Design Characteristics to Eliminate the Need for Parameter Optimization in Nanoflow ESI-MS

  • Yang KangEmail author
  • Bradley B. Schneider
  • Leigh Bedford
  • Thomas R. Covey
Research Article


The sampling efficiency in electrospray ionization-mass spectrometry (ESI-MS) can be improved by decreasing the liquid flow rate to the nanoflow regime, where it is possible to draw a large fraction of the ESI plume into the mass spectrometer. This mode of operation is typically more difficult than ESI-MS at higher flow rates because it requires careful optimization of a number of parameters to achieve optimal sampling efficiency. In this work, we screened the relative impact on signal intensity and spray stability of factors that included sprayer position, spray electrode protrusion, sprayer tip shape, spray angle relative to the MS inlet, nebulizer gas flow rate, ESI potential, and means for generating the electric field to initiate electrospray. Based on the screening results, we explore the possibility of providing fixed optimal values for many of the key source parameters to eliminate much of the tuning that is required for conventional nanoflow sources. This approach has potential to greatly simplify nanoflow ESI-MS, while providing optimized sensitivity, stability, and robustness, with decreased variability between analyses.


Nanospray ESI Optimization Tuning Sensitivity Robustness 



We appreciate the help of Deolinda Fernandes for the preparation of the samples. We also appreciate Stan Potyrala for the prototype source design.


  1. 1.
    Covey, T.R., Schneider, B.B., Javaheri, H., Yves LeBlanc, J.C., Ivosev, G., Corr, J.J., Kovarik, P., ESI, APCI, and MALDI: A comparison of the central analytical figures of merit: sensitivity, reproducibility, and speed. In: Cole, R.B. (ed.) Electrospray and MALDI Mass Spectrometry: Fundamentals, Instrumentation, Practicalities, and Biological Applications, pp. 443–490. John Wiley & Sons, Inc, Hoboken (2010)Google Scholar
  2. 2.
    Gaskell, S.J.: Electrospray: principles and practice. J. Mass Spectrom. 32, 677–688 (1997)CrossRefGoogle Scholar
  3. 3.
    Wilm, M.S., Mann, M.: Electrospray and Taylor-Cone theory, Dole’s beam of macromolecules at last? Int. J. Mass Spectrom. Ion Process. 136, 167–180 (1994)CrossRefGoogle Scholar
  4. 4.
    Kebarle, P., Verkerk, U.H.: Electrospray: from ions in solution to ions in the gas phase, what we know now. Mass Spectrom. Rev. 28, 898–917 (2009)CrossRefGoogle Scholar
  5. 5.
    Covey, T.R., Thomson, B.A., Schneider, B.B.: Atmospheric pressure ion sources. Mass Spectrom. Rev. 28, 870–897 (2009)CrossRefGoogle Scholar
  6. 6.
    El-Faramawy, A., Siu, K.M., Thomson, B.A.: Efficiency of nano-electrospray ionization. J. Am. Soc. Mass Spectrom. 16, 1702–1707 (2005)CrossRefGoogle Scholar
  7. 7.
    Schneider, B.B., Javaheri, H., Covey, T.R.: Ion sampling effects under conditions of total solvent consumption. Rapid Commun. Mass Spectrom. 20, 1538–1544 (2006)CrossRefGoogle Scholar
  8. 8.
    Geromanos, S., Freckleton, G., Tempst, P.: Tuning of an electrospray ionization source for maximum peptide-ion transmission into a mass spectrometer. Anal. Chem. 72, 777–790 (2000)CrossRefGoogle Scholar
  9. 9.
    Emmett, M.R., Caprioli, R.M.: Micro-electrospray mass spectrometry: ultra-high-sensitivity analysis of peptides and proteins. J. Am. Soc. Mass Spectrom. 5, 605–613 (1994)CrossRefGoogle Scholar
  10. 10.
    Krutchinsky, A.N., Padovan, J.C., Cohen, H., Chait, B.T.: Maximizing ion transmission from atmospheric pressure into the vacuum of mass spectrometers with a novel electrospray interface. J. Am. Soc. Mass Spectrom. 26, 649–658 (2015)CrossRefGoogle Scholar
  11. 11.
    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. 80, 6573–6579 (2008)CrossRefGoogle Scholar
  12. 12.
    Manisali, I., Chen, D.D., Schneider, B.B.: Electrospray ionization source geometry for mass spectrometry: past, present, and future. Trends Anal. Chem. 25, 243–256 (2006)CrossRefGoogle Scholar
  13. 13.
    Schmidt, A., Karas, M., Dülcks, 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. 14, 492–500 (2003)CrossRefGoogle Scholar
  14. 14.
    Gelpí, E.: Interfaces for coupled liquid-phase separation/mass spectrometry techniques. An update on recent developments. J. Mass Spectrom. 37, 241–253 (2002)CrossRefGoogle Scholar
  15. 15.
    Amirkhani, A., Wetterhall, M., Nilsson, S., Danielsson, R., Bergquist, J.: Comparison between different sheathless electrospray emitter configurations regarding the performance of nanoscale liquid chromatography–time-of-flight mass spectrometry analysis. J. Chromatogr. A. 1033, 257–266 (2004)CrossRefGoogle Scholar
  16. 16.
    Bruins, A.P., Covey, T.R., Henion, J.D.: Ion spray interface for combined liquid chromatography/atmospheric pressure ionization mass spectrometry. Anal. Chem. 59, 2642–2646 (1987)CrossRefGoogle Scholar
  17. 17.
    Schneider, B.B., Baranov, V.I., Javaheri, H., Covey, T.R.: Particle discriminator Interface for nanoflow ESI-MS. J. Am. Soc. Mass Spectrom. 14, 1236–1246 (2003)CrossRefGoogle Scholar
  18. 18.
    Schneider, B.B., Guo, X., Fell, L.M., Covey, T.R.: Stable gradient nanoflow LC-MS. J. Am. Soc. Mass Spectrom. 16, 1545–1551 (2005)CrossRefGoogle Scholar
  19. 19.
    Kang, Y., Schneider, B.B., Covey, T.R.: On the nature of mass spectrometer analyzer contamination. J. Am. Soc. Mass Spectrom. 28, 2384–2392 (2017)CrossRefGoogle Scholar
  20. 20.
    Collins, B.C., Hunter, C.L., Liu, Y., Schilling, B., Rosenberger, G., Bader, S.L., Chan, D.W., Gibson, B.W., Gingras, A.-C., Held, J.M.: Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry. Nat. Commun. 8, 291 (2017)CrossRefGoogle Scholar
  21. 21.
    Kang, Y., Burton, L., Lau, A., Tate, S.: SWATH-ID: an instrument method which combines identification and quantification in a single analysis. Proteomics. 17, 1500522 (2017)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.SCIEXConcordCanada

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