The Time-of-Flight Analyser

The principal advantages of SIMS, in both its static and dynamic forms, are its surface sensitivity and its very low detection limits for impurities. Only a very small proportion of the detected ions come from the second or lower layers of the materials being analysed. With regard to quantitative analysis, Yickerman (in Yickerman, 

Brown and Reed (1989) has reviewed the theoretical models of SIMS and he concludes that the lack of a fully comprehensive theory has not inhibited the successful empirical application of SIMS to many problems. 

There are two parameters which are of primary importance in the analysis of SIMS data - the relationship between the secondary ion current and the elemental concentration in the sample surface, and the depth scale. 

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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),... 

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 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. 

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. 

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. 

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... 

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. 

With the various experimental techniques, the actual measurement concerns product ions after they have been extracted from the source. That is to say, the decomposition occurs in a source before acceleration, but what is actually measured is translational energy after the product ion has been accelerated. To be still more precise, it is, in most cases, the distribution of the component of velocity along the axis of the mass spectrometer (i.e. in the direction in which the ions were accelerated out of the source) which is, in effect, measured. The measured quantity is, therefore, distinct from the translational energy distribution of the product ion (called the laboratory distribution ) as it was upon its formation in the source (i.e. before acceleration). The measured distribution needs to be analysed to obtain the laboratory distribution. Working with means or averages is much simpler, but there are possible pitfalls (see the discussion of the time-of-flight technique below). 

Metastable ions is a term commonly used for ions which decompose unimolecularly in the field-free regions between the analysers, between the source and analyser, or between analyser and detector of ordinary mass spectrometers [186, 421]. These ions typically have lifetimes of the order of microseconds. The lifetimes are determined by the times of flight through the mass spectrometer. The term is used in this review in a broader sense to mean any ions selected according to lifetimes when those lifetimes are of the order of microseconds [i.e. in terms of eqn. (9), i h /us]. 

There is one obvious difficulty in determining intramolecular kinetic isotope effects with the present PIPECO techniques for metastable ions (Sect. 3.2.1), which is that peaks for product ions from isotopically labelled molecules will overlap. Indeed, peaks for ions separated by only one mass unit will typically be largely superimposed. The time-of-flight technique is, in effect, measuring velocity and what is required is measurement of mass and translational energy in separate analysers. The problem... 

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]. 

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... 

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. 

Beside the most commonly used ion separation systems, such as the quadrupole mass analyser, the ion-trap mass analyser and the double-focusing and tri-sector mass analyser, a new system has encountered increasing interest. This system, the time-of-flight (TOP) mass analyser offers fast scanning opportunities coupled with the possibility of detecting ions with high m/z ratios. This provides a useful tool for rapid quality control of sensorial profiles as well as the detection and identification of toxins and proteins or protein-bound substances [42]. 

Crystal analyser instruments at pulsed sources are used in the time-of-flight mode. There are two main types of instrument those that use a variable final energy and those that use a fixed final energy. There is only one working example of the former t)q)e at present, PRISMA [22] at ISIS. This is used exclusively for coherent inelastie neutron scattering and so will not be considered further here. 

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