Electrospray ionization-time of flight-mass spectrometer

Krutchinsky, A. N., I. V. Chemushevich, V. L. Spicer, W. Ens and K. G. Standing. 1998. Collisional damping interface for an electrospray ionization time-of-flight mass spectrometer. J. Amer. Soc. Mass Spectrom. 9 569-79. 

Electrospray ionization mass spectrometry (ESI-MS) is an analytical method for mass determination of ionized molecules. It is a commonly used method for soft ionization of peptides and proteins in quadmpole, ion-trap, or time-of-flight mass spectrometers. The ionization is performed by application of a high voltage to a stream of liquid emitted from a capillaty. The highly charged droplets are shrunk and the resulting peptide or protein ions are sampled and separated by the mass spectrometer. 

Figeys, D., Lock, C., Taylor, L., and Aebersold, R. (1998). Microfabricated device coupled with an electrospray ionization quadrupole time-of-flight mass spectrometer protein identifications based on enhanced-resolution mass spectrometry and tandem mass spectrometry data. Rapid Commun. Mass Spectrom. 12, 1435 — 1444. 

Major methods for introducing proteins and other macromolecules into mass spectrometers are electrospray and matrix-assisted laser desorption/ionization (MALDI).18-27 Most often, MALDI is used with a time-of-flight mass spectrometer, which can measure mlz up to 106. Typically, 1 p,L of a 10 jxM solution of analyte is mixed with 1 p,L of a 1-100 mM solution of an ultraviolet-absorbing compound such as 2,5-dihydroxybenzoic acid (the matrix) directly on a probe that fits into the source of the spectrometer. Evaporation of the liquid leaves an intimate mixture of fine crystals of matrix plus analyte. 

The main drawback in the resolution of enantiomers and/or determination of the absolute configuration of insect-produced compounds by HPLC is the limited sensitivity, because the epoxides do not have chromophores and thus are poorly detected by the UV detectors commonly used with HPLC. With such detectors, epoxides have to be injected in comparatively large (-microgram) amounts in order to be detected. Alternatively, fractions can be taken by time and then checked by GC. Until recently, LC-MS methods suffered from a similar lack of sensitivity, but the introduction of more sensitive time-of-flight mass spectrometers, operating with electrospray ionization, may eliminate this limitation and produce sensitivities similar to those achievable with GC-MS (Yamazawa et al., 2003). 

Regarding the mass range, DNA ions of 108 Da were weighed by mass spectrometry [77], In the same way, non-covalent complexes with molecular weights up to 2.2 MDa were measured by mass spectrometry [78], Intact viral particles of tobacco mosaic virus with a theoretical molecular weight of 40.5 MDa were analysed with an electrospray ionization charge detection time-of-flight mass spectrometer [6]. 

Fig. 12. Mass spectra of Rice Yellow Mottle Virus (RYMV) and Tobacco Mosaic Virus (TMV) particles analyzed with an electrospray ionization charge detection time-of-flight mass spectrometer. Inset, electron micrographs of the icosahedral RYMV (diameter 28.8 nm) and the cylindrical TMV (-300 nm long and 17 nm in diameter). The known molecular weight of RYMV and TMV are 6.5X106 and 40.5X106 Daltons,respectively...

It is of interest to mention some detailed mass spectrometric results that were obtained by performing distinct experiments (a) ion-molecule reactions in mixtures of haloben-zenes and ammonia under chemical ionization conditions (b) ion-molecule reactions of mass-selected ionized halobenzenes toward ammonia in a quadrupole collision cell of a hybrid tandem mass spectrometer (c) ion-molecule reactions of phenyl diazonium cations with ammonia in the same quadrupole collision cell and, finally, (d) electrospray ionization of anilines in a hybrid quadrupole-time of flight mass spectrometer (QTof). Characterization of the product ions relies on collisional activation experiments in the low or high kinetic energy regime98. 

Mass spectrometry is a powerful qualitative and quantitative analytical tool that is used to assess the molecular mass and primary amino acid sequence of peptides and proteins. Technical advancements in mass spectrometry have resulted in the development of matrix-assisted laser desorption/ion-ization (MALDI) and electrospray ionization techniques that allow sequencing and mass determination of picomole quantities of proteins with masses greater than 100kDa (see Chapter 7). A time-of flight mass spectrometer is used to detect the small quantities of ions that are produced by MALDI. In this type of spectrometer, ions are accelerated in an electrical field and allowed to drift to a detector. The mass of the ion is calculated from the time it takes to reach the detector. To measure the masses of proteins in a mixture or to produce a peptide map of a proteolytic digest, from 0.5 to 2.0 p.L of sample is dried on the tip of tlie sample probe, which is then introduced into tire spectrometer for analysis. With this technique, proteins located on the surfaces of cells are selectively ionized and analyzed. 

Clauwaert, K.M. et al., Investigation of the quantitative properties of the quadrupole orthogonal acceleration time-of-flight mass spectrometer with electrospray ionization using 3,4-mcthylendioxymcthamphctaminc, Rapid Commun. Mass Spectrom., 13,1540, 1999. 

Williams, J.P. et al., Polarity switching accurate mass measurement of pharmaceutical samples using desorption electrospray ionization and a dual ion source interfaced to an orthogonal acceleration time-of-flight mass spectrometer, Anal Chem., 78(21), 7440, 2006. 

SM Michael, BM Chien, DM Lubman. Detection of electrospray ionization using a quadrupole ion trap storage/reflection time-of-flight mass spectrometer. Anal Chem 65 2614, 1993. 

Gomez-Ariza, J.L., Arias-Borrego, A., Garcia-Barrera, T., and Beltran, R., Comparative study of electrospray ionization sources coupled to quadrupole time-of-flight mass spectrometer for olive oil authentication, Talanta, 70, 859-869, 2006. 

FIGURE 9.2 Schematic diagram of electrospray ionization-ion trap-low-pressure ion mobility spectrometer-time-of-flight mass spectrometer (ESI-IT-IMS-TOF). (From Henderson et al., ESI/ion trap/ion mobility/time-of-flight mass spectrometry for rapid and sensitive analysis of biomolecular mixtures, Anal. Chem. 1999,71,291. With permission.)... 

Dodonov AF, Chernushevich IV, and Laiko W (1994) Electrospray ionization on a reflecting time-of-flight mass spectrometer. In Cotter RJ (ed.) Time of Plight Mass Spectrometry, pp. 108-123. Washington DC American Chemical Society. 

Because of the advances in the gas-phase ionization of biomacromolecules, such as electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), mass spectrometry (MS) has become a powerful tool for detection, identification, and structural analysis of proteins, peptides, and polynucleotides. The molecules ionized in a gas phase by these methods are subsequently analyzed by sector, quadrupole, ion-trap, or time-of-flight mass spectrometers. In particular, the MS systems consisting of ESI and triple-stage quadrupole (ESI/TSQ) or ion-trap (IT) mass spectrometry and MALDI time-of-flight (MALDl/TOF) mass spectrometry have been most widely applied to the field of protein chemistry for the accurate determination of molecular mass of proteins and peptides, determination of amino acid sequence, identification of proteins by peptide mass databases, and analysis of posttranslational modifications such as phosphorylation and glycosylation. In general, current techniques allow detenni-... 

Quadrupole/Time of Flight Mass Spectrometer , with electrospray ionization Waters/Micromass Protein/peptide identification... 

After presenting an overview chapter and the fundamentals, the book focuses on instrumentation and ionization sources. It describes an ion-mobility-capable quadrupole time-of-flight mass spectrometer, the differential mobility analyzer, a cryogenic-temperature ion mobility mass spectrometer, the atmospheric solids analysis probe method, and laserspray ionization. In the final applications-oriented chapters, the contributors explore how homebuilt and commercial instruments using electrospray ionization and matrix-assisted laser desorption/ionization (MALDl) methods are employed to solve biological and synthetic issues. 

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