Fourier Transform Time-of-Flight Mass Spectrometry in an Electrostatic Ion Beam Trap S. Ring, ² H. B. Pedersen, ‡ O. Heber, ‡ M. L. Rappaport, § P. D. Witte, | K. G. Bhushan, ‡ N. Altstein, ‡ Y. Rudich,* ,² I. Sagi, ⊥ and D. Zajfman* ,‡ Department of Environmental Sciences, Department of Particle Physics, Physics Services, and Department of Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel, and Max-Planck-Institut fu ¨ r Kernphysik, D-69029, Heidelberg, Germany We report on the application of an electrostatic ion beam trap as a mass spectrometer. The instrument is analogous to an optical resonator; ions are trapped between focusing mirrors. The storage time is limited by the residual gas pressure and reaches up to several seconds, resulting in long ion flight paths. The oscillation of ion bunches between the mirrors is monitored by nondestructive image charge detection in a field-free region and mass spectra are obtained via Fourier transform. The principle of operation is demonstrated by measuring the mass spec- trum of trapped Ar + and Xe + particles, produced by a standard electron impact ion source. Also, mass spectra of heavier PEG n Na + and bradykinin ions from a pulsed MALDI ion source were obtained. The long ion flight path, combined with mass-independent charge detection, makes this system particularly interesting for the investigation of large molecules. Initially, due to its low resolution, time-of-flight mass spec- trometry (TOF-MS) was regarded as a less promising technique compared to other techniques such as quadrupole mass spec- trometry (QMS) and Fourier transform ion cyclotron mass spectrometry (FTICR-MS). The low resolution originated in the fact that the ionization techniques used in TOF-MS, such as electron impact and laser ionization, produced ions with large temporal, spatial, and energy spread, which resulted in a spread in the arrival time. With the advent of schemes for the correction of energy-dependent flight time errors, by time lag focusing 1 and compensating mirrors, 2 time-of-flight instruments became increas- ingly common in various fields of mass spectrometry. The main advantages of TOF-MS techniques lie in fast acquisition time, high throughput, and their virtually unlimited mass range. The latter became particularly important, after methods for the production of ions of large biological molecules in the gas phase were developed by Karas and Hillenkamp (matrix-assisted laser de- sorption/ ionization, MALDI) 3,4 and by Fenn and co-workers (electrospray ionization, ESI). 5 These ionization techniques have been adapted to TOF-MS using orthogonal injection for ESI (e.g., ref 6 and references therein) and delayed extraction (DE) for MALDI. 7,8 With the increasing demand for studying even larger molecules up to the megadalton range, the challenge of mass spectrometry shifted from the ion production step to mass separation and detection. TOF development then focused on the improvement of mass resolution and sensitivity for these large molecules. Improvements in the resolution in TOF instruments are usually made by increasing the length of the flight path. However, simply using longer flight tubes soon reaches practical limits. This can be avoided by folding the flight path into the same physical space before the ions are steered onto a detector. Folding the flight path is usually accomplished by the use of ion mirrors, as introduced by Mamyrin et al. 2 for flight time correction in a single reflecting reflectron-TOF. Several papers on multireflecting instruments based on ion mirrors have been published. 9-12 In these instruments, grids are used to obtain homogeneous electric fields, and the resolution can be increased, at the cost of low transmission for several passes through the grids. 13,14 In a recent publication, Piyadasa et al. 15 reported on a multireflecting instru- ment, where a resolution of R ) m/ ∆m ) 31 000 for bovine insulin ( m/ z ) 5734) was obtained. In that study, DE 7,8 was also used to enhance mass resolution. A gridless multipass reflectron that avoids the problem of low transmission was suggested by Wollnik. 16,17 † Department of Environmental Sciences, Weizmann Institute of Science. ‡ Department of Particle Physics, Weizmann Institute of Science. § Physics Services, Weizmann Institute of Science. | Max-Planck-Institut fu ¨ r Kernphysik. ⊥ Department of Structural Biology, Weizmann Institute of Science. (1) Wiley, W. C.; McLaren, I. H. Rev. Sci. Instrum. 1955 , 26, 1150. (2) Mamyrin, B. A.; Karataev, V. I.; Shmikk, D. V.; Zagulin, V. A. Sov. Phys. JETP 1973 , 37, 45. (3) Karas, M.; Bahr, U.; Ingendoh, A.; Hillenkamp, F. Angew. Chem., Int. Ed. Engl. 1989 , 28, 70. (4) Hillenkamp, F.; Karas, M.; Beavis, R. C.; Chait, B. Anal. Chem. 1991 , 63, 1193A. (5) Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Science 1989 , 246, 64. (6) Guilhaus, M.; Selby, D.; Mlynski, V. Mass Spectrom. Rev. 2000 , 19, 65. (7) Vestal, M. L.; Juhasz, P.; Martin, S. A. Rapid. Commun. Mass Spectrom. 1995 , 9, 1044. (8) Whittal, R. M.; Li, L. Anal. Chem. 1995 , 67, 1950. (9) Su, C. Int. J. Mass Spectrom. 1989 , 88, 21. (10) Beussmann, D. J.; Vlasak, P. R.; McLane, R. D.; Seeterlin, M. A.; Enke, C. G. Anal. Chem. 1995 , 67, 3952. (11) Cornish, T. J.; Cotter, R. J. Anal. Chem. 1993 , 65, 1043. (12) Hanson, C. D. Anal. Chem. 2000 , 72, 448. (13) Hohl, M.; Wurz, P.; Scherer, S.; Altwegg, K.; Balsiger, H. Int. J. Mass Spectrom. 1999 , 188, 189. (14) Amad, M. H.; Houk, R. S. Anal. Chem. 1998 , 70, 4885. (15) Piyadasa, C. K. G.; Hakanson, P.; Ariyaratne, T. R. Rapid Commun. Mass Spectrom. 1999 , 13, 620. Anal. Chem. 2000, 72, 4041-4046 10.1021/ac000317h CCC: $19.00 © 2000 American Chemical Society Analytical Chemistry, Vol. 72, No. 17, September 1, 2000 4041 Published on Web 07/29/2000 Downloaded by WEIZMANN INST OF SCIENCE on September 4, 2015 | http://pubs.acs.org Publication Date (Web): July 29, 2000 | doi: 10.1021/ac000317h