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Whatever their configuration, mass spectrometers comprise three basic components: an ionization source, a mass analyzer, and a detector. The ionization source, as its name implies, produces the charged molecules that can be seen by the detector; the mass analyzer measures their mass—or more accurately, their mass-to-charge (m/z) ratio. Generally speaking, any mass analyzer can be coupled to any ionization source, and both are critical to a properly executed mass spec experiment. As a result, both must be considered when making a purchasing decision.
Labcompare has already profiled different ionization sources; here, we discuss some of the more common mass analyzer configurations to which they may be coupled.
The simplest mass analyzer is the single quadrupole. Named for the four parallel cylindrical rods that run the length of the device, a quadrupole is like a radio: by adjusting the voltage and current applied to the rods, you can tune the instrument to permit only ions of a given m/z to traverse the quadrupole and reach the detector (or in the case of a tandem instrument, the next analyzer); all other ions are lost.
Available from such companies as Agilent Technologies and Shimadzu, single quads typically are capable of only nominal mass accuracy (that is, they can distinguish carbon-12 from carbon-13). Yet, says Scott Kuzdzal, biotech business manager at Shimadzu Scientific Instruments, they "continue to be the workhorse instruments for industry."
Especially popular in synthetic chemistry labs (such as those building combinatorial libraries), single quads are fast, relatively inexpensive, and most importantly, quantitative: Quadrupoles are ideal for determining the absolute (as opposed to relative) amount of a given ion in a sample, because of their excellent sensitivity and dynamic range, says Dominic Gostick, director of the biomarkers MS business at Life Technologies. Yet, precisely because they have to be tuned to a given ion, they can only look at one or a few molecular species at a time.
"A single quad is generally limited for many applications because you can only look at the precursor ions," says Gostick, "But the combination of quadrupoles in triple quads provides excellent specificity and utility."
If quadrupoles are the go-to instruments for quantitative studies, ion traps fill the same role for qualitative, structural work, says Iain Mylchreest, vice president and general manager for life sciences mass spectrometry at Thermo Fisher Scientific.
"Ion trap technology has historically been the engine for structural elucidation, breaking down molecules for structure and substructural identification," Mylchreest says.
Available from Bruker, Shimadzu, Thermo Fisher Scientific, and Varian, among others, ion traps—which can adopt either a 2D linear or standard 3D configuration—are exactly what they sound like: small chambers that use RF and DC voltages to accumulate (or trap) ions. Using those fields, ions can be stored, isolated, fragmented, and then scanned out of the device to create a mass spectrum. In this sense, they are like more traditional tandem mass spectrometers, and it is this ability that makes them so special: By storing, analyzing, fragmenting, and reanalyzing ions over and over again, a process called "MSn," ion traps help confirm both the abundance and identity of given ions by breaking them down into component parts.
Perhaps no mass analyzer is more often associated with a specific ionization source than the time-of-flight (TOF) mass spectrometer is with MALDI (matrix-assisted, laser desorption ionization). But it doesn't have to be MALDI-TOF or nothing; some vendors (including Bruker Daltonics and Agilent) offer ESI-TOF systems, while LECO offers a line of GC- and GCxGC-based systems featuring both electron impact ionization and chemical ionization sources.
TOF mass spectrometers measure m/z based simply on how long it takes a packet of ions to reach the detector (its "time-of-flight"). The instruments come in two basic configurations: linear and reflector (or reflectron). In the former, the ion flight path is a straight line, with a detector at the end of the flight tube. In the latter, a series of ion reflectors bends the ion flight path in a parabolic arc back towards the ion source, thereby nullifying differences in initial kinetic energy of otherwise identical ions while simultaneously doubling the length of the TOF tube, increasing mass resolution and accuracy.
Unlike quadrupoles, TOFs provide full-scan MS spectra with no loss in sensitivity; in other words, for every scan, they detect across the entire m/z range, rather than looking at specific m/z values, providing an increase in data density over other MS instruments. They also offer higher mass accuracy and resolution (though not as high as FT-ICR and Orbitrap systems). "TOFs are typically associated with qualitative work; for example, in compound identification, where accurate mass confirmation is needed," says Gostick.
By far the most accurate, highest resolution, and highest price mass spectrometers available are those based on the Fourier Transform-Ion Cyclotron Resonance (FT-ICR) analyzer.
Available from such vendors as Thermo, Bruker Daltonics, and Varian, FT-ICR instruments are like a cross between a nuclear magnetic resonance spectrometer and an ion trap, using the rotational orbital frequency of ions inside a massive superconducting magnet to determine their m/z values. (A relatively new, and popular variant from Thermo Fisher Scientific, the Orbitrap, applies a similar principle using an electrical field instead of a magnet, making it a smaller, and less expensive option.)
FT-ICR systems offer resolutions up to 100,000 FWHM (full-width at half-maximum) and mass accuracy of 1 ppm or less, says Mylchreest; by comparison, some hybrid TOF instruments provide 30,000 to 40,000 FWHM resolution, and mass accuracies of 2-5 ppm, while quadrupoles offer resolution of between 1,000 and 5,000. That high performance translates directly into confidence in making identifications, says Mylchreest: "As you go up in mass accuracy, there are less possibilities of combinations of elemental composition, and unambiguous assignments can be made."
Many commercial mass spectrometers are so-called hybrid or tandem systems, linking one or more of the mass analyzers above to create a device that is considerably more powerful. Tandem instruments enable users to do more than simply measure the m/z of a set of ions; they can also select ions for further structural study.
A triple quadrupole (or "triple quad") instrument, for instance, combines three single quads in serial, with the first quadrupole functioning as a mass filter, the second as a collision cell, and the third as a mass analyzer for the resulting fragmentation products. This configuration enables so-called SRM (single reaction monitoring) studies, which allows the user not only to quantify a given ion, but to confirm its identity, as well.
A number of variations on this theme have been commercialized, including Q-TOFs, in which the third quadrupole is replaced with a TOF (such as Agilent Technologies' 6500 series Accurate-Mass Q-TOF), and Q-Traps, in which the third quad is actually a linear ion trap. In the case of Life Technologies' QTRAP mass analyzers, the third quad can actually switch back and forth between ion trap and quadrupole modes, providing the best of both worlds, says Gostick: the quantitative accuracy of a triple quad, and the structural power of an ion trap.
Other popular configurations include the tandem TOF (or TOF-TOF, such as Life Technologies' 5800 MALDI TOF/TOF and Shimadzu’s Axima Confidence and Performance MALDI TOF/TOFs), which brings tandem capabilities to TOF mass analyzers, Thermo Fisher Scientific's LTQ-Orbitrap (an ion trap-Orbitrap hybrid), and the Shimadzu LCMS-IT-TOF, which couples the higher MS stages available with an ion trap and the high resolution and mass accuracy of a TOF.
"What these [hybrid] technologies do is extend the capabilities of the base MS system and add high resolution and accurate mass measurements, providing more specificity and accuracy," says Mylchreest.
Ultimately, of course, a mass spectrometer is just a tool, albeit one with nearly limitless potential. Keith Waddell, LC-MS applications solution manager at Agilent Technologies, notes that mass specs can be applied to everything from petrochemicals and pesticides, to forensics and proteomics. "Any compound which will ionize has been analyzed one way or another," Waddell says.
Fortunately, though most researchers have a specific use in mind when making a purchase, they tend to be fairly broadly applicable. Says Lucas Smith, product manager of separation science at LECO, "I wouldn't say that the different mass specs are necessarily tailored for one market or another, as the needs of a lab can be vastly different even within the same industry."
Please check out our Mass Spectrometry section for more information or to find manufacturers that sell these products.