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Metabolite Profiling by Direct Analysis in Real-Time Mass Spectrometry

  • Christina M. Jones
  • María Eugenia Monge
  • Facundo M. Fernández
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1198)

Abstract

Untargeted metabolite profiling is a discovery tool for the identification of metabolites associated with the responses of perturbations to biological systems, such as a disease. Direct analysis in real-time mass spectrometry (DART MS) promises to be a powerful analytical technique for high-throughput metabolome analysis of human blood sera. Here, we describe the steps involved in untargeted blood sera metabolic profiling experiments using DART MS with two different sample introduction methods: probe-mode and transmission-mode geometries. Information regarding the optimization of different DART parameters that directly affect metabolite desorption and ionization, which thus influence sensitivity, is included.

Key words

Direct analysis in real time Metabolite profiling Serum metabolomics Transmission-mode DART Probe-mode DART Ambient mass spectrometry 

Notes

Acknowledgements

The authors acknowledge support from NSF grant CHE-0645094 and an OCRF Program Project Development grant. The authors also thank IonSense, Inc. for useful guidance on initial TM-DART experiments.

References

  1. 1.
    Nicholson JK, Lindon JC (2008) Systems biology – metabonomics. Nature 455: 1054–1056PubMedCrossRefGoogle Scholar
  2. 2.
    Dettmer K, Aronov PA, Hammock BD (2007) Mass spectrometry-based metabolomics. Mass Spectrom Rev 26:51–78PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Moco S, Bino RJ, De Vos RCH, Vervoort J (2007) Metabolomics technologies and metabolite identification. Trends Anal Chem 26:855–866CrossRefGoogle Scholar
  4. 4.
    Dunn W, Erban A, Weber RM, Creek D, Brown M, Breitling R, Hankemeier T, Goodacre R, Neumann S, Kopka J, Viant M (2013) Mass appeal: metabolite identification in mass spectrometry-focused untargeted metabolomics. Metabolomics 9:44–66CrossRefGoogle Scholar
  5. 5.
    Harris GA, Galhena AS, Fernandez FM (2011) Ambient sampling/ionization mass spectrometry: applications and current trends. Anal Chem 83:4508–4538PubMedCrossRefGoogle Scholar
  6. 6.
    Monge ME, Harris GA, Dwivedi P, Fernández FM (2013) Mass spectrometry: recent advances in direct open air surface sampling/ionization. Chem Rev 113(4):2269–2308. doi: 10.1021/cr300309q PubMedCrossRefGoogle Scholar
  7. 7.
    Takats Z, Wiseman JM, Gologan B, Cooks RG (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306:471–473PubMedCrossRefGoogle Scholar
  8. 8.
    Cody RB, Laramee JA, Durst HD (2005) Versatile new ion source for the analysis of materials in open air under ambient conditions. Anal Chem 77:2297–2302PubMedCrossRefGoogle Scholar
  9. 9.
    Cajka T, Riddellova K, Tomaniova M, Hajslova J (2011) Ambient mass spectrometry employing a DART ion source for metabolomic fingerprinting/profiling: a powerful tool for beer origin recognition. Metabolomics 7: 500–508CrossRefGoogle Scholar
  10. 10.
    Dove ADM, Leisen J, Zhou MS, Byrne JJ, Lim-Hing K, Webb HD, Gelbaum L, Viant MR, Kubanek J, Fernandez FM (2012) Biomarkers of whale shark health: a metabolomic approach. PLoS One 7:e49379PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Gu H, Pan Z, Xi B, Asiago V, Musselman B, Raftery D (2011) Principal component directed partial least squares analysis for combining nuclear magnetic resonance and mass spectrometry data in metabolomics: application to the detection of breast cancer. Anal Chim Acta 686:57–63PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Jones C, Fernandez FM (2013) Transmission mode direct analysis in real time mass spectrometry for fast untargeted metabolic fingerprinting. Rapid Commun Mass Spectrom 27(12):1311–1318PubMedCrossRefGoogle Scholar
  13. 13.
    Kim SW, Kim HJ, Kim JH, Kwon YK, Ahn MS, Jang YP, Liu JR (2011) A rapid, simple method for the genetic discrimination of intact Arabidopsis thaliana mutant seeds using metabolic profiling by direct analysis in real-time mass spectrometry. Plant Methods 7:14PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Zhou M, Guan W, Walker LD, Mezencev R, Benigno BB, Gray A, Fernandez FM, McDonald JF (2010) Rapid mass spectrometric metabolic profiling of blood sera detects ovarian cancer with high accuracy. Cancer Epidemiol Biomarkers Prev 19:2262–2271PubMedCrossRefGoogle Scholar
  15. 15.
    Zhou M, McDonald JF, Fernandez FM (2010) Optimization of a direct analysis in real time/time-of-flight mass spectrometry method for rapid serum metabolomic fingerprinting. J Am Soc Mass Spectrom 21:68–75PubMedCrossRefGoogle Scholar
  16. 16.
    Dunn WB, Broadhurst D, Begley P, Zelena E, Francis-McIntyre S, Anderson N, Brown M, Knowles JD, Halsall A, Haselden JN, Nicholls AW, Wilson ID, Kell DB, Goodacre R, Human Serum Metabolome Consortium (2011) Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc 6:1060–1083PubMedCrossRefGoogle Scholar
  17. 17.
    Draper J, Lloyd A, Goodacre R, Beckmann M (2013) Flow infusion electrospray ionisation mass spectrometry for high throughput, non-targeted metabolite fingerprinting: a review. Metabolomics 9:4–29CrossRefGoogle Scholar
  18. 18.
    Aharoni A, Ric de Vos CH, Verhoeven HA, Maliepaard CA, Kruppa G, Bino R, Goodenowe DB (2002) Nontargeted metabolome analysis by use of Fourier transform ion cyclotron mass spectrometry. OMICS 6: 217–234PubMedCrossRefGoogle Scholar
  19. 19.
    Nyadong L, Galhena AS, Fernandez FM (2009) Desorption electrospray/metastable-induced ionization: a flexible multimode ambient ion generation technique. Anal Chem 81:7788–7794PubMedCrossRefGoogle Scholar
  20. 20.
    Harris GA, Falcone CE, Fernandez FM (2012) Sensitivity “hot spots” in the direct analysis in real time mass spectrometry of nerve agent simulants. J Am Soc Mass Spectrom 23:153–161PubMedCrossRefGoogle Scholar
  21. 21.
    Edison SE, Lin LA, Gamble BM, Wong J, Zhang K (2011) Surface swabbing technique for the rapid screening for pesticides using ambient pressure desorption ionization with high-resolution mass spectrometry. Rapid Commun Mass Spectrom 25:127–139PubMedCrossRefGoogle Scholar
  22. 22.
    Chernetsova ES, Bromirski M, Scheibner O, Morlock GE (2012) DART-Orbitrap MS: a novel mass spectrometric approach for the identification of phenolic compounds in propolis. Anal Bioanal Chem 403:2859–2867PubMedCrossRefGoogle Scholar
  23. 23.
    Crawford E, Musselman B (2012) Evaluating a direct swabbing method for screening pesticides on fruit and vegetable surfaces using direct analysis in real time (DART) coupled to an Exactive benchtop orbitrap mass spectrometer. Anal Bioanal Chem 403:2807–2812PubMedCrossRefGoogle Scholar
  24. 24.
    Cajka T, Riddellova K, Zomer P, Mol H, Hajslova J (2011) Direct analysis of dithiocarbamate fungicides in fruit by ambient mass spectrometry. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 28:1372–1382PubMedCrossRefGoogle Scholar
  25. 25.
    Self RL, Wu W-H (2012) Rapid qualitative analysis of phthalates added to food and nutraceutical products by direct analysis in real time/orbitrap mass spectrometry. Food Control 25:13–16CrossRefGoogle Scholar
  26. 26.
    Chernetsova ES, Crawford EA, Shikov AN, Pozharitskaya ON, Makarov VG, Morlock GE (2012) ID-CUBE direct analysis in real time high-resolution mass spectrometry and its capabilities in the identification of phenolic components from the green leaves of Bergenia crassifolia L. Rapid Commun Mass Spectrom 26:1329–1337PubMedCrossRefGoogle Scholar
  27. 27.
    Rummel JL, McKenna AM, Marshall AG, Eyler JR, Powell DH (2010) The coupling of direct analysis in real time ionization to Fourier transform ion cyclotron resonance mass spectrometry for ultrahigh-resolution mass analysis. Rapid Commun Mass Spectrom 24:784–790PubMedCrossRefGoogle Scholar
  28. 28.
    Yu S, Crawford E, Tice J, Musselman B, Wu JT (2009) Bioanalysis without sample cleanup or chromatography: the evaluation and initial implementation of direct analysis in real time ionization mass spectrometry for the quantification of drugs in biological matrixes. Anal Chem 81:193–202PubMedCrossRefGoogle Scholar
  29. 29.
    Harris GA, Fernandez FM (2009) Simulations and experimental investigation of atmospheric transport in an ambient metastable-induced chemical ionization source. Anal Chem 81: 322–329PubMedCrossRefGoogle Scholar
  30. 30.
    Perez JJ, Harris GA, Chipuk JE, Brodbelt JS, Green MD, Hampton CY, Fernandez FM (2010) Transmission-mode direct analysis in real time and desorption electrospray ionization mass spectrometry of insecticide-treated bednets for malaria control. Analyst 135: 712–719PubMedCrossRefGoogle Scholar
  31. 31.
    Harris GA, Kwasnik M, Fernández FM (2011) Direct analysis in real time coupled to multiplexed drift tube ion mobility spectrometry for detecting toxic chemicals. Anal Chem 83: 1908–1915PubMedCrossRefGoogle Scholar
  32. 32.
    Gu HW, Hu B, Li JQ, Yang SP, Han J, Chen HW (2010) Rapid analysis of aerosol drugs using nano extractive electrospray ionization tandem mass spectrometry. Analyst 135: 1259–1267PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Christina M. Jones
    • 1
  • María Eugenia Monge
    • 1
  • Facundo M. Fernández
    • 1
  1. 1.School of Chemistry and BiochemistryGeorgia Institute of TechnologyAtlantaUSA

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