Time-of-Flight Analysers

TOF instruments were first designed and constructed starting in the late 1940s. Key advances were made by William C. Wiley and I.H. McLaren of the Bendix 

Increasing the flight time improves the resolving power of the TOF analyser. Newest developments in commercial TOF mass analysers extend the ion flight path by the use of multiple reflectrons reaching a mass resolving power of up to 50 000. Statements on the achievable ion transmission efficiency and a potential loss of detection sensitivity by multiple reflections have not been made available yet (Xian et al., 2012). 

Acquisition rate (spectra/s) Disulfoton (fit value) Diazinon (fit value) 

The average values of five replicate spectra from independent chromatographic runs are listed, except where low match quality did not provide identification. 

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

The advent of the time-of-flight analyser as part of an MS-MS instrument has already been noted. Its value has been compared with selected-decomposition monitoring (SDM) for the quantitative determination of Idoxifene (Figure 5.66),... 

An MS-MS instrument only relatively recently made available commercially for LC-MS applications is the Q-ToF system, i.e. the combination of a quadrupole mass analyser for precursor-ion selection and a time-of-flight analyser for production detection. As described earlier in Section 3.4.1.4, this instrument has the... 

Eckers, C. Haskins, N. Langridge, J. 1997. The use of liquid chromatography combined with a quadrupole time-of-flight analyser for the identification of trace impurities in drug substance. Rapid Commun. Mass Spectrom., 11,1916-1922. 

Since the signals are very short, simultaneous detection analysers or time-of-flight analysers are required. The probability of obtaining a useful mass spectrum depends critically on the specific physical proprieties of the analyte (e.g. photoabsorption, volatility, etc.). Furthermore, the produced ions are almost always fragmentation products of the original molecule if its mass is above approximately 500 Da. This situation changed dramatically with the development of matrix-assisted laser desorption ionization (MALDI) [17,18]. 

Scheme of a hybrid mass spectrometer including a quadrupole analyser, a quadrupolar collision cell and an orthogonal acceleration time-of-flight analyser. 

Time-of-flight analyser an instrument that measures the time of flight of the ions accelerated to known kinetic energies over a known fixed distance. As this time is a function of the mass, the mass can be calculated. 

Time-of-flight reflectron mass spectrometry with some form of time-delay extraction has become popular for large-molecule characterizations. Resolutions of up to 15,000 can be routinely achieved over very broad mass ranges, extending up to about 300,000 Da. As noted previously, time-of-flight analysers are particularly compatible with laser-based ionization techniques that produce very short bursts of ions. They are also very fast, with mass spectra often obtainable in about 25 p,s. Finally, time-of-flight analysers have been paired with a quadrupole to produce a hybrid two-dimensional mass spectrometry system that has found widespread use in protein analyses. This device will be discussed in more detail in the section on two-dimensional mass spectrometry. 

MALDI is particularly suited for use with time-of-flight analysers because pulsed lasers match well the ion introduction requirements of these instruments. In addition, the high mass ranges and short analysis times of these analysers make MALDI-time-of-flight the method of choice for many large biomolecular applications. Figure 3.13 is an example of a MALDI spectrum of a monoclonal antibody with a molecular weight of 149,000 (Hillenkamp and Karas, 1990). This spectrum is instructive in that it contains... 

The ionisation principle is based on the soft desorption of the solid sample molecules into the vacuum and subsequent ionisation. First, the sample is cocrystallised with a 1,000-10,000 excess of a suitable matrix on a metallic plate. Small, organic, UV-absorbing molecules like sinapinic acid are used as matrix materials (Table 4.1). An electric field is applied between the sample plate and the entrance to the time-of-flight analyser (Fig. 4.2). A pulsed laser beam is then... 

For ion detection in time of flight analysers, usually secondary electron multipliers are used. 

For MALDI, samples are co-crystallised with a matrix and desorbed by laser pulses. The desorption process is very mild and spectra contain hardly any fragments. The method allows the analysis of relatively crude samples with very low limits of detection. Coupling to liquid separation methods is not possible however, the time of flight analyser separates ions according to their m/z ratio in microseconds and thus allows analysis of mixtures without any sample pretreatment. 

Time-of-flight analysers are the fastest MS analysers making them especially suitable for application in high throughput LC/MS. They are well suited for pulsed ionisation methods (method of choice for the majority of MALDl mass spectrometer systems). MS/MS information can be obtained from post-source decay. 

A multipoint ion collector (also called the detector) consists of a large number of miniature electron multiplier elements assembled side by side over a plane. A multipoint collector may be an array, which detects a dispersed beam of ions simultaneously over a range of m/z values and is frequently used with a sector type mass spectrometer. Alternatively, a microchannel plate collector detects all ions of one m/z value. When combined with a time-of-flight analyser, the microchannel plate affords an almost instantaneous mass spectrum. Because of their construction and operation, microchannel plate detectors are cheaper to fit and maintain. 

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