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Recent advances in fibre lasers for nonlinear microscopy

A Corrigendum to this article was published on 28 October 2013

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Abstract

Nonlinear microscopy techniques developed over the past two decades have provided dramatic new capabilities for biological imaging. The initial demonstrations of nonlinear microscopies coincided with the development of solid-state femtosecond lasers, which continue to be the dominant light source for applications of nonlinear microscopy. Fibre lasers offer attractive features for biological and biomedical imaging, and recent advances are promising for the development of high-performance sources with the potential for realizing integrated instruments that are robust and inexpensive. This Review discusses recent advances, and identifies challenges and opportunities for fibre lasers in nonlinear bioimaging.

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Figure 1: Dissipative soliton laser and pulses.
Figure 2: Two-photon fluorescence images obtained using excitation from a dissipative–soliton fibre laser.
Figure 3: Attenuation length in brain tissue as a function of wavelength.
Figure 4: SSFS in a photonic-crystal rod and in vivo 3PM of subcortical structures in a mouse brain.
Figure 5: Fibre source for CARS microscopy and imaging of mouse tissue.

Change history

  • 28 October 2013

    In the version of this Review Article originally published online and in print, no competing financial interests were declared. However, the authors wish to acknowledge relevant patents. The competing financial interests statement in the HTML and PDF versions of the Review Article has been modified.

References

  1. Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

    ADS  Article  Google Scholar 

  2. Yuste, R. & Denk, W. Dendritic spines as basic function units of neuronal integration. Nature 375, 682–684 (1995).

    Article  ADS  Google Scholar 

  3. Williams, R. M., Piston, D. W. & Webb, W. W. Two-photon molecular excitation provides intrinsic 3-dimensional resolution for laser-based microscopy and microphotochemistry. FASEB J. 8, 804–813 (1994).

    Article  Google Scholar 

  4. Denk, W., Piston, D. W. & Webb, W. W. in The Handbook of Confocal Microscopy (ed. Pawley, J. B.) 445–458 (Plenum, 1995).

    Book  Google Scholar 

  5. Helmchen, F. & Denk, W. Deep tissue two-photon microscopy. Nature Methods 2, 932–940 (2005).

    Article  Google Scholar 

  6. 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. USA 93, 10763–10768 (1996).

    Article  ADS  Google Scholar 

  7. Wokosin, D. L., Centonze, V. E., Crittenden, S. & White, J. Three-photon excitation fluorescence imaging of biological specimens using an all-solid-state laser. Bioimaging 4, 208–214 (1996).

    Article  Google Scholar 

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

    Article  ADS  Google Scholar 

  9. 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).

    Article  Google Scholar 

  10. Moreaux, L., Sandre, O. & Mertz, J. Membrane imaging by second-harmonic generation microscopy. J. Opt. Soc. Am. B 17, 1685–1694 (2000).

    Article  ADS  Google Scholar 

  11. Barad, Y., Eisenberg, H., Horowitz, M. & Silberberg, Y. Nonlinear laser scanning microscopy by third harmonic generation. Appl. Phys. Lett. 70, 922–924 (1997).

    Article  ADS  Google Scholar 

  12. Müller, M., Squier, I., Wilson, K. R. & Brakenoff, G. I. 3D microscopy of transparent objects using third-harmonic generation. J. Microsc. 191, 266–274 (1998).

    Article  Google Scholar 

  13. Sánchez, E. J., Novotny, L. & Xie, X. S. Near-field fluorescence microscopy based on two-photon excitation with metal tips. Phys. Rev. Lett. 82, 4014–4017 (1999).

    Article  ADS  Google Scholar 

  14. Jung, J. C. & Schnitzer, M. J. Multiphoton endoscopy. Opt. Lett. 28, 902–904 (2003).

    Article  ADS  Google Scholar 

  15. Hell, S. W. & Wichmann, J. Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. Opt. Lett. 19, 780–782 (1994).

    Article  ADS  Google Scholar 

  16. Shaner, N. C., Steinbach, P. A. & Tsien, R. Y. A guide to choosing fluorescent proteins. Nature Methods 2, 905–909 (2005).

    Article  Google Scholar 

  17. Hoover, E. E. & Squier, J. A. Advances in multiphoton microscopy technology. Nature Photon. 7, 93–101 (2013).

    Article  ADS  Google Scholar 

  18. Duncan, M. D., Reintjes, J. & Manuccia, T. J. Scanning coherent anti-stokes Raman microscope. Opt. Lett. 7, 350–352 (1982).

    Article  ADS  Google Scholar 

  19. 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).

    Article  ADS  Google Scholar 

  20. Ploetz, E., Laimgruber, S., Berner, S., Zinth, W. & Gilch, P. Femtosecond stimulated Raman microscopy. Appl. Phys. B 87, 389–393 (2007).

    Article  ADS  Google Scholar 

  21. Freudiger, C. W. et al. Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy. Science 322, 1857–1861 (2008).

    Article  ADS  Google Scholar 

  22. Spence, D. E., Kean, P. N. & Sibbett, W. 60-fsec pulse generation from a self-mode-locked Ti:sapphire laser. Opt. Lett. 16, 42–44 (1991).

    Article  ADS  Google Scholar 

  23. Negus, D. K., Spinelli, L., Goldblatt, N. & Feuget, G. Sub-100 fs pulse generation by Kerr lens modelocking in Ti: Al203 . in Tech. Digest OSA Top. Meet. Adv. Solid State Las. (OSA, 1991).

  24. Aus der Au, J., Kopf, D., Morier-Genoud, F., Moser, M. & Keller, U. 60-fs pulses from a diode-pumped Nd:glass laser. Opt. Lett. 22, 307–309 (1997).

    Article  ADS  Google Scholar 

  25. Hönninger, C. et al. Efficient and tunable diode-pumped femtosecond Yb: glass lasers. Opt. Lett. 23, 126–128 (1998).

    Article  ADS  Google Scholar 

  26. Druon, F., Balembois, F. & Georges, P. Laser crystals for the production of ultrashort laser pulses. Ann. Chim. Sci. Mat. 28, 47–72 (2003).

    Article  Google Scholar 

  27. Seas, A., Petričević, V. & Alfano, R. R. Generation of sub-100-fs pulses from a cw mode-locked chromium-doped forsterite laser. Opt. Lett. 17, 937–939 (1992).

    Article  ADS  Google Scholar 

  28. Fermann, M. E., Galvanauskas, A., Sucha, G. & Harter, D. Fiber-lasers for ultrafast optics. Appl. Phys. B 65, 259–275 (1997).

    Article  ADS  Google Scholar 

  29. Limpert, J., Roser, F., Schreiber, T. & Tunnermann, A. High-power ultrafast fiber laser systems. IEEE J. Sel. Top. Quant. Electron. 12, 233–244 (2006).

    Article  ADS  Google Scholar 

  30. Ruehl, A., Wandt, D., Morgner, U. & Kracht, D. Normal dispersive ultrafast fiber oscillators. IEEE J. Sel. Top. Quant. Electron. 15, 170–181 (2009).

    Article  ADS  Google Scholar 

  31. Fermann, M. & Hartl, I. Ultrafast fiber laser technology. IEEE J. Sel. Top. Quant. Electron. 15, 191–206 (2009).

    Article  ADS  Google Scholar 

  32. Valdmanis, J. A., Fork, R. L. & Gordon, J. P. Generation of optical pulses as short as 27 femtoseconds directly from a laser balancing self-phase modulation, group-velocity dispersion, saturable absorption, and saturable gain. Opt. Lett. 10, 131–133 (1985).

    Article  ADS  Google Scholar 

  33. Tamura, K., Ippen, E. P., Haus, H. A. & Nelson, L. E. 77-fs pulse generation from a stretched-pulse mode-locked all-fiber ring laser. Opt. Lett. 18, 1080–1082 (1993).

    Article  ADS  Google Scholar 

  34. Ober, M. H., Hofer, M. & Fermann, M. E. 42-fs pulse generation from a mode-locked fiber laser started with a moving mirror. Opt. Lett. 18, 367–369 (1993).

    Article  ADS  Google Scholar 

  35. Chong, A., Buckley, J., Renninger, W. & Wise, F. All-normal-dispersion femtosecond fiber laser. Opt. Express 14, 10095–10100 (2006).

    Article  ADS  Google Scholar 

  36. Renninger, W. H., Chong, A. & Wise, F. W. Dissipative solitons in normal-dispersion fiber lasers. Phys. Rev. A 77, 023814 (2008).

    Article  ADS  Google Scholar 

  37. Zhao, L. M., Tang, D. Y. & Wu, J. Gain-guided soliton in a positive group-dispersion fiber laser. Opt. Lett. 31, 1788–1790 (2006).

    Article  ADS  Google Scholar 

  38. Grelu, P. & Akhmediev, N. Dissipative solitons for mode-locked lasers. Nature Photon. 6, 84–92 (2012).

    Article  ADS  Google Scholar 

  39. Kieu, K., Renninger, W. H., Chong, A. & Wise, F. W. Sub-100-fs pulses at watt-level powers from a dissipative-soliton fiber laser. Opt. Lett. 34, 593–595 (2009).

    Article  ADS  Google Scholar 

  40. Chichkov, N. B. et al. Pulse duration and energy scaling of femtosecond all-normal dispersion fiber oscillators. Opt. Express 20, 3844–3852 (2012).

    Article  ADS  Google Scholar 

  41. Chong, A., Renninger, W. H. & Wise, F. W. Properties of normal-dispersion femtosecond fiber lasers. J. Opt. Soc. Am. B 25, 140–148 (2008).

    Article  ADS  Google Scholar 

  42. Renninger, W. H., Chong, A. & Wise, F. W. Self-similar pulse evolution in an all-normal-dispersion laser. Phys. Rev. A 82, 021805(R) (2010).

    Article  ADS  Google Scholar 

  43. Wise, F. W. Femtosecond fiber lasers based on dissipative processes for nonlinear microscopy. IEEE J. Sel. Top. Quant. Electron. 18, 1412–1421 (2012).

    Article  ADS  Google Scholar 

  44. Oktem, B., Ülgüdür, C. & Ilday, F. Ö. Soliton–similariton fibre laser. Nature Photon. 4, 307–311 (2010).

    Article  Google Scholar 

  45. Liu, G., Kieu, K., Wise, F. W. & Chen, Z. Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe. J. Biophotonics 4, 34–39 (2011).

    Article  Google Scholar 

  46. Galvanauskas, A. Mode-scalable fiber-based chirped pulse amplification systems. IEEE J. Select Top. Quant. Electron 7, 504–517 (2001).

    Article  ADS  Google Scholar 

  47. Lefrançois, S., Kieu, K., Deng, Y., Kafka, J. D. & Wise, F. W. Scaling of dissipative soliton fiber lasers to megawatt peak powers by use of large-area photonic-crystal fiber. Opt. Lett. 35, 1569–1571 (2010).

    Article  ADS  Google Scholar 

  48. Baumgartl, M., Lecaplain, C., Hideur, A., Limpert, J. & Tunnerman, A. 66 W average power from a microjoule-class sub-100 fs fiber oscillator. Opt. Lett. 37, 1640–1642 (2012).

    Article  ADS  Google Scholar 

  49. Ramachandran, S. et al. Light propagation with ultralarge modal areas in optical fibers. Opt. Lett. 31, 1797–1799 (2006).

    Article  ADS  Google Scholar 

  50. Nicholson, J. W. et al. Nanosecond pulse amplification in a 6000 μm2 effective area higher-order mode erbium-doped fiber amplifier. Paper JTh1I.2 in Proc. Conf. Lasers Electro Optics (OSA, 2012).

  51. Svoboda, K., Tank, D. W. & Denk, W. Direct measurement of coupling between dendritic spines and shafts. Science 272, 716–719 (1996).

    Article  ADS  Google Scholar 

  52. Mostany, R. & Portera-Cailliau, C. Absence of large-scale dendritic plasticity of layer 5 pyramidal neurons in peri-infarct cortex. J. Neuroscience 31, 1734–1738 (2011).

    Article  Google Scholar 

  53. Squirrell, J. M., Wokosin, D. L., White, J. G. & Bavister, B. D. Long-term two-photon fluorescence imaging of mammalian embryo without compromising viability. Nature Biotechnol. 17, 763–767 (1999).

    Article  Google Scholar 

  54. Zipfel, W. R. et al. Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc. Natl Acad. Sci. USA 100, 7075–7080 (2003).

    Article  ADS  Google Scholar 

  55. So, P. T. C., Dong, C. Y., Masters, B. R. & Berland, K. M. Two-photon excitation fluorescence microscopy. Annu. Rev. Biomed. Eng. 2, 399–429 (2000).

    Article  Google Scholar 

  56. Centonze, V. E. & White, J. G. Multiphoton excitation provides optical sections from deeper within scattering specimens than confocal imaging. Biophys. J. 75, 2015–2024 (1998).

    Article  ADS  Google Scholar 

  57. Theer, P., Hasan, M. T. & Denk, W. Two-photon imaging to a depth of 1000 μm in living brains by use of a Ti:Al2O3 regenerative amplifier. Opt. Lett. 28, 1022–1024 (2003).

    Article  ADS  Google Scholar 

  58. Leray, A., Odin, C., Huguet, E., Amblard, F. & Le Grand, Y. Spatially distributed two-photon excitation fluorescence in scattering media: experiments and time-resolved Monte Carlo simulations. Opt. Commun. 272, 269–278 (2007).

    Article  ADS  Google Scholar 

  59. Kobat, D., Horton, N. G. & Xu, C. In vivo two-photon microscopy to 1.6-mm depth in mouse cortex. J. Biomed. Opt. 16, 106014 (2011).

    Article  ADS  Google Scholar 

  60. Kobat, D. et al. Deep tissue multiphoton microscopy using longer wavelength excitation. Opt. Express 17, 13354–13364 (2009).

    Article  ADS  Google Scholar 

  61. Balu, M. et al. Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media. J. Biomed. Opt. 14, 010508 (2009).

    Article  ADS  Google Scholar 

  62. Andresen, V. et al. Infrared multiphoton microscopy: subcellular resolved deep tissue imaging. Curr. Opin. Biotechnol. 20, 54–62 (2009).

    Article  Google Scholar 

  63. Horton, N. G. et al. In vivo three-photon microscopy of subcortical structures of an intact mouse brain. Nature Photon 7, 205–209 (2009).

    Article  ADS  Google Scholar 

  64. Maiti, S., Shear, J. B., Williams, R. M., Zipfel, W. R. & Webb, W. W. Measuring serotonin distribution in live cells with three-photon excitation. Science 275, 530–532 (1997).

    Article  Google Scholar 

  65. Gordon, J. P. Theory of the soliton self-frequency shift. Opt. Lett. 11, 662–664 (1986).

    Article  ADS  Google Scholar 

  66. Zysset, B., Beaud, P. & Hodel, W. Generation of optical solitons in the wavelength region 1.37–149 μm. Appl. Phys. Lett. 50, 1027–1029 (1987).

    Article  ADS  Google Scholar 

  67. Liu, X. et al. Soliton self-frequency shift in a short tapered air-silica microstructure fiber. Opt. Lett. 26, 358–360 (2001).

    Article  ADS  Google Scholar 

  68. Knight, J. C., Broeng, J., Birks, T. A. & Russell, P. St. J. Photonic band gap guidance in optical fibers. Science 282, 1476–1478 (1998).

    Article  Google Scholar 

  69. Unruh, J. R. Two-photon microscopy with wavelength switchable fiber laser excitation. Opt. Express 14, 9825–9831 (2006).

    Article  ADS  Google Scholar 

  70. Ouzounov, D. G. Generation of megawatt optical solitons in hollow-core photonic band-gap fibers. Science 301, 1702–1704 (2003).

    Article  ADS  Google Scholar 

  71. Wang, K. & Xu, C. Tunable high-energy soliton pulse generation from a large-mode-area fiber and its application to third harmonic generation microscopy. Appl. Phys. Lett. 99, 071112 (2011).

    Article  ADS  Google Scholar 

  72. Ganikhanov, F. Broadly tunable dual-wavelength light source for coherent anti-Stokes Raman scattering microscopy. Opt. Lett. 31, 1292–1294 (2006).

    Article  ADS  Google Scholar 

  73. Andresen, E. R., Nielsen, C. K., Thøgersen, J. & Keiding, S. R. Fiber laser-based light source for coherent anti-Stokes Raman scattering microspectroscopy. Opt. Express 15, 4848–4856 (2007).

    Article  ADS  Google Scholar 

  74. 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).

    Article  ADS  Google Scholar 

  75. Kieu, K. & Peyghambarian, N. Synchronized picosecond pulses at two different wavelengths from a compact fiber laser source for Raman microscopy. Paper 790310 in SPIE BiOS (SPIE, 2011).

  76. Mosley, P. J., Bateman, S. A., Lavoute, L. & Wadsworth, W. J. Low-noise, high-brightness, tunable source of picosecond pulsed light in the near-infrared and visible. Opt. Express 19, 25337–25345 (2011).

    Article  ADS  Google Scholar 

  77. Baumgartl, M. et al. Alignment-free, all-spliced fiber laser source for CARS microscopy based on four-wave-mixing. Opt. Express 20, 21010–21018 (2012).

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

  80. Lamb, E. et al. Fiber optical parametric oscillator for coherent anti-Stokes Raman scattering microscopy Opt. Lett. 38, 4154–4157 (2013).

    Article  ADS  Google Scholar 

  81. Godil, A. A., Auld, B. A. & Bloom, D. M. Picosecond time-lenses. IEEE J. Quantum Electron. 30, 827–837 (1994).

    Article  ADS  Google Scholar 

  82. Kolner, B. H. Space-time duality and the theory of temporal imaging. IEEE J. Quantum Electron. 30, 1951–1963 (1994).

    Article  ADS  Google Scholar 

  83. Van Howe, J., Hansryd, J. & Xu, C. Multiwavelength pulse generator using time-lens compression. Opt. Lett. 29, 1470–1472 (2004).

    Article  ADS  Google Scholar 

  84. Wang, K. et al. Synchronized time-lens source for coherent Raman scattering microscopy. Opt. Exp. 23, 24019–24024 (2010).

    Article  ADS  Google Scholar 

  85. Wang, K. et al. Time-lens based hyperspectral stimulated Raman scattering imaging and quantitative spectral analysis. J. Biophotonics 6, 815–820 (2013).

    Article  Google Scholar 

  86. Pedersen, M. E. V. et al. Higher-order-mode fiber optimized for energetic soliton propagation. Opt. Lett. 37, 3459–3461 (2012).

    Article  ADS  Google Scholar 

  87. Olivié, G. et al. Wavelength dependence of femtosecond laser ablation threshold of corneal stroma. Opt. Express 16, 4121–4129 (2008).

    Article  ADS  Google Scholar 

  88. Liu, C.-H. Paper ME2 Effectively single-mode chirally-coupled core fiber. Paper ME2 in Advanced Solid-State Photonics (OSA, 2007).

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Acknowledgements

Portions of this work were supported by the National Institutes of Health (EB002019, R01CA133148, R01EB014873 and R21RR032392) and the National Science Foundation (ECCS-0901323, BIS-0967949).

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Correspondence to C. Xu or F. W. Wise.

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Competing interests

F. W. Wise is a named inventor on US patent US 8,416,817 B2 (publication date 04.09.2008, filing date 18.09.2007) and Chinese patent number 200780042670.8, which are related to the dissipative-soliton laser described in this Review Article. European patent application number 7873804.4 has been filed on the same subject. Wise has also submitted a patent application relating to picosecond-pulse sources for coherent anti-Stokes Raman microscopy (international patent PCT/US/2012/058817 (publication date 11.04.2013, filing date 04.10.2011).

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Xu, C., Wise, F. Recent advances in fibre lasers for nonlinear microscopy. Nature Photon 7, 875–882 (2013). https://doi.org/10.1038/nphoton.2013.284

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