Time-of-Flight TOF Analyzers

Although modern TOF analyzers may be rather complicated, the basic principle is simple they are just what they say they are. Pulses of ions are accelerated from the source into the analyzer tube, and the time for an ion to travel through a field-free region to the detector is measured. The time-of-flight for the passage of an ion in a TOF analyzer is a function of its momentum, and therefore its miz. The acceleration voltage and, consequently the kinetic energy (momentum), is the same for all ions. 

Selective use of the rf and dc voltages on the rods can be used to axially eject ions in miz sequence to obtain a spectrum, to pass ions onto another analyzer, or to isolate a specific ion by radially ejecting all other ions with different mIz values. 

Voltages on the entrance and exit grids enable the accumulation and maintenance of ions inside the trap. 

LIT are more sensitive than quadrupole ion traps (QIT) because there are fewer crossover points in the ion paths so the LIT can hold more ions before space-charge effects disrupt instrumeut performance. 

TOF analyzers are nonscanning analyzers because the operating parameters of the analyzer need not be altered to obtain spectra. An important consequence of being nonscanning is that ions must be pulsed into the analyzer as discrete packets that contain all miz values produced in the ion source. In addition, all ions in each packet mnst clear the analyzer prior to the introduction of the next packet of ions. The time for the passage of a set of ions is on the microsecond scale, and there will be distortion of the flight paths and overlap of data if a second packet of ions is allowed to enter the analyzer before the first has arrived at the detector. 

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Upon emerging from the quadrupole, the ions are accelerated through about 40 V and focused into the time-of-flight (TOF) analyzer. A pusher electrode is sited alongside this focused ion beam. Application of a pulse of high electric potential (about 1 kV) to the pusher electrode over a period of about 3 ps causes a short section of the ion beam to be detached and accelerated into the TOF analyzer. A positive potential is used to accelerate positively charged ions and vice versa. 

It should be pointed out that FAB, MALDI, and ESI can be used to provide ions for peptide mass maps or for microsequencing and that any kind of ion analyzer can support searches based only on molecular masses. Fragment or sequence ions are provided by instruments that can both select precursor ions and record their fragmentation. Such mass spectrometers include ion traps, Fourier transform ion cyclotron resonance, tandem quadrupole, tandem magnetic sector, several configurations of time-of-flight (TOF) analyzers, and hybrid systems such as quadrupole-TOF and ion trap-TOF analyzers. 

Obviously, Cf-PD creates ions in a pulsed manner - one burst of ions per fission event - analogous to laser desorption, a fact that restricted the adaptation of Cf-PD to time-of-flight (TOF) analyzers (Chap. 4.2). The second fission fragment is not useless, however, because it serves to trigger the time measurement of... 

Laser desorption intrinsically is a pulsed ionization process, which is therefore ideally combined with time-of-flight (TOF) analyzers (Chap. 4.2). [16,49] Ever since the first MALDI experiments, MALDI and TOF have been forming a unit, and the majority of MALDI applications are MALDI-TOF measurements. Vice versa, it was the success of MALDI that pushed forth the tremendous delevopment of TOF mass analyzers. More recently, MALDI has also been adapted to orthogonal acceleration TOF analyzers. [147]... 

In a time-of-flight (TOF) analyzer the time of flight of ions between the ion source and the detector is measured [61]. This requires that the time at which the ions leave the ion source is well-defined. Therefore, ions are either formed by a pulsed ionization method or various kinds of rapid electric field switching. The single discontinuous laser pulses at distinct time points used in MALDI can be ideally combined with time-of-flight mass separation. TOF analyzers thus received increasing interest with the development of MALDI MS. The schematic draw of a linear MALDI-TOF MS is shown in Fig. (9). 

Another type of dynamic mass spectrometer is the time-of-flight (ToF) analyzer. In 1946, Stephens presented his concept of the linear time-of-flight mass spectrometer (ToF-MS) as the simplest mass separation technique at an American Physical Society meeting in Cambridge, MA.49 Cameron and Eggers first published the design and showed mass spectra for linear ToF-MS in... 

Various mass spectrometer configurations have been used for the detection of explosives, such as ion traps, quadrupoles, and time-of-flight (TOF) analyzers and tandem mass spectrometer (MS/MS) combinations. Also, various modes of ionization have been employed, depending on the specific application in the detection of explosives. 

A time-of-flight (TOF) analyzer allows positively charged peptides to fly through a vacuum tube toward a negatively charged detector source, so that the time of flight can be calibrated in proportion to peptide mass. Typically, the longer the vacuum tube, the more accurate the mass will be because of increased resolution. 

In terms of mass spectrometry instrumentation, the currently available instruments such as time-of-flight (TOF) analyzers and hybrid quadrupole-TOF analyzers are able to acquire complete mass spectra at rates compatible with fast CE separations. As CE or ultrafast chromatography replaces conventional, slow HPEC applications, TOF-based mass spectrometers will be needed to replace the less efficient scanning types of instruments such as quadrupoles and ion traps for most high-throughput applications. FTICR mass spectrometry remains unsurpassed in terms of resolution and mass accuracy for both MS and MS-MS applications. However, the throughput of FTICR mass spectrometric... 

Upon emerging from the quadrupole, the ions are accelerated through about 40 V and focused into the time-of-flight (TOF) analyzer. A pusher electrode is sited alongside this focused ion beam. 

The time-of-flight (ToF) analyzer is the most widely used analyzer in static SIMS. As its name indicates, for this analyzer the flight time of an ion is the parameter for measurement. When ions are obtained with a constant kinetic energy from an acceleration potential (V) of 3-8 kV, the flight time of ions through a distance (L) of flight tube to reach a detector is calculated. 

For time-resolved 2PPE spectroscopy, a combined set-up of an ultrafast laser system and an ultrahigh-vacuum photoemission spectroscopic system is indispensable. Typical electron energy analyzers have been used as the spectrometer, such as a cylindrical mirror analyzer, a hemispherical analyzer and a time-of-flight (TOF) analyzer. The TOF analyzer is mainly used for low repetition rate (<1 kFlz) laser sources, and the others are used for the lasers with multi-kldz or MHz repetition rates [11-14]. 

Preferably, electrospray ionization (ESI) is used in combination with quadrupole mass filters [16,17], whereas MALDI is commonly used in combination with the time-of-flight (TOF) analyzer [18], The relatively simple construction of these two types of analyzers and the resulting price advantage has led to their replacing the traditional magnetic sector instruments as the workhorses of mass spectrometric analysis. A more recent development is the ion-cyclotron-resonance (ICR) analyzer [19] which can be used for both ES-and MALDI-ionization. 

The mass analyzer. After the process of ionization, the ionized molecules of proteins or peptides enter the section of the mass spectrometer called the mass analyzer, where they are separated based on their mass-to-charge ratio by electric and/or magnetic fields or by measuring the time taken by an ion to reach a fixed distance from the point of ionization to the detector. Different kinds of analyzers are available for the separation of ionized molecules. Among the different kinds of analyzers, two particular kinds, called the quadrupole and the time-of-flight (TOF) analyzers, are the most important from the point of proteomics for their use in mass spectrometers. A particular spectrometer may use one or the other or at times a combination of both quadupole and TOF analyzers. Usually, the machine with the electrospray ionization device carries a quadrople analyzer. A spectrometer with a MALDI device has a TOF analyzer or a combination of quadrupole and TOF analyzers in succession to each other. Certain spectrometers called tandem spectrometers (MS/MS) contain two or three quadruples and a TOF analyzer. 

In the past decade, mass spectrometry (MS) has become the method of choice for quality control of synthetic peptides. Historically, plasma desorption (PD) and fast atom bombardment (FAB) were the first ionization methods used for the mass analysis of nonderivatized peptides. More recently, electrospray ionization (ESI) MS and matrix-assisted laser desorption ionization (MALDI) MS have found widespread utility for peptide analysis. Both of the latter methods yield protonated molecules and, thus, provide direct molecular weight information. As will be covered later, ESI can be employed with a variety of mass analyzers, including quadrupole, magnetic sector, ion trap, and time-of-flight (TOF) analyzers. On the other hand,... 

Nonscanning Mass Analyzers 1.3.2.1 Time-of-Flight (TOF) Analyzers... 

Using Time-of-Flight (ToF) analyzers will significantly improve the resolution and in this instance, it is the molecular ions which reflect the surface composition more closely. 

For modem time of flight (TOF) analyzers that can provide resolving power (FWHM definition) >10 via incorporation of the ion detector as an intrinsic component of the m/z analysis, such CEM response time characteristics are inadequate. This is easily illustrated by an ullra-simplified calculation for a typical case in which the spatial and time focusing properties of the TOF analyzer (Section 6.4.7) are sufficient that the resolving power (RP) is limited by the time response of the detector. The time of flight of an ion is given by Equation [6.19] ... 

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