Monte carlo simulation of macromolecular ionization by nanoelectrospray

  • Christopher J. HoganEmail author
  • Pratim Biswas


Electrospray ionization (ESI) is commonly used in macromolecular mass spectrometry, yet the dynamics of macromolecules in ESI droplets are not well understood. In this study, a Monte Carlo based model was developed, which can predict the efficiency of electrospray ionization for macromolecules, i.e., the number of macromolecular ions produced per macromolecules electrosprayed. The model takes into account ESI droplet evaporation, macromolecular diffusion within the droplet, droplet fissions, and the statistical nature of the ESI process. Two idealized representations of macromolecular analytes were developed, describing cluster prone, droplet surface inactive macromolecules and droplet surface active macromolecules, respectively. It was found that surface active macromolecules are preferentially ionized over surface inactive cluster prone macromolecules when the initial droplet size is large and the analyte concentration in solution is high. Simulations showed that ESI efficiency decreases with increasing initial droplet size and analyte molecular weight, and is influenced by analyte surface activity, the properties of the solvent, and the variance of the droplet size distribution. Model predictions are qualitatively supported by experimental measurements of macromolecular electrospray ionization made previously. Overall, this study demonstrates the potential capabilities of Monte Carlo based ESI models. Future developments in such models will allow for more accurate predictions of macromolecular ESI intensity.


Ionization Efficiency Analyte Ionization Droplet Evaporation Initial Droplet Fission Event 
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.

Supplementary material

13361_2011_190801098_MOESM1_ESM.doc (78 kb)
Supplementary material, approximately 79 KB.


  1. 1.
    Constantopoulos, T. L.; Jackson, G. S.; Enke, C. G. Challenges in Achieving a Fundamental Model for ESI. Anal. Chim. Acta 2000, 406, 37–52.CrossRefGoogle Scholar
  2. 2.
    Cech, N. B.; Enke, C. G. Practical Implications of Some Recent Studies in Electrospray Ionization Fundamentals. Mass Spectrom. Rev. 2001, 20, 362–387.CrossRefGoogle Scholar
  3. 3.
    Tang, K. Q.; Smith, R. D. Theoretical Prediction of Charged Droplet Evaporation and Fission in Electrospray Ionization. Int. J. Mass Spectrom. 1999, 187, 97–105.CrossRefGoogle Scholar
  4. 4.
    Dole, M.; Mack, L. L.; Hines, R. L.; Mobley, R. C.; Ferguson, L. D.; Alice, M. B. Molecular Beams of Macroions. J. Chem. Phys. 1968, 49, 2240–2249.CrossRefGoogle Scholar
  5. 5.
    Gamero-Castano, M.; Fernandez de la Mora, J. Direct Measurement of Ion Evaporation Kinetics from Electrified Liquid Surfaces. J. Chem. Phys. 2000, 113, 815–832.CrossRefGoogle Scholar
  6. 6.
    Iribarne, J. V.; Thomson, B. A. On the Evaporation of Small Ions from Charged Droplets. J. Chem. Phys. 1976, 64, 2287–2294.CrossRefGoogle Scholar
  7. 7.
    Hogan, C. J.; Carroll, J. A.; Rohrs, H. W.; Biswas, P.; Gross, M. L. Charge Carrier Field Emission Determines the Number of Charges on Native States Proteins in Electrospray Ionization. J. Am. Chem. Soc. 2008, 130, 6926–6927.CrossRefGoogle Scholar
  8. 8.
    Fernandez de la Mora, J. On the Outcome of the Coulombic Fission of a Charged Isolated Drop. J. Colloid Interface Sci. 1996, 178, 209–218.CrossRefGoogle Scholar
  9. 9.
    Cech, N. B.; Enke, C. G. Effect of Affinity for Droplet Surfaces on the Fraction of Analyte Molecules Charged During Electrospray Droplet Fission. Anal. Chem. 2001, 73, 4632–4639.CrossRefGoogle Scholar
  10. 10.
    Nguyen, S.; Fenn, J. B. Gas-Phase Ions of Solute Species from Charged Droplets of Solutions. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 1111–1117.CrossRefGoogle Scholar
  11. 11.
    Tang, K.; Page, J. S.; Smith, R. D. Charge Competition and the Linear Dynamic Range of Detection in Electrospray Ionization Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2004, 15, 1416–1423.CrossRefGoogle Scholar
  12. 12.
    Cech, N. B.; Enke, C. G. Relating Electrospray Ionization Response to Nonpolar Character of Small Peptides. Anal. Chem. 2000, 72, 2717–2723.CrossRefGoogle Scholar
  13. 13.
    Enke, C. G. A Predictive Model for Matrix and Analyte Effects in Electrospray Ionization of Singly-Charged Ionic Analytes. Anal. Chem. 1997, 69, 4885–4893.CrossRefGoogle Scholar
  14. 14.
    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
  15. 15.
    Bokman, C. F.; Bylund, D.; Markides, K. E.; Sjoberg, P. J. R. Relating Chromatographic Retention and Electrophoretic Mobility to the Ion Distribution Within Electrosprayed Droplets. J. Am. Soc. Mass Spectrom. 2006, 17, 318–324.CrossRefGoogle Scholar
  16. 16.
    Zhou, S.; Cook, K. D. A Mechanistic Study of Electrospray Mass Spectrometry: Charge Gradients within Electrospray Droplets and Their Influence on Ion Response. J. Am. Soc. Mass Spectrom. 2001, 12, 206–214.CrossRefGoogle Scholar
  17. 17.
    Sherman, C. L.; Brodbelt, J. S. Partitioning Model for Competitive Host-Guest Complexation in ESI-MS. Anal. Chem. 2005, 77, 2512–2523.CrossRefGoogle Scholar
  18. 18.
    Haddrell, A. E.; Agnes, G. R. Organic Cation Distributions in the Residues of Levitated Droplets with Net Charge: Validity of the Partition Theory for Droplets Produced by an Electrospray. Anal. Chem. 2004, 76, 53–61.CrossRefGoogle Scholar
  19. 19.
    Felitsyn, N.; Peschke, M.; Kebarle, P. Origin and Number of Charges Observed on Multiply-Protonated Native Proteins Produced by ESI. Int. J. Mass Spectrom. 2002, 219, 39–62.CrossRefGoogle Scholar
  20. 20.
    Fernandez de la Mora, J. Electrospray Ionization of Large Multiply Charged Species Proceeds Via Dole’s Charged Residue Mechanism. Anal. Chim. Acta 2000, 406, 93–104.CrossRefGoogle Scholar
  21. 21.
    Pan, P.; Gunawardena, H. P.; Xia, Y.; McLuckey, S. A. Nanoelectrospray Ionization of Protein Mixtures: Solution pH and Protein pI. Anal. Chem. 2004, 2004, 1165–1174.CrossRefGoogle Scholar
  22. 22.
    Kuprowski, M. C.; Konermann, L. Signal Response of Coexisting Protein Conformers in Electrospray Mass Spectrometry. Anal. Chem. 2007, 79, 2499–2506.CrossRefGoogle Scholar
  23. 23.
    Juraschek, R.; Dulcks, T.; Karas, M. Nanoelectrospray—More than Just a Minimized-Flow Electrospray Ionization Source. J. Am. Soc. Mass Spectrom. 1999, 10, 300–308.CrossRefGoogle Scholar
  24. 24.
    Hogan, C. J.; Biswas, P. Porous Film Deposition by Electrohydrodynamic Atomization of Nanoparticle Sols. Aerosol Sci. Tech. 2008, 42, 75–85.CrossRefGoogle Scholar
  25. 25.
    Hogan, C. J.; Biswas, P. Narrow Size Distribution Nanoparticle Production by Electrospray Processing of Ferritin. J. Aeros. Sci. 2008, 39, 432–440.CrossRefGoogle Scholar
  26. 26.
    Hogan, C. J.; Yun, K.-M.; Chen, D. R.; Lenggoro, I. W.; Biswas, P.; Okuyama, K. Controlled Size: Polymer Particle Production via Electrohydrodynamic Atomization. Colloids Surf. A Physicochem. Eng. Aspects 2007, 311, 67–76.CrossRefGoogle Scholar
  27. 27.
    de Juan, L.; Fernandez de la Mora, J. Charge and Size Distributions of Electrospray Drops. J. Colloid Interface Sci. 1997, 186, 280–293.CrossRefGoogle Scholar
  28. 28.
    Ganan-Calvo, A. M.; Barrero, A. Current and Droplet Size in the Electrospraying of Liquids Scaling Laws. J. Aerosol Sci. 1997, 28, 249–275.CrossRefGoogle Scholar
  29. 29.
    Chen, D. R.; Pui, D. Y. H. Experimental Investigation of Scaling Laws for Electrospraying: Dielectric Constant Effect. Aerosol Sci. Technol. 1997, 27, 367–380.CrossRefGoogle Scholar
  30. 30.
    Hogan, C. J.; Kettleson, E. M.; Ramaswami, B.; Chen, D. R.; Biswas, P. Charge Reduced Electrospray Size Spectrometry of Mega- and Gigadalton Complexes: Whole Viruses and Virus Fragments. Anal. Chem. 2006, 78, 844–852.CrossRefGoogle Scholar
  31. 31.
    Lewis, K. C.; Dohmeier, D. M.; Jorgenson, J. W.; Kaufman, S. L.; Zarrin, F.; Dorman, F. D. Electrospray-Condensation Particle Counter—a Molecule-Counting LC-Detector for Macromolecules. Anal. Chem. 1994, 66, 2285–2292.CrossRefGoogle Scholar
  32. 32.
    Friedlander, S. K. Smoke, Dust, and Haze; Oxford University Press: New York, 2000; 285.Google Scholar
  33. 33.
    Lenggoro, I. W.; Hata, T.; Iskandar, F.; Lunden, M. M.; Okuyama, K. An Experimental and Modeling Investigation of Particle Production by Spray Pyrolysis Using a Laminar Flow Aerosol Reactor. J. Mater. Res. 2000, 15, 733–743.CrossRefGoogle Scholar
  34. 34.
    Principles of Environmental Physics; Monteith, J.; Unsworth, M., 1990.Google Scholar
  35. 35.
    Biophysical Ecology; Gates, D. M., 1980.Google Scholar
  36. 36.
    Kulkarni, P.; Biswas, P. A. Brownian Dynamics Simulation to Predict Morphology of Nanoparticle Deposits in the Presence of Interparticle Interactions. Aerosol Sci. Technol. 2004, 38, 541–554.CrossRefGoogle Scholar
  37. 37.
    Magan, R. V.; Sureshkumar, R. Multiscale-Linking Simulation of Irreversible Colloidal Deposition in the Presence of DLVO Interactions. J. Colloid Interface Sci. 2006, 297, 389–406.CrossRefGoogle Scholar
  38. 38.
    Fundamentals of Fluid Mechanics; Munson, B. R.; Young, D. F.; Okiishi, T. H., 1990.Google Scholar
  39. 39.
    Bacher, G.; Szymanski, W. W.; Kaufman, S. L.; Zollner, P.; Blaas, D.; Allmaier, G. Charge-Reduced Nanoelectrospray Ionization Combined with Differential Mobility Analysis of Peptides, Proteins, Glycoproteins, Noncovalent Protein Complexes, and Viruses. J. Mass Spectrom. 2001, 36, 1038–1052.CrossRefGoogle Scholar
  40. 40.
    Kaddis, C. S.; Lomeli, S. H.; Yin, S.; Berhane, B.; Apostol, M. I.; Kickhoefer, V. A.; Rome, L. H.; Loo, J. A. Sizing Large Proteins and Protein Complexes by Electrospray Ionization Mass Spectrometry and Ion Mobility. J. Am. Soc. Mass Spectrom. 2007, 18, 1206–1216.CrossRefGoogle Scholar
  41. 41.
    Smith, J. N.; Flagan, R. C.; Beauchamp, J. L. Droplet Evaporation and Discharge Dynamics in Electrospray Ionization. J. Phys. Chem. A 2002, 106, 9957–9967.CrossRefGoogle Scholar
  42. 42.
    Li, K. Y.; Tu, H. H.; Ray, A. K. Charge Limits on Droplets During Evaporation. Langmuir 2005, 21, 3786–3794.CrossRefGoogle Scholar
  43. 43.
    Chen, D. R.; Pui, D. Y. H.; Kaufman, S. L. Electrospraying of Conducting Liquids for Monodisperse Aerosol Generation in the 4 nm to 1.8 µm Diameter Range. J. Aerosol Sci. 1995, 26, 963–977.CrossRefGoogle Scholar
  44. 44.
    Gomez, A.; Tang, K. Q. Charge and Fission of Droplets in Electrostatic Sprays. Phys. Fluids 1994, 6, 404–414.CrossRefGoogle Scholar
  45. 45.
    Tang, X.; Bruce, J. E.; Hill, H. H. Characterizing Electrospray Ionization Using Atmospheric Pressure Ion Mobility Spectrometry. Anal. Chem. 2006, 78, 7751–7760.CrossRefGoogle Scholar
  46. 46.
    Scalf, M.; Westphall, M. S.; Smith, L. M. Charge Reduction Electrospray Mass Spectrometry. Anal. Chem. 2000, 72, 52–60.CrossRefGoogle Scholar
  47. 47.
    Pan, P.; McLuckey, S. A. Electrospray Ionization of Protein Mixtures at Low pH. Anal. Chem. 2003, 75, 1491–1499.CrossRefGoogle Scholar
  48. 48.
    Pan, P.; McLuckey, S. A. The Effect of Small Cations on the Positive Electrospray Responses of Proteins at Low pH. Anal. Chem. 2003, 75, 5468–5474.CrossRefGoogle Scholar
  49. 49.
    Nemes, P.; Marginean, I.; Vertes, A. Spraying Mode Effect on Droplet Formation and Ion Chemistry in Electrosprays. Anal. Chem. 2007, 79, 3105–3116.CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2008

Authors and Affiliations

  1. 1.Aerosol and Air Quality Research Laboratory, Department of Energy, Environmental, and Chemical EngineeringWashington University in St. LouisSt. LouisUSA

Personalised recommendations