Hybrid quadrupole TOF

Among these, both LC-MS and LC-MS/MS approaches have been described using different mass analyzers operating in the positive ion mode scan such as triple stage quadrupole (TSQ) mass spectrometers [145, 194, 226, 227, 235, 239, 240, 242-247] and hybrid quadrupole-linear ion trap (LTQ) [173, 193, 218, 238, 241] mass spectrometers working in SRM mode as well as time-of-flight (TOF) [195] and hybrid quadrupole-TOF (Q-TOF) [236,237] mass spectrometers working in the MS mode. 

The ability of this ionization method for the determination of very high molecular weights is illustrated in Figure 1.26 [68], The spectrum displayed is obtained from assemblies of vanillyl alcohol oxidase containing respectively 16 and 24 proteins. The spectrum was obtained with a hybrid quadrupole TOF instrument, Q-TOF Micromass, equiped with a micro-ESI source. To obtain such a spectrum one needs not only a mass spectrometer with sufficient mass range and resolution, but also high skill in protein purification. 

In terms of mass spectrometry instrumentation, the currently available instruments such as time-of-flight (TOF) analyzers and hybrid quadrupole-TOF analyzers are able to acquire complete mass spectra at rates compatible with fast CE separations. As CE or ultrafast chromatography replaces conventional, slow HPEC applications, TOF-based mass spectrometers will be needed to replace the less efficient scanning types of instruments such as quadrupoles and ion traps for most high-throughput applications. FTICR mass spectrometry remains unsurpassed in terms of resolution and mass accuracy for both MS and MS-MS applications. However, the throughput of FTICR mass spectrometric... 

FIGURE 3A Schematic representation of the chip-CE configuration using a disposable nanoelectrospray emitter interfaced to either a triple quadrupole or a hybrid quadrupole TOF mass spectrometer. Reprinted with permission from [56]. Copyright 2000, The American Chemical Society. 

FIGURE 1.5 Schematic of a modified hybrid quadrupole/TOF mass spectrometer (QSTAR XL) and scan functions in a typical mutual storage mode ion/ion reaction (ions of opposite polarities are generated from a pulsed dual ion source). (Reproduced from Xia, Y. Chrisman, P.A. Erickson, D.E. Liu, J. Liang, X.R. Londry, F.A. Yang, M.J. McLuckey, S.A., Anal. Chem. 2006, 78,4146—4154. With permission from American Chemical Society.)... 

As mentioned above, MALDI oa-TOF-MS is feasible and the hybrid quadrupole TOF systems are available to provide the additional feature of MS/ MS. One of the key advantages of MALDI TOF-MS is that it can provide a simple spectrum that reveals the molecular ions from a complex mixture. This is a common experiment in protein analysis, where a list of peptide masses that is referred to as a peptide mass fingerprint (PMF) is generated after digestion of an isolated whole protein with a proteolytic reagent (see Figure 4). The PMF is compared to databases of... 

These ionization techniques can be combined with a variety of instruments for the sensitive determination of peptide masses. Widely used instruments include triple quadrupole, time-of-flight (TOP), hybrid quadrupole-TOF, TOF-TOF, quadrupole-ion trap, and FT-ICR mass spectrometry. 

A major benefit of the oaTOF technology has been the development of hybrid quadrupole/ TOF mass spectrometers. In these instruments a number of RF quadrupole (or other multipole) devices are used to provide the transition from atmospheric pressure sources. 

Low-energy CID is frequently further divided into beam-type CID and ion trap-type CID where the latter type involves lower collision energies than the former. This division is clarified in Figure 16.1 (reproduced from an excellent CID review by McLuckey and Goeringer ), which shows that ion trap collisional activation (CA) and ICR-sustained off-resonance irradiation (SORI) CA (both of which involve multiple collisions) occur over much longer timescales than CA from <100-eV multiple collisions in a beam-type instalment (e.g., a triple quadrupole or hybrid quadrupole/TOF configuration). Thus, each collision imparts less energy in ion trap-type CID compared to beam-type CID. This... 

The time available for MS acquisition can also be used to increase the amount of generated data by means of information-dependent acquisition (IDA). The recently introduced TripleTOF system, a hybrid quadrupole TOF/MS platform, features such capabilities. This system also possesses high mass accuracy (<2 ppm) and resolution (up to 40,000 FWHM) as weU as rapid acquisition rate (i.e., 100 Hz, highly compatible with UHPLC) afforded by TOF/MS technology, which, when combined with its high sensitivity (i.e., low attomolar range), produces quantitation capabilities similar... 

This chapter provides brief descriptions of analyzer layouts for three hybrid instruments. More extensive treatments of sector/TOF (AutoSpec-TOF), liquid chromatography/TOF (LCT or LC/TOF with Z-spray), and quadrupole/TOF (Q/TOF), are provided in Chapters 23, 22, and 21, respectively. 

Chapter 23 Hybrid Quadrupole Time-of-Flight (Q/TOF) Instruments... 

Fast atom bombardment (FAB) Plasma desorption (PD) Liquid secondary-ion mass spectrometry (LSIMS) Thermospray (TSP)/plasmaspray (PSP) Electrohydrodynamic ionisation (EHI) Multiphoton ionisation (MPI) Atmospheric pressure chemical ionisation (APCI) Electrospray ionisation (ESI) Ion spray (ISP) Matrix-assisted laser desorption/ionisation (MALDI) Atmospheric pressure photoionisation (APPI) Triple quadrupole (QQQ) Four sector (EBEB) Hybrid (EBQQ) Hybrid (EB-ToF, Q-ToF) Tandem ToF-ToF Photomultiplier... 

It should be pointed out that FAB, MALDI, and ESI can be used to provide ions for peptide mass maps or for microsequencing and that any kind of ion analyzer can support searches based only on molecular masses. Fragment or sequence ions are provided by instruments that can both select precursor ions and record their fragmentation. Such mass spectrometers include ion traps, Fourier transform ion cyclotron resonance, tandem quadrupole, tandem magnetic sector, several configurations of time-of-flight (TOF) analyzers, and hybrid systems such as quadrupole-TOF and ion trap-TOF analyzers. 

Mass analyzers interrogate and resolve ions produced by an ion source based on their m/z ratios. Several types of mass analyzers are utilized for proteomic analysis including time-of-flight (TOF) quadrupoles, ion traps, and Fourier transform ion cyclotron resonance (FTICR). Mass analyzers may be assembled in hybrid configurations. MS instruments such as quadrupole TOF and quadra-pole ion trap-FTICR facilitate diversified applications and achieved great success. 

TOF analyzers are especially compatible with MALDI ion sources and hence are frequently coupled in aMALDI-TOF configuration. Nevertheless, many commercial mass spectrometers combine ESI with TOF with great success. For proteomics applications, the quadrupole TOF (QqTOF) hybrid instruments with their superior mass accuracy, mass range, and mass resolution are of much greater utility than simple TOF instruments.21,22 Moreover, TOF instruments feature high sensitivity because they can generate full scan data without the necessity for scanning that causes ion loss and decreased sensitivity. Linear mode TOF instruments cannot perform tandem mass spectrometry. This problem is addressed by hybrid instruments that incorporate analyzers with mass selective capability (e.g., QqTOF) in front of a TOF instrument. 

Mass resolution generally increases for instruments in the listed order. Hybrid variants utilising various composites of mass analysers are likewise available and have become commonplace (e.g. quadrupole-ToF). 

Instruments that incorporate two or three mass analysers in a series have been developed to study ion fragmentation. Several of the same type of mass analyser can constitute a tandem mass spectrometer, or they can be constructed using different mass analysers (hybrids). Hybrid spectrometers include the combination of magnetic sector followed by quadrupole, multiple quadrupole, quadrupole TOF, etc. In these instruments, a collision cell is placed between each analyser (Fig. 16.23). Tandem instruments have different scanning modes. 

Mass spectrometers are used not only to detect the masses of proteins and peptides, but also to identify the proteins, to compare patterns of proteins and peptides, and to scan tissue sections for specific masses. MS is able to do this by giving the mass-to-charge ratio of an ionized species as well as its relative abundance. For biological sample analysis, mass spectrometers are connected to an ionizing source, which is usually matrix-assisted laser desorption ionization (MALDI) [14], surface-enhanced laser desorption/ioni-zation (SELDI, a modified form of MALDI) [15], or electrospray ionization [16]. These interfaces enable the transfer of the peptides or proteins from the solid or liquid phase, respectively, to the gas (vacuum) phase inside the mass spectrometer. Both MALDI and electrospray ionization can be connected to different types of mass analyzers, such as quadrupole, quadruple-ion-traps, time of flight (TOF), or hybrid instruments such as quadrupole-TOF or Fourier transform-ion cyclotron resonance. Each of these instruments can... 

Fidder and coworkers (50) developed a versatile procedure that identifies phosphylated butyrylcholi-nesterase. Adducted butyrylcholinesterase is isolated from plasma by affinity chromatography (procainamide column), digested with pepsin, and a nonapep-tide containing the phosphylated active-site serine residue detected using LC/ESI/MS/MS (quadrupole-TOF hybrid instrument). A C18 150 x 0.3-mm LC column was used, eluted with a gradient of water-acetonitrile-0.2 % formic acid. The method was applied successfully to casualties of sarin poisoning from the Tokyo subway attack (see Chapter 17). 

Recent innovations in mass spectrometry have provided incorporation of two, three, and four analyzers into commercially available tandem instruments. In addition, different mass analyzers may be combined to form a hybrid mass spectrometer such as the quadrupole-TOF (Q-TOF). Various types of tandem mass spectrometers include the quadruopole-TOF, time-of-flight-time-of-hight (TOF-TOF), triple-quadrupole, and Orbitrap-FTICR configurations. 

Andersen, J., Molina, H., Moertz, E. et al. (1998) Quadrupole-TOF hybrid mass spectrometers bring improvements to protein identification and MS/MS analysis of intact proteins. The 46th Conference on Mass Spectrometry and Allied Topics, Orlando, Florida, p. 978. 

Triple-quadrupole and more recently hybrid instruments, for instance the quadrupole TOF instrument or the ion trap-FT ion cyclotron resonance mass spectrometer, allow one to obtain a mass spectrum resulting from the decomposition of an ion selected in the first analyser. The time-dependent decomposition of a selected ion can also be observed in ion cyclotron resonance and ion trap instruments. They allow fragments over several generations (MS") to be observed. 

Hoyes, J. B., Jones, C., Langridge, J. I., Miliar, A., Vissers, J. P. (2002). A novel precursor ion discovery method on a hybrid quadrupole orthogonal acceleration time-of-flight (Q-TOF) mass spectrometer for studying protein phosphorylation. 

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