Biases in ion transmission through an electrospray ionization-mass spectrometry capillary inlet

  • Jason S. Page
  • Ioan Marginean
  • Erin S. Baker
  • Ryan T. Kelly
  • Keqi Tang
  • Richard D. Smith


A heated capillary inlet for an electrospray ionization mass spectrometry (ESI-MS) interface was compared with shorter versions of the inlet to determine the effects on transmission and ionization efficiencies for low-flow (nano) electrosprays. Five different inlet lengths were studied, ranging from 6.4 to 1.3 cm. As expected, the electrospray current transmission efficiency increased with decreasing capillary length due to reduced losses to the inside walls of the capillary. This increase in transmission efficiency with shorter inlets was coupled with reduced desolvation of electrosprayed droplets. Surprisingly, as the inlet length was decreased, some analytes showed little or no increase in sensitivity, while others showed as much as a 15-fold gain. The variation was shown to be at least partially correlated with analyte mobilities, with the largest gains observed for higher mobility species, but also affected by solution conductivity, flow rate, and inlet temperature. Strategies for maximizing sensitivity while minimizing biases in ion transmission through the heated capillary interface are proposed.


Enhancement Factor Transmission Efficiency Ionization Efficiency Charged Droplet Capillary Inlet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    El-Faramawy, A.; Siu, K. W. M.; Thomson, B. A. Efficiency of Nano-Electrospray Ionization. J. Am. Soc. Mass Spectrom. 2005, 16, 1702–1707.CrossRefGoogle Scholar
  2. 2.
    Schmidt, A.; Karas, M.; Dulcks, T. Effect of Different Solution Flow Rates on Analyte Ion Signals in Nano-ESI MS, or: When Does ESI Turn into Nano-ESI? J. Am. Soc. Mass Spectrom. 2003, 14, 492–500.CrossRefGoogle Scholar
  3. 3.
    Covey, T. R.; Thomson, B. A.; Schneider, B. B. Atmospheric Pressure Ion Sources. Mass Spectrom. Rev. 2009, DOI 10.1002/mas. 20246.Google Scholar
  4. 4.
    Kebarle, P.; Verberk, U. H. Electrospray: From Ions in Solution to Ions in the Gas Phase, What We Know Now. Mass Spectrom. Rev. 2009, DOI 10.1002/mas. 20247.Google Scholar
  5. 5.
    Gale, D. C.; Smith, R. D. Small Volume and Low Flow-Rate Electrospray Ionization Mass Spectrometry of Aqueous Samples. Rapid Commun. Mass Spectrom. 1993, 7, 1017–1021.CrossRefGoogle Scholar
  6. 6.
    Wilm, M. S.; Mann, M. Electrospray and Taylor-Cone Theory, Dole’s Beam of Macromolecules at Last? Int. J. Mass Spectrom. Ion Processes 1994, 136, 167–180.CrossRefGoogle Scholar
  7. 7.
    Wilm, M.; Mann, M. Analytical Properties of the Nanoelectrospray Ion Source. Anal. Chem. 1996, 68, 1–8.CrossRefGoogle Scholar
  8. 8.
    Fernandez de la Mora, J.; Loscertales, I. The Current Emitted by Highly Conducting Taylor Cones. J. Fluid Mech 1994, 260, 155–184.CrossRefGoogle Scholar
  9. 9.
    Page, J. S.; Kelly, R. T.; Tang, K.; Smith, R. D. Ionization and Transmission Efficiency in an Electrospray Ionization-Mass Spectrometry Interface. J. Am. Soc. Mass Spectrom. 2007, 18, 1582–1590.CrossRefGoogle Scholar
  10. 10.
    Emmett, M. R.; White, F. M.; Hendrickson, C. L.; Shi, S. D. -H.; Marshall, A. G. Application of Micro-Electrospray Liquid Chromatography Techniques to FT-ICR MS to Enable High-Sensitivity Biological Analysis. J. Am. Soc. Mass Spectrom. 1998, 9, 333–340.CrossRefGoogle Scholar
  11. 11.
    Shen, Y.; Tolic, N.; Masselon, C.; Pasa-Tolic, L.; Camp, D. G.; Hixson, K. K.; Zhao, R.; Anderson, G. A.; Smith, R. D. Ultrasensitive Proteomics Using High-Efficiency On-Line Micro-SPE-NanoLC-NanoESI MS and MS/MS. Anal. Chem. 2004, 76, 144–154.CrossRefGoogle Scholar
  12. 12.
    Shen, Y.; Tolic, N.; Masselon, C.; Pasa-Tolic, L.; Camp, D. G.; Lipton, M. S.; Anderson, G. A.; Smith, R. D. Nanoscale Proteomics. Anal. Bioanal. Chem. 2004, 378, 1037–1045.CrossRefGoogle Scholar
  13. 13.
    Electrospray Ionization Mass Spectrometry: Fundamentals, Instrumentation, and Applications; John Wiley and Sons, Inc.: New York, 1997; 107–136.Google Scholar
  14. 14.
    Chowdhury, S. K.; Katta, V.; Chait, B. T. An Electrospray-Ionization Mass Spectrometer with New Features. Rapid Commun. Mass Spectrom. 1990, 4, 81–87.CrossRefGoogle Scholar
  15. 15.
    Busman, M.; Sunner, J.; Vogel, C. R. Space-Charge-Dominated Mass-Spectrometry Ion Sources—Modeling and Sensitivity. J. Am. Soc. Mass Spectrom. 1991, 2, 1–10.CrossRefGoogle Scholar
  16. 16.
    Lin, B. W.; Sunner, J. Ion Transport by Viscous Gas Flow Through Capillaries. J. Am. Soc. Mass Spectrom. 1994, 5, 873–885.CrossRefGoogle Scholar
  17. 17.
    Page, J. S.; Tolmachev, A. V.; Tang, K.; Smith, R. D. Theoretical and Experimental Evaluation of the Low m/z Transmission of an Electrodynamic Ion Funnel. J. Am. Soc. Mass Spectrom. 2006, 17, 586–592.CrossRefGoogle Scholar
  18. 18.
    Kelly, R. T.; Page, J. S.; Luo, Q.; Moore, R. J.; Orton, D. J.; Tang, K.; Smith, R. D. Chemically Etched Open Tubular and Monolithic Emitters for Nanoelectrospray Ionization Mass Spectrometry. Anal. Chem. 2006, 78, 7796–7801.CrossRefGoogle Scholar
  19. 19.
    Tomlinson, E.; Jefferies, T. M.; Riley, C. M. Ion-Pair High-Performance Liquid Chromatography. J. Chromatogr. 1978, 159, 315–358.CrossRefGoogle Scholar
  20. 20.
    Marginean, I.; Kelly, R. T.; Prior, D. C.; LaMarche, B. L.; Tang, K.; Smith, R. D. Analytical Characterization of the Electrospray Ion Source in the Nanoflow Regime. Anal. Chem. 2008, 80, 6573–6579.CrossRefGoogle Scholar
  21. 21.
    Wutz, M.; Adam, H.; Walcher, W. Theory and Practice of Vacuum Technology; Vieweg: Braunschweig, 1989; p. 96.Google Scholar
  22. 22.
    Mason, E. A.; McDaniel, E. W. Transport Properties of Ions in Gases; Wiley: New York, 1988; pp 77–78.Google Scholar
  23. 23.
    Baker, E. S.; Clowers, B. H.; Li, F. M.; Tang, K.; Tolmachev, A. V.; Prior, D. C.; Belov, M. E.; Smith, R. D. Ion Mobility Spectrometry-Mass Spectrometry Performance Using Electrodynamic Ion Funnels and Elevated Drift Gas Pressures. J. Am. Soc. Mass Spectrom. 2007, 18, 1176–1187.CrossRefGoogle Scholar
  24. 24.
    Henderson, S. C.; Valentine, S. J.; Counterman, A. E.; Clemmer, D. E. ESI/Ion Trap/Ion Mobility/Time-of-Flight Mass Spectrometry for Rapid and Sensitive Analysis of Biomolecular Mixtures. Anal. Chem. 1999, 71, 291–301.CrossRefGoogle Scholar
  25. 25.
    Batchelor, G. K. An Introduction to Fluid Dynamics; Cambridge University Press: Cambridge, 1967; p. 233.Google Scholar
  26. 26.
    Yang, F.; Jaitly, N.; Jayachandran, H.; Luo, Q.; Monroe, M. E.; Du, X.; Gritsenko, M. A.; Zhang, R.; Anderson, D. J.; Purvine, S. O.; Adkins, J. N.; Moore, R. J.; Mottaz, H. M.; Ding, S. -J.; Lipton, M. S.; Camp, D. G.; Udseth, H. R.; Smith, R. D.; Rossie, S. Applying a Targeted Label-Free Approach Using LC MS AMT Tags to Evaluate Changes in Protein Phosphorylation Following Phosphatase Inhibition. J. Proteome Res. 2007, 6, 4489–4497.CrossRefGoogle Scholar
  27. 27.
    Guo, X.; Bruins, A. P.; Covey, T. R. Method to Reduce Chemical Background Interference in Atmospheric Pressure Ionization Liquid Chromatography Mass Spectrometry Using Exclusive Reactions with the Chemical Reagent Dimethyl Disulfide. Anal. Chem. 2007, 79, 4013–4021.CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2009

Authors and Affiliations

  • Jason S. Page
    • 1
  • Ioan Marginean
    • 1
  • Erin S. Baker
    • 1
  • Ryan T. Kelly
    • 1
  • Keqi Tang
    • 1
  • Richard D. Smith
    • 1
  1. 1.Biological Sciences DivisionPacific Northwest National LaboratoryRichlandUSA

Personalised recommendations