Mass analyzers configurations

Commercial mass analyzers are based almost entirely on quadrupoles, magnetic sectors (with or without an added electric sector for high-resolution work), and time-of-flight (TOE) configurations or a combination of these. There are also ion traps and ion cyclotron resonance instruments. These are discussed as single use and combined (hybrid) use. 

Typical MS/MS configuration. Ions produced from a source (e.g., dynamic FAB) are analyzed by MS(1). Molecular ions (M or [M + H]+ or [M - H]", etc.) are selected in MS(1) and passed through a collision cell (CC), where they are activated by collision with a neutral gas. The activation causes some of the molecular ions to break up, and the resulting fragment ions provide evidence of the original molecular structure. The spectrum of fragment ions is mass analyzed in the second mass spectrometer, MS(2). 

Mass spectrometer configuration. Multianalyzer instruments should be named for the analyzers in the sequence in which they are traversed by the ion beam, where B is a magnetic analyzer, E is an electrostatic analyzer, Q is a quadrupole analyzer, TOP is a time-of-flight analyzer, and ICR is an ion cyclotron resonance analyzer. For example BE mass spectrometer (reversed-geometry double-focusing instrument), BQ mass spectrometer (hybrid sector and quadrupole instrument), EBQ (double-focusing instrument followed by a quadrupole). 

In the case of carbamate insecticides, both ESI and APCI can be used. However, in this study, the sensitivity of APCI was 3-5-fold less than that of ESI. In this case, the Z-spray configuration was used with APCI, which gives a lower efficiency of ions reaching the mass analyzer than is achieved with other instrumental configurations. 

FIGURE 13.1 Schematic of a comprehensive 2DLC (IEX/RP) configuration with alternating second-dimension analytical RP column sampling of first-dimension eluent. A salt diversion valve is present to divert salts from the IEX dimension to waste, and prevent contamination of downstream collected fractions or mass analyzer. 

Multiple mass analyzers exist that can perform tandem mass spectrometry. Some use a tandem-in-space configuration, such as the triple quadrupole mass analyzers illustrated (Fig.3.9). Others use a tandem-in-time configuration and include instruments such as ion-traps (ITMS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS or FTMS). A triple quadrupole mass spectrometer can only perform the tandem process once for an isolated precursor ion (e.g., MS/MS), but trapping or tandem-in-time instruments can perform repetitive tandem mass spectrometry (MS ), thus adding n 1 degrees of structural characterization and elucidation. When an ion-trap is combined with HPLC and photodiode array detection, the net result is a profiling tool that is a powerful tool for both metabolite profiling and metabolite identification. 

FIGURE 15.1 Overview of configuration of MS and MS-based proteomic analysis. Proteins are extracted from biologic samples and fractionated by a variety of separation methods including gel separation, HPLC, and capillary electrophoresis. The common ion sources and mass analyzers used are indicated. 

Mass analyzers interrogate and resolve ions produced by an ion source based on their m/z ratios. Several types of mass analyzers are utilized for proteomic analysis including time-of-flight (TOF) quadrupoles, ion traps, and Fourier transform ion cyclotron resonance (FTICR). Mass analyzers may be assembled in hybrid configurations. MS instruments such as quadrupole TOF and quadra-pole ion trap-FTICR facilitate diversified applications and achieved great success. 

The first part of this book is dedicated to a discussion of mass spectrometry (MS) instrumentation. We start with a list of basic definitions and explanations (Chapter 1). Chapter 2 is devoted to the mass spectrometer and its building blocks. In this chapter we describe in relative detail the most common ion sources, mass analyzers, and detectors. Some of the techniques are not extensively used today, but they are often cited in the MS literature, and are important contributions to the history of MS instrumentation. In Chapter 3 we describe both different fragmentation methods and several typical tandem MS analyzer configurations. Chapter 4 is somewhat of an outsider. Separation methods is certainly too vast a topic to do full justice in less than twenty pages. However, some separation methods are used in such close alliance with MS that the two techniques are always referred to as one combined analytical tool, for example, GC-MS and LC-MS. In effect, it is almost impossible to study the MS literature without coming across at least one separation method. Our main goal with Chapter 4 is, therefore, to facilitate an introduction to the MS literature for the reader by providing a short summary of the basic principles of some of the most common separation methods that have been used in conjunction with mass spectrometry. 

Fig. 11.16. Representation of three tandem mass spectrometry (MS/MS) scan modes illustrated for a triple quadrupole instrument configuration. The top panel shows the attributes of the popular and prevalent product ion CID experiment. The first mass filter is held at a constant m/z value transmitting only ions of a single mlz value into the collision region. Conversion of a portion of translational energy into internal energy in the collision event results in excitation of the mass-selected ions, followed by unimolecular dissociation. The spectrum of product ions is recorded by scanning the second mass filter (commonly referred to as Q3 ). The center panel illustrates the precursor ion CID experiment. Ions of all mlz values are transmitted sequentially into the collision region as the first analyzer (Ql) is scanned. Only dissociation processes that generate product ions of a specific mlz ratio are transmitted by Q3 to the detector. The lower panel shows the constant neutral loss CID experiment. Both mass analyzers are scanned simultaneously, at the same rate, and at a constant mlz offset. The mlz offset is selected on the basis of known neutral elimination products (e.g., H20, NH3, CH3COOH, etc.) that may be particularly diagnostic of one or more compound classes that may be present in a sample mixture. The utility of the two compound class-specific scans (precursor ion and neutral loss) is illustrated in Fig. 11.17.

A linear quadrupole mass analyzer consists of four hyperbolically or cyclindrically shaped rod electrodes extending in the z-direction and mounted in a square configuration (xy-plane, Figs. 4.31, 4.32). The pairs of opposite rods are each held at the same potential which is composed of a DC and an AC component. 

Various mass spectrometer configurations have been used for the detection of explosives, such as ion traps, quadrupoles and time-of flight mass analyzers and combinations as MS/MS systems. The ionization method is usually APCI with corona discharge [24, 25]. An example is given in Figure 20, which shows the schematic diagram of an explosive mass spectrometer detector [25]. It is based on an ion trap mass analyzer, an APCI source with corona discharge and a counter-flow introduction (CFI) system. The direction of the sample gas flow introduced into the ion source is opposite to that of the ion flow produced by the ion source. 

Fig. 1.8 Di fferential pumping design with heated capilla. This configuration requires a dual stage pumping system before the ions are introduced into the quadrupole mass analyzer which needs to be operated at high vacuum. The role of the lenses is to focus ions. In some systems the lenses are replaced by hexapoles or octapoles.

Fig. 1.18 Schematic of a triple quadrupole instrument. Stage qO focusing quadrupole Ql, Q3 mass analyzing quadrupoles q2 collision cell. In the present configuration the collision energy (CE) is determined by the potential difference between qO and q2.

Mass spectrometers are used primarily as tools for measuring isotopic compositions, although some kinds can also be used to determine elemental abundances. Mass spectrometers have three basic components (1) a means of ionizing the sample (2) a mass analyzer that separates atoms based on their masses and (3) a detector. Most of the time, the mass spectrometer is identified by its source, although the mass analyzer can also be identified. In the next few paragraphs, we will describe the various sources, the different mass analyzers, and the detectors, and then describe the most common configurations used in cosmochem-istry. For more details, see Gross (2008). 

These are not the only types of tandem mass spectrometers. There are numerous configurations of instruments that are based on the type of ion separation and many new terms associated with these instrument types. For example, there are instruments known as ion traps. The ion trap is a device that can measure mass, fragment a selected mass (as could be done in a collision cell) and then measure the mass of the fragment. The product ion produced by this all in one device is the same product ion that would be produced in a tandem quadrupole instrument. However, there is only one mass analyzer that functions as both the collision cell and mass measuring device. These types of instruments are sometimes referred to as tandem mass spectrometers, but are not abbreviated as MS/MS. The MS/MS analysis is done by separating the analysis in time (tandem in time) rather than two devices separated in space. A more generic term is best suited. This term is MS , where the n represents... 

The complications just described can be minimized if there is greater selectivity in the ionization process, as is sometime possible when photoionization is used as the excitation mechanism. Because the ionization energy can be more precisely controlled, it is possible in selected cases to produce only the desired reactant-ion species, or at least to minimize production of other ions. As already noted in the earlier section on formation of excited ions, it is also possible to populate specific internal-energy states of some reactant ions by using a photoionization source. One of the earliest photoionization mass spectrometers used to study interaction of internally excited ions with neutrals was that constructed by Chupka et al.91 Such apparatuses typically incorporate a photon source (either a line or a continuum source) and an optical monochromator, which are coupled to the reaction chamber. Various types of mass analyzer, including sector type, time-of-flight (TOF), and quadrupole mass filters, have been used with these apparatuses. Chupka has described the basic instrumental configuration in some detail.854 Photoionization mass spectrometers employed to study interactions of excited ions with neutral species have also been constructed in several other laboratories.80,1144,142,143 The apparatus recently developed by LeBreton et al.80 is illustrated schematically in Fig. 7 and is typical of such instrumentation. 

The analytical capability of MS has been evolving at an astounding rate as Nobel laureates and developers push what is an inherently powerful analytical technique to even higher levels of capability. During the last decade, numerous ionization and analyzer configurations have been commercialized. Some of the most recent developments have made MS the gold standard for many pharmaceutical analyses, and has made the biopharmaceutical industry the major purchaser of mass spectrometers (Cudiamat, 2005). 

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. 

The Orbitrap-based systems have emerged as the newest option for LC-HRMS. When configured as hybrid linear trap-Grbitrap (LTQ-Orbitrap), the systems are conceptually similar to Q-TOF in that mass analyzer 1 is nominally a unit mass analyzer, and mass analyzer 2 is capable of high resolution. These systems are capable of either LC-HRMS or LC-MS/HRMS operation. A new variant on the commercial Orbitrap, the Exactive, is expected to be released in late 2008. This system, which consists only of the single mass analyzer, has shown promising results in early assessment of quantitation by LC-HRMS (Bateman et al., 2008). 

In a quadrupole device, not as accurate and precise as double-focusing instruments but fast, a quadrupolar electrical field comprising radio-frequency (RF) and direct-current components is used to separate ions. Quadrupole instruments as mass analyzers are used together with ESI as the ion source the configuration employing a three-dimensional quadrupolar RF electric field (Wolfgang Paul, University of Bonn, 1989 Nobel prize for physics) is referred to as an ion trap analyzer (see below). 

Figure 7.8 Excitation (a) and detection (b) of the ion cyclotron motion within an FTMS mass analyzer cell. Reprinted from Marshall, A.G. and Flendrickson, C.L., Fourier transform ion cyclotron resonance detection principles and experimental configurations. International Journal of Mass Spectrometry, 215, 59-75. Copyright (2002), with permission from Elsevier.

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. 

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. 

A quadrupole is small and relatively inexpensive. It serves as an excellent collision cell for collision activations of ions and ion/molecule reactions. It can also be used as a broadband ion transmission device. A quadrupole is readily coupled with other mass analyzers for MS/MS experiments. One of the most popular configurations is a triple quadrupole mass spectrometer that has found wide applications in LC/MS and LC/MS/MS (see section on Tandem MS). 

Permutation of ionization and mass analyzer alternatives presents many instrument configurations to prospective users, and there continues to be significant... 

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