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Adjacent Pulsed Nanoelectrospray Ionization Emitters for the Alternating Generation of Ions of Opposite Polarity Jeremiah J. Bowers, James R. Zimmerman, Robert A. Oglesbee, and Scott A. McLuckey* Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-2084 An approach that allows for adjacent closely spaced nanoelectrospray ionization (nESI) emitters to be pulsed alternately to generate ions of opposite polarity for transmission through a common interface is described. The potential difference between two or more nESI emitters in close proximity is minimized by applying the same polarity to both emitters at any given point in time but with the magnitude of only the active emitter’s potential being sufficiently high to sustain a stable spray. The reduced difference in potential between emitters allows the distance between emitters to be decreased to within a few millimeters so that compromises imposed by the use of multiple emitters for the generation of ions from distinct solutions using a common atmosphere interface are minimized. The use of two ion emitters with a single atmosphere/vacuum interface in biological mass spectrometry can provide enhanced experimental flexibility without implementing additional pumping and hardware, which would be required with separate interfaces for each emitter. Multiple emitter arrangements, for example, have been described for the admission of analyte and reference ions of the same polarity for the purpose of mass calibration.1-7 Multiple sprayer arrangements have also been described to improve sensitivity8 and throughput.9 Some of these reports have employed a single vacuum/atmosphere interface with either electronic or mechanical switching strategies. Multiple ion emitters have also been used to generate oppositely charged ions for ion/ion reaction studies. This has been done using separate emitters of opposite polarity operated continuously and coupled * To whom correspondence should be addressed. Phone: (765) 494-5270. Fax: (765) 494-0239. E-mail:
[email protected]. (1) Jiang, L.; Moini, M. Anal. Chem. 2000, 72, 20–24. (2) Eckers, C.; Wolff, J.-F.; Haskins, N. J.; Sage, A. B.; Giles, K.; Bateman, R. Anal. Chem. 2000, 72, 3683–3688. (3) Hannis, J. C.; Muddiman, D. C. J. Am. Soc. Mass Spectrom. 2000, 11, 876– 883. (4) Takahashi, Y.; Fujimaki, S.; Kobayashi, T.; Morita, T.; Higuchi, T. Rapid Commun. Mass Spectrom. 2000, 14, 947–949. (5) Wolff, J.-C.; Eckers, C.; Sage, A. B.; Giles, K.; Bateman, R. Anal. Chem. 2001, 73, 2605–2612. (6) Zhou, F.; Shui, W.; Lu, Y.; Yang, P.; Guo, Y. Rapid Commun. Mass Spectrom. 2002, 16, 505–511. (7) Satomi, Y.; Kudo, Y.; Sasaki, K.; Hase, T.; Takao, T. Rapid Commun. Mass Spectrom. 2005, 19, 540–546. (8) Tang, K.; Lin, Y.; Matson, D. W.; Kim, T.; Smith, R. D. Anal. Chem. 2001, 73, 1568–1663. (9) Shneider, B. B.; Douglas, D. J.; Chen, D. D. Y. Rapid Commun. Mass Spectrom. 2002, 16, 1982–1990. 10.1021/ac902485e 2010 American Chemical Society Published on Web 01/04/2010
to a Y-tube arrangement for ion/ion reactions prior to sampling into a mass spectrometer.10 The use of continuously operated emitters with separate atmosphere interfaces has also been described.11,12 Pulsed nanoelectrospray emitters for ion/ion reactions have also been coupled with a single interface.13-18 A variety of approaches has been taken for coupling two or more emitters to a single vacuum/atmosphere interface. Some employ mechanical means for sampling ions from continuously operated emitters1,2 by rapidly changing emitter positions while others rely on stationary pulsed emitters.3,13,16 Mechanical means generally lead to few compromises in the relative positioning of the emitters because the position of the emitter relative to the sampling orifice is more-or-less independent of the position of the other emitter. However, mechanical switching is slower than electronic switching. Electronic switching of stationary emitters, on the other hand, can require compromises in the relative positioning of the emitters. This situation is most likely to occur when the range of optimal emitter tip-orifice spacings for ion sampling is small. This is often the case with nanoelectrospray, for example, in which relatively close spacing of the nanospray tip to the sampling orifice is desirable for maximal ion sampling. In this scenario, the close proximity of the nanospray tips can lead to compromises when one tip is grounded while the other is at high potential. In this technical note, we describe an approach to minimize the potential difference between closely spaced nanoelectrospray emitters to allow both to be placed within 3-5 mm of the sampling orifice while allowing the two emitters to be as close as 1 mm relative to one another. It is based on raising and lowering the voltages of both emitters in tandem in such a way that only one of the emitters has a voltage sufficiently high in amplitude to generate a spray. (10) Ogorzalek-Loo, R. R.; Udseth, H. R.; Smith, R. D. J. Am. Soc. Mass Spectrom. 1992, 3, 695–705. (11) Wells, J. M.; Chrisman, P. A.; McLuckey, S. A. J. Am. Soc. Mass Spectrom. 2002, 13, 614–622. (12) Badman, E. R.; Chrisman, P. A.; McLuckey, S. A. Anal. Chem. 2002, 74, 6237–6243. (13) Xia, Y.; Liang, X.; McLuckey, S. A. J. Am. Soc. Mass Spectrom. 2005, 16, 1750–1756. (14) Xia, Y.; Chrisman, P. A.; Erickson, D. E.; Liu, J.; Liang, X.; Londry, F. A.; Yang, M. J.; McLuckey, S. A. Anal. Chem. 2006, 78, 4146–4154. (15) Liang, X.; Han, H.; Xia, Y.; McLuckey, S. A. J. Am. Soc. Mass Spectrom. 2007, 18, 369–376. (16) McAlister, G. C.; Phanstiel, D.; Good, D. M.; Berggren, W. T.; Coon, J. J. Anal. Chem. 2007, 79, 3525–3534. (17) Williams, D. K., Jr.; McAlister, G. C.; Good, D. M.; Coon, J. J.; Muddiman, D. C. Anal. Chem. 2007, 79, 7916–7919.
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MATERIALS AND METHODS Materials. Peptides, proteins, and 1,3-dicarboxylic acid-adamantane (DCA) were purchased from Sigma-Aldrich (St. Louis, MO). Solutions were prepared to 0.5 mg/mL in 50/49/1 (vol/ vol/vol) water/methanol/acetic acid for low pH solutions and 49/ 48/3 (vol/vol/vol) water/methanol/ammonium hydroxide for high pH solutions. The pH of the solutions was less than 7 for emitters intended to yield positive ions whereas pH values greater than 7 were used for solutions intended to generate negative ions. This was done so that the analyte and reagent ions of interest were subjected to “right way round” electrospray conditions,19-21 whereby the analyte or reagent ion polarity in solution matched that of the applied voltage. All solutions were loaded into nanospray emitters that were pulled from borosilicate capillaries (1.55 mm O.D., 0.86 mm I.D.) using a P-87 Flaming/Brown micropipet puller (Sutter Instruments, Novato CA).22 Two independent power supplies for each emitter were initially switched between either two 4140 DEI fast high voltage switch boxes (Directed Energy Inc., Fort Collins, CO) or a custom-built heavy relay switch box with a switching time of ∼3 ms. (Copies of the schematics for this relay switch box are available as Supporting Information.) The 4140 DEI high voltage switch boxes operate with rise times much faster than needed for this application. Therefore, all of the results shown here were collected using the home-built switch box, which easily met the needs for this application (see below). Tandem Pulsed Ionization Source. All data were collected using a home-built adjacent dual nanoelectrospray ionization (nESI) emitter arrangement positioned before a home-built atmosphere/vacuum interface adapted to a Finnigan ITMS (ion trap mass spectrometer).13 (The dual nESI emitter has also been used with other vacuum/atmosphere interfaces in our laboratory and showed equivalent results.) The adjacent spray emitter arrangement typically consisted of two nanoelectrospray sprayers that were clamped together such that the two tips with 15-30 µm orifices were 1-3 mm apart and angled acutely from the centerline as show in Figure 1. Distances of ∼1 mm or less were more difficult to establish without the tips making contact with one another during the process. When such small distances were used, it was found that best performance was noted when the positive emitter was offset longitudinally from the negative emitter such that the negative emitter was slightly closer to the orifice than the positive emitter, as shown in Figure 1b, effectively increasing the tip to tip distance between the two emitters. No particular advantage in ion sampling was observed when tip distances of less than 2 mm distances were used. Tip to interface aperture spacings of ∼3-7 mm were found to be optimal depending upon the instrument used to collect the data. For the Finnigan ITMS, a distance of 3-5 mm was used. (18) Bushey, J. M.; Kaplan, D. A.; Danell, D. M.; Glish, G. L. Instrum. Sci. Technol. 2009, 37, 257–273. (19) Loo, J. A.; Udseth, H. R.; Smith, R. D. Rapid Commun. Mass Spectrom. 1988, 2, 207–210. (20) Kelly, M. A.; Vestling, M. M.; Fenselau, C. C. Org. Mass Spectrom. 1992, 27, 1143–1147. (21) Zhou, S.; Cook, K. D. J. Am. Soc. Mass Spectrom. 2000, 11, 961–966. (22) Van Berkel, G. J.; Asano, K. G.; Schnier, P. D. J. Am. Soc. Mass Spectrom. 2001, 12, 853–862.
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Figure 1. Adjacent spray emitter arrangements for (a) 2 mm or larger tip to tip distances and (b)
