The Time-of-Flight Mass Analyser

In some respects, the time-of-flight (ToF) analyser is the simplest of the mass separation devices. This system relies on the fact that if all of the ions produced 

The operation of this type of device is fundamentally different to those described previously in which ions of one m/z ratio at a time enter the mass analyser. By varying the conditions in the mass analyser, e.g. magnetic field, quadrupole field, etc., ions of different m/z values are brought to the detector and a corresponding mass spectrum obtained. 

The resolution of the ToF analyser is dependent upon the ability to measure the very small differences in time required for ions of a similar m/z to reach the detector. Increasing the distance that the ions travel between source and detector, i.e. increasing the length of the flight tube, would accentuate any such small time-differences. The implication of such an increase is that the instrument would be physically larger and this goes against the current trend towards the miniaturization of all analytical equipment. 

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Reflectron An ion lens nsed in the time-of-flight mass analyser to increase the distance travelled by an ion and thereby increase the resolntion of the instmment. 

Figure 3.7 Schematic of a time-of-flight mass analyser, involving the use of a reflectron .

Matrix-associated laser desorption ionization with a time-of-flight mass analyser (MALDl-ToF) was used to examine the crude tryptic peptide mixture from a number of the proteins, without HPLC separation, to provide a mass map, i.e. a survey of the molecular weights of the peptides generated by the digestion process. 

Q-ToF The combination of quadrupole and time-of-flight mass analysers. This allows the m/z ratios of ions produced during a product-ion scan to be measured accurately and the elemental composition of these ions to be determined. 

Contrary to most other ionization sources that yield a continuous ion beam, MALDI is a pulsed ionization technique that produces ions in bundles by an intermittent process. The pulsed nature of the MALDI source is well suited for the time-of-flight (TOF) analyser. In addition, the TOF analyser has the ability to analyse ions over a wide mass range and thus... 

Schematic description of a continuous extraction mode and a delayed pulsed extraction mode in an linear time-of-flight mass analyser, o = ions of a given mass with correct kinetic energy = ions of the same mass but with a kinetic energy that is too high. Delayed pulsed extraction corrects the energy dispersion of the ions leaving the source with the same mjz ratio.

A TOF mass analyser requires a pulsed ion introduction. In an electrospray-TOF combination, the duty cycle is an important issue. A significant improvement in the duty cycle can be achieved in an ion-trap-TOF hybrid instmment the ions from a continuous ion source are accumulated in the ion trap between two ion introduction events. An ion-trap-TOF hybrid instrument was first described by the group of Lubman [68-69]. The system consists of an atmospheric-pressure ion source with a vacuum interface, a set of Einzel lenses, an ion-trap device, and a reflectron time-of-flight mass analyser. The system was applied for fast analysis in combination with a variety of separation techniques [70]. 

Figure 9.8 Schematic of a reflectron time of flight mass analyser. Reflectron lenses act as an electrostatic mirror to both increase the effective length of the flight path, but also to compensate for ion kinetic energy variations (Uq), resulting in higher mass accuracy relative to purely linear time of flight mass analyzers. Consequently, linear time of flight analyzers are nowadays largely obsolete.

Fig. 3.5. Schematic representation of a time-of-flight mass analyser with reflectron and external ion storage for time-delay extraction. Ions that enter the field-free drift region migrate to the detector at a rate that is dependent on their m/z ratio. The reflectron lenses compensate for variations in kinetic energies of the injected ions these variations would otherwise produce broadened peaks and loss of spectral resolution.

Post ionisation and desolvation, analyte ions are separated according to their m/z ratio by a mass analyser. The analyte ions are usually separated using static or dynamic electric/magnetic fields. An exception to this would be time-of-flight which does not utilise a magnetic/electric field, excepf if a reflection is used, which employs a static electric held. Although many mass analysers and their variants have been developed, only the principles of a quadrupole and time-of-flight mass analysers will be described in this section in accordance with the techniques used in later chapters. 

The source designs described so far are used in combination with a (triple) quadrupole instrument. Modifications of this design are required in the coupling to other types of mass analysers, e.g. the implementation of a gate or ion pulse electrode for use in combination with ion-trap and time-of-flight mass analysers. 

Figure 1.8 Mass spectrum derived from a PTR-MS instrument containing a time-of-flight mass analyser. This spectrum was recorded using a gas mixture containing methanol, acetaldehyde, trans-2-butene, acetone, methacrolein, cyclohexanone and p-pinene. Spectrum (a) shows a survey scan while (b) shows an expanded view of part of the mass spectrum in (a). Data were accumulated for 20 s and the vertical scale expresses the signal as the total number of Ions detected In that 20 s period for a given m/z. The higher mass resolving power of a time-of-flight mass spectrometer compared with a quadrupole mass spectrometer is evident from comparison of this mass spectrum with that in Figure 1.7.

In Laser Ionization Mass Spectrometry (LIMS, also LAMMA, LAMMS, and LIMA), a vacuum-compatible solid sample is irradiated with short pulses ("10 ns) of ultraviolet laser light. The laser pulse vaporizes a microvolume of material, and a fraction of the vaporized species are ionized and accelerated into a time-of-flight mass spectrometer which measures the signal intensity of the mass-separated ions. The instrument acquires a complete mass spectrum, typically covering the range 0— 250 atomic mass units (amu), with each laser pulse. A survey analysis of the material is performed in this way. The relative intensities of the signals can be converted to concentrations with the use of appropriate standards, and quantitative or semi-quantitative analyses are possible with the use of such standards. 

When a pulsed laser is used, ions are only produced for the duration of the pulse, i.e. they are not produced continuously and the mass spectrometer used must be capable of producing a mass spectrum from these pulses of ions. As discussed below in Section 3.3.4, the time-of-flight (ToF) mass analyser is the most appropriate for this purpose and has the added advantage of being able to measure very high m/z ratios. Indeed, the recent dramatic developments in the performance of the ToF mass analyser have largely been occasioned by the requirement to produce useful spectra from MALDI. 

Tandem Mass Spectrometry on the Time-of-Flight Analyser... 

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