Time-of-flight-mass spectrometry

Principles and Characteristics Time-of-flight (ToF) mass spectrometry was proposed in 1946, and the first 

ToF analysers are able to provide simultaneous detection of all masses of the same polarity. In principle, the mass range is not limited. Time-of-flight mass analysis is more than an alternative method of mass dispersion it has several special qualities which makes it particularly well suited for applications in a number of important areas of mass spectrometry. These qualities are fast response time, compatibility with pulsed ionisation events (producing a complete spectrum for each event) ability to produce a snapshot of the contents of the source volume on the millisecond time-scale ability to produce thousands of spectra per second and the high fraction of the mass analysis cycle during which sample ions can be generated or collected. 

In ToF-MS, the ion source is pulsed to create packets of ions. In the conventional procedure, the system waits for all the ions in a packet to reach the detector before injecting the next packet of ions. Complications arise when ToF-MS is coupled to a continuous ion source. Such coupling is therefore often accomplished by the orthogonal extraction approach, in which a segment of the ion stream is accelerated orthogonally by a push-out pulse. However, in this process, up to 95 % of the information contained in the ion steam is lost. Recently, Hadamard transform time-of-flight mass spectrometry (HT-ToFMS) was developed to couple continuous ion 

State-of-the-art ToF-MS employs reflection lenses and delayed extraction [176] to improve resolution by minimising small differences in ion energies, and in these cases up to 12000 mass resolution (FWHM, m/z 600) is available. This is sufficient for most modern applications. Solid probe ToF-MS (or direct inlet high-resolution mass spectrometry, DI-HRMS) is a breakthrough. DIP-ToFMS is a thermal separation technique. Advantages of DIP-ToFMS are  

ToFs can also be used in combination with other mass analysers. Both hybrid sector and quadrupole systems are available. oaToF-MS has been interfaced to a quadrupole mass filter and hexapole gas collision cell, such as to allow recording of mass spectra and product ion spectra with good mass resolution (ca. 10000), high sensitivity, high mass range (ca. 10 000 Da) and high mass accuracy ( 5ppm) [177,178]. QqToFMS may be fitted with API sources with flow-rates from nL 

With soft ionization techniques such as MALDI, ions of m/z 200000 can be routinely detected. The mass range is mainly limited by the fact that with the detector the response decreases with increasing m/z of the ions. The mass resolution of a TOF mass analyzer is relatively poor (unit mass resolution and less) and is affected by factors that create a distribution in the flight time of ions with the same m/z. The simplest way to increase the mass resolution is to increase the length of flight tube or to reduce the kinetic energy spread of the ions leaving the source. 

One way to reduce the kinetic energy spread is to introduce a time delay between ion formation and acceleration, referred to as delayed pulsed extraction. After a certain time delay ranging from nanoseconds to microseconds a voltage pulse is applied to accelerate the ions out of the source. 

The second way to improve the mass resolution significantly is to use an electrostatic mirror (mass reflectron) placed in the drift region of ions (Fig. 1.27). 

In general the commercial TOP instruments have two detectors one for the linear mode and one for the reflectron mode. The combination of MALDI with TOP is ideal because both techniques are pulsed techniques. However, it is also possible to arrange a continuous beam as generated by electrospray ionization. Por that purpose orthogonal acceleration was developed [65]. The ion beam is introduced perpendicularly to the TOP and packets are accelerated orthogonally (oa-TOP) at similar frequencies improving the sensitivity. While a packet of ions is analyzed, a new beam is formed in the orthogonal acceleration. 

Due to their fast acquisition rate and high resolution capabilities TOP mass analyzers are often used as the last mass analyzing stage in hybrid tandem mass 

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Guilhaus M 1995 Principles and instrumentation in time-of-flight mass spectrometry physical and instrumental concepts J. Mass Spectrom. 30 1519-32... 

Orthogonal TOP is the name commonly given to orthogonally accelerated time-of-flight mass spectrometry. It is sometimes referred to by the acronym oa-TOF, especially in official publications, but it is more usual for it to be referred to simply as orthogonal TOP this abbreviation is used here. 

Cotter, R.J., Time-of-Flight Mass Spectrometry, ACS Symposium Series, Vol. 549, American Chemical Society, Washington, DC, 1994. 

Molecular orbital calculations indicate that cyclo C-18 carbyne should be relatively stable and experimental evidence for cyclocarbynes has been found [25], Fig. 3B. Diederich et al [25] synthesised a precursor of cyclo C-18 and showed by laser flash heating and time-of flight mass spectrometry that a series of retro Diels-Alder reactions occurred leading to cyclo C-18 as the predominant fragmentation pattern. Diederich has also presented a fascinating review of possible cyclic all-carbon molecules and other carbon-rich nanometre-sized carbon networks that may be susceptible to synthesis using organic chemical techniques [26]. 

TOP (Section 12.4) Time-of flight mass spectrometry a sensitive method of mass detection accurate to about 3 ppm. 

The molecular weights and molecular weight distributions (MWD) of phenolic oligomers have been evaluated using gel permeation chromatography (GPC),23,24 NMR spectroscopy,25 vapor pressure osmometry (VPO),26 intrinsic viscosity,27 and more recently matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).28... 

Maleamic acid, cyclization of, 293 Maleic anhydride, 59 Maleimido azine, 307 Manganese diacetate catalysts, 71 Mark-Houwink-Sakurada equation, 57 Material safety data sheets (MSDSs), 246 Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), 385, 388 McGrath, J. E., 327 MDI isomers, 210 MDIs. See Methylene diphenyl diisocyanates (MDIs)... 

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry... 

Martinez Bueno MJM, Agiiera A, Gomez MJ, Hernando MD, Garcia JE, Fernandez-Alba AR (2007) Application of liquid chromatography/quadrupole-linear ion trap mass spectrometry and time-of-flight mass spectrometry to the determination of pharmaceuticals and related contaminants in wastewaters. Anal Chem 79 9372-9384... 

Figure 5.67 Reconstructed ion chromatograms for Idoxifene and internal standard (ds-Idoxifene using LC-ToF-MS for (a) double-blank human plasma extract, (b) extract of blank human plasma containing internal standard (IS), and (c) control-blank human plasma spiked with Idoxifene at 5 gml , the LOQ of the method. Reprinted from 7. Chromatogr., B, 757, Comparison between liquid chromatography-time-of-flight mass spectrometry and selected-reaction monitoring liquid chromatography-mass spectrometry for quantitative determination of Idoxifene in human plasma , Zhang, H. and Henion, J., 151-159, Copyright (2001), with permission from Elsevier Science.

Starting from 27, cyclo-Cig was prepared in the gas phase by laser flash heating and the neutral product, formed by stepwise elimination of three anthracene molecules in retro-Diels-Alder reactions, was detected by resonant two-photon-ionization time-of-flight mass spectrometry [23]. However, all attempts to prepare macroscopic quantities of the cyclocarbon by flash vacuum pyrolysis using solvent-assisted sublimation [50] only afforded anthracene and polymeric material. 

There are at least three approaches to fast GC/MS (1) use of microbore columns with time-of-flight mass spectrometry (TOFMS) (2) use of low-pressure (LP)-GC/MS to aid separations at increased flow rate " and (3) use of supersonic molecular beam mass spectrometry (SMBMS) (also known as supersonic GC/MS), which can accept increased flow rates and short analytical columns."... 

An advantage of the microbore gas chromatrography/time-of-flight mass spectrometry (GC/TOFMS) method over the other two approaches is that separation efficiency need not be compromised for speed of analysis. The rapid deconvolution of spectra ( scan rate ) with TOFMS makes it the only MS approach to achieve several data points across a narrow peak in full-scan operation. However, the injection of complex extracts deteriorates performance of microbore columns quickly, and an increased LOD and decreased ruggedness result. Microbore columns may be used in water analysis if the LOD is sufficiently low, but they can rarely be used in real-life applications to complicated extracts. 

Whittal, R.M., Russon, L.M., and Li, L., Development of liquid chromatogra-phy-mass spectrometry using continuous-flow matrix-assisted laser desorption ionization time-of-flight mass spectrometry, /. Chromatogr. A, 794, 367, 1998. 

Choudhary, G., Chakel, J., Hancock, W., Torres-Duarte, A., McMahon, G., and Wainer, I., Investigation of the potential of capillary electrophoresis with offline matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for clinical analysis examination of a glycoprotein factor associated with cancer cachexia, Anal. Chem. 71, 855, 1999. 

In mass spectrometers, ions are analysed according to the ml7. (mass-to-charge) value and not to the mass. While there are many possible combinations of technologies associated with a mass-spectrometry experiment, relatively few forms of mass analysis predominate. They include linear multipoles, such as the quadrupole mass filter, time-of-flight mass spectrometry, ion trapping forms of mass spectrometry, including the quadrupole ion trap and Fourier-transform ion-cyclotron resonance, and sector mass spectrometry. Hybrid instruments intend to combine the strengths of the component analysers. 

E.W. Schlag (ed.), Time-of-Flight Mass Spectrometry and Its Applications, Elsevier, Amsterdam (1994). 

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