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Coherent Raman spectro-imaging with laser frequency combs


Advances in optical spectroscopy and microscopy have had a profound impact throughout the physical, chemical and biological sciences. One example is coherent Raman spectroscopy, a versatile technique interrogating vibrational transitions in molecules. It offers high spatial resolution and three-dimensional sectioning capabilities that make it a label-free tool1,2 for the non-destructive and chemically selective probing of complex systems. Indeed, single-colour Raman bands have been imaged in biological tissue at video rates3,4 by using ultra-short-pulse lasers. However, identifying multiple, and possibly unknown, molecules requires broad spectral bandwidth and high resolution. Moderate spectral spans combined with high-speed acquisition are now within reach using multichannel detection5 or frequency-swept laser beams6,7,8,9. Laser frequency combs10 are finding increasing use for broadband molecular linear absorption spectroscopy11,12,13,14,15. Here we show, by exploring their potential for nonlinear spectroscopy16, that they can be harnessed for coherent anti-Stokes Raman spectroscopy and spectro-imaging. The method uses two combs and can simultaneously measure, on the microsecond timescale, all spectral elements over a wide bandwidth and with high resolution on a single photodetector. Although the overall measurement time in our proof-of-principle experiments is limited by the waiting times between successive spectral acquisitions, this limitation can be overcome with further system development. We therefore expect that our approach of using laser frequency combs will not only enable new applications for nonlinear microscopy but also benefit other nonlinear spectroscopic techniques.

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Figure 1: Principle of dual-comb CARS.
Figure 2: Experimental setup for dual-comb CARS spectro-imaging.
Figure 3: High-resolution dual-comb CARS of a mixture of liquid chemicals.
Figure 4: Hyperspectral image of a capillary plate with holes filled with a chemical mixture.

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  1. Nafie, L. A. Recent advances in linear and nonlinear Raman spectroscopy. Part VI. J. Raman Spectrosc. 43, 1845–1863 (2012)

    Article  ADS  CAS  Google Scholar 

  2. Cheng J. X., Xie X. S., eds. Coherent Raman Scattering Microscopy (CRC Press, 2012)

  3. Evans, C. L. et al. Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy. Proc. Natl Acad. Sci. USA 102, 16807–16812 (2005)

    Article  ADS  CAS  Google Scholar 

  4. Saar, B. G. et al. Video-rate molecular imaging in vivo with stimulated Raman scattering. Science 330, 1368–1370 (2010)

    Article  ADS  CAS  Google Scholar 

  5. Knutsen, K. P., Messer, B. M., Onorato, R. M. & Saykally, R. J. Chirped coherent anti-Stokes Raman scattering for high spectral resolution spectroscopy and chemically selective imaging. J. Phys. Chem. B 110, 5854–5864 (2006)

    Article  CAS  Google Scholar 

  6. Ozeki, Y. et al. High-speed molecular spectral imaging of tissue with stimulated Raman scattering. Nature Photon. 6, 845–851 (2012)

    Article  ADS  CAS  Google Scholar 

  7. Kong, L. et al. Multicolor stimulated Raman scattering microscopy with a rapidly tunable optical parametric oscillator. Opt. Lett. 38, 145–147 (2013)

    Article  ADS  Google Scholar 

  8. Pegoraro, A. F. et al. Optimally chirped multimodal CARS microscopy based on a single Ti:sapphire oscillator. Opt. Express 17, 2985–2996 (2009)

    ADS  Google Scholar 

  9. Fu, D., Holtom, G., Freudiger, C., Zhang, X. & Xie, X. S. Hyperspectral imaging with stimulated Raman scattering by chirped femtosecond lasers. J. Phys. Chem. B 117, 4634–4640 (2013)

    Article  CAS  Google Scholar 

  10. Hänsch, T. W. Nobel Lecture. Passion for precision. Rev. Mod. Phys. 78, 1297–1309 (2006)

    Article  ADS  Google Scholar 

  11. Schliesser, A., Picqué, N. & Hänsch, T. W. Mid-infrared frequency combs. Nature Photon. 6, 440–449 (2012)

    Article  ADS  CAS  Google Scholar 

  12. Bernhardt, B. et al. Cavity-enhanced dual-comb spectroscopy. Nature Photon. 4, 55–57 (2010)

    Article  ADS  CAS  Google Scholar 

  13. Coddington, I., Swann, W. C. & Newbury, N. R. Coherent multiheterodyne spectroscopy using stabilized optical frequency combs. Phys. Rev. Lett. 100, 013902 (2008)

    Article  ADS  Google Scholar 

  14. Diddams, S. A., Hollberg, L. & Mbele, V. Molecular fingerprinting with the resolved modes of a femtosecond laser frequency comb. Nature 445, 627–630 (2007)

    Article  CAS  Google Scholar 

  15. Thorpe, M. J. et al. Broadband cavity ringdown spectroscopy for sensitive and rapid molecular detection. Science 311, 1595–1599 (2006)

    Article  ADS  CAS  Google Scholar 

  16. Ideguchi, T., Bernhardt, B., Guelachvili, G., Hänsch, T. W. & Picqué, N. Raman-induced Kerr effect dual-comb spectroscopy. Opt. Lett. 37, 4498–4500 (2012)

    Article  ADS  CAS  Google Scholar 

  17. Boyd, R. W. Nonlinear Optics 3rd edn, Ch. 10.3 (Academic, 2008)

    Google Scholar 

  18. Yan, Y., Gamble, E. B. & Nelson, K. A. Impulsive stimulated scattering: general importance in femtosecond laser pulse interaction with matter, and spectroscopy applications. J. Chem. Phys. 83, 5391–5399 (1985)

    Article  ADS  CAS  Google Scholar 

  19. Mukamel, S. Principles of Nonlinear Optical Spectroscopy (Oxford Univ. Press, 1995)

    Google Scholar 

  20. Dudovich, N., Oron, D. & Silberberg, Y. Single-pulse coherently controlled nonlinear Raman spectroscopy and microscopy. Nature 418, 512–514 (2002)

    Article  ADS  CAS  Google Scholar 

  21. Weiner, A. M., Leaird, D. E., Wiederrecht, G. P. & Nelson, K. A. Femtosecond multiple-pulse impulsive stimulated Raman scattering spectroscopy. J. Opt. Soc. Am. B 8, 1264–1275 (1991)

    Article  ADS  CAS  Google Scholar 

  22. Volkmer, A., Book, L. D. & Xie, X. S. Time-resolved coherent anti-Stokes Raman scattering microscopy: imaging based on Raman free induction decay. Appl. Phys. Lett. 80, 1505–1507 (2002)

    Article  ADS  CAS  Google Scholar 

  23. Ogilvie, J. P., Beaurepaire, E., Alexandrou, A. & Joffre, M. Fourier-transform coherent anti-Stokes Raman scattering microscopy. Opt. Lett. 31, 480–482 (2006)

    Article  ADS  Google Scholar 

  24. Bartels, A., Heinecke, D. & Diddams, S. A. 10-GHz self-referenced optical frequency comb. Science 326, 681 (2009)

    Article  ADS  CAS  Google Scholar 

  25. Kippenberg, T. J., Holzwarth, R. & Diddams, S. A. Microresonator-based optical frequency combs. Science 332, 555–559 (2011)

    Article  ADS  CAS  Google Scholar 

  26. Steuwe, C., Kaminski, C. F., Baumberg, J. J. & Mahajan, S. Surface enhanced coherent anti-Stokes Raman scattering on nanostructured gold surfaces. Nano Lett. 11, 5339–5343 (2011)

    Article  ADS  CAS  Google Scholar 

  27. Frontiera, R. R., Henry, A. I., Gruenke, N. L. & Van Duyne, R. P. Surface-enhanced femtosecond stimulated Raman spectroscopy. J. Phys. Chem. Lett. 2, 1199–1203 (2011)

    Article  CAS  Google Scholar 

  28. Hiramatsu, K. et al. Observation of Raman optical activity by heterodyne-detected polarization-resolved coherent anti-Stokes Raman scattering. Phys. Rev. Lett. 109, 083901 (2012)

    Article  ADS  Google Scholar 

  29. Ichimura, T., Hayazawa, N., Hashimoto, M., Inouye, Y. & Kawata, S. Tip-enhanced coherent anti-Stokes Raman scattering for vibrational nanoimaging. Phys. Rev. Lett. 92, 220801 (2004)

    Article  ADS  Google Scholar 

  30. Cleff, C. et al. Ground-state depletion for subdiffraction-limited spatial resolution in coherent anti-Stokes Raman scattering microscopy. Phys. Rev. A 86, 023825 (2012)

    Article  ADS  Google Scholar 

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We thank P. Hommelhoff, M. Schultze and W. Schweinberger for the loan of optical components, and A. Hipke for experimental support. Research was conducted in the scope of the European Laboratory for Frequency Comb Spectroscopy. We acknowledge support from the Max Planck Foundation, the Munich Center for Advanced Photonics, Eurostars and the European Research Council (Advanced Investigator grant no. 267854).

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T.I. and S.H. contributed equally to the experimental work. All authors contributed extensively to the work presented in this paper.

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Correspondence to Nathalie Picqué.

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The authors declare no competing financial interests.

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Ideguchi, T., Holzner, S., Bernhardt, B. et al. Coherent Raman spectro-imaging with laser frequency combs. Nature 502, 355–358 (2013).

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