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Coherent anti-Stokes Raman scattering microscopy of single nanodiamonds

Nature Nanotechnology volume 9, pages 940–946 (2014)Cite this article

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Abstract

Nanoparticles have attracted enormous attention for biomedical applications as optical labels, drug-delivery vehicles and contrast agents in vivo. In the quest for superior photostability and biocompatibility, nanodiamonds are considered one of the best choices due to their unique structural, chemical, mechanical and optical properties. So far, mainly fluorescent nanodiamonds have been utilized for cell imaging. However, their use is limited by the efficiency and costs in reliably producing fluorescent defect centres with stable optical properties. Here, we show that single non-fluorescing nanodiamonds exhibit strong coherent anti-Stokes Raman scattering (CARS) at the sp3 vibrational resonance of diamond. Using correlative light and electron microscopy, the relationship between CARS signal strength and nanodiamond size is quantified. The calibrated CARS signal in turn enables the analysis of the number and size of nanodiamonds internalized in living cells in situ, which opens the exciting prospect of following complex cellular trafficking pathways quantitatively.

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Figure 1: Raman micro-spectroscopy of nanodiamonds.
Figure 2: Optical extinction of single nanodiamonds versus size.
Figure 3: CARS micro-spectroscopy of single nanodiamonds.
Figure 4: Quantitative DIC microscopy of single nanodiamonds.
Figure 5: CARS imaging of single nanodiamonds in fixed and living cells.

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References

  1. Schrand, A. M., Ciftan Hens, S. A. & Shenderova, O. A. Nanodiamond particles: properties and perspectives for bioapplications. Crit. Rev. Solid State Mater. Sci. 34, 18–74 (2009).

    Article  CAS  Google Scholar 

  2. Mochalin, V. N., Shenderova, O., Ho, D. & Gogotsi, Y. The properties and applications of nanodiamonds. Nature Nanotech. 7, 11–23 (2012).

    Article  CAS  Google Scholar 

  3. Kaur, R. & Badea, I. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems. Int. J. Nanomed. 8, 203–220 (2013).

    Article  Google Scholar 

  4. Wu, T-J. et al. Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds. Nature Nanotech. 8, 682–689 (2013).

    Article  CAS  Google Scholar 

  5. Weng, M-F., Chang, B-J., Chiang, S-Y., Wang, N-S. & Niu, H. Cellular uptake and phototoxicity of surface-modified fluorescent nanodiamonds. Diamond Relat. Mater. 22, 96–104 (2012).

    Article  CAS  Google Scholar 

  6. Liu, K-K., Wang, C-C., Cheng, C-L. & Chao, J-I. Endocytic carboxylated nanodiamond for the labeling and tracking of cell division and differentiation in cancer and stem cells. Biomaterials 30, 4249–4259 (2009).

    Article  CAS  Google Scholar 

  7. Krueger, A. & Lang, D. Functionality is key: recent progress in the surface modification of nanodiamond. Adv. Funct. Mater. 22, 890–906 (2012).

    Article  CAS  Google Scholar 

  8. Neugart, F. et al. Dynamics of diamond nanoparticles in solution and cells. Nano Lett. 7, 3588–3591 (2007).

    Article  CAS  Google Scholar 

  9. McGuinness, L. P. et al. Quantum measurement and orientation tracking of fluorescent nanodiamonds inside living cells. Nature Nanotech. 6, 358–363 (2011).

    Article  CAS  Google Scholar 

  10. Hui, Y. Y. et al. Two-photon fluorescence correlation spectroscopy of lipid-encapsulated fluorescent nanodiamonds in living cells. Opt. Express 18, 5896–5905 (2010).

    Article  CAS  Google Scholar 

  11. Grotz, B. et al. Charge state manipulation of qubits in diamond. Nature Commun. 3, 729 (2012).

    Article  Google Scholar 

  12. Smitha, B. R., Niebertc, M., Plakhotnika, T. & Zvyagin, A. V. Transfection and imaging of diamond nanocrystals as scattering optical labels. J. Lumin. 127, 260–263 (2007).

    Article  Google Scholar 

  13. Perevedentseva, E. et al. The interaction of the protein lysozyme with bacteria E. coli observed using nanodiamond labelling. Nanotechnology 18, 315102 (2007).

    Article  Google Scholar 

  14. Zumbusch, A., Langbein, W. & Borri, P. Nonlinear vibrational microscopy applied to lipid biology. Prog. Lipid Res. 52, 615–632 (2013).

    Article  CAS  Google Scholar 

  15. Osswald, S., Mochalin, V. N., Havel, M., Yushin, G. & Gogotsi, Y. Phonon confinement effects in the Raman spectrum of nanodiamond. Phys. Rev. B 80, 075419 (2009).

    Article  Google Scholar 

  16. Payne, L. M., Langbein, W. & Borri, P. Polarization-resolved extinction and scattering cross-section of individual gold nanoparticles measured by wide-field microscopy on a large ensemble. Appl. Phys. Lett. 102, 131107 (2013).

    Article  Google Scholar 

  17. Pope, I., Langbein, W., Watson, P. & Borri, P. Simultaneous hyperspectral differential-CARS, TPF and SHG microscopy with a single 5 fs Ti:Sa laser. Opt. Express 21, 7096–7106 (2013).

    Article  CAS  Google Scholar 

  18. McPhee, C. I., Zoriniants, G., Langbein, W. & Borri, P. Measuring the lamellarity of giant lipid vesicles with differential interference contrast microscopy. Biophys. J. 105, 1414–1420 (2013).

    Article  CAS  Google Scholar 

  19. Davis, M. E., Chen, Z. & Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature Rev. Drug Discov. 7, 771–782 (2008).

    Article  CAS  Google Scholar 

  20. Kim, H., Taggart, D. K., Xiang, C., Penner, R. M. & Potma, E. O. Spatial control of coherent anti-Stokes emission with height-modulated gold zigzag nanowires. Nano Lett. 8, 2373–2377 (2008).

    Article  CAS  Google Scholar 

  21. Masia, F., Langbein, W., Watson, P. & Borri, P. Resonant four-wave mixing of gold nanoparticles for three-dimensional cell microscopy. Opt. Lett. 34, 1816–1818 (2009).

    Article  Google Scholar 

  22. Moger, J., Johnston, B. D. & Tyler, C. R. Imaging metal oxide nanoparticles in biological structures with CARS microscopy. Opt. Express 16, 3408–3419 (2008).

    Article  CAS  Google Scholar 

  23. Jung, Y., Tong, L., Tanaudommongkon, A., Cheng, J. X. & Yang, C. In vitro and in vivo nonlinear optical imaging of silicon nanowires. Nano Lett. 9, 2440–2444 (2009).

    Article  CAS  Google Scholar 

  24. Kim, H., Sheps, T., Collins, P. G. & Potma, E. O. Nonlinear optical imaging of individual carbon nanotubes with four-wave-mixing microscopy. Nano Lett. 9, 2991–2995 (2009).

    Article  CAS  Google Scholar 

  25. Wang, Y., Lin, C-Y., Nikolaenko, A., Raghunathan, V. & Potma, E. O. Four-wave mixing microscopy of nanostructures. Adv. Opt. Photon. 3, 1–52 (2011).

    Article  Google Scholar 

  26. Aggarwal, R. et al. Measurement of the absolute Raman cross section of the optical phonons in type Ia natural diamond. Solid State Commun. 152, 204–209 (2012).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge the Cardiff University Large Research Equipment Fund for providing high-resolution TEM facilities, and thank G. Lalev and K. Cleal for their assistance. This work was funded by the UK BBSRC Research Council (grant nos BB/J021008/1 and BB/H006575/1). P.B. acknowledges the UK EPSRC Research Council for her Leadership fellowship award (grant no. EP/I005072/1).

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Authors and Affiliations

  1. Cardiff University School of Biosciences, Museum Avenue, Cardiff, CF10 3AX, UK

    Iestyn Pope, Lukas Payne, George Zoriniants, Peter Watson & Paola Borri

  2. Cardiff University School of Physics and Astronomy, The Parade, CF24 3AA, Cardiff, UK

    Evan Thomas, Oliver Williams & Wolfgang Langbein

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  1. Iestyn Pope
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  7. Wolfgang Langbein
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Contributions

P.B. and W.L. conceived and designed the experiments, interpreted the results and wrote the manuscript. I.P. performed the CARS experiments and analysed the data. L.P. performed the optical extinction cross-section measurements and analysed the data. G.Z. performed the quantitative DIC experiments and analysed the data. E.T. performed the SEM experiments and analysed the data. O.W. provided the bulk diamond and nanodiamond materials. P.W. performed the cell culture work. All authors discussed the results and commented on the manuscript.

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Correspondence to Paola Borri.

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The authors declare no competing financial interests.

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Pope, I., Payne, L., Zoriniants, G. et al. Coherent anti-Stokes Raman scattering microscopy of single nanodiamonds. Nature Nanotech 9, 940–946 (2014). https://doi.org/10.1038/nnano.2014.210

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