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MS/MS Instrumentation With prices on the way down, the user community is growing Since the emergence of tandem mass spectrometry (MS/MS) research in the 1970s, the use of this complex and expensive technique has been concentrated to a large extent in the academic community. But today there are indications that MS/MS may be entering a new phase in its life cycle, with the appearance of a number of less expensive MS/MS instruments that should appeal to a broader range of users both in and beyond the academic sphere. This is not to say that tandem mass spectrometers will instantly become as widespread as instruments for gas chromatography/ mass spectrometry (GC/MS), a technique with which MS/MS is often compared. But with a wide variety of different mass spectrometer geometries now available for MS/MS applications, the technique seems to be attracting a wider audience. In one type of MS/MS spectrometer, the first of two sequential mass analyzers is used to select parent ions by mass/charge ratio. These parent ions are then reacted to form daughter ions, which are selected in a second mass analyzer. Fourier transform and ion trap mass spectrometers represent a second type of instrument design in which MS/MS takes place in a single analyzer instead of in two sequential analyzers. Both types of MS/MS instruments make it possible to analyze mixtures for particular components without a need for chromatographic preseparation or extensive sample preparation. "In every case where the analysis of targeted compounds in a mixture has been developed around MS/MS, the amount of sample workup has been dramatically decreased, sometimes to zero, because of the high selectivity of the technique," explains Chris Enke of Michigan State University. "And limits of detection are improved in MS/MS due to a reduction in chemical interference in the spectrum." In addition to its analytical applications, MS/MS is also a powerful technique for molecular-structure détermina-
tions of macromolecules, such as those found in biomedical samples, plant materials, petroleum products, and commercial polymers. Because selection of parent ions in the first stage of an MS/MS instrument is similar to chromatographic preseparation in GC/MS and liquid chromatography/MS (LC/MS), the techniques are often compared. But
I think people will just purchase an instrument with tandem MS capabilities and then use it for MS/MS, GC/MS, or GC/MS/MS, as the occasion demands. most researchers see MS/MS as more of a complement to GC/MS and LC/MS than as a competitor. R. A. Yost of the University of Florida has pointed out, for example, that GC/MS is excellent for identification of a large number of unknown compounds in a complex mixture, but that individual targeted compounds can often be determined more rapidly with MS/MS because of the "essentially simultaneous access to mixture components" that is possible in MS/MS. An excellent example of this, according to Yost, is the rapid screening of environmental samples for priority pollutants by MS/MS. "Because MS/MS is so useful," adds R. G. Cooks of Purdue University, "I don't think there's going to be any competition with GC/MS. I think people will just purchase an instrument with tandem MS capabilities and then use it for MS/MS, GC/MS, or GC/ MS/MS, as the occasion demands." MS/MS spectrometers are classified according to the type of analyzers they contain. The most common designs in-
406 A • ANALYTICAL CHEMISTRY, VOL. 58, NO. 3, MARCH 1986
volve magnetic (B) and electrostatic (E) analyzers (referred to as sectors), quadrupoles (Q), and Fourier transform (FT) cells. Sector instruments Sector MS/MS spectrometers are composed of electrostatic and magnetic sectors only. Major advantages of these instruments are their high resolution (at least in MS-1) and their potential ability to handle parent and daughter ions of high mass—10,000 daltons or more. Thus, sector instruments can be used in conjunction with some of the soft ionization techniques (such as fast atom bombardment) for the analysis and characterization of large biological molecules. A number of companies are involved in the sector MS/MS business. The first company with a commercial triple-sector instrument was Kratos, which delivered a custom-designed EBE instrument to Michael Gross's laboratory at the University of Nebraska in 1980. According to Kratos's Roger Greathead, the company now has several of these EBE instruments in the field and has two European orders pending for the company's foursector EBEB instruments. The first commercial four-sector spectrometer, a BEEB design, was built by VG Instruments for the National Institute of Environmental Health Sciences, and VG has a second BEEB instrument ready for delivery to Smith Kline Beckman. VG also markets three-sector BEB and four-sector EBEB MS/MS instruments. Another early commercial four-sector instrument was the high-mass EBEB spectrometer built by JEOL and delivered to Klaus Biemann's laboratory at the Massachusetts Institute of Technology. All three of JEOL's current mass spectrometer product lines are now available with MS/MS capabilities. Quadrupole instruments The most widely available MS/MS instruments today are the triple quadrupoles (QQQ), which contain two 0003-2700/86/0358-406A$01.50/0 © 1986 American Chemical Society
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quadrupole mass analyzers and a third quadrupole that serves as an interme diate collision region where daughter ions are generated. Quadrupole instru ments are less expensive than sector instruments and are more easily auto mated, but their mass range is gener ally limited to 2000-3000 daltons at unit mass resolution. Among the com panies manufacturing triple-quadru pole instruments are Extrel, Finnigan, Nermag, Sciex, and VG. Extrel Corporation (formerly Extranuclear Laboratories Inc.) announced
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its new name at the 1985 American Society for Mass Spectrometry meet ing in San Diego. According to A. G. Craske, Extrel's strength is in manual triple-quadrupole systems for research applications. The company has so far deemphasized the complex data sys tems and software that are usually re quired for more routine analytical ap plications. Extrel also supplies quad r u p l e s to other instrument companies, such as Kratos. Finnigan MAT offers the TSQ 70, a triple-stage quadrupole spectrometer that is being shown for the first time at this month's Pittsburgh Confer ence. According to Finnigan, the new instrument represents a complete re design and includes a new solids inlet valve that is easier to use, a mass range of 2000 daltons at unit resolu tion, and expert system-based soft ware that can dynamically alter in strument parameters based on incom ing data. It supports a variety of inlet configurations (including capillary GC/MS and thermospray or movingbelt LC/MS) and ionization methods (including fast atom bombardment and chemical ionization). At a base price of around $250,000, the TSQ 70 costs about $100,000 less than the in struments it replaces (the TSQ 45 and 46), bringing it into the same cost neighborhood as top-of-the-line GC/MS instruments. This reduction is one indication that prices of triplequadrupole instrumentation are in deed on the way down.
408 A • ANALYTICAL CHEMISTRY, VOL. 58, NO. 3, MARCH 1986
Nermag introduced its triple-quad rupole MS/MS spectrometer, the R 30-10, at last year's Pittsburgh Con ference. System enhancements for 1986 include higher collision energy (0-250 eV) and three new plug-in ion sources: fast atom bombardment, thermospray LC/MS/MS, and a source for GC/MS/MS and desorptive chemical ionization. Nermag has four R 3010s in the field in Europe. The first U.S. delivery will be to Abbott Laboratories in Chicago this March. Sciex sells a triple-quadrupole MS/MS instrument with a unique at mospheric-pressure ionization source. The TAGA 6000 is configured either as a laboratory instrument or as a mo bile instrument that can be driven to field sites. VG Instruments offers a line of tri ple-quadrupole instruments with inte grated data systems that is manufac tured by the company's Masslab group. Hybrid spectrometers A third type of MS/MS instrument is the hybrid spectrometer, the name of which refers to the presence of both sectors and quadrupoles. Hybrid in struments are designed to provide the best features of sector and quadrupole spectrometers: High resolution of par ent ions is provided by the sectors while lower cost and ease of automa tion are provided by the quadrupoles. Hybrid spectrometer vendors in clude Finnigan MAT, Kratos, and VG. Finnigan MAT offers a hybrid BEQQ spectrometer, the H-SQ 30, and VG sells hybrid BEQQ and EBQQ spec trometers. Kratos's MS80RFAQ hy brid spectrometer is making its formal commercial debut at this year's Pitts burgh Conference. The MS80RFAQ has a strong-focusing magnet that pro vides an ultimate mass range of 14,000 daltons, a new software package that makes it possible to set up and acti vate multiple MS/MS scans, and a re designed computer and console that have been combined into a single, in tegrated unit. The base price of the new instrument is approximately $400,000. Other designs Some MS/MS applications may be performed with F T - M S or ion trap in struments, both of which separate daughter from parent ions in time rather than in space. According to Fred McLafferty of Cornell Universi ty, "The real advantage of F T - M S is that you can do tandem mass spec trometry without buying a second mass spectrometer. In addition, it is
Focus possible to obtain unusually high reso lution in either MS-1 or MS-2 with a new tailored excitation function of Alan Marshall's at Ohio State that re cently appeared in the literature." Although the MS/MS capabilities of an F T - M S instrument are somewhat limited relative to sector, quadrupole, and hybrid spectrometers, McLafferty explains that there are also "things you can do with it that you can't do with the high-energy [sector] or triplequadrupole instruments. For example, because of the long residence time of
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There has to be a big price reduction. . . .The market forces are all there. There is too much demand and too much competition.
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ions in the F T - M S analyzer cell, it is more convenient to do ion-molecule reactions, ion photodissociation, and multistage MS/MS experiments." F T - M S spectrometers are manufac tured by Nicolet and Bruker Spectrospin. Finnigan is currently accepting spe cial orders for an ion trap mass spec trometer with MS/MS capabilities. As is the case with F T - M S instruments, the ion trap serves as both MS-1 and MS-2, with parent and daughter ions separated in time rather than in space. This spectrometer, which sells for ap proximately $150,000, represents the least expensive route to MS/MS capa bility available today. One of these in struments is now located in R. G. Cooks's laboratory at Purdue. Another MS/MS design that may become more important in the future involves time-of-flight (TOF) tubes. Although TOF spectrometers are lowresolution instruments, they can pro vide spectra on high-mass biological compounds, especially when used in conjunction with Cf-252 plasma desorption ion sources. No commercial TOF MS/MS instruments are avail able at this time. One company that does not sell any MS/MS spectrometers is HewlettPackard, a company whose absence from this market "has been a surprise to people for a long time," according to Cooks. Hewlett-Packard's market ing manager for scientific instruments, Larry Catran, explains that the com-
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pany put together an experimental prototype of an MS/MS instrument a few years ago but decided that it didn't fit into its overall strategy. "It really was a business decision that we made not to invest a whole lot more in it back at that time," says Catran, "and yet we don't want to lose touch with it. If it does emerge as a hot technique, I certainly would not rule Hewlett-Packard out from getting into that business." Prices: On the way down? One negative for MS/MS up to now has been the higher cost of the technique relative to GC/MS. MS/MS spectrometers cost more than many laboratories want to pay for analytical instruments, although MS/MS offers productivity advantages over GC/MS that tend to offset the initial price disadvantage. Nevertheless, many MS/MS practitioners do expect an eventual price reduction. According to Fred McLafferty (Science, 1981, 214, 280-87), "I believe that. . .demand will bring the price of computerized MS/MS instruments down to $50,000; the present price appears to be the major deterrent to MS/MS growth rivaling that of GC/MS and LC/MS."
"There has to be a big price reduction," adds R. G. Cooks. "There has to be a big drop from the current prices of triple quadrupoles, for example. Whether the triple quadrupoles themselves come out in cheaper form or whether an ion trap instrument with MS/MS software takes over is a different question, but there has to be a major price reduction. Finnigan's ion trap and Hewlett-Packard's mass-selective detector represented big steps toward cheaper GC/MS instruments, and the same volume-driven situation is going to cause MS/MS to come down in price. There have been too many triple quadrupoles sold for that not to happen. The market forces are all there. There is too much demand and too much competition." "Certainly, the intention of every manufacturer is to bring their prices down," responds Bori Shushan of Sciex. "GC/MS is down as low as $50,000 per unit, which is a remarkable price for such a powerful type of instrument. But we'll never catch up to the GC/MS vendors. They'll always have the drop on us, because they have one less stage of mass spectrometry to build in and supply software for." S.A.B.
Expanding Markets for Thermal Analysis Since it was first commercialized in the early 1960s, thermal analysis (TA), the measurement of physical properties as a function of temperature, has become a standard technique in industrial research and development laboratories for materials characterization. TA can be used to characterize polymers and plastics in composite materials, and industrial laboratories are increasingly using TA for quality control and product development work. With this increased industrial use, manufacturers are seeing a shift in market demand from sophisticated, versatile research-grade analyzers to instruments that offer the high productivity and low-cost data analysis needed for quality control applications. In the past, manufacturers typically provided only two products, a low-cost basic instrument with little or no data analysis capability and a more expensive, sophisticated research in-
412 A • ANALYTICAL CHEMISTRY, VOL. 58, NO. 3, MARCH 1986
Industrial laboratories are increasingly using TA for quality control and product development work. strument. But several manufacturers, including Du Pont, Perkin-Elmer, Mettler, Stanton Redcroft, and Omnitherm, are now offering TA systems that allow users to tailor a system to their specific needs. For example, Du Pont introduced a new modular design for its TA systems last November at the Eastern Analytical Symposium. Although it
