Skip to main content
SpringerLink
Log in

Negative mode nanostructure-initiator mass spectrometry for detection of phosphorylated metabolites

  • Original Article
  • Published:
Metabolomics Aims and scope Submit manuscript

Abstract

The chemical complexity of the metabolome requires the development of new detection methods to enlarge the range of compounds detectable in a biological sample. Recently, a novel matrix-free laser desorption/ionization method called nanostructure-initiator mass spectrometry (NIMS) [Northen et al., Nature 449(7165):1033–1036, 2007] was reported. Here we investigate NIMS in negative ion mode for the detection of endogenous metabolites, namely small phosphorylated molecules. 3-Aminopropyldimethylethoxysilane was found to be suitable as initiator for the analytes studied and a limit of detection in the tens of femtomoles was reached. The detection of different endogenous cell metabolites in a yeast cell extract is demonstrated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Amantonico, A., Oh, J. Y., Sobek, J., Heinemann, M., & Zenobi, R. (2008). Mass spectrometric method for analyzing metabolites in yeast with single cell sensitivity. Angewandte Chemie International Edition, 47, 5382–5385. doi:10.1002/anie.200705923.

    Article  CAS  Google Scholar 

  • Cohen, L. H., & Gusev, A. I. (2002). Small molecule analysis by MALDI mass spectrometry. Analytical and Bioanalytical Chemistry, 373, 571–586. doi:10.1007/s00216-002-1321-z.

    Article  PubMed  CAS  Google Scholar 

  • Dettmer, K., Aronov, P. A., & Hammock, B. D. (2007). Mass spectrometry-based metabolomics. Mass Spectrometry Reviews, 26, 51–78. doi:10.1002/mas.20108.

    Article  PubMed  CAS  Google Scholar 

  • Dunn, W. B., Bailey, N. J., & Johnson, H. E. (2005). Measuring the metabolome: Current analytical technologies. Analyst (London), 130, 606–625. doi:10.1039/b418288j.

    Article  CAS  Google Scholar 

  • Edwards, J. L., Chisolm, C. N., Shackman, J. G., & Kennedy, R. T. (2006). Negative mode sheathless capillary electrophoresis electrospray ionization-mass spectrometry for metabolite analysis of prokaryotes. Journal of Chromatography A, 1106, 80–88. doi:10.1016/j.chroma.2005.08.082.

    Article  PubMed  CAS  Google Scholar 

  • Edwards, J. L., & Kennedy, R. T. (2005). Metabolomic analysis of eukaryotic tissue and prokaryotes using negative mode MALDI time-of-flight mass spectrometry. Analytical Chemistry, 77, 2201–2209. doi:10.1021/ac048323r.

    Article  PubMed  CAS  Google Scholar 

  • Fiehn, O. (2002). Metabolomics—the link between genotypes and phenotypes. Plant Molecular Biology, 48, 155–171. doi:10.1023/A:1013713905833.

    Article  PubMed  CAS  Google Scholar 

  • Fiehn, O., & Kind, T. (2007). Metabolite profiling in blood plasma. In W. Weckwerth (Ed.), Metabolomics, methods and protocols (pp. 3–18). Totowa, NJ: Humana Press, Inc.

  • Halimaoui, A. (1997). Porous silicon formation by anodisation. In L. Canham (Ed.), Properties of porous silicon (pp. 11–27). London: INSPEC.

    Google Scholar 

  • Hillenkamp, F., & Karas, M. (2007). The MALDI process and method. In F. Hillenkamp & J. Peter-Katalinić (Eds.), MALDI MS: A practical guide to instrumentation, methods and applications (p. 3). Weinheim: WILEY-VCH.

    Google Scholar 

  • Hollywood, K., Brison, D. R., & Goodacre, R. (2006). Metabolomics: Current technologies and future trends. Proteomics, 6, 4716–4723. doi:10.1002/pmic.200600106.

    Article  PubMed  CAS  Google Scholar 

  • Nordstrom, A., Want, E., Northen, T., Lehtio, J., & Siuzdak, G. (2008). Multiple ionization mass spectrometry strategy used to reveal the complexity of metabolomics. Analytical Chemistry, 80, 421–429. doi:10.1021/ac701982e.

    Article  PubMed  Google Scholar 

  • Northen, T. R., Yanes, O., Northen, M. T., Marrinucci, D., Uritboonthai, W., Apon, J., et al. (2007). Clathrate nanostructures for mass spectrometry. Nature, 449, 1033–1036. doi:10.1038/nature06195.

    Article  PubMed  CAS  Google Scholar 

  • Peterson, D. S. (2007). Matrix-free methods for laser desorption/ionization mass spectrometry. Mass Spectrometry Reviews, 26, 19–34. doi:10.1002/mas.20104.

    Article  PubMed  CAS  Google Scholar 

  • Shrestha, B., Li, Y., & Vertes, A. (2008). Rapid analysis of pharmaceuticals and excreted xenobiotic and endogenous metabolites with atmospheric pressure infrared MALDI mass spectrometry. Metabolomics, 4, 297–311. doi:10.1007/s11306-008-0120-8.

    Article  CAS  Google Scholar 

  • Soga, T., Ueno, Y., Naraoka, H., Ohashi, Y., Tomita, M., & Nishioka, T. (2002). Simultaneous determination of anionic intermediates for Bacillus subtilis metabolic pathways by capillary electrophoresis electrospray ionization mass spectrometry. Analytical Chemistry, 74, 2233–2239. doi:10.1021/ac020064n.

    Article  PubMed  CAS  Google Scholar 

  • Sun, G., Yang, K., Zhao, Z. D., Guan, S. P., Han, X. L., & Gross, R. W. (2007). Shotgun metabolomics approach for the analysis of negatively charged water-soluble cellular metabolites from mouse heart tissue. Analytical Chemistry, 79, 6629–6640. doi:10.1021/ac070843+.

    Article  PubMed  CAS  Google Scholar 

  • Tomita, M., & Nishioka, T. (2005). Metabolomics: The frontier of systems biology. Tokyo: Springer-Verlag.

    Google Scholar 

  • Trauger, S. A., Go, E. P., Shen, Z. X., Apon, J. V., Compton, B. J., Bouvier, E. S. P., et al. (2004). High sensitivity and analyte capture with desorption/ionization mass spectrometry on silylated porous silicon. Analytical Chemistry, 76, 4484–4489. doi:10.1021/ac049657j.

    Article  PubMed  CAS  Google Scholar 

  • Vaidyanathan, S., Jones, D., Ellis, J., Jenkins, T., Chong, C., Anderson, M., et al. (2007). Laser desorption/ionization mass spectrometry on porous silicon for metabolome analyses: Influence of surface oxidation. Rapid Communications in Mass Spectrometry, 21, 2157–2166. doi:10.1002/rcm.3078.

    Article  PubMed  CAS  Google Scholar 

  • Villas-Boas, S. G., Mas, S., Akesson, M., Smedsgaard, J., & Nielsen, J. (2005). Mass spectrometry in metabolome analysis. Mass Spectrometry Reviews, 24, 613–646. doi:10.1002/mas.20032.

    Article  PubMed  CAS  Google Scholar 

  • Weckwerth, W. (2003). Metabolomics in systems biology. Annual Review of Plant Biology, 54, 669–689. doi:10.1146/annurev.arplant.54.031902.135014.

    Article  PubMed  CAS  Google Scholar 

  • Wei, J., Buriak, J. M., & Siuzdak, G. (1999). Desorption–ionization mass spectrometry on porous silicon. Nature, 399, 243–246. doi:10.1038/20400.

    Article  PubMed  CAS  Google Scholar 

  • Woo, H. K., Northen, T. R., Yanes, O., & Siuzdak, G. (2008). Nanostructure-initiator mass spectrometry: A protocol for preparing and applying NIMS surfaces for high-sensitivity mass analysis. Nature Protocols, 3, 1341–1349. doi:10.1038/nprot.2008.110.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Jennifer Ewald, Benjamin Volkmer and Dr. Matthias Heinemann from the Institute of Molecular System Biology for the yeast cultivation, metabolism quenching, and metabolites extraction. We also thank Dr. Frank Krumeich for the SEM measurements. This work was supported by the ETH-INIT “Single cell metabolomics” project.

Author information

Authors and Affiliations

  1. Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093, Zurich, Switzerland

    Andrea Amantonico, Luca Flamigni, Reto Glaus & Renato Zenobi

Authors
  1. Andrea Amantonico
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luca Flamigni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reto Glaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Renato Zenobi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Renato Zenobi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amantonico, A., Flamigni, L., Glaus, R. et al. Negative mode nanostructure-initiator mass spectrometry for detection of phosphorylated metabolites. Metabolomics 5, 346–353 (2009). https://doi.org/10.1007/s11306-009-0163-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11306-009-0163-5

Keywords

Search

Navigation