Tandem-in-space instruments

Ion traps are tandem-in-time instruments, i.e., they perform the steps of precursor ion selection, ion activation and acquisition of fragment ion spectra in the very same place. This advantageous property allows the multiple use of a single QTT to perform not only MS but also MS and higher order MS experiments - indeed a very economic concept. Depending on the abundance of the initial precursor ion, its fragmentation behavior - and of course, on the performance of the QIT - MS experiments are possible. [138] However, in contrast to tandem-in-space instruments, tandem-in-time instruments do not support constant neutral loss and precursor ion scans. 

Tandem Mass Spectrometer An instrument capable of performing multiple mass (mjz) analyses. There are two major categories (1) tandem-in-space instruments (triple quadmpole and Q-TOF), (2) tandem-in-time instruments (QIT and FTICR). 

There are two classes of tandem instrument. The original development was CID tandem-in-space MS involving arrangement of two mass analyzers separated by a collision cell. A cartoon of a tandem-in-space instrument is shown in Fig. 10. 

Common tandem-in-space instruments employ a quadrupole as the first mass analyzer, a multipole collision cell (usually hexapole) operated in RF-only mode, and then either a second quadrupole or a TOF tube as the second mass analyzer. These instruments are termed triple or tandem quadrupole and quadrupole-time-of-flight mass spectrometers. 

There are three MS/MS experiments that are of use in carbohydrate analysis. These can be depicted schematically (Fig. 11) and are described using a tandem quadrupole instrument as an example. Quadrupole-based tandem-in-space instruments operate at low CID energies (up to 100-200 eV). 

If a reactant gas is introduced into the collision cell, ion-molecule collisions can lead to the observation of gas-phase reactions. Tandem-in-time instruments facilitate the observation of ion-molecule reactions. Reaction times can be extended over appropriate time periods, typically as long as several seconds. It is also possible to vary easily the reactant ion energy. The evolution of the reaction can be followed as a function of time, and equilibrium can be observed. This allows the determination of kinetic and thermodynamic parameters, and has allowed for example the determination of basicity and acidity scales in the gas phase. In tandem-in-space instruments, the time allowed for reaction will be short and can be varied over only a limited range. Moreover, it is difficult to achieve the very low collision energies that promote exothermic ion-molecule reactions. Nevertheless, product ion spectra arising from ion-molecule reactions can be recorded. These spectra can be an alternative to CID to characterize ions. 

Figure 7 Scan modes for a tandem-in-space instrument, the triple quadruple (QqQ). (a) Full scan all source ions are passed through to Q3 while Q1 and q (collision cell) are set to the RF-only mode, (b) Production scan Qi is set to pass a selected ion (precursor ion). This is fragmented in the collision cell and products are analyzed by scanning Q3. (c) Precursor scan Q1 scans all the source ions into the collision cell for collision-induced dissociation (CID). Q3 is set to pass a selected product ion. A signal recorded at Q3 is correlated with the corresponding precursor ion passing through Q-i. (d) Neutral loss scan Q-i is set to scan ions into the collision cell for CID. The Q3 scan is offset by a specified mass, equal to the mass of the neutral, relative to Qi. (e) Selected reaction monitoring (SRM) an ion selected in Q1 is fragmented and a specific fragment is then recorded after selection by Q3. SRM is commonly used in quantitative work to improve assay selectivity and sensitivity.

In the precursor ion scan, the first mass analyzer (Qj) sequentially scans all precursor ions into the collision cell (Figure 7(c)) for fragmentation. The second analyzer (Qj) is then set to transmit a single specified ion product. The resulting mass spectrum is then a record of all the precursor ions that give rise to the specified common product ion, such as, for example, the metabolites of a particular drug, or class of compounds, which can be fragmented to a common structural moiety. The precursor ion scan can be carried out only with tandem-in-space instruments. 

The types of tandem mass spectrometers capable of performing MS/MS experiments fall into two basic categories tandem in space and tandem in time. Tandem-in-space instruments have discrete mass analyzers for each stage of mass spectrometry examples include multisector, triple-quadru-pole, and hybrid instruments (instruments having mixed types of analyzers such as a magnetic sector and a quadrupole). Tandem-in-time instruments have only one mass analyzer where each stage of mass spectrometry takes place in the same analyzer but is separated in time via a sequence of events. Examples of this type of instrument include Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers and quadrupole ion traps, described in Chapter 3. 

Tandcm-in-Time Spectrometers. Tandem-in-iime instruments form the ions in a certain spatial region and then at a later lime expel the unwanted ions and leave the selected ions to be dissociated and mass analyzed in the same spatial region. This process can be repeated many limes over to perform not only MS/MS experiments, but also MS/MS/MS and MS" experiments. Fourier transform ICR and quadrupole ion-trap instruments are well suited lor performing MS" cxperimenls. In principle, tandem-in-time spectrometers can perform M.S/MS experiments much more simply than tandem-in-space instruments because of the dilTiculty in providing different ion focal positions in the latter. Although tandem-in-time spectrometers can readily provide product ion scans, other scans, such as precursor ion scans and neui ral loss scans, are much more difficult to perform than they arc with tandem in space instruments. 

R. K. Boyd, Linked-scan techniques for MS/MS using tandem-in-space instruments. Mass Spectrom. Rev. 13, 359-410 (1994). 

In the tandem in-time instruments, all three steps of MS/MS operation are performed in the same region, but are separated in time, whereas in the tandem in-space instruments, these steps are carried out in different regions. 

As trapping mass analysers, ions are either formed within the volume of the trap (as in GC/MS) or injected into the trap (as in LC/MS) where they are trapped and stored for m/z analysis. The various stages of the MS" analyses are performed by applying appropriate voltages to the three trap electrodes as a function of time. Thus, ion traps are often called tandem-in-time instruments, vs QqQs which are called tandem-in-space instruments, i.e. the first mass analyses, dissociation and second mass analysis steps are performed in different spatial regions of the instrument. 

Tandem-in-Space Spectrometers. In tandem-in-space instruments, two independent mass analyzers are used in two different regions in space. The triple quadrupole mass spectrometer is the most common of these instruments. In commercial triple quadrupole instruments, such as the instrument illustrated in Figure 20-2,3, the sample is introduced into a soft ionization source, such as a Cl or FAB source. The ions are then accelerated into quadrupole 1 (Q), which is an ordinary quadrupole mass filter. The selected fast-moving ions pass into quadrupole 2 (q), which is a collision chamber where dissociation of the ions selected by quadrupole 1 occurs. This quadrupole is operated in a radio-frequency-only mode in which no dc voltage is applied across the rods. This mode basically traps the precursor and product ions in a relatively high concentration of collision gas so that CAD can occur. Quadrupole 3 (Q) then allows mass analysis of the product ions formed in the collision cell. The configuration is known as the QqQ configuration. 

Fig. 9.1. Comparison of tandem-in-space and tandem-in-time MS. Obviously, higher order MS" can be better realized by tandem-in-time setups, whereas tandem-in-space instrumentation is usually designed for MS with MS representing already the rare exception.

Note In contrast to tandem-in-space instruments, tandem-in-time instruments neither support precursor ion nor constant neutral loss scanning. While product ion scans just need a precursor to be isolated prior to its fragmentation, both precursor ion and constant neutral loss scan rely on the simultaneous application of selection plus scanning or double scanning, respectively. Fulfilling two criteria at the same time requires two distinct analyzers at work. 

Boyd, R.K. Linked-Scan Techniques for MS/MS Using Tandem-in-Space Instruments. Mass Spectrom. Rev. 1994, 73, 359-410. 

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