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P.S.P. MSGlossary from :

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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

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

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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]

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 Mass Spectrometry: 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,
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]
Narrower term nanoelectrospray
A mass spectrometry technique used for analysis of nonvolatile compounds such as
proteins and macromolecules. The technique involves preparing electrically charged
droplets from analyte molecules dissolved in solvent. The electrically charged droplets
enter a vacuum chamber where the solvent is evaporated. Evaporation of solvent reduces
the droplet size, thereby increasing the coulombic repulsion within the droplet. As the
charged droplets get smaller, the excess charge within them causes them to disintegrate
and release analyte molecules. The volatilized analyte molecules are then analyzed by
mass spectrometry. [MeSH, 2001]
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

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patterns. Can also be used with mixtures of proteins. Fully automated. Identification is
achieved by correlating these data with information in sequence databases. [CHI
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]

FIA/MS: See Flow Injection Analysis
Fast Atom Bombardment Mass Spectrometry FAB/MS: A mass spectrometric
technique that is used for the analysis of a wide range of biomolecules, such as
glycoalkaloids, glycoproteins, polysaccharides, and peptides. Positive and negative fast
atom bombardment spectra are recorded on a mass spectrometer fitted with an atom gun
with xenon as the customary beam. The mass spectra obtained contain molecular weight
recognition as well as sequence information. [MeSH, 1991]
Flow Injection Analysis: The analysis of a chemical substance by inserting a sample
into a carrier stream of reagent using a sample injection valve that propels the sample
downstream where mixing occurs in a coiled tube, then passes into a flow- through
detector and a recorder or other data handling device [MeSH, 1992].
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 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

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ion trap glossary: See under quadrupole ion trap.

ionization source: Related terms detector, mass analyzer

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]
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 Mass Spectrometry: 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]
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
Narrower terms MALDI- TOF, MALDI- TOF- PMF

P.S.P. MSGlossary from : 5

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]
MALDI (Matrix-Assisted Laser Desorption-Ionization) TOF (Time Of Flight) mass
spectrometry DNA sequencing also has promise. The MALDI-TOF mass spectrometer
measures the exact mass of DNA fragments and is capable of accurately predicting the
sequence of a DNA fragment based on the molecules mass. MALDI (Matrix-Assisted
Laser Desorption-Ionization) TOF (Time Of Flight) mass spectrometry DNA sequencing
also has promise. ... The [Sequenom] MALDI-TOF mass spectrometer measures the
exact mass of DNA fragments and is capable of accurately predicting the sequence of a
DNA fragment based on the molecules mass. [CHI High Throughput Genomics]
Genomic Report, Dec. 2001.
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
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

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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]
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. 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
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,

P.S.P. MSGlossary from : 7

pyrolysis mass spectrometry, quadrupole ion trap, TOF, tandem mass spectrometer, triple
mass spectrum analysis: Analysis of the mass of an object through means of
determining the wave length(s) at which electromagnetic energy is absorbed by that
object. [MeSH, 1974]
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]

Peptide Mass Fingerprinting: Proteins glossary
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]
post- translational modification identification: Proteomics glossary
protein identification: Proteins glossary

P.S.P. MSGlossary from : 8

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]

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]
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]

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

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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.
Secondary Ion Mass Spectrometry SIMS: A mass- spectrometric technique that is used
for microscopic chemical analysis. A beam of primary ions with an energy of 5- 20
kiloelectronvolts (keV) bombards a small spot on the surface of the sample under ultra-
high vacuum conditions. Positive and negative secondary ions sputtered from the surface
are analyzed in a mass spectrometer in regards to their mass- to- charge ratio. [MeSH,
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
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
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