Tandem analyzer combinations

Tandem mass spectrometers most commonly used for MS/MS smdies include the following analyzer combinations, although many others are possible ... 

Tandem MS has been more or less successfully performed with a wide variety of analyzer combinations. What analyzers to combine for a certain application is determined by many different factors, such as sensitivity, selectivity, and speed, but also size, cost, and availability. The two major categories of tandem MS methods are tandem-in-space and tandem-in-time, but there are also hybrids where tandem-in-time analyzers are coupled in space or with tandem-in-space analyzers. Moreover, the ongoing development of faster electronics and high-voltage circuits as well as better software tools and hardware control devices constandy open up new possibilities of making innovative combinations of analyzers for specific applications. In this chapter a few examples of commercially available tandem MS instruments are presented. A brief summary of their weaknesses, strengths, and main areas of applications is given. 

Analyzers may be combined, almost in a mix-and-match manner, into sophisticated tandem instruments, e.g., QqQ, QTOF, and LIT-FT-ICR, which are capable of providing signihcantly more information than single analyzer systems. Tandem analyzers are also referred to as mass spectrometer/mass spectrometer (MS/MS) instruments. These terms apply to the combination of two (or more) analyzers to attain improved detection limits or to provide hitherto unavailable structural information. Tandem often implies that the instruments utilize like analyzers, such as in... 

While the development of ESI and MALDI provided techniques that ionize polar compounds effectively the spectra provide little or no structural information because molecular species are the only ions formed. The need to investigate not only the mass but also the structure of ions was an important factor in the development of multianalyzer mass spectrometers. There are several formats of MS/MS systems based on combinations of quadrupole, ion trap (Q and FT), and TOF analyzers. Combinations that use the same type of analyzers are tandem instruments, whereas different separation methods are used in sequence in hybrid systems. In MS/MS instruments, the first analyzer is used (usually) to select an ion of interest that is then passed, with or without fragmentation, into a second analyzer, which is often of higher resolving power and can be used for accurate mass measurement. 

The GCQ Tandem MS detector (for the first time introduced on the PITCON 1995) is an integrated analytical instrument presented by Finnigan MAT. GCQ Tandem system combines the ion source and detection system used in TSQ and SSQ Finningan systems, with the high sensitivity quadrupole ion trap mass analyzer. 

Tandem mass spectrometry (MS/MS) is a method for obtaining sequence and structural information by measurement of the mass-to-charge ratios of ionized molecules before and after dissociation reactions within a mass spectrometer which consists essentially of two mass spectrometers in tandem. In the first step, precursor ions are selected for further fragmentation by energy impact and interaction with a collision gas. The generated product ions can be analyzed by a second scan step. MS/MS measurements of peptides can be performed using electrospray or matrix-assisted laser desorption/ionization in combination with triple quadruple, ion trap, quadrupole-TOF (time-of-flight), TOF-TOF or ion cyclotron resonance MS. Tandem... 

Different mass analysers can be combined with the electrospray ionization source to effect analysis. These include magnetic sector analysers, quadrupole filter (Q), quadrupole ion trap (QIT), time of flight (TOF), and more recently the Fourrier transform ion cyclotron resonance (FTICR) mass analysers. Tandem mass spectrometry can also be effected by combining one or more mass analysers in tandem, as in a triple quadrupole or a QTOF. The first analyzer is usually used as a mass filter to select parent ions that can be fragmented and analyzed by subsequent analysers. 

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. 

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. 

FIGURE 15.3 Outline of experimental protocol used for ICAT differential protein expression profiling. Protein mixtures from two cell populations are labeled with light or heavy isotopic versions of a cleavable ICAT reagent. Labeled proteins are combined, subject to multidimensional separation by SCX, RP, and avidin affinity chromatography, then analyzed by tandem MS for peptide and protein identification. Based on the relative ratio of the two isotopically labeled peptides, a relative abundance of protein expression can be determined. 

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. 

In order to perform two consecutive mass-analyzing steps, two mass analyzers may be mounted in tandem. This technique is applied with beam transmitting devices, i.e., TOF, sector and quadrupole analyzers can be combined that way tandem-in-space, Fig. 4.15). Alternatively, a suitable mass analyzer may be operated by combining selection, activation, and analysis in the very same place. Quad-mpole ion trap (QIT) and ion cyclotron resonance (ICR) instruments can perform such tandem-in-time experiments. 

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