A Mass Spectrometry Glossary

Every scientific discipline develops its own specialized nomenclature, and also a tendency to spawn new terms and acronyms to reflect the evolution of the science and its applications. Mass spectrometry (MS) is no different, but because modern MS is a particularly dynamic and rapidly evolving mixture of applications, instrumentation, and data interpretation, MS might be the complex exemplar for just how nomenclature develops. A list of approved terms generated with much care by a committee of the American Society for Mass Spectrometry is available (1). A new print publication, Dictionary of Mass Spectrometry (2), has recently become available and almost certainly will need to be updated regularly. The Mass Spec Desk Reference by David Sparkman can be treated as a definitive source for terms in MS (3). The specialized terms in MS describe instruments, procedures, interpretations, and results. These terms are often used without definition or explanation in technical presentations that involve MS.

Kenneth L. Busch

The first iteration of this glossary appeared in 2002 in Spectroscopy to provide some basic guidance. Many web-based glossaries of MS terms have appeared subsequently, and most have since disappeared, casualties of the need for constant revision. The purpose of this glossary, now revised and expanded, remains to compile some of the more widely used terms that may be encountered in MS, and for which a simple definition might prove helpful to start (not end) the process of comprehension. The definitions given here are necessarily brief, definitely neither committee-derived nor authoritative, and should be sufficient to provide basic understanding. Note that each term encompasses subtle and changing shades of meaning in use; if it becomes static, then the definition is archival. While the mavens of precise and unchanging meaning debate every nuance of use, the rest of us marvel at the underlying science and how terms morph to describe it. This glossary, like the printed dictionary, will shrivel if not refreshed and renewed regularly.

Clearly, some manner of a selection process has been exercised by this author to keep the length of this glossary within reason. Responsibility for selection and definition of these glossary terms resides solely with the author. Those in search of more authoritative and comprehensive compilations would do well to begin with references 1 or 3, or Price's archival ASMS compilation (4). Earlier IUPAC recommendations for terms for use in MS can be found in an article by J.F.J. Todd (5). Sparkman's current glossary (3) is an update of a previous version, and is expanded to contain new terms from several application areas of biological MS, terms specific to instrumental MS, and terms derived from keywords used by the American Society for Mass Spectrometry to organize abstracts and presentations for its annual meeting. Definitions for more-specialized MS terms are available in several glossaries found on the web, or the terms can be used as search string targets for a search engine. The arrangement of terms here is strictly alphabetical, in contrast to some web glossaries that separate terms within broad general areas. After all, if one has to look up the meaning of a term, it's not likely that one would know which category to start with. Many of these terms are associated with acronyms or abbreviations, which are given in parentheses. A listing of acronyms and abbreviations is regularly published in Spectroscopy. Positive ions are used as the default descriptive example throughout the text.

A

Accelerating voltage (V)

The accelerating voltage is applied to the source to move ions formed in the source into the mass analyzer of the instrument. This accelerating voltage can range from a few tens of volts in quadrupole mass spectrometers to several thousand volts in sector instruments or in time-of-flight mass spectrometers. The accelerating voltage establishes the velocity of the ions through the instrument via the equation equating potential energy to kinetic energy, equal to ½mv², where v is the velocity of the ion and m is its mass.

Accelerator mass spectrometry (AMS)

In this specialized method, atomic ions are formed from the sample by charge stripping in a very high voltage source, usually coupled to a Van de Graff accelerator. AMS is used for low-level analysis of ¹⁴C isotopes in radiocarbon dating and biological tracer studies.

Accurate mass

The accurate mass (or exact mass) of an ion of specified isotopic composition is calculated by summation of the exact masses of the constituent atoms. Conversely, the empirical formula of an ion can be deduced from the measured accurate mass of the ion if the ion mass is low enough to limit the number of formulaic possibilities and if the exact mass value is known accurately enough.

Analyzer

The analyzer is the section of the mass spectrometer in which ions (formed in the source) are differentiated on the basis of their mass-to-charge ratios. The detector of the instrument is located after the mass analyzer in a beam-type instrument.

Aperture

An aperture is a small hole through which an electron or ion beam passes that controls the path or direction of the beam. The size of the aperture is important in maintaining a focus for imaging applications. A conductance-limited aperture is also used to maintain differential pressures in various physical regions of a mass spectrometer.

Array detector

In MS, an array detector is an electronic device that detects ions arriving at different spots along the array. A film (photoplate) detector for a mass spectrograph was an early example of an array detector; the film has since been replaced by electronic devices. Advantages are derived from the fact that scanning to bring ions of different m/z values to a point detector may be avoided.

Atmospheric pressure chemical ionization (APCI)

In this method of ionization, an aerosol of sample solution is sprayed at atmospheric pressure into a heated region in which a sharp metal pin held at high potential sustains a corona discharge. The action of the discharge on the solvent creates reagent ions that react with the neutral sample molecules to create protonated ions of the molecule. These ions then pass through a sampling aperture into the mass analyzer of the mass spectrometer.

Atmospheric pressure photoionization (APPI)

In this method of ionization, closely related to APCI, a UV source is used to ionize either sample molecule or added donor molecules that can then react together in a variety of ion–molecule reactions. Although protonated molecules are often formed, the ionization chemistry can be modified through judicious choice of the solvents and donor molecules.

Atomic mass unit (amu)

The atomic mass unit represents the relative scale in which the mass of ¹H is given an integral value of 1, ¹²C is 12, and so on. The amu is an older unit, replaced by the unified atomic mass unit u. More recently the u has been replaced by the unit dalton (Da).

Auxiliary gas

Some APCI and electrospray source designs use a flow of what is called the auxiliary gas (or sheath gas) to help control the dispersal of droplets and aid in the reproducibility of the ionization process.

Average mass

The average mass of an ion of a known empirical formula is calculated by summing the relative average atomic mass of each atom present. For example, carbon has an average atomic mass of 12.01115 Da, hydrogen is 1.00797 Da, and so on. The average mass of the molecular ion of a chemical compound is also the mass that appears on the bottle. However, a mass spectrum actually does not contain any peak at the average mass. Instead, signals appear for ions of various isotopic compositions. The average mass corresponds to the center of the centroid signal recorded for higher mass ions at lower instrumental resolutions.

B

Base peak

The base peak in a mass spectrum (within the user-selected mass range) is the ion with the highest measured abundance. The relative abundance of the base peak ion is assigned a value of 100, and the abundances of all the other ions plotted in that mass spectrum are normalized to that value. The y-axis in a mass spectrum is therefore given in terms of relative abundance.

Beam divergence

Beam divergence is the angular spread (usually measured in degrees) of an electron or ion beam emitted by a source. Minimized beam divergence is important in maintaining focus in imaging mass spectrometry, and in maintaining coherence of an ion beam as it transits a beam mass spectrometer. Beam density (related to beam divergence) is important in assessing space charge effects.

Beam mass spectrometer

In a beam mass spectrometer, an ion beam emanating from the source transits through a mass analyzer component through to the detector of the instrument. The total ion beam flight path in a mass spectrometer can be a few tens of centimeters to as long as several meters.

Bottom-up sequencing

This is an approach to peptide sequencing in which MS analysis of the smaller sections of sequences (as might be obtained after a digestion or degradation) provides overlapping chains of amino acids that are stitched together into the final sequence.

C

Calibration

Calibration is a process in which the operation of the mass spectrometer in a specified manner is adjusted and certified to produce the accurate and known ion masses in the spectrum of a standard compound.

Charge stripping

Charge stripping is a process by which atomic ions are transformed into a higher charge state, thereby changing their mass-to-charge ratios. Different cross-sections for charge stripping of isobaric atomic ions allow their differentiation and subsequent trace-level analysis.

Chemical ionization (CI)

Chemical ionization is a process of ionization that involves the reaction of a reagent ion and a neutral molecule to yield a charged ionic form of the molecule. The first step in chemical ionization is creation of the reagent ion through electron ionization of the reagent gas molecules present in great excess. A stable population of reagent ions is formed through ion/molecule reactions, and these ions will eventually react with the neutral gas-phase sample molecules. In a common case, methane gas is ionized to form predominantly CH₅⁺, which then reacts with the neutral sample molecule in a process of protonation to form (M + H)⁺.

Collision energy

In a collision between an ion (moving with some kinetic energy imposed in a mass spectrometer by the accelerating potential) and a neutral gas molecule (as forms the basis of collision-induced dissociation), it is often convenient to adopt a frame of reference in which the neutral gas molecule is considered to be stationary, and the collision energy is the translational kinetic energy of the ion.

Collision-induced dissociation (CID)

In a collision between an ion and a neutral species, a portion of the ion translational energy is converted to internal energy. This internal energy causes dissociation of the ion into smaller fragment ions and can also cause changes in the ion charge. Collision-induced dissociation is also known as collisionally activated dissociation. CID is common in MS-MS experiments.

Constant neutral loss scan

In an MS-MS experiment, mass-selected precursor ions are induced to dissociate into product ions, which are then mass analyzed by a second analyzer. There are three common scans in a single-step MS-MS experiment: the product ion scan, the precursor ion scan, and the constant neutral loss scan. In the latter, both mass analyzers are scanned at the same rate, with a mass offset between them. Therefore, only ions that dissociate by loss of the specified neutral species mass will form a precursor–product ion pair that is passed through to the detector.

D

Dalton (Da)

This is a newer unit of mass taken as identical to u (the unified atomic mass unit), but not accepted as standard nomenclature by the IUPAC or IUPAP. The dalton or u is equal in mass to 1/12 the mass of a ¹²C atom. Mass is often expressed by biologists as kilodaltons and abbreviated kDa, and this unit sometimes appears as the label on the x-axis of a mass spectrum.

Decade

In MS, the term decade is used in a description of the scan range in which the ion masses at either end differ by a factor of ten. For example, a scan of a mass analyzer from m/z 60–600 covers one decade of mass. The term is used especially to describe the scanning speed of a mass analyzer, usually as seconds per decade.

Deconvolution

In MS, deconvolution has several different meanings. In gas chromatography (GC)–MS, deconvolution is the use of detailed mass spectral information to establish the presence and peak profiles for coeluted or closely eluted compounds. In mass spectral interpretation, deconvolution is used to resolve isobaric interferences that result in summed ion intensities at particular m/z values. Deconvolution is also the term to describe the mathematic process through which a series of multiple charged ions in an electrospray ionization mass spectrum are transformed into a single molecular mass.

Delayed extraction (DE)

Delayed extraction is an experimental technique in time-of-flight mass spectrometry in which improved mass resolution is obtained by using a controlled time delay between the initial pulse of ion formation and acceleration of the ions into the flight tube of the instrument. The technique is also called time-lag focusing.

Derivatization

As part of sample preparation for subsequent MS analysis, samples can be derivatized to create new forms of molecules that are more stable, shifted in mass, or ionized with higher efficiency.

Desorption ionization (DI)

This is a general term used to group various methods (secondary ion mass spectrometry, fast atom bombardment, californium fission fragment desorption, and plasma desorption) in which ions are generated directly from a sample by rapid energy input into the condensed phase sample. There may be no discrete process of desorption (in the thermal sense), but instead a transfer of usually nonvolatile sample molecules into the gas phase as ions that can be mass-analyzed subsequently.

Detection limit

The detection limit of an instrument or system is the smallest flow of sample into the source of the mass spectrometer (or the lowest partial pressure of sample gas) that gives a signal that can be distinguished from background noise. Often this is listed as the limit of detection, and specified at a signal-to-noise ratio of 3. The limit of quantitation is usually higher. The detection limit of a method is not the sensitivity of the method. The detection limit is a value. It is not "lower than" some value, a statement that is as meaningless as it is common.

Differential pumping

Different pressures can be maintained in different regions of a mass spectrometer with limiting conductance apertures and independent pumping systems. For instance, electrospray ionization sources usually operate near atmospheric pressure, while most mass analyzers operate at much lower pressures. Accurate measurement of the pressure profile along an ion flight path is often difficult.

Direct analysis in real time (DART)™

Energized species formed in a plasma are entrained in a nitrogen gas stream that is directed into the surface to be analyzed. The energized species cause the formation of ions from neutral sample molecules resident at the surface. The ions are extracted from the surface in a flow of gas and pass through a series of conductance-limiting apertures into the mass spectrometer.

Direct electrospray ionization (DESI)

Charged droplets from the needle in an electrospray source are used to bombard a surface. A fraction of the molecules on the surface are entrained within the solvent droplets, which are directed in a gas flow through conductance-limiting apertures into a mass spectrometer.

Direct exposure probe (DEP)

This is a variant of the direct insertion probe (or direct probe) in which the sample is coated on a surface that is inserted within the ion source of the mass spectrometer, and thus exposed to the ionization beam in the source directly. The direct exposure probe can be used to generate mass spectra of otherwise nonvolatile sample molecules.

Direct insertion probe (DIP)

The direct insertion probe is a shaft having a sample holder at one end. The probe is inserted through a vacuum lock to place the sample holder near the ion source. The sample is vaporized by heat from the ion source or by heat from a separate heater surrounding the sample holder. The sample molecules are evaporated into the ion source where they are then ionized as gas-phase molecules.

Distonic ion

In a distonic ion, the charge site and the site of the radical are formally located on different atoms in the molecule.

Divert valve

A divert valve is located between a chromatograph (gas or liquid) and the source of a mass spectrometer, and acts to either allow the flow from the chromatograph to enter the source or not.

Double-focusing mass spectrometer

A magnetic analyzer and an electric analyzer are combined in a specified geometrical configuration and sequence to accomplish both direction and velocity focusing of an ion beam from an ion source. This combination provides a higher instrumental resolving power and the ability to make more accurate mass measurements for ions.

E

Electric sector (E)

The electric sector is a device constructed of curved, parallel metal plates that creates an electrostatic field perpendicular to the ion path. The sector (or analyzer) selects and focuses ions of the same kinetic energy. The electric sector does not separate ions according to mass or charge, and therefore is always used in conjunction with a magnetic analyzer, often in a double-focusing mass spectrometer. The electric sector also is sometimes called an electrostatic sector or electrostatic analyzer.

Electron affinity

Strictly, the electron affinity is the enthalpy change for the process M^– → M + e^–. In more general terms, the electron affinity is used to describe the relative ability of a molecule to capture a thermal electron without dissociation. Electophoric is a related term, and electron attachment is the generic term for the process that is used to describe ionization processes.

Electron attachment

Electron attachment is a process in which an electron of thermal energy is added to an atom or molecule (M) to form a stable ion (M^–⋅). The molecule must have a positive electron affinity (for example, be electrophoric). Thermal electrons are required so as not to cause dissociation of the molecular ion.

Electron capture dissociation (ECD)

Alternatives to collision-induced dissociation have been developed recently, with applications in sequencing of peptides via MS-MS. One such method is electron capture dissociation, exemplified by a reaction in which a multiply positive charged molecular ion (M + nH)ⁿ⁺ captures a low-energy electron to create an ion of the same mass, but with one less positive charge. Because this ion usually is formed in an excited state, that excess energy causes dissociation. The advantage is that the excitation energy can be channeled into dissociations different from those accessed in other forms of induced dissociation, allowing a fuller coverage of the sequence information in a top-down sequencing experiment.

Electron energy

The electron energy is the potential difference through which electrons are accelerated in the ionization source; these electrons are those used to initiate the electron ionization process. The term ionizing voltage is used sometimes in place of electron energy. The electron energy for standard electron ionization mass spectra is 70 eV, chosen to maximize ion production and provide reproducible mass spectra.

Electron ionization (EI)

Electron ionization is the process of molecular ionization initiated by interaction of the gas-phase molecule with an energetic electron. The beam of electrons is emitted from a heated metal filament in the source, and the electrons are accelerated through a potential difference of 70 V. The collision between the molecule and the electron causes the ejection of an electron from the molecule (M) and produces a radical molecular ion in which the unpaired electron is indicated by the superscripted dot (M^–⋅). The overall process is: M + e^– → M^+⋅ + 2e^–. An older term for electron ionization is electron impact.

Electron multiplier (EM)

An electron multiplier is a detection device inside the vacuum of the mass spectrometer that converts the arrivals of ions at its front dynodes into a detectable, amplified electron current at the back lead of the device. The overall gain (signal out/signal in) can be as high as 10⁴ –10⁸. Positive ions exiting from the mass analyzer impact the first dynode surface, and the impact causes the release of several electrons, which are then accelerated through a potential to the next electrode. There, each electron impact causes the release of several secondary electrons, which are accelerated into the next dynode for a repetition of the impact–release process. A cascade of electrons is produced, generating a current that is further amplified and then sampled by an analog-to-digital converter to be recorded by the data system.

Electron transfer dissociation (ETD)

Electophoric compounds easily create radical anions when reacted with thermal electrons. These negative molecular anions are reacted in an ion–ion reaction with multiply charged positive ions (M + nH)ⁿ⁺. That reaction involves an electron transfer that creates an ion of the same mass, but with one less positive charge. Because this ion is usually formed in an excited state, that excess energy causes dissociation. The advantage is that the energy can be channeled into dissociations different from those in other forms of induced dissociations, allowing a fuller coverage of the sequence information in a top-down sequencing experiment.

Electrospray ionization (ESI)

In the electrospray ionization process, a solution containing the molecules of interest is pumped through a metal capillary tube held at a high potential. The solution is sprayed from the tube into a chamber held at ground and open to atmospheric pressure. The sample solution spray creates small droplets that carry a charge induced by the needle potential. The droplets in the mist become progressively smaller as the neutral solvent molecules evaporate. The charge is maintained on the surfaces of the droplets, eventually causing an instability that results in the expulsion of solventless, highly charged ions of the dissolved sample molecules. Multiple protonation can occur to form highly charged sample molecules of the form (M + nH)ⁿ⁺.

Even-electron ion

An even-electron ion contains no unpaired electrons; for example, CH₃⁺.

F

Faraday cage

A Faraday cage is a hollow metal cylinder used as an ion detector. Ions enter the open end and then impact the metal walls or the closed end. The summed ion current carried by the ions is measured directly. Each singly charged ion carries a charge of 1.6 × 10^–19 coulombs. The term Faraday cup is also used for this device, which often is used to measure ion current in absolute terms, without any possible mass discrimination as might be encountered with an electron multiplier detector.

Fast-atom bombardment (FAB)

Fast-atom bombardment uses a beam of neutral atoms (created by neutralization of ions of about 5 keV energy) to sputter sample molecules from a liquid solution held on the surface of a beam-intersecting sample probe. The atom impact deposits energy into the semivolatile matrix, causing desorption of many species including ions, neutral molecules, and clusters of solvent and sample molecules. Desolvation follows desorption, and molecules (M) usually are ionized in a process of protonation to form (M + H)⁺. The mass spectra usually contain a large background of ions from the energy moderating solvent. Glycerol was the first widely used FAB solvent, but many others have been developed.

Field-free region (FFR)

In the flight path of an ion from the source of the mass spectrometer through the mass analyzer to the detector, the ion may pass through regions in which there is no specific magnetic or electric field. These are field-free regions, as in the portion of the ion path between the electric and magnetic analyzers in a double-focusing mass spectrometer, or between the source and the first sector of both single- and double-focusing mass spectrometers. Unimolecular ion dissociations in these regions can occur to give rise to signals in the mass spectrum recorded under normal conditions (metastable ions), or can be investigated specifically.

Fragment ion

A fragment ion is the charged product of an ion dissociation. A fragment ion may be stable itself or may dissociate further to form other charged fragment ions and neutral species of successively lower mass. Molecular ions formed in the initial ionization process dissociate to fragment ions because of the excess internal energy that remains after ionization. Note that ions dissociate rather than decompose.

G

Glow discharge (GD)

In a glow discharge source for MS, the sample to be analyzed is formed into a cathode that supports a plasma discharge created from argon gas. Positive argon ions formed in the plasma sputter the cathode surface and release both molecules and ions from the surface of the cathode. Neutral molecules are ionized in the plasma, and then all ions are drawn into the mass analyzer of the instrument for mass analysis. GD sources typically are used for trace-level elemental quantitation in a wide variety of insulating and noninsulating solid samples.

H

Hybrid mass spectrometer

A hybrid instrument for MS-MS includes any instrumental configuration in which at least two component "mass" analyzers (selectors) of different types are arranged in sequence from ion source to ion detector.

I

Ion cyclotron resonance (ICR)

An ion cyclotron resonance mass spectrometer is a device for storage and mass analysis of ions. The ions are held in the cell by a combination of a static magnetic field and a coincident electrical field generated by potentials applied to all walls of the metal cell. Ions attain a coherent cyclotron orbit with frequency proportional to mass. In a modern instrument, ions are detected by monitoring the alternating electrical current generated in detector plates by their regular orbits. A mathematical process termed a Fourier transformation (FT) converts the monitored frequency to ion mass.

Ionization energy

The ionization energy is the minimum energy required to remove an electron from an atom or molecule in order to produce a positive ion.

Ionization gauge

An ionization gauge is a device used to measure pressure in the range of 10^–3 to 10^–10 torr. A regulated electron current emitted from a filament traverses a volume and ionizes a relatively constant fraction of the gas molecules. Those ionized gas molecules are collected on a wire (the collector wire), and the current is amplified and displayed on a gauge calibrated in units of pressure. The response of the ionization gauge is strictly dependent upon the composition of the gas, but the device has been thoroughly calibrated for use in the designated pressure range when pumping from atmosphere.

Ion/molecule reaction (I/M rxn)

This reaction occurs between an ion and a neutral gas-phase molecule to cause ionization (as in the process of protonation in chemical ionization), or changes in the internal energy of one or both of the reactants.

Ion trap analyzer

An ion trap analyzer consists of two end caps and a ring electrode assembled into a compact device that serves as a mass analyzer. The three-dimensional, rotationally symmetric quadrupole field stores ions (externally generated) at its center. An additional electrical signal is then applied to selectively eject ions to an external detector.

Isobaric ion

Isobaric ions have identical masses (at whatever level of accuracy chosen) but have different atomic compositions. A common example is a positive ion at m/z 28, which can have the empirical formulas of CO⁺, N₂⁺, or C₂H₄⁺.

Isotope

Isotopes are atomic forms of elements that contain the same numbers of protons and electrons, but different numbers of neutrons. For example, chlorine consists of two naturally occurring isotopes: ³⁵Cl, atoms of which consist of 17 protons, 17 electrons, and 18 neutrons; and ³⁷Cl, which has atoms containing 17 protons, 17 electrons, and 20 neutrons. Mass spectrometry does not usually deal with radioactive isotopes, except in special instances such as some forms of isotope ratio MS.

Isotope ratio mass spectrometry (IRMS)

Isotope ratio mass spectrometry provides high-accuracy, high-precision measurements to determine ratios of atomic isotopes, usually in small amounts of gaseous samples. These ratios are used in geochemistry, cosmological chemistry, dating, and tracer studies.

K

Kendrick mass

The Kendrick mass (and associated Kendrick mass defect and Kendrick map) was a computational aid developed to highlight a series of homologous ions differing by the mass of the methylene unit CH₂ in complex data usually derived from petroleum and fossil fuel samples. It can be especially useful in aiding the examination of higher-resolution data obtained with FTMS instruments.

L

Linked scan

In a sector instrument with both magnetic and electric sectors, a linked scan is an experiment in which both sector field values (the magnetic and the electric sector values) are changed simultaneously so that ion mass- and charge-changing reactions that occur after the ion source, but before the sectors, or in the field-free region between the sectors, can be recorded in a mass spectrum.

M

Magnetic analyzer (B)

A magnetic analyzer creates a magnetic field perpendicular to the ion path and, in conjunction with entrance and exit slits along the flight path, selects and focuses ions of a selected momentum (and, nominally, then, with the same mass-to-charge ratio) through to the detector. A magnetic analyzer is also called a magnetic sector. An instrument that includes magnetic or electric analyzers is called a sector mass spectrometer.

Mass (range) chromatogram

A selected ion chromatogram is a reconstruction of data that plots the relative intensity of a single ion with time. It is a form of mass chromatogram, which in the more general sense plots the relative intensities of one ion, several ions, or all ions within a specified mass range with time.

Mass defect

The term mass defect has an "official" meaning that is quite different from one of its meanings in MS. Officially, the mass defect is the difference in the mass of a polyatomic atom and the sum of the masses of all of the particles (electrons, protons, and neutrons) of which it is composed. This mass defect occurs because matter is converted into energy according to the Einstein equation; this energy binds the nucleus together and overcomes the mutual repulsion between protons. In MS, the mass defect is the term also used for the difference (whether positive or negative) between the exact mass of an ion and the nearest integer mass.

Mass spectrometry–mass spectrometry (MS-MS)

MS-MS is a concept that recognizes ions as reactive entities that can be interrogated. The prototype MS-MS instrument consists of two independently operated mass analyzers linked by a reaction region in which the ion can be induced to react. Induction often occurs through collision (collision-induced dissociation), in which a selected higher-mass ion dissociates to a smaller product fragment ion. Even in this simple conceptual instrument, three experiments are possible: precursor ion scan, product ion scan, and constant neutral loss scan. MS-MS that recurs over multiple steps is known as MSⁿ. MS-MS is also known as tandem MS, but this latter term is allied more closely with the instrument than with the experiment.

Mathieu stability diagram

A graphical representation for reduced variables that incorporate the values of dc and ac voltages applied either to the four rods of a quadrupole mass filter or to the electrodes of an ion trap. The stability diagram illustrates areas of ion stability and ion instability and designates scan lines for the changes in those voltages so that the device can serve as a mass-to-charge ratio analyzer.

Matrix

For the analysis of a targeted compound, the matrix is everything else other than the targeted compound in the actual sample. Sample cleanup and sample preparation usually remove most of the matrix, which usually is considered detrimental to an accurate analysis. Matrix effects work in both directions, though, and ionization methods such as MALDI depend upon the presence of the matrix to work well.

Matrix-assisted laser desorption ionization (MALDI)

In MALDI, sample molecules are mixed with an excess of an energy-absorbing (usually solid) matrix. The mixture is co-crystallized in a thin film on an inert metal support. Repetitive irradiation of the film with a pulsed laser releases ions from the surface, which usually are accelerated into a time-of-flight mass spectrometer. Because the matrix is usually a solid organic acid, the predominant mode of ionization is protonation of the sample molecule M to form (M + H)⁺.

Mean free path

The mean free path is the average distance that an ion or a neutral molecule will travel between collisions. The mean free path is an inverse function of pressure; the lower the pressure, the longer the mean free path. In MS, in order to extract, focus, and mass analyze ions, the mean free path should be longer than the physical distances over which the extraction, focusing, or mass analysis processes occur. At the usual pressures used in mass analyzers of MS instruments, the mean free path is hundreds of centimeters.

Membrane inlet mass spectrometry (MIMS)

A membrane inlet system consists of a semipermeable membrane that permits passage of gas-phase volatile sample molecules directly into the mass spectrometer ion source, which usually is operated as an electron ionization or chemical ionization source.

Metastable ion

A metastable ion is a precursor ion that dissociates into a fragment ion and neutral species after leaving the ion source (that is, after acceleration) but before reaching the detector. The dissociation is observed most readily when it takes place in one of the field-free regions of a sector mass spectrometer.

Molecular ion

A molecular ion is formed by the removal (positive ions) or addition (negative ions) of one or more electrons from a molecule M to form M^+⋅ or M^–⋅. The mass of the molecular ion corresponds to the nominal or monoisotopic mass of the molecule, with the mass of the electron added or lost usually inconsequential. Of course, the mass of such a molecular ion reflects the isotopic composition of the ion, rather than the average molecular mass of the molecule. Thus, the molecular ion mass is the sum of the relative masses of the most abundant naturally occurring isotopes of the various atoms that make up the molecule.

Monoisotopic ion mass

The monoisotopic mass of an ion is defined as the mass of an ion for a given empirical formula calculated using the exact mass of the most abundant isotope of each element; for example, ¹²C = 12.000000 Da (exactly), ¹H = 1.007825 Da, ¹⁶O = 15.994915 Da.

Multiple-reaction monitoring (MRM)

The MS-MS experiment uses two sequential stages of independent mass analysis. In the product ion MS-MS scan, a precursor ion is selected by mass with the first mass analyzer, and the fragment ions formed as a result of collision-induced dissociation are measured with a scan of the second mass analyzer and recorded in a mass spectrum. In an analogy to selected ion monitoring, if both mass analyzers in an MS-MS instrument are set on a specific mass, the signal represents the precursor-to-product ion transition for a specific ion pair. This experiment is called reaction monitoring. If several different precursor–product ion pairs are monitored, as is most often the case, the experiment is multiple-reaction monitoring (MRM).

m/z

The x-axis of a plotted mass spectrum often is labeled in units of m/z, where m denotes the mass of the ion (in Daltons), and z represents the total number of charges on the ion (in units of the elementary charge). An older abbreviation is m/e, where e represents the charge. The term Thomson has also been suggested. Da (daltons) and kDa are also used as labeling units for the x-axis of a mass spectrum.

N

Nanospray

The term describes a design for a miniaturized electrospray ionization source using a pulled and coated glass capillary as the spray tip. This design achieves a flow rate of 20–50 nL/min, much lower than the usual electrospray ionization source.

Neutral

The adjective neutral is often used as a noun in MS to describe a molecular or atomic species that has no charge.

Nitrogen rule

Simply put, an organic molecule containing the elements C, H, O, S, P, or a halogen atom will have an odd nominal mass if it contains an odd number of nitrogen atoms.

Nominal (ion) mass

The nominal ion mass is the mass of an ion for a given empirical formula calculated using the integer mass of the most abundant isotope of each element (for example, C is 12 Da, H is 1 Da, and O is 16 Da).

O

Octapole

The MS community uses octapole, but the original spelling seems to be octupole. An octupole device is used in many physics instruments to focus beams of charged particles. It consists of eight electrodes or magnetic poles arranged in a circular pattern, and energized with alternating polarities.

Odd-electron ion

An odd-electron ion contains an unpaired electron; for example, CH₄^+⋅. The superscripted dot denotes the unpaired electron. The molecular ion initially formed in electron ionization is an odd-electron ion.

Orbitrap™

An Orbitrap is a recently invented mass spectrometer consisting of a surrounding barrel-shaped electrode and a spindle inner electrode. Ions injected into the space between the outer and inner electrodes are trapped there in a balance of electrostatic attraction and centrifugal force. The ions also oscillate with a regular frequency parallel to the spindle axis, and the frequency of these oscillations is inversely proportional to the square root of the mass-to-charge ratio. Measurement of the frequency provides (via a Fourier transformation) a measure of the ion mass.

P

Parent ion

The term parent ion is synonymous with the term precursor ion and denotes the ion that dissociates to a lower mass fragment ion, usually as a result of collision-induced dissociation in an MS-MS experiment. Precursor ion is the preferred term. A precursor ion also can evolve into an ion with a different charge state.

Paul ion trap

In a Paul ion trap, a three-dimensional symmetric electric field confines the ions. The ions in the trap can be analyzed by their m/z values by application of a variable destabilizing field that causes ions of successive m/z values to be ejected from within the confines of the trap to an external detector.

Penning ion trap

In a Penning ion trap, a static magnetic field confines the ions. Once inside the magnetic field, the ions are subject to the Lorentz force, which will act to cause ions to follow orbits of a specific frequency (the cyclotron frequency) that is proportional to their m/z value.

Percent accuracy

In the experimental measurement of an exact mass, the percent accuracy is calculated as the ([true mass – observed mass]/true mass) × 100%. The percent accuracy often is expressed in parts per million (ppm). For example, 0.01% accuracy is 100 ppm. A 100-ppm accuracy for an ion with a mass of 1000 Da is 0.1 Da.

Plasma

This term is often used inaccurately, despite the fact that it has a precise meaning. A plasma designates a state of matter in which electrons and ions move freely.

Postsource decay (PSD)

Postsource decay processes are ion dissociations that occur within the drift region of a time-of-flight mass analyzer. After initial ion formation and acceleration out of the source into the flight tube, ions can dissociate or neutralize. In a linear time-of-flight instrument, these fragment ions and neutral species reach the detector at the same time as the precursor ions from which they are formed. However, these reactions can be studied specifically by using a reflectron (adjusting the ratio of accelerating to reflectron voltages in a stepwise manner) to bring fragment ions formed in postsource decay processes into focus at the detector.

Posttranslational modification (PTM)

A peptide is a chain of amino acids that often is modified to alter its structure or reactivity with a number of reactions called posttranslational modifications. These include phosphorylation, glycosylation, the additional of small functional groups, or perhaps the formation of disulfide bridges, among many other reactions. The mass shifts associated with PTM are tabulated for use in MS.

Precursor ion scan

In an MS-MS experiment, mass-selected precursor ions are induced to dissociate into product ions, which are then mass analyzed by a second analyzer. The three common scans in the single-step MS-MS experiment are: product ion scan, precursor ion scan, and then the constant neutral loss scan. In the precursor ion scan, the second mass analyzer is set at the mass of the selected product ion, and then the first mass analyzer is scanned from that mass upward. The result is a mass spectrum that contains signals for all the precursor ions that dissociate to that selected product ion.

Product ion scan

In an MS-MS experiment, mass-selected precursor ions are induced to dissociate into product ions, which are then mass analyzed by a second analyzer. The three common scans in the single-step MS-MS experiment are: product ion scan, precursor ion scan, and then the constant neutral loss scan. In the product ion scan, the first mass analyzer is set at the mass of the selected precursor ion, and then the second mass analyzer is scanned from that mass downward. The result is a mass spectrum that contains signals for all the product ions formed from that selected precursor ion.

Proton affinity (PA)

The proton affinity is the enthalpy change for the process (M + H)⁺ → M + H⁺. As with electron affinity, be careful of the sign conventions used for the expression of these values.

Protonated molecule

A protonated molecule is (usually) an ion formed by addition of a proton to the neutral molecule M, namely, (M + H)⁺. The process of chemical ionization using a reagent gas such as methane forms such a protonated molecule. The transfer of a proton from one molecule to the other in the gas phase is an acid–base reaction in which the relative proton affinities of the reacting species describe the energetics of the reaction. Protonated molecules formed in other ionization sources (such as fast atom bombardment, electrospray ionization, or MALDI) may not be the end result of such well-defined acid–base reactions. The term protonated molecular ion has been used to describe (M + H)⁺, but is usually discouraged. A protonated ion, in simplistic terms, would have two charges.

Pyrolysis MS (PyMS)

In a pyrolysis source interfaced with a mass spectrometer, the sample is thermally decomposed in a reproducible pyrolysis. The gaseous products formed are then analyzed either as a mixture by MS, or are analyzed by GC–MS. PyMS can be used for the analysis of otherwise nonvolatile samples.

Q

Quadrupole mass filter (Q)

In the quadrupole mass filter, the application of a particular combination of dc (direct current) and rf (radio frequency) voltages to four parallel metal rods creates a filtering device through which only ions of a defined m/z value are transmitted. Changing the ratio of the voltages changes the m/z value of the ion that is passed through to the detector. The quadrupole mass filter also can be operated in other modes, such as passing a mass range of ions through to the detector. If only the rf portion of the voltage is applied to the rods, essentially all ions are passed through to the detector.

R

Rearrangement ion

A rearrangement ion is a fragment ion formed in a dissociation in which atoms or groups of atoms have transferred from one part of the molecule to another during the fragmentation process. Because the structural requirements to form rearrangement fragment ions are constrained, the identification and rationalization of rearrangement fragment ions are especially important in spectral interpretation.

Reconstructed ion chromatogram (RIC)

A normal MS data set consists of full mass spectra recorded sequentially in time as sample is admitted to the ion source, either from a direct-insertion probe or from a chromatograph (for example, GC–MS). The total ion current trace is the sum of ion abundances in each mass spectrum plotted versus time. Clearly, each mass spectrum also will contain a pattern of molecular and fragment ions. Ions of these particular masses can be specified, and the data system can plot the scan-by-scan abundances of these specific ions versus time, which is known as a reconstructed ion chromatogram. The reconstructed ion chromatogram can be used to identify all ions that belong together in a single mass spectrum by virtue of their coincident peaks in time (and discriminate against background ions), and also can be used to screen a GC–MS run for related classes of compounds by reconstruction of ion chromatograms for common structurally specific ions.

Reflectron time-of-flight mass spectrometer

A reflectron is a device incorporated into the flight tube of a time-of-flight mass spectrometer that operates as an electrostatic mirror. Ions with a range of kinetic energies from the ionization source traverse the first portion of the flight tube and then spend different amounts of time in the reflectron. The net result is that these (reflected) ions all come into focus at the detector located at the end of the second portion of the flight tube, leading to higher mass resolution.

Relative abundance (RA)

The relative abundance of an ion is the measured intensity for the ion beam at that designated m/z value. To be precise, ion beams have intensities, and ions have abundances. Relative abundance is a term related to the practice of assigning the most abundant ion in a measured and plotted mass spectrum a relative abundance of 100% and normalizing all other ion abundances to that value.

Resolution

Resolution is defined in several different ways relative to the commonly given formula of m/Δm, where m is the mass of the ion at which resolution is specified. For two adjacent, symmetric peaks of equal height in a mass spectrum, the instrumental (physical or electrical) parameters are adjusted such that the peaks at masses m and (m/Δm) are separated by a valley that, at its lowest point, is just 10% of the height of either peak. Then, the resolution (10% valley definition) is m/Δm. The definition also can be given for 50% valley or 5% valley separations. For a single peak, the resolution is still calculated as m/Δm, but now Δm is the width of the peak at a height that is a specified fraction of the maximum peak height. A 5% peak width definition is technically equivalent to the 10% valley definition of resolution. A common standard is the definition of resolution based upon Δm being the full width of the peak at half its maximum height (fwhm).

Resolving power (RP)

Resolving power is the ability of a mass spectrometer to distinguish between ions that differ only slightly in their m/z ratios. It is a definition that is distinct from resolution.

S

Secondary ion mass spectrometry (SIMS)

In secondary ion mass spectrometry, a beam of energetic ions (usually around 5 keV energy) is used to sputter sample atoms and molecules from a thin solid film or surface (classic SIMS), or organic molecules that can be present as a thin film or dissolved in a liquid or solid solution (molecular SIMS or liquid SIMS) held on the surface of a beam-intersecting sample probe. In liquid SIMS, the ion impact deposits energy into the semivolatile matrix, causing desorption of many species, including ions, neutral molecules, and clusters of solvent (when present), matrix, and sample molecules. Desolvation follows desorption, and molecules (M) are usually ionized in a process of protonation to form (M + H)⁺. The mass spectra recorded using the liquid SIMS ionization method usually contain a large background of ions from the energy-moderating solvent or matrix, if used. The same matrix solvents are used in liquid SIMS and FAB.

Selected ion monitoring (SIM)

Selected ion monitoring is the practice of monitoring and recording ion currents at one or more selected ion m/z values with time, rather than recording full mass spectra, as sample is introduced into the ion source. Because the detector is integrating signal for a longer time at the relevant ion, limits of detection can be lowered, albeit at a cost of susceptibility of the experiment to unexpected interferences. The terms multiple ion detection, multiple ion (peak) monitoring, and mass fragmentography have also been used. The terms single ion monitoring or multiple ion monitoring also are used sometimes in the context of MS-MS.

Sensitivity

The proper definition of sensitivity is that of a system response measured per amount of sample placed in the system. In mass spectrometry, the units are most often given in terms of coulombs per microgram. An electron ionization source may provide 2 × 10^–7 C/μg for a standard test compound at a specified instrumental resolution, and a specified means of introducing sample into the ionization source. Clearly, sensitivity is a system parameter. An alternative specification for sensitivity is based upon the change of ion current correlated to the change of partial pressure of the sample in the ion source. Here the unit is amperes per pascal, and system parameters must be specified. Most often, sensitivity is documented by examples of applications of system response for given conditions and sample input. System performance is then evaluated by the confluence of performance results exemplified by all the examples. Sensitivity is distinct from detection limit, which is the amount of sample required for a signal of a prescribed signal-to-noise ratio.

Shotgun proteomics

In this approach, a complex protein mixture is first digested into smaller peptides. The peptides usually are separated with liquid chromatography (LC), and the masses of the peptides are established by MS, and then product ion MS-MS is used to establish sequence information. Mathematical algorithms (including statistical and probability-based methods) then link the peptides to proteins to determine the original content of the mixture.

Single-focusing mass spectrometer

In a single-focusing mass spectrometer, a single magnetic sector is used to generate the magnetic field that differentiates ions according to their m/z values (strictly, according to their momenta). The addition of an electric sector in a specified configuration provides a double-focusing mass spectrometer that can achieve higher mass resolution than a single-focusing mass spectrometer.

Source (S)

The source (more specifically, the ionization source) is the device within the mass spectrometer in which ionization of sample molecules occurs. The source can be under vacuum, or it can operate at atmospheric pressure. A chromatographic method can interface with the source, or samples might be introduced via a probe or an automated sample introduction system. Ions are accelerated out of the source into the mass analyzer of the instrument.

Space charge

The space charge is the electric field generated as the result of ions or electrons resident in a specified volume. Space charge can affect the movement of ions in this space, limiting the effectiveness of mass analysis resulting from the imposition of an external potential gradient.

Surface-induced dissociation (SID)

Surface-induced dissociation is the fragmentation of an ion induced by an energetic collision of that ion with a solid surface, which can be placed between two mass analyzers. The surface then takes the place of the neutral gas molecule that is the collision target in collision-induced dissociation.

T

Tesla (T)

The tesla is the SI unit of magnetic flux density. It is equal to the magnitude of the magnetic field vector necessary to produce a force of I N on a charge of 1 C moving perpendicular to the direction of the magnetic field vector with a velocity of 1 m/s. It is named after Nikola Tesla.

Thoria

Thoria is a common name used for thorium oxide (ThO₂), used as a coating on filaments in an electron ionization source because of its low work function.

Time-of-flight (TOF) analyzer

A time-of-flight mass spectrometer is a mass analyzer that provides a measurement of mass via determination of the flight time of ions having the same kinetic energy over a fixed distance. Ions are formed in the same place at the same time, and are given the same energy by an acceleration voltage as they pass into a flight tube. The time-of-flight mass spectrometer acts as a racetrack for ions, with lower mass ions moving with higher velocity and the higher mass ions moving with slower velocities. Determination of the time of arrival of ions after the start signal then serves as a means of differentiating their masses.

Top-down sequencing

In top-down sequencing, no external digestion of a large protein is completed. Rather, intact molecular ions of the protein are induced to dissociate within the mass spectrometer, and then MS-MS is used to determine sequence information. The complete top-down sequencing approach usually requires complex higher performance instrumentation.

Torr

The Torr is a unit of pressure that is defined as 1/760 of a standard atmosphere (ergo, a standard atmosphere is 760 Torr). 1 Torr is approximately equal to the fluid pressure exerted by 1 mm of mercury. The Torr is named after Evangelista Torricelli, who discerned the principle of the barometer in 1644. The SI unit of pressure is the pascal. Mass spectrometrists speak Torr.

Total-ion current (TIC)

The total-ion current trace is the sum of the relative abundances of all the ions in each mass spectrum plotted against the time (or number of scans) in a data-collection sequence. For example, the total-ion current trace in a GC–MS run is analogous to the output of a single-channel GC detector. The trace allows eluted peaks to be identified by an increase in the total-ion current over background. The scans corresponding to the eluted peak are averaged together to create the mass spectrum of the sample corresponding to that peak.

Tuning

Tuning is the process of carefully adjusting the physical and electrical components of the mass spectrometer so that, for example, ion beams are focused properly, ion beams have the proper shapes, ion energies are correct, and electronic noise is minimized. In the old days, instruments had knobs and dials for such a purpose.

U

Unified mass scale

IUPAC & IUPAP (1959–1960) agreed upon a standardized mass scale in which 1 u (the unified atomic mass unit) is defined as equal to 1/12 the mass of the most abundant form of carbon, the ¹²C isotope. There had previously been two slightly different mass scales — the physical scale and the chemical scale. The unified scale brought coherence to mass metrology.

Unimolecular dissociation

Unimolecular dissociation is the isolated, spontaneous dissociation of a neutral or an ion, based upon the amount and distribution of its internal energy. In the electron ionization source, initial ionization of the molecule by the electrons leads to molecular ions, which then undergo rapid unimolecular dissociations leading to the fragment ions observed in the mass spectrum. Unimolecular dissociation that occurs after the ions leave the source and in the field-free regions of the mass spectrometer leads to metastable ions that can be observed with special methods. Unimolecular dissociation is contrasted with collision-induced dissociation, at least in concept. True unimolecular dissociation evolves into collision-induced dissociation as the operating pressure of the mass spectrometer increases. The transition can be calculated by derivation of the mean free path of an ion at the given pressure.

V

Vacuum

Much of the expense and size of an MS instrument can be attributed to the pumping system, which creates the requisite vacuum at the proper place in the instrument. With atmosphere at 760 Torr, an instrument operating pressure of 10^–5 Torr represents almost an 8 order-of-magnitude decrease in pressure. Those low pressures are needed to increase the mean free path of the ions in the system so that we can manipulate them properly. When instrument performance starts to degrade, always look to the vacuum system first.

W

Work function

The work function is a measure of the work-per-unit charge needed to cause the emission of a charged particle (usually an electron) from a surface. The value of the work function is material-dependent. Low-work-function materials (see thoria, for example) are often used to coat filaments used in electron ionization sources.

X

xyz axes

A set of coordinates describe the movement of ions through a beam mass spectrometer. The x-axis corresponds to the movement of ions from the source through the mass analyzer to the detector. The y-axis is set by historical tradition to be parallel with the magnetic vector in a magnetic sector instrument. The remaining axis is the z-axis.

Kenneth L. Busch (in his spare time) is compiling a glossary of eponymous terms in mass spectrometry. An eponymous term contains the name of a particular individual, such as a Nier ion source, a McLafferty re-arrangement, or a Busch beer. If you have a suggestion, please contact the author at wyvernassoc@yahoo.com Responsibility for this column rests solely with the author.

References

(1) The most current compilation of terms, and a bit of history, can be found at http://mass-spec.lsu.edu:16080/msterms/index.php/Main_Page.

(2) A. Mallett and S. Down, Dictionary of Mass Spectrometry (John Wiley, New York, 2009).

(3) O.D. Sparkman, Mass Spec Desk Reference, Second Edition (Global View Publishing, Pittsburgh, June 2006).

(4) P. Price, J. Am. Soc. Mass Spectrom. 2, 336–348 (1991).

(5) J.F.J. Todd, Pure Appl. Chem. 63, 1541–1566 (1991).