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.

  • Article
  • Published:

The rational design of nitric oxide selectivity in single-walled carbon nanotube near-infrared fluorescence sensors for biological detection

Abstract

A major challenge in the synthesis of nanotube or nanowire sensors is to impart selective analyte binding through means other than covalent linkages, which compromise electronic and optical properties. We synthesized a 3,4-diaminophenyl-functionalized dextran (DAP-dex) wrapping for single-walled carbon nanotubes (SWNTs) that imparts rapid and selective fluorescence detection of nitric oxide (NO), a messenger for biological signalling. The near-infrared (nIR) fluorescence of SWNTDAP-dex is immediately and directly bleached by NO, but not by other reactive nitrogen and oxygen species. This bleaching is reversible and shown to be caused by electron transfer from the top of the valence band of the SWNT to the lowest unoccupied molecular orbital of NO. The resulting optical sensor is capable of real-time and spatially resolved detection of NO produced by stimulating NO synthase in macrophage cells. We also demonstrate the potential of the optical sensor for in vivo detection of NO in a mouse model.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic illustration for NO detection using SWNT–polymer hybrid.
Figure 2: nIR fluorescence response of SWNTDAP-dex hybrid (6) to NO.
Figure 3: Selectivity, sensitivity and bleaching rate of SWNTDAP-dex hybrid (6) for NO.
Figure 4: Spectroscopic analysis for the fluorescence bleaching mechanism of the SWNTDAP-dex hybrid by NO.
Figure 5: Biological NO detection using SWNTDAP-dex hybrid.

Similar content being viewed by others

References

  1. Moncada, S., Palmer, R. M. J. & Higgs, E. A. Nitric-oxide – physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43, 109–142 (1991).

    CAS  PubMed  Google Scholar 

  2. Bredt, D. S. & Snyder, S. H. Nitric oxide – a physiological messenger molecule. Ann. Rev. Biochem. 63, 175–195 (1994).

    Article  CAS  Google Scholar 

  3. Murad, F. Discovery of some of the biological effects of nitric oxide and its role in cell signaling (Nobel lecture). Angew. Chem. Int. Ed. 38, 1857–1868 (1999).

    Article  Google Scholar 

  4. Furchgott, R. F. Endothelium-derived relaxing factor: discovery, early studies, and identification as nitric oxide (Nobel lecture). Angew. Chem. Int. Ed. 38, 1870–1880 (1999).

    Article  CAS  Google Scholar 

  5. Ignarro, L. J. Nitric oxide: a unique endogenous signaling molecule in vascular biology (Nobel lecture). Angew. Chem. Int. Ed. 38, 1882–1892 (1999).

    Article  CAS  Google Scholar 

  6. Nagano, T. & Yoshimura, T. Bioimaging of nitric oxide. Chem. Rev. 102, 1235–1269 (2002).

    Article  CAS  Google Scholar 

  7. Kojima, H. et al. Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins. Anal. Chem. 70, 2446–2453 (1998).

    Article  CAS  Google Scholar 

  8. Sasaki, E. et al. Highly sensitive near-infrared fluorescent probes for nitric oxide and their application to isolated organs. J. Am. Chem. Soc. 127, 3684–3685 (2005).

    Article  CAS  Google Scholar 

  9. Lim, M. H., Xu, D. & Lippard, S. J. Visualization of nitric oxide in living cells by a copper-based fluorescent probe. Nature Chem. Biol. 2, 375–380 (2006).

    Article  CAS  Google Scholar 

  10. Lim, M. H. & Lippard, S. J. Metal-based turn-on fluorescent probes for sensing nitric oxide. Acc. Chem. Res. 40, 41–51 (2007).

    Article  CAS  Google Scholar 

  11. Robinson, J. K., Bollinger, M. J. & Birks, J. W. Luminol/H2O2 chemiluminescence detector for the analysis of nitric oxide in exhaled breath. Anal. Chem. 71, 5131–5136 (1999).

    Article  CAS  Google Scholar 

  12. Dubey, M., Bernasek, S. L. & Schwartz, J. Highly sensitive nitric oxide detection using X-ray photoelectron spectroscopy. J. Am. Chem. Soc. 129, 6980–6981 (2007).

    Article  CAS  Google Scholar 

  13. Barone, P. W., Baik, S., Heller, D. A. & Strano, M. S. Near-infrared optical sensors based on single-walled carbon nanotubes. Nature Mater. 4, 86–92 (2005).

    Article  CAS  Google Scholar 

  14. Barone, P. W., Parker, R. S. & Strano, M. S. In vivo fluorescence detection of glucose using a single-walled carbon nanotube optical sensor: design, fluorophore properties, advantages, and disadvantages. Anal. Chem. 77, 7556–7562 (2005).

    Article  CAS  Google Scholar 

  15. Barone, P. W. & Strano, M. S. Reversible control of carbon nanotube aggregation for a glucose affinity sensor. Angew. Chem. Int. Ed. 45, 8138–8141 (2006).

    Article  CAS  Google Scholar 

  16. Jeng, E. S., Moll, A. E., Roy, A. C., Gastala, J. B. & Strano, M. S. Detection of DNA hybridization using the near-infrared band-gap fluorescence of single-walled carbon nanotubes. Nano Lett. 6, 371–375 (2006).

    Article  CAS  Google Scholar 

  17. Heller, D. A. et al. Optical detection of DNA conformational polymorphism on single-walled carbon nanotubes. Science 311, 508–511 (2006).

    Article  CAS  Google Scholar 

  18. Jin, H. et al. Divalent ion and thermally induced DNA conformational polymorphism on single-walled carbon nanotubes. Macromolecules 40, 6731–6739 (2007).

    Article  CAS  Google Scholar 

  19. Bachilo, S. M. et al. Structure-assigned optical spectra of single-walled carbon nanotubes. Science 298, 2361–2366 (2002).

    Article  CAS  Google Scholar 

  20. O'Connell, M. J. et al. Band gap fluorescence from individual single-walled carbon nanotubes. Science 297, 593–596 (2002).

    Article  CAS  Google Scholar 

  21. Heller, D. A., Baik, S., Eurell, T. E. & Strano, M. S. Single-walled carbon nanotube spectroscopy in live cells: towards long-term labels and optical sensors. Adv. Mater. 17, 2793–2799 (2005).

    Article  CAS  Google Scholar 

  22. Jin, H., Heller, D. A. & Strano, M. S. Single-particle tracking of endocytosis and exocytosis of single-walled carbon nanotubes in NIH-3T3 cells. Nano Lett. 8, 1577–1585 (2008).

    Article  Google Scholar 

  23. Strano, M. S. & Jin, H. Where is it heading? Single-particle tracking of single-walled carbon nanotubes. ACS Nano 2, 1749–1752 (2008).

    Article  CAS  Google Scholar 

  24. Choi, J. H. et al. Multimodal biomedical imaging with asymmetric single-walled carbon nanotube/iron oxide nanoparticle complexes. Nano Lett. 7, 861–867 (2007).

    Article  CAS  Google Scholar 

  25. Satishkumar, B. C. et al. Reversible fluorescence quenching in carbon nanotubes for biomolecular sensing. Nature Nanotech. 2, 560–564 (2007).

    Article  CAS  Google Scholar 

  26. Cognet, L. et al. Stepwise quenching of exciton fluorescence in carbon nanotubes by single-molecule reactions. Science 316, 1465–1468 (2007).

    Article  CAS  Google Scholar 

  27. Cherukuri, P. et al. Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence. Proc. Natl Acad. Sci. USA 103, 18882–18886 (2006).

    Article  CAS  Google Scholar 

  28. Cherukuri, P., Bachilo, S. M., Litovsky, S. H. & Weisman, R. B. Near-infrared fluorescence microscopy of single-walled carbon nanotubes in phagocytic cells. J. Am. Chem. Soc. 126, 15638–15639 (2004).

    Article  CAS  Google Scholar 

  29. Welsher, K., Liu, Z., Daranciang, D. & Dai, H. Selective probing and imaging of cells with single walled carbon nanotubes as near-infrared fluorescent molecules. Nano Lett. 8, 586–590 (2008).

    Article  CAS  Google Scholar 

  30. O'Connell, M. J., Eibergen, E. E. & Doorn, S. K. Chiral selectivity in the charge-transfer bleaching of single-walled carbon-nanotube spectra. Nature Mater. 4, 412–418 (2005).

    Article  CAS  Google Scholar 

  31. Walsh, A. G. et al. Screening of excitons in single, suspended carbon nanotubes. Nano Lett. 7, 1485–1488 (2007).

    Article  CAS  Google Scholar 

  32. Choi, J. H. & Strano, M. S. Solvatochromism in single-walled carbon nanotubes. Appl. Phys. Lett. 90, 223114 (2007).

    Article  Google Scholar 

  33. Klinke, C., Chen, J., Afzali, A. & Avouris, P. Charge transfer induced polarity switching in carbon nanotube transistors. Nano Lett. 5, 555–558 (2005).

    Article  CAS  Google Scholar 

  34. Shim, M., Javey, A., Kam, N. W. S. & Dai, H. Polymer functionalization for air-stable n-type carbon nanotube field-effect transistors. J. Am. Chem. Soc. 123, 11512–11513 (2001).

    Article  CAS  Google Scholar 

  35. Usrey, M. L., Lippmann, E. S. & Strano, M. S. Evidence for a two-step mechanism in electronically selective single-walled carbon nanotube reactions. J. Am. Chem. Soc. 127, 16129–16135 (2005).

    Article  CAS  Google Scholar 

  36. Cui, Y., Wei, Q. Q., Park, H. K. & Lieber, C. M. Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293, 1289–1292 (2001).

    Article  CAS  Google Scholar 

  37. Eisenhut, M. et al. Melanoma uptake of Tc-99 m complexes containing the N--(2-diethylaminoethyl) benzamide structural element. J. Med. Chem. 45, 5802–5805 (2002).

    Article  CAS  Google Scholar 

  38. Mauzac, M. & Jozefonvicz, J. Anticoagulant activity of dextran derivatives. 1. Synthesis and characterization. Biomaterials 5, 301–304 (1984).

    Article  CAS  Google Scholar 

  39. Li, B. et al. Aqueous phosphoric acid as a mild reagent for deprotection of tert-butyl carbamates, esters, and ethers. J. Org. Chem. 71, 9045–9050 (2006).

    Article  CAS  Google Scholar 

  40. Kikuchi, K., Nagano, T. & Hirobe, M. Novel detection method of nitric oxide using horseradish peroxidase. Biol. Pharm. Bull. 19, 649–651 (1996).

    Article  CAS  Google Scholar 

  41. Zheng, M. & Diner, B. A. Solution redox chemistry of carbon nanotubes. J. Am. Chem. Soc. 126, 15490–15494 (2004).

    Article  CAS  Google Scholar 

  42. Jin, H., Heller, D. A., Kim, J. H. & Strano, M. S. Stochastic analysis of stepwise fluorescence quenching reactions on single-walled carbon nanotubes: single molecule sensors. Nano Lett. 8, 4299–4304 (2008).

    Article  CAS  Google Scholar 

  43. Kuimova, M. K., Yahioglu, G. & Ogilby, P. R. Singlet oxygen in a cell: spatially dependent lifetimes and quenching rate constants. J. Am. Chem. Soc. 131, 332–340 (2009).

    Article  CAS  Google Scholar 

  44. Ricciardolo, F. L. M., Sterk, P. J., Gaston, B. & Folkerts, G. Nitric oxide in health and disease of the respiratory system. Physiol. Rev. 84, 731–765 (2004).

    Article  CAS  Google Scholar 

  45. Zhuang, J. C. & Wogan, G. N. Growth and viability of macrophages continuously stimulated to produce nitric oxide. Proc. Natl Acad. Sci. USA 94, 11875–11880 (1997).

    Article  CAS  Google Scholar 

  46. Pike, C. J., Overman, M. J. & Cotman, C. W. Amino-terminal deletions enhance aggregation of beta-amyloid peptides in-vitro. J. Biol. Chem. 270, 23895–23898 (1995).

    Article  CAS  Google Scholar 

  47. Fenoglio, I. et al. Reactivity of carbon nanotubes: free radical generation or scavenging activity? Free Radic. Biol. Med. 40, 1227–1233 (2006).

    Article  CAS  Google Scholar 

  48. Galano, A. Carbon nanotubes as free-radical scavengers. J. Phys. Chem. C 112, 8922–8927 (2008).

    Article  CAS  Google Scholar 

  49. Bartberger, M. D. et al. The reduction potential of nitric oxide (NO) and its importance to NO biochemistry. Proc. Natl Acad. Sci. USA 99, 10958–10963 (2002).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a Beckman Young Investigator Award to M.S.S., the National Science Foundation and a seed grant from the Center for Environmental Health and Science at the Massachusetts Institute of Technology (MIT). J.H. Kim is grateful for a postdoctoral fellowship from the Korea Research Foundation Grant funded by the Korean Government (KRF-2007-357-D00086). We also thank W.M. Deen in the Department of Chemical Engineering at MIT for discussions on NO diffusion.

Author information

Authors and Affiliations

Authors

Contributions

J.H.K. and M.S.S. conceived and designed the experiments. J.H.K. performed the experiments and analysed the data. D.A.H., H.J., P.W.B., C.S. and J.Z. assisted in doing experiments. L.J.T., G.N.W. and S.R.T. discussed the results of biological NO detection and commented on them. J.H.K. and M.S.S. co-wrote the paper.

Corresponding author

Correspondence to Michael S. Strano.

Supplementary information

Supplementary information

Supplementary information (PDF 1894 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, JH., Heller, D., Jin, H. et al. The rational design of nitric oxide selectivity in single-walled carbon nanotube near-infrared fluorescence sensors for biological detection. Nature Chem 1, 473–481 (2009). https://doi.org/10.1038/nchem.332

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.332

This article is cited by

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