Mass spectrometry

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Mass spectrometry (MS) is an analytical technique that produces spectra (singular spectrum) of the masses of the atoms or molecules comprising a sample of material. The spectra are used to determine the elemental or isotopic signature of a sample, the masses of particles and of molecules, and to elucidate the chemical structures of molecules, such as peptides and other chemical compounds. Mass spectrometry works by ionizing chemical compounds to generate charged molecules or molecule fragments and measuring their mass-to-charge ratios.[1]

In a typical MS procedure, a sample, which may be solid, liquid, or gas, is ionized, for example by bombarding it with electrons. This may cause some of the sample's molecules to break into charged fragments. These ions are then separated according to their mass-to-charge ratio, typically by accelerating them and subjecting them to an electric or magnetic field: ions of the same mass-to-charge ratio will undergo the same amount of deflection.[1] The ions are detected by a mechanism capable of detecting charged particles, such as an electron multiplier. Results are displayed as spectra of the relative abundance of detected ions as a function of the mass-to-charge ratio. The atoms or molecules in the sample can be identified by correlating known masses to the identified masses or through a characteristic fragmentation pattern.


The word spectrograph had become part of the international scientific vocabulary by 1884.[2][3] The linguistic roots are a combination and removal of bound morphemes and free morphemes which relate to the terms spectr-um and phot-ograph-ic plate.[4] Early spectrometry devices that measured the mass-to-charge ratio of ions were called mass spectrographs which consisted of instruments that recorded a spectrum of mass values on a photographic plate.[5][6] A mass spectroscope is similar to a mass spectrograph except that the beam of ions is directed onto a phosphor screen.[7] A mass spectroscope configuration was used in early instruments when it was desired that the effects of adjustments be quickly observed. Once the instrument was properly adjusted, a photographic plate was inserted and exposed. The term mass spectroscope continued to be used even though the direct illumination of a phosphor screen was replaced by indirect measurements with an oscilloscope.[8] The use of the term mass spectroscopy is now discouraged due to the possibility of confusion with light spectroscopy.[1][9] Mass spectrometry is often abbreviated as mass-spec or simply as MS.[1]




Replica of an early mass spectrometer

Parts of a mass spectrometer[edit]



Theoretical example[edit]


Creating ions[edit]


Techniques for ionization have been key to determining what types of samples can be analyzed by mass spectrometry. Electron ionization and chemical ionization are used for gases and vapors. In chemical ionization sources, the analyte is ionized by chemical ion-molecule reactions during collisions in the source. Two techniques often used with liquid and solid biological samples include electrospray ionization (invented by John Fenn[12]) and matrix-assisted laser desorption/ionization (MALDI, initially developed as a similar technique "Soft Laser Desorption (SLD)" by K. Tanaka[13] for which a Nobel Prize was awarded and as MALDI by M. Karas and F. Hillenkamp[14]).

Inductively coupled plasma[edit]

Inductively coupled plasma (ICP) sources are used primarily for cation analysis of a wide array of sample types. In this type of Ion Source Technology, a 'flame' of plasma that is electrically neutral overall, but that has had a substantial fraction of its atoms ionized by high temperature, is used to atomize introduced sample molecules and to further strip the outer electrons from those atoms. The plasma is usually generated from argon gas, since the first ionization energy of argon atoms is higher than the first of any other elements except He, O, F and Ne, but lower than the second ionization energy of all except the most electropositive metals. The heating is achieved by a radio-frequency current passed through a coil surrounding the plasma.

Other ionization techniques[edit]

Others include glow discharge, field desorption (FD), fast atom bombardment (FAB), thermospray, desorption/ionization on silicon (DIOS), Direct Analysis in Real Time (DART), atmospheric pressure chemical ionization (APCI), secondary ion mass spectrometry (SIMS), spark ionization and thermal ionization (TIMS).[15] Ion attachment ionization is an ionization technique that allows for fragmentation free analysis.

Hard ionisation and soft ionisation[edit]

In mass spectrometry (MS), ionisation (or ionization) refers to the production of gas phase ions suitable for resolution in the mass analyser or mass filter. Ionisation occurs in the instrument ion source. There are a plethora of ion sources available, each has advantages and disadvantages for particular applications. For example, Electron Impact (EI) ionisation gives a high degree of fragmentation, yielding highly detailed mass spectra which when skilfully analysed can provide important information for structural eluciation/characterisation and facilitate identification of unknown compounds by comparison to mass spectral libraries obtained under identical operating conditions. However, EI is not suitable for coupling to HPLC, i.e. LC-MS, since at atmospheric pressure, the filaments used to generate electrons burn out rapidly. Thus EI is coupled predominantly with GC, i.e. GC-MS, where the entire system is under high vacuum.

Ionisation techniques can be described as belonging to one of the following categories:

Hard ionisation[edit]

Hard ionisation techniques are processes which impart high quantities of residual energy in the subject molecule invoking large degrees of fragmentation (i.e. the systematic rupturing of bonds acts to remove the excess energy, restoring stability to the resulting ion). Resultant ions tend to have m/z lower than the molecular mass (other than in the case of proton transfer and not including isotope peaks). The most common example of hard ionisation is Electron Impact Ionisation (EI).

Soft ionisation[edit]

Soft ionisation refers to the processes which impart very little residual energy onto the subject molecule and as such result in very little fragmentation. Examples include:

Mass selection[edit]


\mathbf{F} = Q (\mathbf{E} + \mathbf{v} \times \mathbf{B}) (Lorentz force law);
\mathbf{F}=m\mathbf{a} (Newton's second law of motion in non-relativistic case, i.e. valid only at ion velocity much lower than the speed of light).



(m/Q)\mathbf{a} = \mathbf{E}+ \mathbf{v} \times \mathbf{B}.




Sector instruments[edit]




Quadrupole mass filter[edit]


Ion traps[edit]

Three-dimensional quadrupole ion trap[edit]





Linear quadrupole ion trap[edit]


A toroidal ion trap can be visualized as a linear quadrupole curved around and connected at the ends or as a cross section of a 3D ion trap rotated on edge to form the toroid, donut shaped trap. The trap can store large volumes of ions by distributing them throughout the ring-like trap structure. This toroidal shaped trap is a configuration that allows the increased miniaturization of an ion trap mass analyzer. Additionally all ions are stored in the same trapping field and ejected together simplifying detection that can be complicated with array configurations due to variations in detector alignment and machining of the arrays.[21]



Orbitraps have a high mass accuracy, high sensitivity and a good dynamic range.[22]

Fourier transform ion cyclotron resonance[edit]




A continuous dynode particle multiplier detector.



Tandem mass spectrometry[edit]




Common mass spectrometer configurations and techniques[edit]

When a specific configuration of source, analyzer, and detector becomes conventional in practice, often a compound acronym arises to designate it, and the compound acronym may be better known among nonspectrometrists than the component acronyms. The epitome of this is MALDI-TOF, which simply refers to combining a matrix-assisted laser desorption/ionization source with a time-of-flight mass analyzer. The MALDI-TOF moniker is more widely recognized by the non-mass spectrometrists than MALDI or TOF individually. Other examples include inductively coupled plasma-mass spectrometry (ICP-MS), accelerator mass spectrometry (AMS), thermal ionization-mass spectrometry (TIMS) and spark source mass spectrometry (SSMS). Sometimes the use of the generic "MS" actually connotes a very specific mass analyzer and detection system, as is the case with AMS, which is always sector based.


Chromatographic techniques combined with mass spectrometry[edit]


Gas chromatography[edit]



Liquid chromatography[edit]


Ion mobility[edit]



Data and analysis[edit]

Mass spectrum of a peptide showing the isotopic distribution

Data representations[edit]




Data analysis[edit]








Interpretation of mass spectra






As an analytical technique it possesses distinct advantages such as: 1. Increased sensitivity over most other analytical techniques because the analyzer, as a mass-charge filter, reduces background interference 2. Excellent specificity from characteristic fragmentation patterns to identify unknowns or confirm the presence of suspected compounds. 3. Information about molecular weight. 4. Information about the isotopic abundance of elements. 5. Temporally resolved chemical data.

A few of the disadvantages of the method is that often fails to distinguish between optical and geometrical isomers and the positions of substituent in o-, m- and p- positions in an aromatic ring. Also, its scope is limited in identifying hydrocarbons that produce similar fragmented ions.

Isotope ratio MS: isotope dating and tracking[edit]



Trace gas analysis[edit]


Atom probe[edit]





Protein characterization[edit]


Glycan analysis[edit]

Mass spectrometry (MS), with its low sample requirement and high sensitivity, has been predominantly used in glycobiology for characterization and elucidation of glycan structures.[37] Mass spectrometry provides a complementary method to HPLC for the analysis of glycans. Intact glycans may be detected directly as singly charged ions by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) or, following permethylation or peracetylation, by fast atom bombardment mass spectrometry (FAB-MS).[38] Electrospray ionization mass spectrometry (ESI-MS) also gives good signals for the smaller glycans.[39] Various free and commercial software are now available which interpret MS data and aid in Glycan structure characterization.

Space exploration[edit]

As a standard method for analysis, mass spectrometers have reached other planets and moons. Two were taken to Mars by the Viking program. In early 2005 the Cassini–Huygens mission delivered a specialized GC-MS instrument aboard the Huygens probe through the atmosphere of Titan, the largest moon of the planet Saturn. This instrument analyzed atmospheric samples along its descent trajectory and was able to vaporize and analyze samples of Titan's frozen, hydrocarbon covered surface once the probe had landed. These measurements compare the abundance of isotope(s) of each particle comparatively to earth's natural abundance.[40] Also on board the Cassini–Huygens spacecraft is an ion and neutral mass spectrometer which has been taking measurements of Titan's atmospheric composition as well as the composition of Enceladus' plumes. A Thermal and Evolved Gas Analyzer mass spectrometer was carried by the Mars Phoenix Lander launched in 2007.[41]

Mass spectrometers are also widely used in space missions to measure the composition of plasmas. For example, the Cassini spacecraft carries the Cassini Plasma Spectrometer (CAPS),[42] which measures the mass of ions in Saturn's magnetosphere.

Respired gas monitor[edit]




See also[edit]


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External links[edit]

Mass Spectrometry on the Open Directory Project