Anal. Chem. 2005, 77, 4448-4452
Pulsed Oscillating Mass Spectrometer: A Miniaturized Type of Time-of-Flight Mass Spectrometer Peter G. Hughes, Ondrej Votava,† Marc B. A. West,‡ Fangtong Zhang, and Scott H. Kable*
School of Chemistry, University of Sydney, Sydney, NSW, 2006, Australia
We report the development, characterization, and performance of a new type of time-of-flight mass analyzer that employs an oscillatory ion flight path and uses secondary electrons to record the mass spectrum. The analyzer is simple in concept and design and inexpensive to build and has been made as small as 6-cm total length. The oscillating ions produce a periodic secondary electron signal whose frequency is mass dependent in mathematically the same way as a conventional time-of-flight analyzer. Because of the oscillating nature of the ions, we have called the analyzer the pulsed oscillating mass spectrometer. Mass spectrometers are among the most sensitive and powerful analytical instruments for identifying chemical and biological substances. They are capable of providing information about the qualitative and quantitative composition of both inorganic1 and organic analytes,2,3 the structures of a wide variety of complex molecular species,1-4 isotopic ratios of atoms in samples,5-7 and the structure and composition of solid surfaces.2,8 Their utility and versatility has led to them being ubiquitous components in analytical laboratories both in their own right and coupled to other techniques, such as the various types of chromatography.9,10 The function of the mass analyzer is to separate ions according to their mass (m) to charge (z) ratio before they reach the detector. Several mass analyzers are available for separating ions, * To whom correspondence should be addressed. E-mail: s.kable@ chem.usyd.edu.au. † Present address: Heyrovsky Institute for Physical Chemistry, Prague, Czech Republic. ‡ Present address: Defense Science and Technology Organisation, Pyrmont, NSW, 2009. (1) Trevor, J. L.; Mencer, D. E.; Lykke, K. R.; Pellin, M. J.; Hanley, L. Anal. Chem. 1997, 69, 4331-4338. (2) Kornienko, O.; Ada, E. T.; Tinka, J.; Wijesundara, M. B. J.; Hanley, L. Anal. Chem. 1998, 70, 1208-1213. (3) Maekawa, M.; Nohmi, T.; Zhan, D.; Kiselev, P.; Fenn, J. B. J. Mass Spectrom. Soc. Jpn. 1999, 47, 76-83. (4) Metelmann, W.; Vukelic, Z.; Peter-Katalinic, J. J. Mass Spectrom. 2001, 36, 21-29. (5) Liu, Y.; Masuda, A.; Inoue, M. J. Anal. Chem. 2000, 72, 3001-3005. (6) Smolka, M. B.; Zhou, H.; Purkayastha, S.; Aebersold, R. Anal. Biochem. 2001, 297, 25-31. (7) Hunter, T. C.; Yang, I.; Zhu, H.; Majidid, V.; Bradbury, E. M.; Chen, X. J. Anal. Chem. 2001, 73, 4891-4902. (8) Bakhtiar, R.; Nelson, R. W. Biochem. Pharm. 2000, 59, 891-905. (9) Sigman, M. E.; Ma, C. Y.; Ilgner, R. H. J. Anal. Chem. 2001, 73, 792-798. (10) Ablonczy, Z.; Kono, M.; Crouch, R. K.; Knapp, D. R. J. Anal. Chem. 2001, 73, 4774-4779.
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including magnetic field, combined electrical and magnetic field, quadrupole, ion cyclotron resonance, quadrupole ion storage trap, and time of flight (TOF). Time-of-flight mass spectrometers (TOFMS) are conceptually among the simplest type of mass analyzer. The performance of early versions of TOF analyzers suffered from lack of mass resolution, in comparison with other analyzers. However, they have always had the important advantage that the mass spectrum is multiplexed, which is that the whole mass spectrum is measured for every pulse of analyte. In the mid-1980s two important innovations revolutionized mass spectrometry. The development of the electrospray11 and matrixassisted laser desorption and ionization (MALDI)12 sources led to the ability to place very high molecular weight species (hundreds of kDa) into the gas phase for mass analysis. At this time, the second, hitherto less important, advantage of TOF mass analyzers became crucial, which is their effectively limitless mass range (albeit with reducing resolution with mass). Since this development in MS sources, there has been a renaissance in research into improving the performance of TOF analyzers. The most straightforward way to improve the resolution of a TOF analyzer is to increase the flight time of the ions in the analyzers by simply increasing the length of the flight tube. This quickly leads to unfeasible instrument dimensions. The first successful attempt to improve the resolution of TOF-MS without lengthening the flight tube was achieved by Wiley and McLaren in 1955.13 They realized that the ability to separate two ions of different masses was limited by small variations in the kinetic energy differences imparted to the ions. They developed a method known as time lag focusing, now commonly known as delayed extraction, which focuses ions of same mass, but with different initial kinetic energy to a point in space. Time lag focusing is achieved by providing a delay between the creation of the ions and switching on the acceleration voltage required to extract them into the analyzer’s field-free region. In doing so, ions with less kinetic energy spend more time in the extraction region and are accelerated with more energy than ions with greater initial energies, consequently allowing them to catch up at a point in space. Wiley and McLaren showed that an improvement in resolution from a 40-cm flight tube provided resolution comparable to that earlier achieved with a 2-m flight tube. (11) Fenn, J. B.; Yamashita, M. J. Phys. Chem. 1984, 88, 4451. (12) Karas, M.; Bachmann, D.; Bahr, U.; Hillenkamp, F. Int. J. Mass Spectrom. Ion Processes 1987, 78, 53-68. (13) Wiley: W. C.; McLaren, I. H. Rev. Sci. Instrum. 1955, 26, 1150. 10.1021/ac050082f CCC: $30.25
© 2005 American Chemical Society Published on Web 05/26/2005
Figure 1. Schematic of the POMS analyzer depicting three coaxially aligned electrodes separated by 50 mm and an ion detector. The central electrode is maintained at high negative electrical potential while the outer electrodes are grounded. Sample is introduced into the analyzer via a pulsed nozzle midway between two electrodes.
The development of the ion mirror, commonly known as the reflectron, was first described by Mamyrin et al. in 197314 and can be considered as the next evolutionary step for reducing the size of TOF-MS. A reflectron is a sequence of electrodes parallel to one another that increases in positive electrical potential. Reflectrons are typically situated at the end of a field-free drift region in a TOF-MS and fold the flight path of the incident ions. The sequence of electrodes is generally tilted slightly so that the ions are reflected back into the field-free drift region at a slight angle and onto a detector. As well as the advantage of a longer flight path, reflectrons improve mass resolution by focusing kinetic energy differences in the ions. The focusing works on the principle that ions with a higher velocity will penetrate deeper into the retarding field of the reflectron and consequently spend more time being reflected than ions having the same mass but lower kinetic energies. As a result the ions of same mass will become focused and the mass resolution will be improved. Since its initial development, the reflectron has undergone many advances in design, which have been made to improve the resolution of TOF-MS while concurrently reducing its size.15-25 A dual-reflectron TOF-MS has been reported by Cotter and Cornish.26 They reported that a TOF-MS consisting of two reflectrons (14) Mamyrin, B. A.; Karataev, V. I.; Shmikk, D. V.; Zagulin, V. A. Sov. Phys. JETP 1973, 37, 45. (15) Cornish, T. J.; Cotter, R. J. J. Anal. Chem. 1993, 65, 1043-1047. (16) Mamyrin, B. A. U.S. Patent 4072862, 1978. (17) Hanson, C. D. The University of Northern Iowa, U.S. Patent 6013913, 2000. (18) Cotter, R. J.; Fancher, C.; Cornish, T. J. J. Mass Spectrom. 1999, 34, 13681372. (19) Badman, E. R.; Cooks, R. G. J. Mass Spectrom. 2000, 35, 659-671. (20) Cornish, T. J.; Bryden W. A., Johns Hopkins APL Tech. Dig. 1999, 20, 335342. (21) Davis, S. C.; Evans, S. Kratos Analytical Ltd. EP Patent 046517B1, 1991. (22) Cornish, T. J.; Ecelberger, S.; Brinckerhoff, W. Rapid Commun. Mass Spectrom. 2000, 14, 2408-2411. (23) Cornish, T. J.; Cotter, R. J.J. Anal. Chem. 1997, 69, 4615-4618. (24) Bryden, W. A.; Benson, R. C.; Ecelberger, S. A.; Phillips, T. E.; Cotter, R. J.; Fenselau, C. Johns Hopkins APL Tech. Dig. 1995, 16, 296-310. (25) Dahen, M.; Fishman, R.; Heber, O.; Rappaprt, M.; Altstein, N.; Zajfman, D.; van der Zande, W. J. Rev. Sci. Instrum. 1997, 69, 76-83.
has approximately double the resolving power of a TOF-MS using only a single reflectron. The ion’s trajectory in a dual reflectron system is typically based on a “Z” configuration. Multireflectron TOF-MS’s have been reported27 which are configured for N + 1 reflections where the flight path of the ions is continually folded by a plurality of ion mirrors. The development of the coaxial multiple reflection TOF-MS28 allows for multiple passes of ions between only two reflectrons, hence increasing the flight path and consequently improving the mass resolution. The advantage the coaxial multiple reflection TOF-MS has over the multireflectron TOF-MS’s is that only two reflectrons are incorporated in the design, hence potentially allowing for a much smaller unit. Detection of the ions is achieved by selectively removing the retarding field from one of the reflectrons and allowing the ions to pass through to the detector. The commercial value of MS to the analytical community has also led to an extensive patent literature on improved and miniaturised TOF analyzers. This paper describes a miniature TOF-MS analyzer with a novel detection regime. The analyzer separates ions based on the principles of TOF but in an oscillatory, rather than a linear configuration. Because of its mode of operation, we have dubbed the analyzer the pulsed oscillating mass spectrometer (POMS). EXPERIMENTAL SECTION Mass Analyzer Design and Operation. The POMS analyzer was constructed in-house from readily available and inexpensive materials. The design is shown in Figure 1 and incorporates a circular brass base, 13 cm in diameter and 1 cm thick. Cantilevered from the base was a Channeltron ion detector (Burle 4700 Series) and four nylon threaded rods, (35 cm × 1.2 cm) spaced 6 cm apart in a square configuration. The nylon rods serve as supports for the electrodes, which are circular aluminum disks (26) Cotter, R. J.; Cornish, T. The John Hopkins University, U.S. Patent 5202563, 1993. (27) Wollinik, H. GB Patent 2080021A, 1982. (28) Park, M. Bruker Daltonics Inc., U.S. Patent 6107625, 2000.
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(2 mm thick, 11-cm diameter). At the center of each electrode is a 25-mm-diameter hole. Stretched across the hole is an 85% transparent nickel mesh (MicroMesh, Buckbee-Mears Inc.). The electrodes were positioned with nylon washers and nuts, threaded above and below the electrodes to lock them into place. The typical spacing between the central and end electrodes was 50 mm. The Channeltron detector was situated 10 mm behind the end electrode and was typically operated at -2 kV. The analyzer was mounted in the center of a stainless steel six-way cross, and evacuated by a 4-in. diffusion pump. Ultimate vacuum in the chamber was typically 0) and represents the number of full cycles, phase shifted by a quarter cycle so that the time corresponds to that at which the cations strike the central mesh resulting in a signal at the detector. Thus, according to eq 2, for constant electrical potential and constant oscillation amplitude, x, the time spent in each POMS oscillation by an ion is directly proportional to the square root of its mass-to-charge ratio, in the same way as conventional TOF-MS. RESULTS AND DISCUSSION Single Analyte. Figure 3 shows an experimentally measured POMS spectrum for fluorobenzene (FB, Merck, 96 amu). The spectrum shows a series of decaying peaks with a regular spacing after the first one. In the inset, the timing of each peak is shown plotted against n, also highlighting regular spacing. The line through the data represents the predictions of eq 2 for E ) 1000 V/cm and x ) 2.5 cm. This corresponds to an applied potential of 5000 V and a grid spacing of 5 cm because the laser intersects the center of electrodes E1 and E2 as shown in Figure 1. The timing of the peaks agrees quantitatively with eq 2. The spacing between the first two peaks, labeled “0” and “1” in Figure 3, is clearly one-quarter of the cycle time that shows up subsequently. The peak at t ) 0 is a result of the primary photoelectrons generated from the initial ionization event and provides a convenient (though ultimately unnecessary) internal clock. The primary photoelectron signal was only observed when the voltage on the central grid was about twice that of the detector because these photoelectrons originate from approximately halfway in the trap (V ≈ 0.5 Vapplied) as opposed to the secondary electrons, which experience the full repulsion of the central grid. The intensity (area) of each peak drops as a power law, (0.85)2n, where as above n is the number of full cycles, and therefore, the
Figure 3. POMS spectrum of FB (96 amu) and pDFB (114 amu). Each peak results from a collision with the central mesh, and the number of cycles corresponding to each peak is numbered. Signal at t ) 0 is due to photelectrons created during the initial ionization event. The inset shows the time of each peak plotted against the cycle number (symbols) compared with the predictions of eq 2 (lines, using E ) 1000 V/cm, x ) 2.5 cm).
ion packet has intercepted the central electrode twice during any one cycle. The signal was only observed when the voltage on the central electrode was more negative than the voltage on the Channeltron detector as electrons born with kinetic energy less than -2 keV are repelled by the negatively charged detector and never reach it. Multiple Analytes. For a POMS spectrum consisting of several analytes, we would expect to see multiple series of peaks where each series had a distinct frequency that was dependent on the mass of the ion. Figure 3 shows a second such series, with the series of peaks due to a small amount (∼12%) of p-difluorobenzene (pDFB, Aldrich, 114 amu) separating further from the FB series with each pass. The inset also shows the time of these peaks in comparison with eq 2, as well as the time difference between the two masses for each cycle. Figure 4 shows a small part of a POMS spectrum of FB, pDFB, and 1-bromo-4-fluorobenzene (pBrFB, Aldrich, 174 and 176 amu). The spectrum starts at the fourth cycle through the analyzer for each ion, where the ion packets for each mass have not yet overtaken each other. The spectrum shows the two equally abundant Br isotopomers of pBrFB clearly resolved. There is an out-of-phase peak to the right of the major pDFB peak. This does not correspond to an integer mass and seems to be a lighter fragment peak whose path has overlapped with the path of the major peaks. Also, there are some lighter masses formed, with masses 75 and 70 amu, which are presumably due to fragmentation of one of the analytes. The minimal amount of fragmentation is due to the ionization wavelength of 266 nm being close to resonant for these benzene derivatives and also almost half of the ionization potential. Consequently, there is little excess energy in the ion to form fragments. Analysis of the mass spectrum presents an interesting compromise between mass resolution, which is achieved at maximum number of passes, and sensitivity, achieved at minimum number of passes. In practice, one can choose the resolution needed for Analytical Chemistry, Vol. 77, No. 14, July 15, 2005
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Figure 4. One cycle of a POMS mass spectrum of FB (mass 96), pDFB (mass 114), and pBrFB (masses 174 and 176).
the job; in Figure 4 where m/∆m ) 100 is needed to resolve the Br isotopes, cycle 4 is sufficient. The separation of the peaks increases linearly with cycles as shown in Figure 3. Relative amounts of each ion are determined by integrating all cycles. Where early cycles are unresolved, the information is still included, but as a blended mass peak. Resolution and Peak Broadening. The peaks in the POMS spectrum in Figure 3 broaden with successive passes. The broadening is due to the finite spatial distribution of ions created in the initial ionization process. Ions created at different positions in the analyzer (along the oscillation axis) act like ions of a different mass, and therefore have a slightly different oscillation frequency (see eq 2). Therefore, the broadening increases with successive cycles. Although the laser is focused, the high efficiency of the near-resonant two-photon ionization in pDFB (and the other substituted benzenes discussed later) allows ionization away from the focal region and a broader spatial distribution than is ideal. We have even been able to measure POMS spectra of pDFB with an unfocused laser, and in these cases, the peak broadening is pronounced and excessive. Secondary Electron Emission. We have made an analysis of the efficiency of secondary electron emission from the central grid using the primary photoelectrons from the initial laser ionization as a primary internal standard. The primary photoelectrons are created in the half of the analyzer that contains the detector (see Figure 1). Of course, for every cation in the trap, one primary photoelectron is produced, and this photoelectron is ejected from the trap straight toward the detector. This photoelectron can only be detected when the potential applied to the central electrode is more than twice that of the detector, because the electron is born in the center of the trap and therefore experiences about half of the full potential. The signal from the photoelectrons shows up in Figure 3 as the t ) 0 peak and is representative of the total ion population. The POMS peak after the first quarter cycle should be produced from 15% of the ions, yet the electron signal is almost as strong as the photoelectron peak. Assuming that the collection efficiency of the photoelectrons and secondary electrons is the same, we estimate that each ion that collides with the central mesh produces about 4-6 electrons at 4-keV kinetic energy. 4452
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CONCLUSIONS A miniature TOF mass analyzer incorporating a novel detection regime, known as a pulsed oscillatory mass spectrometer, was designed, tested, and shown to separate ions of different m/z ratio. The device employed in this work used an electrode spacing of 10 cm; however, we have since made detectors with a total length (E1 to E3) of less than 6 cm. The analyzer is similar in some regards to the coaxially aligned dual reflectron MS, as described by Park28 in that it continually folds the flight path of the ions with the assistance of two ion mirrors. The Park system detects ions by removing a potential on one of the electrodes to allow their migration to a detector. In comparison, our system detects secondary electrons as the ions oscillate between the ion mirrors allowing us to record their cycle time. The benefit of detecting electrons as opposed to ions is that contamination of the ion detector is avoided, resulting in a prolonged lifetime. Furthermore, as the Park design detects ions after an undetermined number of cycles (if the mass is unknown), ions of different masses may have undergone a different number of cycles and as a consequence could be assigned an incorrect mass. The POMS system avoids this by monitoring each ion cycle. The POMS analyzer demonstrated its ability to resolve multiple analytes. But there are complexities in such an oscillating signal when the number of analytes becomes large. At present, we analyze the spectrum by hand, but we are working on a mathematical transform technique to convert the oscillating signal into a regular mass spectrum. The resolution of the POMS analyzer, as demonstrated in this paper, is still only fairly rudimentary (m/∆m ≈ 200 at m/z ) 200). The main limitation is the initial spatial distribution of ions formed in the laser pulse because ions formed at different regions experience a different potential with the result that the ion packet spreads and the POMS peak broadens for successive cycles. We are currently investigating techniques for narrowing this initial spatial distribution and exploring different electrode geometries to minimize subsequent spreading. Nonetheless, this is a simple device. The analyzer itself is small, low cost, and simple to fabricate and uses only dc electric fields. Finally, in this work, we have a used a laser crossing a molecular beam to produce the ions for analysis. This was done only for convenience, as this was the original purpose of the instrument in which the POMS concept was developed. We see no fundamental impediment to the incorporation of other ion sources, for example, MALDI or electrospray sources, and we are currently investigating the coupling of these more inherently useful ion sources to a POMS analyzer. ACKNOWLEDGMENT We gratefully acknowledge the support of the University of Sydney Sesqui grant scheme for supporting this work in its earliest days. We also acknowledge Mr. Joseph Guss for coining the acronym “POMS”.
Received for review January 14, 2005. Accepted May 3, 2005. AC050082F
