Hybrid instruments tandem mass spectrometers

Figure 9 Product ion spectra resulting from 25 eV collisions of the pyrazine molecular ion (mlz 80) with (A) a D-SAM surface and (B) an F-SAM surface. Reproduced with permission from Winger BE, Laue H-J, Homing etal, (1992) Hybrid BEEQ tandem mass spectrometer for the study of ion/surface collision processes Review of Scientific Instruments 63 5613-5625.

Fig. 8.1.1 Simple illustrations of a various mass spectrometers, a The triple-quadrupole tandem mass spectrometer (top panel). The middle set of quadrupoles are part of the collision cell (CC) and do not perform mass separation. MSI and MS2 indicate the first and second quadrupole mass separation devices, respectively. The bold arrow shows the path of ions, b Ion-trap mass spectrometer (middle left). The charged sections of the ion trap are not elliptical as drawn, but rather hyperbolic. The diagram is also two-dimensional, whereas the ion trap is three-dimensional. The ion path is such that ions enter the device and are trapped until a specific voltage ejects these ions, c Time of Flight mass spectrometer with a Reflectron (middle left). Ions are separated by the time it takes to pass through the instrument. The Reflectron improves/focuses the ions, d Hybrid Tandem mass spectrometer (bottom). The diagram shows that a quadrupole instrument can be combined with a different type of mass spectrometer, forming a tandem hybrid instrument...

Finally, it is important to note there are many other instruments and configurations that are often referred to as tandem mass spectrometers. There are hybrid instruments that use another form of mass separation, time-of-flight (TOF) mass spectrometry. TOF mass spectrometry separates ions based on the time it takes to... 

Instruments that incorporate two or three mass analysers in a series have been developed to study ion fragmentation. Several of the same type of mass analyser can constitute a tandem mass spectrometer, or they can be constructed using different mass analysers (hybrids). Hybrid spectrometers include the combination of magnetic sector followed by quadrupole, multiple quadrupole, quadrupole TOF, etc. In these instruments, a collision cell is placed between each analyser (Fig. 16.23). Tandem instruments have different scanning modes. 

The most common types of MS/MS instruments available to researchers in food chemistry include triple quadrupole mass spectrometers and ion traps. Less common but commercially produced tandem mass spectrometers include magnetic sector instruments, Fourier transform ion cyclotron resonance (FTICR) mass spectrometers, and quadrupole time-of-flight (QTOF) hybrid instruments (Table A.3A.1). Beginning in 2001, TOF-TOF tandem mass spectrometers became available from instrument manufacturers. These instruments have the potential to deliver high-resolution tandem mass spectra with high speed and should be compatible with the chip-based chromatography systems now under development. 

Hybrid Mass Spectrometer A tandem mass spectrometer comprised of multiple mass analyzers of different types. A Q-TOF is a hybrid, but a triple quadmpole is not. Ideally, a hybrid instrument harnesses the best features of each mass analyzer type to produce a system perhaps greater than the sum of the parts. 

Recent innovations in mass spectrometry have provided incorporation of two, three, and four analyzers into commercially available tandem instruments. In addition, different mass analyzers may be combined to form a hybrid mass spectrometer such as the quadrupole-TOF (Q-TOF). Various types of tandem mass spectrometers include the quadruopole-TOF, time-of-flight-time-of-hight (TOF-TOF), triple-quadrupole, and Orbitrap-FTICR configurations. 

Low-energy CID spectra are measured using triple quadrupole, ion trap, ICR or hybrid instruments. For tandem mass spectrometers in space, the collision chamber is most often a quadrupole in the RF mode only, which allows one to focus the ions that are angularly dispersed by the collision. The pressure difference between the collision cell and the rest of the analyser is obtained through differential pumping. 

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. 

Sector instruments and hybrid quadrupole-scctor instruments have also been u>od in a tandem manner. The first tandem mass spectrometers were sector instruments that combined an electric sector speciromc-ler with a magnetic sector spccironieier. cither in forward geometry (electric sector followed by magnetic... 

Time-of-fiight instruments are configured as either a stand-alone TOF mass analyzer (TOF MS) or as a hybrid quadrupole time-of-fiight (QqTOF) mass spectrometer the latter consists of a quadmpole front-end and an orthogonal acceleration TOF back-end for MS/MS experiments (Fig. 6.10). The orthogonal design minimizes the ions initial velocity spread as they are accelerated into the TOF by a pulsed potential. A QqTOF can be operated as a TOF mass analyzer (QqTOF MS, full-scan) or a quadmpole TOF tandem mass spectrometer (QqTOF MS/MS, product ion scan). Compared to a TOF MS, the... 

Various hybrid tandem mass spectrometers, which combine two or more distinct types of mass analyzers, have been developed to maximize analytical performance and functionality. From the standpoint of ion/ion reactions, the incorporation of an electrodynamic ion trap into a hybrid instrument allows for the physical separation of the three basic steps involved in an ion/ion reaction experiment, that is, ionization, ion/ion reaction, and mass analysis of reaction products. The separation of these processes provides for the highest degree of flexibility and minimal compromises in the optimization of each step. To date, three major types of hybrid instrnments have been described for ion/ion reaction studies using an electrodynamic ion trap as the reaction vessel. The three major types of hybrid instruments are (i) quadrupole/TOF tandem mass spectrometer (ii) Orbitrap and (iii) LIT /FT-ICR. 

The fundamental process of MS/MS (in a tandem mass spectrometer) is that a particular precursor ion is fragmented (decomposed) into a smaller product ion accompanied by the loss of a neutral fragment. The precursor ion is usually selected in the first analyzer, reacted by some means in a specialized chamber (see below) to produce product ions that are then separated in a second analyzer, hence the terms mass spectrometry/mass spectrometry and tandem mass spectrometry. As discussed later, precmsor and product ion analyses can be separated in space, using sequential analyzers that are either of the same type or in hybrid configurations, or separated in time in the latter the two analytical processes are carried out sequentially, within the same analyzer. There are several MS/MS instrument combinations, including QqQ, QIT, LIT, TOF/TOF, QTOF, LlT-orbitrap, and LIT-FT-ICRMS. 

Linear Ion Trap-Orbitrap Mass Spectrometer A recent addition to the family of hybrid tandem mass spectrometers is a linear ion trap (LTQ)-orbitrap mass spectrometer [69,70]. Conceptually, this instrument is similar to the LTQ/FT-ICR tandem mass spectrometer discussed above but uses an orbitrap in place of a Penning trap, thus avoiding the complexity and cost of a superconducting magnet. The working principle of an orbitrap was described in Section 3.9 [71,72]. A schematic diagram of the LTQ/orbitrap mass spectrometer is shown in Figure 4.14. This hybrid tandem mass spectrometer consists of an... 

Improvement with respect to these SRM methods was rendered possible by the availability of data-dependent acquisition or information-dependent acquisition (IDA), by which a tandem mass spectrometer can automatically switch from a survey mode to a dependent (or confirmation), full-spectrum MS/MS mode. In addition, the introduction of linear ion-trap-triple quadrupole (LIT-QqQ) hybrid instruments further extended the possibilities of LC-MS/MS in STA or GUS. In this instrument, the second mass analyzer can be used as either a conventional quadrupole mass analyzer or a linear ion trap, which by accumulation of ions provides enhanced full-spectrum sensitivity compared to a conventional quadrupole. The group of Weinmann used targeted SRM with up to 700 transitions as the survey detection mode, and the enhanced product ion (EPI) spectrum mode as the dependent mode (11). Whereas this procedure seems to be a more specific approach to STA as it allows searching rich spectra against those entered in libraries, the use of SRM as the survey mode cannot answer the more general clinical question as to whether an individual has been intoxicated at all, rather than intoxicated with a compound from a predefined list (12). Also, the use of only the positive-ion mode narrows the detection window. 

Various tandem MS instrument configurations have been developed, e.g. sector instruments, such as CBCE, CBCECB or CECBCE, and hybrid instruments, e.g. BCECQQ (B = magnetic sector analyser, E = electrostatic analyser, C = collision cell, Q = quadrupole mass spectrometer), all with specific performance. Sector mass spectrometers have been reviewed [168],... 

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. 

The instrumental analysis for the identification of UV filters degradation products formed during the fungal treatment process was performed by means of HPLC coupled to tandem mass spectrometry using a hybrid quadrupole-time-of-flight mass spectrometer (HPLC-QqTOF-MS/MS). Chromatographic separation was achieved on a Hibar Purospher STAR HR R-18 ec. (50 mm x 2.0 mm, 5 pm, from Merck). In the optimized method, the mobile phase consisted of a mixture of HPLC grade water and acetonitrile, both with 0.15% formic acid. The injection volume was set to 10 pL and the mobile phase flow-rate to 0.3 mL/min. 

TOF analyzers are especially compatible with MALDI ion sources and hence are frequently coupled in aMALDI-TOF configuration. Nevertheless, many commercial mass spectrometers combine ESI with TOF with great success. For proteomics applications, the quadrupole TOF (QqTOF) hybrid instruments with their superior mass accuracy, mass range, and mass resolution are of much greater utility than simple TOF instruments.21,22 Moreover, TOF instruments feature high sensitivity because they can generate full scan data without the necessity for scanning that causes ion loss and decreased sensitivity. Linear mode TOF instruments cannot perform tandem mass spectrometry. This problem is addressed by hybrid instruments that incorporate analyzers with mass selective capability (e.g., QqTOF) in front of a TOF instrument. 

Use of Mass Analyzer Scan Types Depending on the configuration of the instrument, tandem and hybrid mass spectrometers are capable of far more than simply identifying the mass of a species that emerges from the source. The following is a brief list of relevant terminology and scan types that can be useful in generating additional information to support the identification of an unknown. Note that not all scan types are feasible on all types of instrument. 

Figure 4. Effects of ion kinetic energy on the MS/MS of 5-indanol (a) MS/MS obtained on MIKES instrument with 7000 eV translational energy (b) spectrum obtained on hybrid BQ (magnet followed by quadrupole) mass spectrometer 95 eV (c) spectrum obtained with QQ (tandem quadrupole) mass spectrometer at 35 eV...

---