-matrix mixture into free (gas phase) matrix and analyte molecules and molecular ions. In general, only molecular ions of the analyte molecules are produced and almost no fragmentation occurs. This makes the method well suited for molecular weight determinations and mixture analysis. [MESH]

A critical step in the mass spectrometric characterization of biological materials (analytes) is the process of desorbing the analyte from a surface or matrix into the vacuum of the mass spectrometer. Laser irradiation of a light- absorbing matrix doped with analyte results in release of molecules into the vacuum of the mass spectrometer. Progress is being made in developing quantitative MALDI mass spectrometric methods.  [National Center for Research Resources "Integrated Genomics Technologies Workshop Report" Jan 1999]  http://www.ncrr.nih.gov/newspub/genomic.pdf 

In MALDI, sample molecules are laser- desorbed from a solid or liquid matrix containing a highly UV- absorbing substance. 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 Munster, 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. [S Borman, "A brief history of mass spectrometry instrumentation" May 1998 http://masspec.scripps.edu/Hist-ms-htm]

Narrower terms MALDI- TOF, MALDI- TOF- PMF

MALDI-TOF Matrix Assisted Laser Desorption Ionization-Time of Flight mass spectrometry: With MALDI-TOF (matrix-assisted laser desorption-ionization time-of-flight) mass spectrometry, a laser beam passes through the substances to be analyzed, and the laser causes these elements to vaporize and their molecules to fly upward into a tube. Time of flight through the tube correlates directly to mass, with lighter molecules having a shorter time of flight than heavier ones. [CHI Breaking Bottlenecks]

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. ... Key advances were made by William C. Wiley and I. H. McLaren of Bendix Corp., Detroit MI -  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 time- lag focusing scheme that improved mass resolution by simultaneously correcting for the initial spatial and kinetic energy distributions of the ions … When commercial TOF instruments first came out "their performance in resolution was so poor that they never lived up to even single- focusing magnetic instruments," says [Klaus] Biemann. However, he adds, "this analyzer has been greatly improved recently … to almost match the most sophisticated, and very expensive, double- focusing mass spectrometers." . [S Borman, "A brief history of mass spectrometry instrumentation" May 1998 http://masspec.scripps.edu/Hist-ms-htm]

Related term affinity mass spectrometry.

MALDI-TOF/PMF Matrix Assisted Laser Desorption Ionization-Time of Flight /Peptide Mass Fingerprinting: Currently the fastest standard mass spectrometry approach. Can process only about 100 samples in several hours. [CHI Proteomics] Related term PMF.

MCA Mass Correlated Acceleration: A new pulsed ion extraction technique, which will revolutionise the drug discovery process. This proprietary technology, known as Mass Correlated Acceleration (MCA), has been licensed exclusively to Kratos Analytical (part of Shimadzu Biotech) and will be incorporated into its AXIMA range of MALDI mass spectrometers later this year. MCA produces high mass resolution over a far wider mass range than traditional pulsed extraction technologies. Where previously several different settings of the extraction delay would have been necessary, MCA needs only one. This is important for high throughput, where the number of experiments is critical. [PR Newswire Press Release Shimadzu Biotech, June 6, 2001]  Poster presented by Andrew Bowdler et. al at "Combining Mass Correlated Acceleration and a Curved Field Reflectron" American Society of Mass Spectrometry meeting 2001]

MIMS Multi-isotope Imaging Mass Spectrometry: A cutting edge technology which enables visual and quantitative assessment of intra- and trans- cellular metabolic pathways, signal transduction, virus penetration, and localization of drugs. The world’s first prototype MIMS instrument [was] manufactured by the French company CAMECA, [which] donated  the $2 million instrument to Dr. [Claude] Lechene’s laboratory at Brigham and Women's Hospital in Boston MA.  [NCRR Reporter Oct. 2000]   http://www.ncrr.nih.gov/newspub/oct00rpt/News-sal.htm 

MS/MS scans: Related term tandem mass spectrometry.

MS/MS/MS: See multiple mass spectrometry.

mass analysis: A process by which a mixture of ionic or neutral species is identified according to the mass- to- charge (m/ z) ratios (ions) or their aggregate atomic masses (neutrals). The analysis may be qualitative and/ or quantitative. [IUPAC Compendium]

mass analyzer: A device that separates a mixture of ions by their mass-to-charge ratios. http://chemed.chem.purdue.edu/analyticalreview/mass_spec/msglossary.htm   Related terms detector, ionization source

mass spectrometers:  Generally couple three devices: an ionization device, a mass analyzer, and a detector. The most common ionization techniques used in biology are matrix- assisted laser desorption ionization (MALDI) and electrospray ionization (ESI). ... Once a sample has been ionized, it must be mass analyzed. ...  The most commonly used mass analyzers for protein biochemistry applications are time- of- flight (TOF), triple- quadrupole, quadrupole- TOF, and ion trap instruments. [Jeffrey Perkel "Mass Spectrometry Applications for Proteomics" Scientist 15[16]:31, Aug. 20, 2001 http://www.the-scientist.com/yr2001/aug/profile1_010820.html

mass spectrometry MS: This technique for measuring and analyzing molecules involves introducing enough energy into a target molecule to cause its ionization and disintegration. The resulting fragments are then analyzed, based on their mass/ charge ratios, to produce a "molecular fingerprint." [CHI Breaking Bottlenecks]

This technique can be used to both measure and analyze molecules under study. It involves introducing enough energy into a target molecule to cause its ionization and disintegration. The resulting fragments are then analyzed, based on the mass/ charge ratio to produce a "molecular fingerprint." [CHI Microarrays]

A significant force behind progress in proteomics. [CHI Summit Proteomics]

Narrower terms 2D CE-IMLS 2D Capillary Electrophoresis with inverted Mass Ladder Sequencing, CE-MS, ESI, ESI- MS/MS, ESI- TOF, FT, ICR, hybrid mass spectrometry, ion trap mass spectrometry, LC/MS, MALDI, MALDI- TOF, MALDI- TOF/ PMF, MIMS, MS/MS, MS/MS/MS, multiple mass spectrometry, nanoelectrospray- MS/MS, pyrolysis mass spectrometry, quadrupole ion trap, TOF, tandem mass spectrometer, triple quadrupole 

Mass spectrometry link
Spectroscopy Now, Base Peak mass spectrometry resource, John Wiley & Sons, Ltd., UK http://www.spectroscopynow.com/Spy/basehtml/SpyH/1,9076,4-0-0-0-0-home-0-0,00.html

mass-to-charge ratio m/z: The abbreviation m/ z is used to denote the dimensionless quantity formed by dividing the mass number of an ion by its charge number. It has long been called the mass- to- charge ratio although m is not the ionic mass nor is z a multiple or the elementary (electronic) charge e. The abbreviation m/z therefore, is not recommended. [IUPAC Compendium] 

multiple mass spectrometry MS/MS/MS: Provides even greater certainty of identification and additional characterization information than electrospray ionization/ tandem mass spectrometry. Fully automated. [CHI Proteomics] 

When more than two stages are involved, the technique is called multi- dimensional MS (MS ⁿ where n indicates the number of stages). [Glick]

m/z: See mass to charge ratio

nanoelectrospray-MS/MS: A newer adaptation of ESI methodology in conjunction with MS/MS. Pioneered by Matthias Mann while at EMBL. Only a very small amount of the unseparated peptide mixture is sprayed directly into the MS machine. Many consider this the most sensitive current technique. Can be used with minimal protein sequence (EST) information, but can only be used with purified proteins. Can be used for de novo protein sequencing and study of post-translational modifications. [CHI Proteomics]  Alternatively "nanospray MS/MS". Broader term electrospray

neutral: To the mass spectrometrist, neutral means uncharged, whereas to the biochemist, neutral means underivatized.  [Bill Boggess, Review of Mass Spectrometry Desk Reference by O. David Sparkman, 2000] http://jchemed.chem.wisc.edu/Journal/Issues/2001/Feb/abs168_2.html

parent ion: 

Photoionization Mass Spectrometry PI MS: Is emerging as an important tool for high - throughput pharmaceutical analysis. PI MS meets the requirements for many applications where ESI and atmospheric pressure chemical ionization (APCI) underperform. [Jack Syage et. al "Photoionization Mass Spectrometry} PittCon Mar. 5, 2001]  http://pittcon.omnibooksonline.com/2001/papers/0248.pdf

post- translational modification identification: Proteomics glossary

protein identification: Proteins glossary

pyrolysis mass spectrometry (PyMS): Pyrolysis is the thermal degradation of complex material in an inert atmosphere or a vacuum. It causes molecules to cleave at their weakest points to produce smaller, volatile fragments called pyrolysate (Irwin 1982). Curie- point pyrolysis is a particularly reproducible and straightforward version of the technique, in which the sample, dried onto an appropriate metal is rapidly heated to the Curie- point of the metal. A mass spectrometer can then be used to separate the components of the pyrolysate on the basis of their mass- to- charge ratio (m/z) to produce a pyrolysis mass spectrum (Meuzelaar et al 1982), which can then be used as a "chemical profile" or fingerprint of the complex material analysed. The combined technique is then known as pyrolysis mass spectrometry (PyMS).  [Pyrolysis Mass Spectrometry at Aberystwyth, 1996]  http://gepasi.dbs.aber.ac.uk/roy/pymshome.htm

quadrupole analyzers:

quadrupole ion trap: A quadrupole ion trap is an instrument roughly the size of a tennis ball whose size is inversely proportional to its versatility. Three hyperbolic electrodes, consisting of a ring and two end caps, form the core of this instruments. In the early 1950’s, Wolfgang Paul and co- workers invented … the quadrupole mass filter … [and] the quadrupole ion trap … The chemistry community’s interest in the trap was confined to several research groups until 1983 when George Stafford and co- workers at Finnigan MAT made two major advances. First they developed the mass-selective instability mode of operation ..and [then] greatly improved the mass resolution. [K Jonscher and JR Yates III "Whys and Wherefores of Quadrupole Ion Trap Mass Spectrometry" ABRF News Sept 1996, includes ion trap glossary] http://abrf.org/ABRFNews/1996/September1996/sep96iontrap.html

quadrupole mass analyzer: Arrangements in which ions with a desired quotient mass/ charge are made to describe a stable path under the effect of a static and a high- frequency electric quadrupole field, and are then detected. Ions with a different mass/ charge are separated from the detected ions because of their unstable paths. [IUPAC Mass Spectrometry, IUPAC Compendium].

REMPI Resonance Enhanced MultiPhoton Ionization: Similar in detection methods to FTIR; however, it has much higher sensitivity capabilities for an entirely different species of gases.  REMPI has proven very successful in the monitoring and characterization of trace amounts of dioxins in the air, including benzene, chlorobenzene and a variety of benzene derivatives.  One of the most astounding characteristics of REMPI is its ability to separate various isomers. ... Typically coupled with mass spectrometry in monitoring of atmospheric constitutents. [Philip Sheehy "The Air We Breathe" MIT, 2001] http://web.mit.edu/sheehy/www/The%20Air%20We%20Breathe/techniques/REMPI.htm

SEQUEST: http://fields.scripps.edu/sequest/  Software which correlates uninterpreted tandem mass spectra of peptides with amino acid sequences from protein and nucleotide databases. SEQUEST will determine the amino acid sequence and thus the protein(s) and organism(s) that correspond to the mass spectrum being analyzed. [Jimmy Eng, John Yates "SEQUEST HomePage Scripps Research Institute, 1999]

SIFT-MS Selected Ion Flow Tube Mass Spectrometry:  A sensitive and quantitative technique for trace gas analyses using the chemical ionisation of the sample trace gases by selected positive ions during a well- defined time period along a flow tube. A major motivation for its development was a need for on- line quantification of trace gases in human breath for clinical diagnosis and therapeutic monitoring. SIFT-MS has also great potential as a tool for non-invasive physiological monitoring. http://sift.hyperlink.cz/

Secondary Ion Mass Spectrometry SIMS:

soft ionization techniques: Include MALDI and ESI. 

TOF Time-Of-Flight mass spectrometer: An arrangement using the fact that ions of different mass- charge need different times to travel through a certain distance in a field- free region after they have all been initially given the same translational energy. [IUPAC Mass Spectrometry, IUPAC Compendium] Narrower term ESI- TOF, MALDI- TOF

tandem mass spectrometer MS/MS: An arrangement in which ions are subjected to two or more sequential stages of analysis (which may be separated spatially or temporally) according to the quotient mass- charge. A hybrid mass spectrometer is an instrument which combines analysers of different types, e.g. magnetic plus electric sector combined with quadrupole. The study of ions involving two stages of mass analysis has been termed mass spectrometry/ mass spectrometry. [IUPAC Mass Spectrometry, IUPAC Compendium]

In tandem MS the first spectrometer determines an initial molecular weight for the peptides. A first mass film selects a specific peptide, transmit it into a collision cell, which breaks the peptide into smaller fragments. A second spectrometer determines the mass of these fragments. Finally, specially designed computer tools analyse the peptide sequences.  [EMBL Heidelberg, Germany, Annual Report 1996 "Scientific Programmes"] http://www.embl-heidelberg.de/ExternalInfo/ScientificProgrammes/AR96/Biochemical2.html

triple quadrupole: 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, Australia, helped Yost and Enke reduce the technique to practice. [S Borman, "A brief history of mass spectrometry instrumentation" May 1998 http://masspec.scripps.edu/Hist-ms-htm]

Bibliography

[IUPAC Mass Spectrometry] Recommendations for nomenclature and symbolism for mass spectroscopy, Pure and Applied Chemistry 63:1541-1563, 1991

[JASMS] ASMS terms published Journal of the American Society of Mass Spectrometry 2(4):336-448 1991: Next compilation to be published in the next 18 months (11/99) 

[Micromass] Glossary http://www.micromass.co.uk/basics/Glossary.html

[Protein Peptide] Microanalytical Lab, Terms, definitions & bibliography California Institute of Technology, US, 2001. http://www.cco.caltech.edu/~ppmal/sample_prep/term_def.html

Purdue Univ. (US) Analytical Chemistry, Glossary of Common Mass Spectrometry Terms, 2001. http://chemed.chem.purdue.edu/analyticalreview/mass_spec/msglossary.htm

Spectroscopy Now Mass Spectrometry glossary, Prof. Anthony Mallet, 2001. http://www.spectroscopynow.com/Spy/basehtml/SpyH/1,9076,4-1-2-0-0-news_detail-0-34,00.html

Alpha glossary index

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.