Tandem TOF mass spectrometers

Tandem mass spectrometry is a critical methodology used for the structural analysis of all types of molecule. The procedure involves selecting a precursor ion, fragment- 

For the metastable decay fragments, groups conducting research into MALDl-TOF have made a rather arbitrary distinction between in-source decay (ISD) [24, 

The kinetic energy of the ions entering the collision cell is controlled by adjusting the offset potential. For example, if the source generates ions at lOkeV per charge, then the collision cell could be held at 9500 V to allow ions to collide at 500eV per 

The lift TOP mass spectrometers [50, 57] can be used for top-down mass spectrometry of whole proteins. Although this has been achieved in practice, it either yields huge numbers of very small peptide fragments (e.g., rmmonium ions) or it sequences the termini of the protein nicely, but does not yield the large complementary ions needed for good top-down analyses. However, this top- down mass spectrometry parameter space has not yet been fully explored for TOP/TOF instruments. 

The ion-transfer optics include at least one quadrupole (or hexa- or octopole) at elevated pressure of about 1 mbar for thermahzation of the ions, to stabiUze them for the longer analysis time. The transfer optics also essentially decouples the TOF analyzer from the ion source for high laser pulse repetition rates the transfer optics actually converts the pulsed ion source into a continuous source. Ions are either continuously transferred into the pulser region of the TOF, or accumulated and extracted discontinuously. The fast pusher then injects them into the TOF section of the instrument The maximum rate of ion injection is Umited by the transit time of the largest ion through the TOF analyzer to typically a few kHz. Unfortunately, oTOF instruments have their Umitations  

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To overcome many of the limitations associated with PSD, several tandem TOF mass spectrometers (TOF/TOF) have been designed. Two of these tandem TOF mass spectrometers are commercially available, one sold by Applied Biosystems and the other by Bruker. The basic principle of these two instruments is to use a short linear TOF as the first mass... 

An AutoSpec-TOF mass spectrometer has a magnetic sector and an electron multiplier ion detector for carrying out one type of mass spectrometry plus a TOF analyzer with a microchannel plate multipoint ion collector for another type of mass spectrometry. Either analyzer can be used separately, or the two can be run in tandem (Figure 20.4). 

Figure 2.3. A. Mass spectrometer consisting of an ionization source, a mass analyzer and an ion detector. The mass analyzer shown is a time-of -flight (TOF) mass spectrometer. Mass-to-charge (m/z) ratios are determined hy measuring the amount of time it takes an ion to reach the detector. B. Tandem mass spectrometer consisting of an ion source, a first mass analyzer, a collision cell, a second mass analyzer and a detector. The first mass analyzer is used to choose a particular peptide ion to send to the collision cell where the peptide is fragmented. The mass of the spectrum of fragments is determined in the second mass analyzer and is diagnostic of the amino acid sequence of the peptide. Figure adapted from Yates III (2000).

The TOF mass analyzer has a low duty cycle, and the combination with an ion accumulation device such as an ion trap is therefore very advantageous. It offers also MS capabilities with accurate mass measurement. In all acquisition modes, the ions are accelerated into the time of flight for mass analysis. Various other hybrid mass spectrometers with TOF have been described, including quadrupole ion trap [70] and linear ion trap [58]. High energy tandem mass spectrometry can be performed on TOF-TOF mass spectrometers [71, 72]. 

ToF mass spectrometers as dynamic instruments gained popularity with the introduction of matrix assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) as effective pulsed ion sources for the soft ionization of large biomolecules (up to 10s dalton) due to their high ion transmission.38 ToF mass spectrometers, quadrupole analyzers and/or magnetic sector fields can be combined in tandem mass spectrometers (MS/MS) for the analysis of organic compounds. 

Superior sensitivity, efficiency, and specificity have made high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the predominant analytical technique for characterization and quantitative analysis of metabolites (Kostiainen et al., 2003 Ma et al., 2006 Prakash et al., 2007). Ion trap, triple-quadrupole, and quadmpole time-of-flight (Q-TOF) mass spectrometers are routinely used to profile and characterize metabolites in plasma and excreta (Ma et al., 2006). The combination of scan types and features available on mass spectrometers of different design (product ion, MS", neutral loss, precursor ion scans, accurate mass measurements) allows identification and characterization of putative and unexpected metabolites with or without little prior knowledge of biotransformation pathways of a given dmg molecule. 

Verentchikov AN, Hayden K, Vestal ML. Tandem TOF-Orthogonal TOF Mass Spectrometer with MALDI Ion Source. Proceedings of 48 Long Beach (CA), ASMS 2000... 

A quadrupole time-of-flight (Q-TOF) mass spectrometer incorporates a QMF as the first mass analyzer and a TOF as the second mass analyzer. A collision cell is usually available to facilitate tandem MS. Figure 3.15 illustrates the design of a Q-TOF mass spectrometer that consists of a reflectron TOF mass analyzer in its last stage. Such a setup is similar to QqQ-MS except that QMF II is replaced by the reflectron TOF mass analyzer. When entering... 

Molecular identification was performed with tandem mass spectrometry using a QIT-TOF mass spectrometer (AXIMA-QIT Shimadzu, Kyoto, Japan) to ensure the molecular assignment which was performed using only mass. The MS analysis was performed directly on the sections of tissue sections in the mid-mass range mode. 

Many classes of polar lipids have been characterized by MALDI-MS [94]. MALDI-MS has also been employed for characterization of nonpolar lipid classes such as cholesterol and TAG species. Positive-ion MALDI mass spectra of TAG species exclusively display the sodiated species. MALDI mass spectra of TAG species also display the ions corresponding to the loss of sodium fatty acyl carboxy-late(s) due to postsource decay [93]. An extensive list of lipid classes detected by MALDI-MS and corresponding matrices has been documented [101], which should be consulted for those interested. Previously, postsource decay techniques have been commonly employed for characterization of polar lipids [93]. However, since both MALDI-TOF/TOF and MALDI Q-TOF mass spectrometers are now commercially available, true tandem MS analysis of lipids by MALDI-MS is feasible [102-104]. 

Ilchenko S, Cotter RJ. Collision energetics in a tandem time-of-flight (TOF/TOF) mass spectrometer with a curved-field reflectron. Int J Mass Spec 2007 265(2—3) 372—81. 

FIGURE 5.3 Schematic of the tandem arrangement of SEADM s P4 parallel plate DMA with MDS/Sciex s Q-Star quadrupole-TOF mass spectrometer. (Courtesy of Dr. C. Hogan.)... 

Fig. 6 Tandem mass spectra of a tryptic peptide from Escherichia coli ribosomal protein L18. a Spectrum produced from singly charged peptide molecular ions by a MALDI TOF/TOF mass spectrometer, b Spectrum produced from triply charged peptide molecular ions by an ESI Q-TOF mass spectrometer. Reproduced from [38] with permission from American Chemical Society, 2006...

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