Abstract

An environmentally-stable low-repetition rate fiber oscillator is developed to produce narrow-bandwidth pulses with several tens of picoseconds duration. Based on this oscillator an alignment-free all-fiber laser for multi-photon microscopy is realized using in-fiber frequency conversion based on four-wave-mixing. Both pump and Stokes pulses for coherent anti-Stokes Raman scattering (CARS) microscopy are readily available from one fiber end, intrinsically overlapped in space and time, which drastically simplifies the experimental handling for the user. The complete laser setup is mounted on a home-built laser scanning microscope with small footprint. High-quality multimodal microscope images of biological tissue are presented probing the CH-stretching resonance of lipids at an anti-Stokes Raman-shift of 2845 cm−1 and second-harmonic generation of collagen. Due to its simplicity, compactness, maintenance-free operation, and ease-of-use the presented low-cost laser is an ideal source for bio-medical applications outside laser laboratories and in particular inside clinics.

© 2012 OSA

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    [CrossRef] [PubMed]
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2012 (3)

2011 (3)

2010 (2)

2009 (5)

2008 (2)

C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif)1(1), 883–909 (2008).
[CrossRef] [PubMed]

W. H. Renninger, A. Chong, and F. W. Wise, “Giant-chirp oscillators for short-pulse fiber amplifiers,” Opt. Lett.33(24), 3025–3027 (2008).
[CrossRef] [PubMed]

2007 (1)

2003 (1)

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

1999 (1)

Andresen, E. R.

Balu, M.

Bateman, S. A.

Baumgartl, M.

Becker, T. W.

Bégin, S.

Blake, J. A.

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7(3), 137–145 (2011).
[CrossRef] [PubMed]

Burgoyne, B.

Chemnitz, M.

Chen, Z.

Cheng, X.

Chong, A.

Christie, R.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Côté, D.

Danielson, D. C.

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7(3), 137–145 (2011).
[CrossRef] [PubMed]

Dietzek, B.

Dong, L.

Dupriez, P.

Evans, C. L.

C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif)1(1), 883–909 (2008).
[CrossRef] [PubMed]

Fermann, M. E.

Fischer, P.

Fu, D.

Fu, L.

Gong, Y.

Halbhuber, K. J.

Hanke, T.

Herda, R.

Holtom, G. R.

Hyman, B. T.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Jauregui, C.

Keiding, S. R.

Kennedy, D. C.

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7(3), 137–145 (2011).
[CrossRef] [PubMed]

Knight, J. C.

Kong, L.

König, K.

Krafft, C.

C. Krafft, B. Dietzek, and J. Popp, “Raman and CARS microspectroscopy of cells and tissues,” Analyst (Lond.)134(6), 1046–1057 (2009).
[CrossRef] [PubMed]

Krauss, G.

Lavoute, L.

Lefrancois, S.

Leitenstorfer, A.

Limpert, J.

Lin, C.

Liu, G.

Lyn, R. K.

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7(3), 137–145 (2011).
[CrossRef] [PubMed]

Mercier, V.

Meyer, T.

Moffatt, D. J.

Mosley, P. J.

Nielsen, C. K.

Nikitin, A. Y.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Nodop, D.

Ortaç, B.

M. Baumgartl, B. Ortaç, J. Limpert, and A. Tünnermann, “Impact of dispersion on pulse dynamics in chirped-pulse fiber lasers,” Appl. Phys. B107(2), 263–274 (2012).
[CrossRef]

Pegoraro, A. F.

Pezacki, J. P.

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7(3), 137–145 (2011).
[CrossRef] [PubMed]

A. F. Pegoraro, A. Ridsdale, D. J. Moffatt, J. P. Pezacki, B. K. Thomas, L. Fu, L. Dong, M. E. Fermann, and A. Stolow, “All-fiber CARS microscopy of live cells,” Opt. Express17(23), 20700–20706 (2009).
[CrossRef] [PubMed]

Popp, J.

Potma, E. O.

Renninger, W. H.

Ridsdale, A.

Riemann, I.

Schimpf, D.

Schneider, P.

Sell, A.

Selm, R.

Shum, P. P.

Singaravelu, R.

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7(3), 137–145 (2011).
[CrossRef] [PubMed]

Stolow, A.

Sunney Xie, X.

Tang, M.

Thøgersen, J.

Thomas, B. K.

Tian, X.

Träutlein, D.

Tromberg, B. J.

Tünnermann, A.

Vallée, R.

Villeneuve, A.

Wadsworth, W. J.

Webb, W. W.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Williams, R. M.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Winterhalder, M.

Wise, F. W.

Xie, X. S.

C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif)1(1), 883–909 (2008).
[CrossRef] [PubMed]

Zach, A.

Zipfel, W. R.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Zumbusch, A.

Analyst (Lond.) (1)

C. Krafft, B. Dietzek, and J. Popp, “Raman and CARS microspectroscopy of cells and tissues,” Analyst (Lond.)134(6), 1046–1057 (2009).
[CrossRef] [PubMed]

Annu Rev Anal Chem (Palo Alto Calif) (1)

C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif)1(1), 883–909 (2008).
[CrossRef] [PubMed]

Appl. Phys. B (1)

M. Baumgartl, B. Ortaç, J. Limpert, and A. Tünnermann, “Impact of dispersion on pulse dynamics in chirped-pulse fiber lasers,” Appl. Phys. B107(2), 263–274 (2012).
[CrossRef]

Biomed. Opt. Express (1)

Nat. Chem. Biol. (1)

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7(3), 137–145 (2011).
[CrossRef] [PubMed]

Opt. Express (7)

E. R. Andresen, C. K. Nielsen, J. Thøgersen, and S. R. Keiding, “Fiber laser-based light source for coherent anti-Stokes Raman scattering microspectroscopy,” Opt. Express15(8), 4848–4856 (2007).
[CrossRef] [PubMed]

P. J. Mosley, S. A. Bateman, L. Lavoute, and W. J. Wadsworth, “Low-noise, high-brightness, tunable source of picosecond pulsed light in the near-infrared and visible,” Opt. Express19(25), 25337–25345 (2011).
[CrossRef] [PubMed]

M. Baumgartl, M. Chemnitz, C. Jauregui, T. Meyer, B. Dietzek, J. Popp, J. Limpert, and A. Tünnermann, “All-fiber laser source for CARS microscopy based on fiber optical parametric frequency conversion,” Opt. Express20(4), 4484–4493 (2012).
[CrossRef] [PubMed]

X. Tian, M. Tang, X. Cheng, P. P. Shum, Y. Gong, and C. Lin, “High-energy wave-breaking-free pulse from all-fiber mode-locked laser system,” Opt. Express17(9), 7222–7227 (2009).
[CrossRef] [PubMed]

A. F. Pegoraro, A. Ridsdale, D. J. Moffatt, J. P. Pezacki, B. K. Thomas, L. Fu, L. Dong, M. E. Fermann, and A. Stolow, “All-fiber CARS microscopy of live cells,” Opt. Express17(23), 20700–20706 (2009).
[CrossRef] [PubMed]

M. Balu, G. Liu, Z. Chen, B. J. Tromberg, and E. O. Potma, “Fiber delivered probe for efficient CARS imaging of tissues,” Opt. Express18(3), 2380–2388 (2010).
[CrossRef] [PubMed]

L. Lavoute, J. C. Knight, P. Dupriez, and W. J. Wadsworth, “High power red and near-IR generation using four wave mixing in all integrated fibre laser systems,” Opt. Express18(15), 16193–16205 (2010).
[CrossRef] [PubMed]

Opt. Lett. (5)

Proc. Natl. Acad. Sci. U.S.A. (1)

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

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Figures (6)

Fig. 1
Fig. 1

Schematic of the all-fiber CARS laser source, showing the ps oscillator (upper part) and the amplification and frequency conversion stages (lower part).

Fig. 2
Fig. 2

Oscillator pulse characterization: (a) Temporal characteristic measured with a fast photo diode (19ps response time) and a 70GHz sampling oscilloscope; (b) Spectrum measured with a resolution of 0.02nm.

Fig. 3
Fig. 3

(a) FWM phase-matching diagram for the PCF showing the frequency shift and the corresponding signal wavelength over pump wavelength; (b) Microscope image of the splice between Yb-doped SIF (left) and PCF (right), the splice transmission is 74%.

Fig. 4
Fig. 4

(a)-(c) Characterization of the generated pulses at 26mW of signal power: Spectral shape of FWM signal (a) and corresponding residual pump (b), temporal shapes accordingly, measured with a fast photo diode (c) and signal pulse autocorrelation trace (c, inset). (d) Spectral width of FWM signal and residual pump for different signal power.

Fig. 5
Fig. 5

Schematic of the CARS microscopy setup, SP short pass, LP long pass, BP band pass, PMT photo multiplier tube.

Fig. 6
Fig. 6

Microscopic images of atherosclerotic plaque deposition at the inner human arterial wall. (a)-(c) show the same sample section: (a) CARS image probing lipids at 2844 cm−1, the atherosclerotic plaques appear bright due to their high lipid content, (b) combined SHG and TPEF signal of the elastic fibers of the arterial wall predominantly composed of collagen (SHG) and elastin (TPEF), (c) Multimodal composite image showing an overlay of the CARS and the SHG/TPEF signals. The images were sampled with 16.8 Mpixels with a pixel dwell time of 1 μs, 2 scans averaged, 50 mW total laser power on the sample. (d) Multimodal composite image as in (c) showing a different aorta section, recorded with 20 mW total laser power on the sample.

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