FT-ICR Instruments

Although resolution and mass accuracy are already high in broadband spectra (R = 3 X lO -lO Am 10 u), the performance of FT-ICR instruments further improves by storing only narrow m/z ranges, because fewer ions in the cell mean less distortion by coulombic interactions. 

Note The need for almost perfect vacuum, i.e., extremely long mean free paths, in FT-ICR mass spectrometers arises from the combination of high ion velocities of several 10 m s , observation intervals in the order of seconds, and the effect of collisions on peak shape. 

Ion traps, ICR cells as well as QFTs, are best operated with the number of trapped ions close to their respective optimum, because otherwise ion trajectories are distorted by coulombic repulsion. Hence, external ion sources in combination with ion transfCT optics capable of controlling the number of injected ions are ideally attached to ion traps. Currently, MALDI [202] and even more so ESI [182,185,186,201,203] ion sources predominate in FT-ICR. The ion current is not solely regulated by the source but by some device to collect and store the desired amount of ions until the package is ready for injection into the ICR cell. Linear RF-multipole ion traps are normally employed for that purpose (Chap. 4.4.6) [98,204], but other systems are also in use [187]. RF-only multipoles are com- 

Note Occasionally, FT-ICR-MS is inaccurately referred to as FTMS. Of course, ICR without Fourier transformation would not have become as successful as it has, but Fourier transformation alone cannot separate ions according to m/z. With the advent of the orbitrap analyzer (below), there is a second system that makes use of Fourier transformation. Hence, the acronym FT-MS is proposed for all FT-based methods such as FT-ICR and orbitrap. 

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The Orbitrap allows very high resolution to be achieved (the resolving power in commercial instruments is 100000, rivalling that of FT-ICR instruments) and routine mass measurement accuracies less than 2 ppm. It finds applications in many fields, such as biology, proteomics, food chemistry and cultural heritage. 

The question remains whether the mass of the electron m (0.548 mmu) has really to been taken into account in accurate mass work as demanded by the lUPAC convention (Chap. 3.1.4). This issue was almost only of academic interest as long as mass spectrometry never yielded mass accuracies better than several mmu. Nowadays, extremely accurate FT-ICR instruments become more widespread in use, and thus, the answer depends on the intended application The electron mass has to be included in calculations if the result is expected to report the accurate mass of the ion with highest accuracy. Here, neglecting the electron mass would cause an systematic error of the size of m. This cannot be tolerated when mass measurement accuracies in the order of 1 mmu or better are to be achieved. 

With few exceptions, magnetic sector instruments are comparatively large devices capable of high resolution and accurate mass determination, and suited for a wide variety of ionization methods. Double-focusing sector instruments are the choice of MS laboratories with a large chemical diversity of samples. In recent years, there is a tendency to substitute these machines by TOE or by Fourier transform ion cyclotron resonance (FT-ICR) instruments. 

LITs capable of scanning, axial or radial excitation of ions, and precursor ion selection for MS/MS experiments [118,134-136] have lately been incorporated in commercial mass spectrometers (Fig. 4.39). The replacement of Q3 in a QqQ instrument with a scanning LIT, for example, enhances its sensitivity and offers new modes of operation (Applied Biosystems Q-Trap). Introduction of a scanning LIT [118,135] as MSI in front of an FT-ICR instrument (Thermo Electron LTQ-FT) shields the ultrahigh vacuum of the FT-ICR from collision gas and decomposition products in order to operate under optimum conditions. In addition, the LIT accumulates and eventually mass-selects ions for the next cycle while the ICR cell is still busy with the previous ion package. 

Fig. 4.54. Ion transfer optics and differential pumping stages to adapt an ESI source to an FT-ICR instrument. Only the ICR cell is inside the superconducting magnet. By courtesy of Bruker Daltonik, Bremen.

Classically, high-resolution work is the domain of double-focusing magnetic sector instruments. More recently, TOP and to a certain degree triple quadrupole instruments are also capable of resolutions up to about 20,000. However, the rapid development of FT-ICR instruments has established those as the systems of choice if ultrahigh-resolution (>100,000) and highest mass accuracy (1 ppm) are required (Chap. 4.6). 

The particularity of the LIT-orbitrap instrument is the independent operation of the orbitrap and the LIT. Because high resolution requires longer transient time, further data can already be collected in the LIT at the same time. As an example accurate mass measurements of the precursor ion can be performed in the orbitrap while MS and MS spectra are recorded with the linear ion trap. The LIT-orbitrap has less resolution than a FT-ICR instrument with similar duty cycle, but its maintenance costs are far lower than for the FT-ICR. Both instruments will have a major impact in mainly qualitative analysis of low molecular weight compounds and macromolecules. 

As instrumentation developed, tandem-in-time approaches were developed using ion trap and Fourier transform ion cyclotron resonance (FT-ICR) instruments. During tandem-in-time experiments, the sequential stages of mass selection, CID, and mass analysis are performed within the same, trapping, mass analyzer. 

Ion detection in FT-ICR instruments is unique (Fig. 18). It is a non-destructive detection method, which means multiple measurements can be performed on the same ions. 

FT-ICR instruments are also capable of performing MS" experiments. The most popular method of ion activation is sustained off-resonance irradiation (SORI), where ions are excited to a larger cyclotron radius using rf energy, undergo collisions with a neutral gas pulsed into the cell and dissociate. Other methods are available, including infrared multiphoton dissociation (IRMPD)65 and electron capture dissociation (ECD)66 which is of particular value in glyco-peptide analysis (Section VIA). 

In the literature many examples of attacks of nucleophiles upon carbonyl centres can be found and they have been covered adequately in a recent review (Bowie, 1984b). These attacks are rarely observed, however, without competition from other reaction channels. This is well demonstrated by the reactions of NH2 with methyl formate deuterated in the formyl position, where at least five different primary product ions are formed as summarized in eqns (15a)-(15f). Some of these product ions are consumed by reaction with the NH3 and DC02CH3 molecules present as can be seen from Fig. 5. This shows how the chemistry evolves as a function of reaction time in the FT-ICR instrument, and the results are in excellent agreement with the observations made for the same system in a FA apparatus (DePuy et at.,... 

The next stage in the development of GD-FT-ICR instrumentation involved a collaboration with scientists (primarily Dr. Clifford Watson) at Bruker Instruments, Inc. Using the improved ion injection schemes and differential pumping of... 

Additional studies addressed the advantages of pulsed gas glow discharges coupled to the FT-ICR instrument. The FT-ICR technique requires quite low pressures in the analyzer cell to obtain the highest possible mass resolving power, since... 

Figure 19 Schematic representation of glow discharge Fourier transform ion cyclotron resonance (GD-FT-ICR) instrumentation currently in use at the University of Florida.

The most notable feature of the process described above is that ions are not destroyed by the detection process. Therefore ions can be further manipulated after detection. The simplest example is the remeasurement of ions (i.e., repeating the excite and/or detect sequence to obtain another mass spectrum of the same group of ions). More complex manipulations include multiple stages of MS/MS. The facts that ions are detected nondestructively and that they are trapped in a region of space mean that very complex sequences of ion manipulations are possible, making FT-ICR instruments the most versatile of all mass spectrometers. 

Like the QIT, ionization in the FT-ICR maybe performed either internally or externally to the cell. For several reasons, external ionization has become the technique of choice. External ionization allows the use of virtually any ionization method, and commercially available instruments are typically designed as general purpose instruments incorporating interchangeable ion sources. All three major suppliers of FT-ICR instruments (lonSpec, Bruker Daltonics, and Finnigan) offer external sources. 

Fig. 1.84. Catalytic cycles of the Pty ion in a 1 6 mixture of CO and N2O. The experiment was carried out under single collision conditions in an FT-ICR instrument, (a) The catalytic cycles involving PtrO and Pt702 are identical to the Pt cycles in Fig. 1.83. (b) In addition, a cycle involving the initial formation of PtyCO is observed. Additional CO molecules, however, increasingly poison the cluster. The conversion of Pt7(CO)2 back to Pt7CO+ might contribute to a minor extent to the catalytic activity [424]...

Apart from the proton transfer reactions discussed in Section II, phosphorus species undergo a range of other ion-molecule reactions in the gas phase. The types of instruments which have been used to study ion-molecule reactions of phosphorus species include ion cyclotron resonance (ICR) mass spectrometers and the related FT-ICR instruments, flowing afterglow (FA) instruments and their related selected-ion flow tubes (SIFT) and also more conventional instruments This section is divided into four topics (A) positive ion-molecule reactions (B) negative ion-molecule reactions (C) neutralization-reionization reactions and (D) phosphorus-carbon bond formation reactions. 

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