TOP analyzers

A multipoint ion collector (also called the detector) consists of a large number of miniature electron multiplier elements assembled, or constructed, side by side over a plane. A multipoint collector can 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 TOP analyzer, the microchannel plate affords an almost instantaneous mass spectrum. Because of their construction and operation, microchannel plate detectors are cheaper to fit and maintain. Multipoint detectors are particularly useful for situations in which ionization occurs within a very short space of time, as with some ionization sources, or in which only trace quantities of any substance are available. For such fleeting availability of ions, only multipoint collectors can measure a whole spectrum or part of a spectrum satisfactorily in the short time available. 

If, just before the ion beam reaches the ion detector, a pusher electrode is used alongside it to deflect the beam at right angles (orthogonal) to its original direction into the flight tube of a time-of-flight sector (TOP analyzer), the m/z values can be measured by the TOP section. 

The pusher electrode must be operated by placing very short pulses of electric potential on it. The short pulses are required to ensure that all the ions are started at the same time along the TOP analyzer, since the latter must time the flights of the ions very accurately in order to measure m/z values. 

After passing through the hexapoles, the ion beam emerges in front of a pusher electrode built into the end of the TOP analyzer. 

The TOP analyzer is positioned at right angles (orthogonal) to the incoming ion beam. 

Application of a pulse of high electric potential (about IkV) to the pusher electrode over a period of about 3 psec causes a short section of the ion beam to be detached and accelerated into a TOP analyzer. A positive potential is used to accelerate positively charged ions and vice versa for negative ions. 

The detached section of ions sets off along the TOP analyzer, with the ions having velocities proportional to the square roots of their m/z values. 

The reflectron increases the spatial separation of the ions of different m/z values by making them travel up and down the flight tube, so the distance traveled is twice what it would be if the ions simply passed once along the tube from one end to the other. The reflectron also narrows the energy spread for individual m/z values, thus improving mass resolution. TOP analyzers are not necessarily equipped with a reflectron. 

The TOP analyzer provides the full mass spectrum of all the ions in the main ion beam at the time the pulse of electric potential was applied, m/z values being derived from the flight times of the ions along the TOP analyzer. 

Thus, it can be said that conventional magnetic sectors separate ions into individual m/z values by dispersion in space (spatially) and not according to their flight times. Contrarily, TOP analyzers separate ions of different m/z values according to their velocities (temporally) but not spatially. 

Apart from the quadrupole and TOP analyzers described in Sect. 3.2.2, the most important types of mass analyzer used in common dynamic SIMS instruments employ a magnetic-sector field. 

Separate component parts of some field samples in the field—e.g., carrots from carrot tops —if they are to be analyzed separately for parathion content. As an illustration of this point, airplane-dusted carrots were put through a commercial washer and divided into two lots. One lot was topped and stored 4 days in a paper bag the untopped lot was treated similarly but topped during the normal processing. The tops analyzed 1.2 p.p.m. of parathion. The field-topped carrots analyzed nil parathion, whereas the lot untopped during storage analyzed 0.2 p.p.m. of parathion. 

An exact mathematical treatment of the TOP analyzers as needed for the construction of such instmments of course has to include all contributions to the total time-of-flight. [32,33]... 

The transmittance of a linear TOP analyzer approaches 90 % because ion losses are solely caused by collisional scattering due to residual gas or by poor spatial focusing of the ion source. With a sufficiently large detector surface located in not a too large distance from the ion source exit, a very high fraction of the ions will be collected by the detector. 

Note The detection of neutrals formed by metastable fragmentation in linear TOP analyzers is one of the few exceptions where neutrals are handled and give rise to a signal in mass spectrometry. 

The ability of the ReTOP to compensate for the initial energy spread of ions largely increases the resolving power of TOP instruments. While a typical continuous extraction TOP instmment in linear mode cannot resolve isotopic patterns of analytes above about m/z 500, it will do when operated in reflector mode (Pig. 4.7). At substantially higher m/z, the ReTOP still fails to resolve isotopic patterns, even though its esolution is still better than that of a linear TOP analyzer. 

The essential independence of mean ion velocities on the molecular weight of the analyte leads to an approximate linear increase of the mean initial kinetic energies of the analyte ions with mass. High-mass ions therefore carry tens of elec-tronvolts of translational energy before ion acceleration. [33,41,50] The initial velocity of the ions is superimposed onto that obtained from ion acceleration, thereby causing considerable losses in resolution with continuous extraction TOP analyzers, in particular when operated in the linear mode. 

Nitrogen or argon is generally used as collision gas. The ion modulator pushes the ions orthogonally to their initial direction into the TOP analyzer. 

As we optimized Tethering we used a variety of mass spectrometers. In our experience, the sensitivity and high resolution of TOP analyzers has provided the most rapid and accurate analyses of intact proteins. An example of an ESI-TOF data set from a standard experiment is illustrated in Fig. 9.2. Figure 9.2A is the deconvoluted mass spectrum of a Cys-mutant target protein after equilibration... 

E369 Nanji, A.A., Poon, R. and Hinberg, I. (1987). Interference by cephalosporins with creatinine measurement by desk-top analyzers. Europ. J. Clin. Pharmacol. 33, 427-429. 

ENlOl Gregory, L.C., Duh, S.-H. and Christenson, R.H. (1992). An evaluation of total cholesterol measurements by desk-top analyzers. Clin. Chem. 38, 1037, Abstr. 439. 

R126 Saxena, S., Endahl, G.L. and Shulman, I.A. (1988). Use of a table-top analyzer for predonation screening for alanine aminotransferase - A cost-effective approach Am. J. Clin. Pathol. 90, 296-299. 

A further important property of the two instruments concerns the nature of any ion sources used with them. Magnetic-sector instruments work best with a continuous ion beam produced with an electron ionization or chemical ionization source. Sources that produce pulses of ions, such as with laser desorption or radioactive (Californium) sources, are not compatible with the need for a continuous beam. However, these pulsed sources are ideal for the TOP analyzer because, in such a system, ions of all m/z values must begin their flight to the ion detector at the same instant in... 

The term Q/TOF is used to describe a type of hybrid mass spectrometer system in which a quadrupole analyzer (Q) is used in conjunction with a time-of-flight analyzer (TOP). The use of two analyzers together (hybridized) provides distinct advantages that cannot be achieved by either analyzer individually. In the Q/TOF, the quadrupole is used in one of two modes to select the ions to be examined, and the TOP analyzer measures the actual mass spectrum. Hexapole assemblies are also used to help collimate the ion beams. The hybrid orthogonal Q/TOF instrument is illustrated in Figure 23.1. 

Schematic diagram of an orthogonal Q/TOF instrument. In this example, an ion beam is produced by electiospray 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 TOP analyzer is used to produce the final mass spectrum.

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