Not your run-of-the-mill test tube - Analytical Chemistry (ACS

Oct 1, 2006 - Not your run-of-the-mill test tube. Karen Jonscher. Anal. Chem. , 2006, 78 (19), pp 6709–6713. DOI: 10.1021/ac069468w. Publication Dat...
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Not your run-of-the-mill test tube High sensitivity, capacity, and performance are hallmarks of the new generation of ion trap mass spectrometers. Karen Jonscher

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ver the past decade, quadrupole ion trap MS has emerged as a core technology for large-scale proteomics, structural analysis of individual proteins and peptides, forensic analysis, and pharmaceutical drug discovery. R. Graham Cooks of Purdue University describes it as a “test tube for ions.” He says, “It really is just a variable electromagnetic field, the frequency and strength of which is set so as to be able to trap ions in a plane or at a point in three dimensions, depending upon the parameters that are used.” Originally a curiosity, ion traps began as simple storage devices. Later, helium was introduced both to cool the ion motion and to serve as a collision partner, and ion traps became chemical reactors. Next, scan functions were developed to provide sensitive, in-depth analytical measurements, which generated information on mass-to-charge ratios and the abundance of analytes present in biomolecular samples. Altogether, these advances, along with the development of nanoflow technology and evolutionary software suites, have propelled ion traps to the position of industry workhorse in the fast-paced field of proteomics. The life-science MS industry has been growing at a rate of ~12% per year for the past several years, and according to the report World Life Science Mass Spectrometry Markets by the firm Frost & Sullivan, it generated revenues of $880 million in 2003. The report predicts that the market is likely to reach ~$1.36 billion by 2010. With ion traps’ prominence in proteomics and protein characterization, Linda Lopez of Agilent Technologies estimates that trap systems have captured ~40% of the market, with MALDI TOF and quadrupole TOF (QTOF) instruments competing for much of the remainder. Although proteomics is the best known application for ion trap MS, metabolomics is on the rise. A search of the CRISP database reveals 1353 hits for proteomics grants and 81 hits in 2006 alone for those that specifically include metabolomics. This is up from only 5 in 2003. “In the metabolism field, if you want to get structural information, you need an ion trap for MSn,” notes Julian Phillips of Thermo Electron. All of the major mass spectrometer vendors are currently developing software to address the complexities of metabolic profiling, and this is certain to be an area of expansion. © 2006 AMERICAN CHEMICAL SOCIETY

With the advent of the new linear traps, the commercialization of the hybrid ion-trap–TOF technology, and the development of rapidly scanning high-capacity traps and novel fragmentation mechanisms, researchers have various options to select from for both protein and metabolite profiling. Table 1 lists some of the quadrupole ion traps, linear traps, and hybrids currently on the market. The table is not meant to be comprehensive and is representative only of instrumentation that is available commercially.

Elucidating structures in complex mixtures According to Cooks, “Ion traps are so good over such a wide range of applications that they are normally the place to start for most types of experiments.” Their primary advantage over other instruments is their ability to automatically perform MSn. Their rapid scanning capability is another bonus. This allows traps to dig into complex peptide and metabolite mixtures and access structural information that will lead to the identification of analytes and the determination of biologically significant modifications. Traps are versatile and affordable. Basic systems typically cost ~$150,000, a price that helps to bring this advanced technique within the reach of academic researchers as well as pharma and biotech labs. In conventional instruments, the ion traps themselves are about the size of a tennis ball and consist of three hyperbolic O C T O B E R 1 , 2 0 0 6 / A N A LY T I C A L C H E M I S T R Y

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Table 1a. Selected 2D ion trap instruments.1 Product /Company

Ionization sources

Fragmentation methods

Mass range (m/z)

Scan speed (amu/s)

Resolution (m/$m fwhm)

Sensitivity

4000 Q TRAP Applied Biosystems/ MDS Sciex www.appliedbiosystems.com

ESI, nanoESI, turbo spray, APCI, duo spray (ESI/APCI), compatible with NanoMate chipbased ion source

CID

Model 4000: 50–2800; Model 3200: 50–1700

Trap: 250; enhanced resolution: 1000; for proteomics: 4000

0.2, 0.4, or 0.6 at 250, 1000, or 4000 amu/ s, respectively