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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References
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).
Mochalin, V. N., Shenderova, O., Ho, D. & Gogotsi, Y. The properties and applications of nanodiamonds. Nature Nanotech. 7, 11–23 (2012).
Kaur, R. & Badea, I. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems. Int. J. Nanomed. 8, 203–220 (2013).
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).
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).
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).
Krueger, A. & Lang, D. Functionality is key: recent progress in the surface modification of nanodiamond. Adv. Funct. Mater. 22, 890–906 (2012).
Neugart, F. et al. Dynamics of diamond nanoparticles in solution and cells. Nano Lett. 7, 3588–3591 (2007).
McGuinness, L. P. et al. Quantum measurement and orientation tracking of fluorescent nanodiamonds inside living cells. Nature Nanotech. 6, 358–363 (2011).
Hui, Y. Y. et al. Two-photon fluorescence correlation spectroscopy of lipid-encapsulated fluorescent nanodiamonds in living cells. Opt. Express 18, 5896–5905 (2010).
Grotz, B. et al. Charge state manipulation of qubits in diamond. Nature Commun. 3, 729 (2012).
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).
Perevedentseva, E. et al. The interaction of the protein lysozyme with bacteria E. coli observed using nanodiamond labelling. Nanotechnology 18, 315102 (2007).
Zumbusch, A., Langbein, W. & Borri, P. Nonlinear vibrational microscopy applied to lipid biology. Prog. Lipid Res. 52, 615–632 (2013).
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).
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).
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).
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).
Davis, M. E., Chen, Z. & Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature Rev. Drug Discov. 7, 771–782 (2008).
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).
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).
Moger, J., Johnston, B. D. & Tyler, C. R. Imaging metal oxide nanoparticles in biological structures with CARS microscopy. Opt. Express 16, 3408–3419 (2008).
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).
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).
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).
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).
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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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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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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DOI: https://doi.org/10.1038/nnano.2014.210
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