Electrospray ionization orthogonal

Jorgensen, T. J. D., Hvelplund, P., Andersen, J. U., Roepstorff, P. Tandem mass spectrometry of specific vs. nonspecific noncovalent complexes of vancomycin antibiotics and peptide ligands. Int J Mass Spectrom 2002, 219, 659-670. Tahallah, N., Pinkse, M., Maier, C. S., Heck, A. J. The effect of the source pressure on the abundance of ions of noncovalent protein assemblies in an electrospray ionization orthogonal time-of-fiight instrument. Rapid... 

Bahr, U., and Karas, M. (1999). Differentiation of isobaric peptides and human milk oligosaccharides by exact mass measurements using electrospray ionization orthogonal time-of-flight analysis. Rapid Commun. Mass Spectrom. 13 1052-1058. 

Schematic diagram of an orthogonal Q/TOF instrument. In this example, an ion beam is produced by electrospray ionization. The solution can be an effluent from a liquid chromatography column or simply a solution of an analyte. The sampling cone and the skimmer help to separate analyte ions from solvent, The RF hexapoles cannot separate ions according to m/z values and are instead used to help confine the ions into a narrow beam. The quadrupole can be made to operate in two modes. In one (wide band-pass mode), all of the ion beam passes through. In the other (narrow band-pass mode), only ions selected according to m/z value are allowed through. In narrow band-pass mode, the gas pressure in the middle hexapole is increased so that ions selected in the quadrupole are caused to fragment following collisions with gas molecules. In both modes, the TOF analyzer is used to produce the final mass spectrum.

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. 

Figure 4.4. Schematic of an orthogonal Q-TOF mass spectrometer. In this example, an ion beam is produced by electrospray ionization (ESI). The solution introduced to the mass spec-trometer-ESI source may be an effluent from a liquid chromatography column or simply an infusion solution of an analyte.

Valaskovic, G.A. Lee, M.S. Orthogonal Control Sytems for Electrospray Ionization Mass Spectrometry, in Proceedings ofthe 50th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL, June 2-6, 2002. 

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. 

Figure 9.5. Schematic diagram of the Agilent orthogonal electrospray ionization source for LC-MS. (From ref. [29] Elsevier)...

As we have seen in this book, three developments appear to have provided the necessary momentum, and all three are still works in progress . The first was the development of TOF instruments, which could accomodate electrospray ionization by using orthogonal extraction or combining ion trapping with the TOF analyzer, which led to the possibility of carrying out on-line HPLC analysis. Considerable improvements are required to enable ESI-TOF instruments to be commercially competitive with existing quadrupole (and triple quadrupole) ESI mass spectrometers, but this is sure to be a major focus of development by both University laboratories and instrument manufacturers. 

As noted above, temperature ramping capabilities offer only moderate sq)aiation capabihty according to compound volatility, but at the expense of speed of analysis, and the method is not adequate for complex mixtures. Ion mobility spectrometry/mass spectrometry (MS/MS) offers two highly orthogonal dimensions of rapid separafion allowing decongestion of complexity and is thus well suited for direct ionization methods as was shown by Weston et aL< in their study on the use of desorption electrospray ionization (DESI) combined with IMS/MS for the analysis of pharmaceutical formulations. 

In atmospheric pressure MALDI (AP-MALDI) the MALDI process takes place under atmospheric pressure in dry nitrogen gas. The desorbed ions are then transferred into the vacuum of the mass analyzer by means of an atmospheric pressure ionization (API) interface which is typically provided by an electrospray ionization (ESI, Chap. 11) source. AP-MALDI was first presented in combination with an orthogonal acceleration TOE (oaTOF, Chap. 4.2.6) analyzer whae the original ESI ion source was modified to accommodate a sinple MALDI target plus laser instead of the ESI spray capillary [208]. AP-MALDI has also been adapted to a quadrupole ion trap (QIT, Chap. 4.5) [209] where an inproved design was realized by extending the heated transfer capillary of a Finnigan LCQ ion trap instru... 

Figure 3 A schematic diagram of an orthogonal-injection TOF instrument with an electrospray ionization source. Collisional cooling is used in a quadrupole ion guide to produce a beam with a small energy spread, and a small cross section. The pressure in the ion guide is typically tens of millitorr the main TOF chamber is under high vacuum, typically torr. Ions are pulsed into...

Figure 14.5 Modified-ESI source for the direct infusion of undiluted ILs. A stainless steel wire is placed in the spray, leading to the optimal vaporization of the IL. Additionally, an orthogonal ESI source is used. Only a part of the IL ions is transferred into the MS, thus minimizing pollution of the source. (Modified from Dyson, R J. et al.. Direct probe electrospray (and nanospray) ionization mass spectrometry of neat ionic liquids. Chem. Commun., 2204, 2004. Reproduced by permission of the Royal Society of Chemistry.)...

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