Introduction to Time-of-Flight Mass Spectrometry
A mass spectrometer is capable of identifying a sample chemical (analyte) by measuring its molecular weight. It is therefore analogous to a very sensitive balance.
There are a number of different ways that mass spectrometers separate molecules of different mass. Some systems measure the deflection of an ionised and accelerated beam of analyte in a magnetic or electric field. This deflection is dependent on the mass and therefore ions of different mass are separated spatially. Another method is to filter the beam by passing it through a high frequency electrical field. The particular field applied determines which ion masses are able to pass through an aperture and hit a detector. However, as the name implies, a time-of-flight mass analyser identifies sample atoms, or molecules, by measuring their flight time.
This picture shows the working principle of a linear time of flight mass spectrometer. To allow the ions to fly through the flight path without hitting anything else, all the air molecules have been pumped out to create an ultra high vacuum. In the typical vacuum inside a time-of-flight mass spectrometer an ion can fly on average 600 metres (mean free path) before it will hit an air molecule.
Time-of-flight mass spectrometers identify molecules by measuring the time that sample molecules, all starting with the same kinetic energy, require to fly a known distance. As the sample molecules are moved about in the vacuum, using electrical fields, it is necessary to ionise or put charge on them. Charging of the molecules can be achieved by bombarding them with electrons emitted from a filament. When a molecule is hit, it is very likely to loose one or more of its electrons and therefore will be charged and becomes an ion.
Once the sample molecules are ionised, an electrical field accelerates them all to the same energy. The velocity a molecule gains is then:
It can be seen that the speed of an ion is dependent upon its mass, with heavy ions having a lower velocity than light ones. All the accelerated ions then enter a field free "drift" or time measurement region. As they all travel the same distance through the drift region, and their start velocity is dependent upon their mass, measuring the flight time each ion takes to fly through the drift region is just proportional to the square root of their mass.
From this equation the mass corresponding to each measured flight time can be calculated. The time measurement is done by the timing electronics, which applies a pulse of voltage to accelerate the ions and measures the time between this pulse, and the electrical pulses as the ions impact a detector located at the end of the ion flight path.
The initial pulse of ions needs to be "very short". An indication of the timings involved in a time-of-flight mass spectrometer can illustrated by Kore's smallest mass spectrometer, the MS200.This has a flight path length of around 0.6m. A molecule with a mass of 26 amu (atomic mass units) requires 6 µsec (6 x 10-6 seconds) to fly through the flight path. For a sufficient distinction between different masses the timing electronics is capable of measurement with a resolution of 2 nsec (2 x 10-9 seconds). Every 20 µsec the analyte in the ionisation area is accelerated and the masses of the molecules are recorded. In an experiment of 1 second, 50,000 analysis cycles are performed. Therefore the gathered spectra are a good representation of the sample.
The above description of a time-of-flight mass spectrometer is very simplified. We have assumed all ions produced leave the source at the same time, with the same kinetic energy, and neglected the extraction time from the source. In practice, the force the voltage pulse gives to the ions in the acceleration region depends upon their spatial distribution and energy distribution. So a kinetic energy distribution for each mass exists, lowering the mass resolution by creating a time-of-flight distribution for each mass . This is usually corrected by using a reflectron at the end of the drift region [2,3]. In its simplest form a reflectron uses a series of electric fields that repulse the ions back along the flight tube at a slightly displaced angle, resulting in a refocusing of ions with the same mass value on the ion detector. So the time-of- flight mass spectrometer is likely to be a space and time (energy) focusing electrostatic analyser to enhance sensitivity and mass resolution, although linear time-of-flight mass analysers are still used, generally with delayed ion extraction. Similarly the time of ion extraction must be known to a high degree of accuracy. In practice the pulse of ions can be produced by for example a pulsed laser or ion beam impinging on a solid sample, as well as by electron bombardment or chemical ionisation in a sample gas.
However the simple description serves to illustrate the main attribute of a time-of-flight mass spectrometer, namely parallel ion detection. Because ions of different mass will arrive at the detector sequentially it is possible, with a perfect detector, to detect all the ion masses contained in each ion pulse. This is the fundamental reason why a TOFMS has extremely high overall sensitivity compared to other analyser systems. Similarly parallel ion detection means there is no inherent limitation on mass range, from unit mass upwards, as long as high mass ions can be produced intact and the detector can register them.
Today's time-of-flight mass spectrometers offer extreme sensitivity and high mass range as well as high-speed analysis. This has made TOFMS an essential instrument for biological analysis applications - typically with MALDI and ESI ionisation-particularly with the development of high-resolution and hybrid instruments (for example Q-TOF and TOF-TOF configurations). The TOFMS suitability for the analysis of fast transient signals has seen it applied to studying fast gas phase chemical reactions and to hyphenated flow or injection analysis techniques such as ICP-TOF and GC-TOF. In addition time-of-flight mass spectrometry is the dominant instrument for static SIMS.
1. Cotter, R.J.; Analytical Chemistry, 64(21), (1992), p1027A-1039A
2. Mamyrin, B.A.; Karataev, V.I.; Shmikk, D.V.; Zagulin, V.A.; Soviet Physics - JETP, 37(1), (1973), p45-48
3. Mamyrin, B.A.; International Journal of Mass Spectrometry and Ion Processes, 131, (1994), p1-19
A tutorial review of TOFMS was published in the Physical and Instrumental Concepts Series
Principles and Instrumentation in Time-of-Flight Mass Spectrometry Guilhaus, M; Journal of Mass Spectrometry, 30, (1995), p1519-1532
Books on TOFMS
Time of Flight Mass Spectrometry: Instrumentation and Applications in Biological Research Cotter, R.J. (Ed.); ACS: Washington D.C., 350 pages (1997).
Time of Flight Mass Spectrometry and Its Applications Schlag, E.W. (Ed.); Elsevier: New York; 420 pages (1994).
A good book on TOF-SIMS
TOF-SIMS:Surface Analysis by Mass Spectrometry Edited by John C. Vickerman and David Briggs More detail here
Electrospray & TOFMS
Electrospray in Flight: Orthogonal acceleration brings the advantages of time of flight to electrospray, Henry, C.M.; Anal. Chem. 71, (1999), p197A-201A .
Reviews on MALDI-TOFMS
Bahr U.; Karas M.; Hillenkamp F.; Fresenius' Journal of Analytical Chemistry, 348 (1994), p783.
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry: An Overview; Limbach, P.A.; Spectroscopy 13, (1998), p16-27.
Other review papers on time of flight mass analysis
The New Time-of-Flight Mass Spectrometry; Cotter, R.J.; Anal. Chem. 71, (1999), p445A-451A.
Mass Spectrometry; Burlingame, A.L., Boyd, R.K., Gaskell, S.J.; Anal. Chem. 70 (16), p467R-716R (section on TOFMS 657R-661R)
Perfect Timing: Time-of-Flight Mass Spectrometry; Guilhaus, M.; Mlynski, V.; Selby, D.; Rapid Commun. Mass Spectrom. 11, (1997), p951-962.
Time-of-Flight Mass Analyzers Wollnick, H.; Mass Spectrom. Rev. 12, (1993), p89-114.
The secrets of time-of-flight mass spectrometry revealed; Uphoff A.; Grotemeyer J.; Eur. J. Mass Spectrom. 9, (2003), p151-164
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