High-contrast, fast chemical imaging by coherent Raman scattering using a self-synchronized two-colour fibre laser

Cihang Kong; Christian Pilger; Henning Hachmeister; Xiaoming Wei; Tom H. Cheung; Cora S. W. Lai; Nikki P. Lee; Kevin. K. Tsia; Kenneth K. Y. Wong; Thomas Huser

doi:10.1038/s41377-020-0259-2

Go to Nature Website

Your Location：

Home >

Browse articles >

High-contrast, fast chemical imaging by coherent Raman scattering using a self-synchronized two-colour fibre laser

Article

- High-contrast, fast chemical imaging by coherent Raman scattering using a self-synchronized two-colour fibre laser
- Light: Science & Applications Vol. 9, Issue 2, Pages: 254-265(2020)
- Affiliations：
  
  1.Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
  2.Biomolecular Photonics, Department of Physics, University of Bielefeld, Universit?tsstr, 25, 33615 Bielefeld, Germany
  3.Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China
  4.Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
  5.Department of Surgery, The University of Hong Kong, Pokfulam Road, Hong Kong, China
  6.Present address: Division of Engineering and Applied Science, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
- Author bio：
  
  Xiaoming Wei (xmwei@caltech.edu)
  Kenneth K. Y. Wong (kywong@eee.hku.hk)
  Thomas Huser (thomas.huser@physik.uni-bielefeld.de)
- Funds：
- DOI：10.1038/s41377-020-0259-2
  CLC：
- Published：2020，
  
  Published Online：24 February 2020，
  
  Received：14 May 2019，
  
  Revised：23 January 2020，
  
  Accepted：09 February 2020
- Accepted：
Scan QR Code
Kong, C. H. et al. High-contrast, fast chemical imaging by coherent Raman scattering using a self-synchronized two-colour fibre laser. Light: Science & Applications, 9, 254-265 (2020).
DOI：

Kong, C. H. et al. High-contrast, fast chemical imaging by coherent Raman scattering using a self-synchronized two-colour fibre laser. Light: Science & Applications, 9, 254-265 (2020). DOI： 10.1038/s41377-020-0259-2.

摘要

Abstract

Coherent Raman scattering (CRS) microscopy is widely recognized as a powerful tool for tackling biomedical problems based on its chemically specific label-free contrast

high spatial and spectral resolution

and high sensitivity. However

the clinical translation of CRS imaging technologies has long been hindered by traditional solid-state lasers with environmentally sensitive operations and large footprints. Ultrafast fibre lasers can potentially overcome these shortcomings but have not yet been fully exploited for CRS imaging

as previous implementations have suffered from high intensity noise

a narrow tuning range and low power

resulting in low image qualities and slow imaging speeds. Here

we present a

novel high-power self-synchronized two-colour pulsed fibre laser that achieves excellent performance in terms of intensity stability (improved by 50 dB)

timing jitter (24.3 fs)

average power fluctuation (

0.5%)

modulation depth (

20 dB) and pulse width variation (

1.8%) over an extended wavenumber range (2700–3550 cm

-1

). The versatility of the laser source enables

for the first time

high-contrast

fast CRS imaging without complicated noise reduction via balanced detection schemes. These capabilities are demonstrated in this work by imaging a wide range of species such as living human cells and mouse arterial tissues and performing multimodal nonlinear imaging of mouse tail

kidney and brain tissue sections by utilizing second-harmonic generation and two-photon excited fluorescence

which provides multiple optical contrast mechanisms simultaneously and maximizes the gathered information content for biological visualization and medical diagnosis. This work also establishes a general scenario for remodelling existing lasers into synchronized two-colour lasers and thus promotes a wider popularization and application of CRS imaging technologies.

关键词

Keywords

references

Yun, S. H.&Kwok, S. J. J. Light in diagnosis, therapy and surgery.Nat. Biomed. Eng.1, 0008 (2017)..

Zumbusch, A., Holtom, G. R.&Xie, X. S. Three-dimensional vibrational imaging by coherent anti-stokes Raman scattering.Phys. Rev. Lett.82, 4142–4145 (1999)..

Ploetz, E., Laimgruber, S., Berner, S., Zinth, W.&Gilch, P. Femtosecond stimulated Raman microscopy.Appl. Phys. B87, 389–393 (2007)..

Freudiger, C. W. et al. Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy.Science322, 1857–1861 (2008)..

Nandakumar, P., Kovalev, A.&Volkmer, A. Vibrational imaging based on stimulated Raman scattering microscopy.N. J. Phys.11, 033026 (2009)..

Ozeki, Y., Dake, F., Kajiyama, S., Fukui, K.&Itoh, K. Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy.Opt. Express17, 3651–3658 (2009)..

Denk, W., Strickler, J. H.&Webb, W. W. Two-photon laser scanning fluorescence microscopy.Science248, 73–76 (1990)..

Xu, C., Zipfel, W., Shear, J. B., Williams, R. M.&Webb, W. W. Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy.Proc. Natl Acad. Sci. USA93, 10763–10768 (1996)..

Wokosin, D. L., Centonze, V. E., Crittenden, S.&White, J. Three-photon excitation fluorescence imaging of biological specimensusing an all-solid-state laser.Bioimaging4, 208–214 (1996)..

Hell, S. W. et al. Three-photon excitation in fluorescence microscopy.J. Biomed. Opt.1, 71–74 (1996)..

Campagnola, P. J., Wei, M. D., Lewis, A.&Loew, L. M. High-resolution nonlinear optical imaging of live cells by second harmonic generation.Biophys. J.77, 3341–3349(1999)..

Moreaux, L., Sandre, O.&Mertz, J. Membrane imaging by second-harmonic generation microscopy.J. Opt. Soc. Am. B17, 1685–1694 (2000)..

Guesmi, K. et al. Dual-color deep-tissue three-photon microscopy with a multiband infrared laser.Light. Sci. Appl.7, 12 (2018)..

Shi, L. et al. Optical imaging of metabolic dynamics in animals.Nat. Commun.9, 2995 (2018)..

Wei, L. et al. Super-multiplex vibrational imaging.Nature544, 465–470 (2017)..

Ozeki, Y. et al. Stimulated Raman scattering microscope with shot noise limited sensitivity using subharmonically synchronized laser pulses.Opt. Express18, 13708–13719 (2010)..

Wang, K. et al. Synchronized time-lens source for coherent Raman scattering microscopy.Opt. Express23, 24019–24024 (2010)..

Nose, K. et al. Sensitivity enhancement of fiber-laser-based stimulated Raman scattering microscopy by collinear balanced detection technique.Opt. Express20, 13958–13965 (2012)..

Karpf, S., Eibl, M., Wieser, W., Klein, T.&Huber, R. A time-encoded technique for fibre-based hyperspectral broadband stimulated Raman microscopy.Nat. Commun.6, 6784 (2015)..

Zhai, Y. H. et al. Multimodal coherent anti-Stokes Raman spectroscopic imaging with a fiber optical parametric oscillator.Appl. Phys. Lett.98, 191106 (2011)..

Baumgartl, M. et al. All-fiber laser source for CARS microscopy based on fiber optical parametric frequency conversion.Opt. Express20, 4484–4493 (2012)..

Lefrancois, S. et al. Fiber four-wave mixing source for coherent anti-Stokes Raman scattering microscopy.Opt. Lett.37, 1652–1654 (2012)..

Yang, K. et al. Low-repetition-rate all-fiber integrated optical parametric oscillator for coherent anti-Stokes Raman spectroscopy.Opt. Express26, 17519–17528 (2018)..

Andresen, E. R., Nielsen, C. K., Thøgersen, J.&Keiding, S. R. Fiber laser-based light source for coherent anti-Stokes Raman scattering microspectroscopy.Opt. Express15, 4848–4856 (2007)..

Pegoraro, A. F. et al. All-fiber CARS microscopy of live cells.Opt. Express17, 20700–20706 (2009)..

Krauss, G. et al. Compact coherent anti-Stokes Raman scattering microscope based on a picosecond two-color Er:fiber laser system.Opt. Lett.34, 2847–2849 (2009)..

Andresen, E. R., Berto, P.&Rigneault, H. Stimulated Raman scattering microscopy by spectral focusing and fiber-generated soliton as Stokes pulse.Opt. Lett.36, 2387–2389 (2011)..

Xie, R. et al. Multi-modal label-free imaging based on a femtosecond fiber laser.Biomed. Opt. Express5, 2390–2396 (2014)..

Crisafi, F. et al. Multimodal nonlinear microscope based on a compact fiber-format laser source.Spectrochim. Acta A Mol. Biomol. Spectrosc.188, 135–140 (2018)..

Gambetta, A. et al. Fiber-format stimulated-Raman-scattering microscopy from a single laser oscillator.Opt. Lett.35, 226–228 (2010)..

Selm, R. et al. Ultrabroadband background-free coherent anti-Stokes Raman scattering microscopy based on a compact Er:fiber laser system.Opt. Lett.35, 3282–3284 (2010)..

Freudiger, C. W. et al. Stimulated Raman scattering microscopy with a robust fibre laser source.Nat. Photon8, 153–159 (2014)..

Chen, K., Wu, T., Zhou, T., Wei, H.&Li, Y. Cascaded dual-soliton pulse stokes for broadband coherent Anti-Stokes Raman spectroscopy.IEEE Photonics J.8, 1–8 (2016)..

Tu, H. et al. Stain-free histopathology by programmable supercontinuum pulses.Nat. Photon10, 534–540 (2016)..

Orringer, D. A. et al. Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy.Nat. Biomed. Eng.1, 0027 (2017)..

Jackson, S. D. Towards high-power mid-infrared emission from a fibre laser.Nat. Photon6, 423–431 (2012)..

Jauregui, C., Limpert, J.&Tünnermann, A. High-power fibre lasers.Nat. Photon7, 861–867 (2013)..

Fermann, M. E.&Hartl, I. Ultrafast fibre lasers.Nat. Photon7, 868–874 (2013)..

Xu, C.&Wise, F. W. Recent advances in fibre lasers for nonlinear microscopy.Nat. Photon7, 875–882 (2013)..

Spiegelberg, C. et al. Low-noise narrow-linewidth fiber laser at 1550 nm (June 2003).J. Lightwave Technol.22, 57–62 (2004)..

Xu, S. et al. 400 mW ultrashort cavity low-noise single-frequency Yb3+-doped phosphate fiber laser.Opt. Lett.36, 3708–3710 (2011)..

Snitzer, E., Po, H., Hakimi, F., Tumminelli, R.&McCollum, B. C.Double Clad, Offset Core Nd Fiber Laser in Optical Fiber Sensors, Vol. 2, paper PD5 of OSA Technical Digest Series (OSA, 1988).

Zenteno, L. High-power double clad fiber lasers.J. Lightwave Technol.11, 1435–1446 (1993)..

Jeong, Y., Sahu, J. K., Payne, D. N.&Nilsson, J. Ytterbium-doped large-core fiber laser with 1.36 kW continuous-wave output power.Opt. Express12, 6088–6092 (2004)..

Strickland, D.&Mourou, G. Compression of amplified chirped optical pulses.Opt. Commun.56, 219–221 (1985)..

Wei, X. et al. Breathing laser as an inertia-free swept source for high-quality ultrafast optical bioimaging.Opt. Lett.39, 6593–6596 (2014)..

Sobon, G. et al. 260 fs and 1 nJ pulse generation from a compact, mode-locked Tm-doped fiber laser.Opt. Express23, 31446–31451 (2015)..

Leitenstorfer, A., Fürst, C.&Laubereau, A. Widely tunable two-color mode-locked Ti:sapphire laser with pulse jitter of less than 2 fs.Opt. Lett.20, 916–918 (1995)..

Chong, A., Buckley, J., Renninger, W.&Wise, F. All-normal-dispersion femtosecond fiber laser.Opt. Express14, 10095–10100 (2006)..

Weiner, A. M.Ultrafast Optics(Wiley, 2009).

Rusu, M., Herda, R.&Okhotnikov, O. G. Passively synchronized two-color mode-locked fiber system based on master-slave lasers geometry.Opt. Express12, 4719–4724 (2004)..

Yoshitomi, D. et al. Ultralow-jitter passive timing stabilization of a mode-locked Er-doped fiber laser by injection of an optical pulse train.Opt. Lett.31, 3243–3245 (2006)..

Hsiang, W., Chang, C., Cheng, C.&Lai, Y. Passive synchronization between a self-similar pulse and a bound-soliton bunch in a two-color mode-locked fiber laser.Opt. Lett.34, 1967–1969 (2009)..

Taverner, D. et al. Highly efficient second-harmonic and sum-frequency generation of nanosecond pulses in a cascaded erbium-doped fiber: periodically poled lithium niobate source.Opt. Lett.23, 162–164 (1998)..

Wei, Z., Kobayashi, Y., Zhang, Z.&Torizuka, K. Generation of two-color femtosecond pulses by self-synchronizing Ti:sapphire and Cr:forsterite lasers.Opt. Lett.26, 1806–1808 (2001)..

Kiani, L., Lu, T.&Sharping, J. E. Comparison of amplitude noise of a fiber-optical parametric oscillator and a supercontinuum source.J. Opt. Soc. Am. B31, 1986–1990 (2014)..

Lamb, E. S.&Wise, F. W. Multimodal fiber source for nonlinear microscopy based on a dissipative soliton laser.Biomed. Opt. Express6, 3248–3255 (2015)..

Kim, J.&Song, Y. Ultralow-noise mode-locked fiber lasers and frequency combs: principles, status, and applications.Adv. Opt. Photon8, 465–540 (2016)..

Lai, C. S., Franke, T. F.&Gan, W. B. Opposite effects of fear conditioning and extinction on dendritic spine remodelling.Nature483, 87–91 (2012)..

Latka, I., Dochow, S., Krafft, C., Dietzek, B.&Popp, J. Fiber optic probes for linear and nonlinear Raman applications—current trends and future development.Laser Photon. Rev.7,698–731 (2013)..

Lombardini, A. et al. High-resolution multimodal flexible coherent Raman endoscope.Light. Sci. Appl.7, 10 (2018)..

Lu, F. K. et al. Label-free DNA imaging in vivo with stimulated Raman scattering microscopy.Proc. Natl Acad. Sci. USA112, 11624 (2015)..

Huber, R., Wojtkowski, M.&Fujimoto, J. G. Fourier domain mode locking (FDML): a new laser operating regime and applications for optical coherence tomography.Opt. Express14, 3225–3237 (2006)..

Runcorn, T. H. et al. Fiber-integrated frequency-doubling of a picosecond Raman laser to 560 nm.Opt. Express23, 15728–15733 (2015)..

Pologruto, T. A., Sabatini, B. L.&Svoboda, K. ScanImage: flexible software for operating laser scanning microscopes.Biomed. Eng. Online2, 13 (2003)..

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

⁰