Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Rapid characterization of complex viscous samples at molecular levels by neutral desorption extractive electrospray ionization mass spectrometry

Abstract

In this protocol, the sample (which could be a bulk or heterogeneous fluid, or a greasy surface) is treated with a neutral desorption (ND) sampling gas beam, and the resulting analyte mixtures are directly characterized by extractive electrospray ionization mass spectrometry (EESI-MS). The ND device can be specifically constructed such that the sampling gas beam is bubbled through the liquid sample (microjet sampling) or directed to impact the sample surface (e.g., for the analysis of a material like cheese). The ND-EESI-MS analysis process requires no sample pretreatment because it can tolerate an extremely complex matrix. ND-EESI-MS allows real-time, online chemical profiling of highly viscous samples under ambient conditions. Both volatile and nonvolatile analytes from viscous samples can easily be detected and quantified by ND-EESI-MS, thereby providing an MS-based analytical platform for multiple disciplines (e.g., for the food industry, for drug discovery, and for the biological and life sciences). Here we describe the ND-EESI-MS protocol for viscous sample analysis, including the experimental design, equipment setup, reagent preparation, data acquisition and analysis steps. The data collection process takes <1 min per sample, although the time required for the whole procedure, which largely depends on the experimental preparation processes, might be considerably longer.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Schematic diagrams of seven types of ND sampling devices.
Figure 2: The viscosity spectrum, in which the viscosities of various viscous samples (20 °C, atmospheric pressure) are presented.
Figure 3: Schematic diagram of EESI-MS combined with a simplified open-air ND sampling device for the analysis of perfume samples.
Figure 4: Schematic diagram of EESI-MS combined with a typical sealable ND sampling device for the analysis of toothpaste samples.
Figure 5: Schematic diagram of EESI-MS combined with a microjet ND sampling device for the analysis of low- and medium-viscosity liquid samples.
Figure 6: Schematic diagram of EESI-MS combined with a GIND sampling device.
Figure 7: Mass spectra of three different perfume products recorded by EESI-MS combined with a simplified ND sampling device.
Figure 8: Mass spectra of four types of edible oils recorded by EESI-MS combined with a microjet ND sampling device.
Figure 9: Mass spectra of two different grades of honey recorded by EESI-MS combined with a microjet ND sampling device.
Figure 10: Mass spectra of four types of cheese products (Emmentaler, Gruyère, Saint Paulin and Tilsiter) recorded by EESI-MS combined with a sealable ND sampling device.
Figure 11: Mass spectra for fructose dehydration reaction.
Figure 12: MS/MS spectrum of DEP in perfume samples analyzed by ND-EESI-MS.
Figure 13: MS/MS and MS/MS/MS spectra of DEG in toothpaste samples analyzed by ND-EESI-MS.
Figure 14: Quantification of DEP in 'le Male' perfume using the standard addition method.
Figure 15: Quantification of DEG in toothpaste using the standard addition method.

References

  1. Cooks, R.G., Ouyang, Z., Takats, Z. & Wiseman, J.M. Ambient mass spectrometry. Science 311, 1566–1570 (2006).

    CAS  Article  Google Scholar 

  2. Reed, R.I. Ion Production by Electron Impact (Academic Press, 1962).

  3. Munson, M.S.B. & Field, F.H. Chemical ionization mass spectrometry. I. General introduction. J. Am. Chem. Soc. 88, 2621–2630 (1966).

    CAS  Article  Google Scholar 

  4. Yamashita, M. & Fenn, J.B. Electrospray ion source: another variation on the free-jet theme. J. Phys. Chem. 88, 4451–4459 (1984).

    CAS  Article  Google Scholar 

  5. Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F. & Whitehouse, C.M. Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64–71 (1989).

    CAS  Article  Google Scholar 

  6. Garcia, D.M., Huang, S.K. & Stansbury, W.F. Optimization of the atmospheric pressure chemical ionization liquid chromatography mass spectrometry interface. J. Am. Soc. Mass Spectrom. 7, 59–65 (1996).

    CAS  Article  Google Scholar 

  7. Smith, C.J. et al. Determination of selected monohydroxy metabolites of 2-, 3- and 4-ring polycyclic aromatic hydrocarbons in urine by solid-phase microextraction and isotope dilution gas chromatography-mass spectrometry. J. Chromatogr. B 778, 157–164 (2002).

    CAS  Article  Google Scholar 

  8. de la Cal, A ., Eljarrat, E. & Barceló, D. Determination of 39 polybrominated diphenyl ether congeners in sediment samples using fast selective pressurized liquid extraction and purification. J. Chromatogr. A 1021, 165–173 (2003).

    CAS  Article  Google Scholar 

  9. Galceran, M.T. & Moyano, E. Determination of hydroxy polycyclic aromatic hydrocarbons by liquid chromatography-mass spectrometry comparison of atmospheric pressure chemical ionization and electrospray. J. Chromatogr. A. 731, 75–84 (1996).

    CAS  Article  Google Scholar 

  10. Van-de-Wiele, T.R., Peru, K.M., Verstraete, W., Siciliano, S.D. & Headley, J.V. Liquid chromatography-mass spectrometry analysis of hydroxylated polycyclic aromatic hydrocarbons, formed in a simulator of the human gastrointestinal tract. J. Chromatogr. B. 806, 245–253 (2004).

    CAS  Article  Google Scholar 

  11. Xu, X., Zhang, J.F., Zhang, L., Liu, W.L. & Weisel, C.P. Selective detection of monohydroxy metabolites of polycyclic aromatic hydrocarbons in urine using liquid chromatography/triple quadrupole tandem mass spectrometry. Rapid Commun. Mass Spectrom. 18, 2299–2308 (2004).

    CAS  Article  Google Scholar 

  12. Takats, Z., Wiseman, J.M., Gologan, B. & Cooks, R.G. Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306, 471–473 (2004).

    CAS  Article  Google Scholar 

  13. Ifa, D.R., Manicke, N.E., Rusine, A.L. & Cooks, R.G. Quantitative analysis of small molecules by desorption electrospray ionization mass spectrometry from polytetrafluoroethylene surfaces. Rapid Commun. Mass Spectrom. 22, 503–510 (2008).

    CAS  Article  Google Scholar 

  14. Shin, Y.S., Drolet, B., Mayer, R., Dolence, K. & Basile, F. Desorption electrospray ionization-mass spectrometry of proteins. Anal. Chem. 79, 3514–3518 (2007).

    CAS  Article  Google Scholar 

  15. Cody, R.B., Laramée, J.A. & Durst, H.D. Versatile new ion source for the analysis of materials in open air under ambient conditions. Anal. Chem. 77, 2297–2302 (2005).

    CAS  Article  Google Scholar 

  16. Haefliger, O.P. & Jeckelmann, N. Direct mass spectrometric analysis of flavors and fragrances in real applications using DART. Rapid Commun. Mass Spectrom. 21, 1361–1366 (2007).

    CAS  Article  Google Scholar 

  17. Nemes, P. & Vertes, A. Laser ablation electrospray ionization for atmospheric pressure, in vivo, and imaging mass spectrometry. Anal. Chem. 79, 8098–8106 (2007).

    CAS  Article  Google Scholar 

  18. Nemes, P., Barton, A.A. & Vertes, A. Three-dimensional imaging of metabolites in tissues under ambient conditions by laser ablation electrospray ionization mass spectrometry. Anal. Chem. 81, 6668–6675 (2009).

    CAS  Article  Google Scholar 

  19. Shrestha, B. & Vertes, A. In situ metabolic profiling of single cells by laser ablation electrospray ionization mass spectrometry. Anal. Chem. 81, 8265–8271 (2009).

    CAS  Article  Google Scholar 

  20. Na, N., Zhao, M.X., Zhang, S.C., Yang, C.D. & Zhang, X.R. Development of a dielectric barrier discharge ion source for ambient mass spectrometry. J. Am. Soc. Mass Spectrom. 18, 1859–1862 (2007).

    CAS  Article  Google Scholar 

  21. Chen, H.W. et al. Surface desorption atmospheric pressure chemical ionization mass spectrometry for direct ambient sample analysis without toxic chemical contamination. J. Mass Spectrom. 42, 1045–1056 (2007).

    CAS  Article  Google Scholar 

  22. Yang, S.P. et al. Detection of melamine in milk products by surface desorption atmospheric pressure chemical ionization mass spectrometry. Anal. Chem. 81, 2426–2436 (2009).

    CAS  Article  Google Scholar 

  23. McEwen, C.N., McKay, R.G. & Larsen, B.S. Analysis of solids, liquids, and biological tissues using solids probe introduction at atmospheric pressure on commercial LC/MS instruments. Anal. Chem. 77, 7826–7831 (2005).

    CAS  Article  Google Scholar 

  24. Harper, J.D. et al. Low-temperature plasma probe for ambient desorption ionization. Anal. Chem. 80, 9097–9104 (2008).

    CAS  Article  Google Scholar 

  25. Huang, G.M., Ouyang, Z. & Cooks, R.G. High-throughput trace melamine analysis in complex mixtures. Chem. Commun. 2009, 556–558 (2009).

    Article  Google Scholar 

  26. Huang, M.Z. et al. Characterization of the chemical components on the surface of different solids with electrospray-assisted laser desorption ionization mass spectrometry. Rapid Commun. Mass Spectrom. 21, 1767–1775 (2007).

    CAS  Article  Google Scholar 

  27. Lin, S.Y., Huang, M.Z., Chang, H.C. & Shiea, J. Using electrospray-assisted laser desorption/ionization mass spectrometry to characterize organic compounds separated on thin-layer chromatography plates. Anal. Chem. 79, 8789–8795 (2007).

    CAS  Article  Google Scholar 

  28. Shiea, J. et al. Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids. Rapid Commun. Mass Spectrom. 19, 3701–3704 (2005).

    CAS  Article  Google Scholar 

  29. Andrade, F.J. et al. Atmospheric pressure chemical ionization source. 1. Ionization of compounds in the gas phase. Anal. Chem. 80, 2646–2653 (2008).

    CAS  Article  Google Scholar 

  30. Haapala, M. et al. Desorption atmospheric pressure photoionization. Anal. Chem. 79, 7867–7872 (2007).

    CAS  Article  Google Scholar 

  31. Huang, G.M., Chen, H., Zhang, X.R., Cooks, R.G. & Ouyang, Z. Rapid screening of anabolic steroids in urine by reactive desorption electrospray ionization. Anal. Chem. 79, 8327–8332 (2007).

    CAS  Article  Google Scholar 

  32. Chen, H.W., Hu, B. & Zhang, X. Principle and application of ambient mass spectrometry for direct analysis of complex samples. Chinese J. Anal. Chem. 38, 1069–1088 (2010).

    CAS  Article  Google Scholar 

  33. Fuerstenau, S., Kiselev, P. & Fenn, J.B. in Proceedings of the 47th ASMS Conference on Mass Spectrometry and Allied Topics (Dallas, Texas, USA 1999).

  34. Wu, C., Siems, W.F. & Hill, H.H.J. Secondary electrospray ionization ion mobility spectrometry/mass spectrometry of illicit drugs. Anal. Chem. 72, 396–403 (2000).

    CAS  Article  Google Scholar 

  35. Shieh, I.F., Lee, C.Y. & Shiea, J. Eliminating the interferences from TRIS buffer and SDS in protein analysis by fused-droplet electrospray ionization mass spectrometry. J. Proteome Res. 4, 606–612 (2005).

    CAS  Article  Google Scholar 

  36. Chen, H.W., Venter, A. & Cooks, R.G. Extractive electrospray ionization for direct analysis of undiluted urine, milk and other complex mixtures without sample preparation. Chem. Commun. 2006, 2042–2044 (2006).

    Article  Google Scholar 

  37. Law, W.S. et al. On the mechanism of extractive electrospray ionization. Anal. Chem. 82, 4494–4500 (2010).

    CAS  Article  Google Scholar 

  38. Venter, A., Sojka, P.E. & Cooks, R.G. Droplet dynamics and ionization mechanisms in desorption electrospray ionization mass spectrometry. Anal. Chem. 78, 8549–8555 (2006).

    CAS  Article  Google Scholar 

  39. Zhou, Z.Q. et al. Rapid detection of atrazine and its metabolite in raw urine by extractive electrospray ionization mass spectrometry. Metabolomics 3, 101–104 (2007).

    CAS  Article  Google Scholar 

  40. Chingin, K., Gamez, G., Chen, H.W., Zhu, L. & Zenobi, R. Rapid classification of perfumes by extractive electrospray ionization mass spectrometry (EESI-MS). Rapid Commun. Mass Spectrom. 22, 2009–2014 (2008).

    CAS  Article  Google Scholar 

  41. Chen, H.W., Wortmann, A., Zhang, W.H. & Zenobi, R. Rapid in vivo fingerprinting of nonvolatile compounds in breath by extractive electrospray ionization quadrupole time-of-flight mass spectrometry. Angew. Chem. Int. Ed. 46, 580–583 (2007).

    CAS  Article  Google Scholar 

  42. Ding, J. et al. Development of extractive electrospray ionization ion trap mass spectrometry for in vivo breath analysis. Analyst 134, 2040–2050 (2009).

    CAS  Article  Google Scholar 

  43. Chingin, K., Chen, H.W., Gamez, G., Zhu, L. & Zenobi, R. Detection of diethyl phthalate in perfumes by extractive electrospray ionization mass spectrometry. Anal. Chem. 81, 123–129 (2009).

    CAS  Article  Google Scholar 

  44. Zhu, L. et al. Real-time, on-line monitoring of organic chemical reactions using extractive electrospray ionization tandem mass spectrometry. Rapid Commun. Mass Spectrom. 22, 2993–2998 (2008).

    CAS  Article  Google Scholar 

  45. Law, W.S. et al. Rapid characterization of complex viscous liquids at the molecular level. Angew. Chem. Int. Ed. 48, 8277–8280 (2009).

    CAS  Article  Google Scholar 

  46. Ding, J.H. et al. Selective detection of diethylene glycol in toothpaste products using neutral desorption reactive extractive electrospray ionization tandem mass spectrometry. Anal. Chem. 81, 8632–8638 (2009).

    CAS  Article  Google Scholar 

  47. Zhu, L. et al. Simultaneous sampling of volatile and nonvolatile analytes in beer for fast fingerprinting by extractive electrospray ionization mass spectrometry. Anal. Bioanal. Chem. 398, 405–413 (2010).

    CAS  Article  Google Scholar 

  48. Law, W.S. et al. Rapid fingerprinting and classification of extra virgin olive oil by microjet sampling and extractive electrospray ionization mass spectrometry. Analyst 135, 773–778 (2010).

    CAS  Article  Google Scholar 

  49. Wu, Z.C. et al. Sampling analytes from cheese products for fast detection using neutral desorption extractive electrospray ionization mass spectrometry. Anal. Bioanal. Chem. 397, 1549–1556 (2010).

    CAS  Article  Google Scholar 

  50. Weston, D.J. Ambient ionization mass spectrometry: current understanding of mechanistic theory; analytical performance and application areas. Analyst 135, 661–668 (2010).

    CAS  Article  Google Scholar 

  51. Chen, H.W., Wortmann, A. & Zenobi, R. Neutral desorption sampling coupled to extractive electrospray ionization mass spectrometry for rapid differentiation of biosamples by metabolomic fingerprinting. J. Mass Spectrom. 42, 1123–1135 (2007).

    CAS  Article  Google Scholar 

  52. Chen, H.W., Yang, S.P., Wortmann, A. & Zenobi, R. Neutral desorption sampling of living objects for rapid analysis by extractive electrospray ionization mass spectrometry. Angew. Chem. Int. Ed 46, 7591–7594 (2007).

    CAS  Article  Google Scholar 

  53. Chen, H.W. & Zenobi, R. Neutral desorption sampling of biological surfaces for rapid chemical characterization by extractive electrospray ionization mass spectrometry. Nat. Protoc. 3, 1467–1475 (2008).

    CAS  Article  Google Scholar 

  54. Chen, H.W. et al. Neutral desorption using a sealed enclosure to sample explosives on human skin for rapid detection by EESI-MS. J. Am. Soc. Mass Spectrom. 20, 719–722 (2009).

    CAS  Article  Google Scholar 

  55. Chen, H.W. et al. Manipulation of charge states of biopolymer ions by atmospheric pressure ion/molecule reactions implemented in an extractive electrosprau ionization source. Eur. J. Mass Spectrom. 13, 273–279 (2007).

    Article  Google Scholar 

  56. Chen, H.W. et al. Sensitive detection of native proteins using extractive electrospray ionization mass spectrometry. Angew. Chem. Int. Ed. 49, 3053–3056 (2010).

    CAS  Article  Google Scholar 

  57. Gu, H.W. et al. Geometry-independent neutral desorption device for the sensitive EESI-MS detection of explosives on various surfaces. Analyst 135, 779–788 (2010).

    CAS  Article  Google Scholar 

  58. Chen, H.W., Sun, Y.P., Wortmann, A., Gu, H.W. & Zenobi, R. Differentiation of maturity and quality of fruit using noninvasive extractive electrospray ionization quadrupole time-of-flight mass spectrometry. Anal. Chem. 79, 1447–1455 (2007).

    CAS  Article  Google Scholar 

  59. Zhao, H.B., Holladay, J.E., Brown, H. & Zhang, Z.C. Metal chlorides in ionic liquid solvents convert sugars to 5-hydroxymethylfurfural. Science 316, 1597–1600 (2007).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We acknowledge the valuable help from R. Zenobi, W. Law, S. Yang, L. Zhu and Z. Hu in performing some of the EESI experiments shown here. We also acknowledge financial support from the Innovation Method Fund (no. 2008IM040400) and grants from MOST of China (nos. 2009DFA30800 and 2009DFA41880).

Author information

Authors and Affiliations

Authors

Contributions

X.L. prepared the manuscript, discussed its implications and commented on the manuscript at all stages; B.H. was involved in most of the experiments; J.D. performed the experiment of selective detection of diethylene glycol in toothpaste products; H.C. conceived the concept, designed all the experiments, outlined the protocol and revised the manuscript.

Corresponding author

Correspondence to Huanwen Chen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Li, X., Hu, B., Ding, J. et al. Rapid characterization of complex viscous samples at molecular levels by neutral desorption extractive electrospray ionization mass spectrometry. Nat Protoc 6, 1010–1025 (2011). https://doi.org/10.1038/nprot.2011.337

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nprot.2011.337

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing