Abstract

We demonstrate heterodyne detection of CARS signals using a cascaded phase-preserving chain to generate the CARS input wavelengths and a coherent local oscillator. The heterodyne amplification by the local oscillator reveals a window for shot noise limited detection before the signal-to-noise is limited by amplitude fluctuations. We demonstrate an improvement in sensitivity by more than 3 orders of magnitude for detection using a photodiode. This will enable CARS microscopy to reveal concentrations below the current mMolar range.

© 2007 Optical Society of America

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  1. J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19, 1363-1375 (2002).
    [CrossRef]
  2. A. Voroshilov, C. Otto, and J. Greve, "Secondary Structure of Bovine Albumin as Studied by Polarization-Sensitive Multiplex CARS Spectroscopy," Appl. Spectrosc. 50, 78-85 (1996).
    [CrossRef]
  3. G. Petrov and V. Yakovlev, "Enhancing red-shifted white-light continuum generation in optical fibers for applications in nonlinear Raman microscopy," Opt. Express 13, 1299-1306 (2005).
    [CrossRef] [PubMed]
  4. H. Kano and H. Hamaguchi, "In-vivo multi-nonlinear optical imaging of a living cell using a supercontinuum light source generated from a photonic crystal fiber," Opt. Express 14, 2798-2804 (2006).
    [CrossRef] [PubMed]
  5. X. Nan, E. Potma, X. S. Xie, "Nonperturbabtive chemical imaging of organelle transport in living cells with CARS microscopy," Biophysical J. 91, 728-735 (2006).
    [CrossRef]
  6. B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
    [CrossRef] [PubMed]
  7. E. O. Potma, C. L. Evans, and X. S. Xie, "Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging," Opt. Lett. 31, 241-243 (2006).
    [CrossRef] [PubMed]
  8. R.W. Boyd, Nonlinear Optics, Second Edition, (Academic Press) 2003.
  9. M. Jurna, J. P. Korterik, H. L. Offerhaus and C. Otto, "Noncritical phase-matched lithium triborate optical parametric oscillator for high resolution coherent anti-Stokes Raman scattering spectroscopy and microscopy," Appl. Phys. Lett. 89, 251116 (2006).
    [CrossRef]
  10. T. Tukker, "A high repetition rate picosecond infrared light source for a sum frequency vibration spectrometer," Thesis University of Twente, The Netherlands, ISBN 90-365 11860 (1998).
  11. C. L. Evans, E. O. Potma, M. Puoris’haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
    [CrossRef] [PubMed]
  12. J. X. Cheng, Y. K. Jia, G. F. Zheng, and X. S. Xie, "Laser-scanning coherent anti-stokes Raman scattering microscopy," Biophys. J. 83, 502-509 (2002).
    [CrossRef] [PubMed]
  13. E. R. Andresen, S. R. Keiding, and E. O. Potma, "Picosecond anti-Stokes generation in a photonic-crystal fiber for interferometric CARS microscopy," Opt. Express 14, 7246-7251 (2006).
    [CrossRef] [PubMed]
  14. B. von Vacano, T. Buckup and M. Motzkus, "Highly sensitive single-beam heterodyne coherent anti-Stokes Raman scattering," Opt. Lett. 31, 2495-2498 (2006).
    [CrossRef] [PubMed]
  15. E. M. H. P. van Dijk, "Single Nanoparticles, ultrafast and unltrasensitive detection," Thesis Universiteit Twente, The Netherlands ISBN 90-365-2136-X (2005).

2006 (7)

H. Kano and H. Hamaguchi, "In-vivo multi-nonlinear optical imaging of a living cell using a supercontinuum light source generated from a photonic crystal fiber," Opt. Express 14, 2798-2804 (2006).
[CrossRef] [PubMed]

X. Nan, E. Potma, X. S. Xie, "Nonperturbabtive chemical imaging of organelle transport in living cells with CARS microscopy," Biophysical J. 91, 728-735 (2006).
[CrossRef]

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

E. O. Potma, C. L. Evans, and X. S. Xie, "Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging," Opt. Lett. 31, 241-243 (2006).
[CrossRef] [PubMed]

M. Jurna, J. P. Korterik, H. L. Offerhaus and C. Otto, "Noncritical phase-matched lithium triborate optical parametric oscillator for high resolution coherent anti-Stokes Raman scattering spectroscopy and microscopy," Appl. Phys. Lett. 89, 251116 (2006).
[CrossRef]

E. R. Andresen, S. R. Keiding, and E. O. Potma, "Picosecond anti-Stokes generation in a photonic-crystal fiber for interferometric CARS microscopy," Opt. Express 14, 7246-7251 (2006).
[CrossRef] [PubMed]

B. von Vacano, T. Buckup and M. Motzkus, "Highly sensitive single-beam heterodyne coherent anti-Stokes Raman scattering," Opt. Lett. 31, 2495-2498 (2006).
[CrossRef] [PubMed]

2005 (2)

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

G. Petrov and V. Yakovlev, "Enhancing red-shifted white-light continuum generation in optical fibers for applications in nonlinear Raman microscopy," Opt. Express 13, 1299-1306 (2005).
[CrossRef] [PubMed]

2002 (2)

J. X. Cheng, Y. K. Jia, G. F. Zheng, and X. S. Xie, "Laser-scanning coherent anti-stokes Raman scattering microscopy," Biophys. J. 83, 502-509 (2002).
[CrossRef] [PubMed]

J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19, 1363-1375 (2002).
[CrossRef]

1996 (1)

Andresen, E. R.

Belanger, S.

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

Buckup, T.

Cheng, J. X.

J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19, 1363-1375 (2002).
[CrossRef]

J. X. Cheng, Y. K. Jia, G. F. Zheng, and X. S. Xie, "Laser-scanning coherent anti-stokes Raman scattering microscopy," Biophys. J. 83, 502-509 (2002).
[CrossRef] [PubMed]

Cote, D.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Evans, C. L.

E. O. Potma, C. L. Evans, and X. S. Xie, "Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging," Opt. Lett. 31, 241-243 (2006).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Evans, C.L.

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

Greve, J.

Hamaguchi, H.

Jia, Y. K.

J. X. Cheng, Y. K. Jia, G. F. Zheng, and X. S. Xie, "Laser-scanning coherent anti-stokes Raman scattering microscopy," Biophys. J. 83, 502-509 (2002).
[CrossRef] [PubMed]

Jurna, M.

M. Jurna, J. P. Korterik, H. L. Offerhaus and C. Otto, "Noncritical phase-matched lithium triborate optical parametric oscillator for high resolution coherent anti-Stokes Raman scattering spectroscopy and microscopy," Appl. Phys. Lett. 89, 251116 (2006).
[CrossRef]

Kano, H.

Keiding, S. R.

Korterik, J. P.

M. Jurna, J. P. Korterik, H. L. Offerhaus and C. Otto, "Noncritical phase-matched lithium triborate optical parametric oscillator for high resolution coherent anti-Stokes Raman scattering spectroscopy and microscopy," Appl. Phys. Lett. 89, 251116 (2006).
[CrossRef]

Lin, C. P.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Motzkus, M.

Nan, X.

X. Nan, E. Potma, X. S. Xie, "Nonperturbabtive chemical imaging of organelle transport in living cells with CARS microscopy," Biophysical J. 91, 728-735 (2006).
[CrossRef]

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

Noestheden, M.

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

Offerhaus, H. L.

M. Jurna, J. P. Korterik, H. L. Offerhaus and C. Otto, "Noncritical phase-matched lithium triborate optical parametric oscillator for high resolution coherent anti-Stokes Raman scattering spectroscopy and microscopy," Appl. Phys. Lett. 89, 251116 (2006).
[CrossRef]

Otto, C.

M. Jurna, J. P. Korterik, H. L. Offerhaus and C. Otto, "Noncritical phase-matched lithium triborate optical parametric oscillator for high resolution coherent anti-Stokes Raman scattering spectroscopy and microscopy," Appl. Phys. Lett. 89, 251116 (2006).
[CrossRef]

A. Voroshilov, C. Otto, and J. Greve, "Secondary Structure of Bovine Albumin as Studied by Polarization-Sensitive Multiplex CARS Spectroscopy," Appl. Spectrosc. 50, 78-85 (1996).
[CrossRef]

Petrov, G.

Pezacki, J.P.

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

Potma, E.

X. Nan, E. Potma, X. S. Xie, "Nonperturbabtive chemical imaging of organelle transport in living cells with CARS microscopy," Biophysical J. 91, 728-735 (2006).
[CrossRef]

Potma, E. O.

Puoris’haag, M.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Rakic, B.

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

Sagan, S.M.

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

Volkmer, A.

von Vacano, B.

Voroshilov, A.

Xie, X. S.

E. O. Potma, C. L. Evans, and X. S. Xie, "Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging," Opt. Lett. 31, 241-243 (2006).
[CrossRef] [PubMed]

X. Nan, E. Potma, X. S. Xie, "Nonperturbabtive chemical imaging of organelle transport in living cells with CARS microscopy," Biophysical J. 91, 728-735 (2006).
[CrossRef]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

J. X. Cheng, Y. K. Jia, G. F. Zheng, and X. S. Xie, "Laser-scanning coherent anti-stokes Raman scattering microscopy," Biophys. J. 83, 502-509 (2002).
[CrossRef] [PubMed]

J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19, 1363-1375 (2002).
[CrossRef]

Xie, X.S.

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

Yakovlev, V.

Zheng, G. F.

J. X. Cheng, Y. K. Jia, G. F. Zheng, and X. S. Xie, "Laser-scanning coherent anti-stokes Raman scattering microscopy," Biophys. J. 83, 502-509 (2002).
[CrossRef] [PubMed]

Appl. Phys. Lett. (1)

M. Jurna, J. P. Korterik, H. L. Offerhaus and C. Otto, "Noncritical phase-matched lithium triborate optical parametric oscillator for high resolution coherent anti-Stokes Raman scattering spectroscopy and microscopy," Appl. Phys. Lett. 89, 251116 (2006).
[CrossRef]

Appl. Spectrosc. (1)

Biophys. J. (1)

J. X. Cheng, Y. K. Jia, G. F. Zheng, and X. S. Xie, "Laser-scanning coherent anti-stokes Raman scattering microscopy," Biophys. J. 83, 502-509 (2002).
[CrossRef] [PubMed]

Biophysical J. (1)

X. Nan, E. Potma, X. S. Xie, "Nonperturbabtive chemical imaging of organelle transport in living cells with CARS microscopy," Biophysical J. 91, 728-735 (2006).
[CrossRef]

Chem. Biol. (1)

B. Rakic, S.M. Sagan, M. Noestheden, S. Belanger, X. Nan, C.L. Evans, X.S. Xie and J.P. Pezacki, "Peroxisome peroliferator-activated receptor α antagonism inhibits hepatitis C virus replication," Chem. Biol. 13, 23-30 (2006).
[CrossRef] [PubMed]

J. Opt. Soc. Am. B (1)

Opt. Express (3)

Opt. Lett. (2)

Proc. Natl. Acad. Sci. USA (1)

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Other (3)

R.W. Boyd, Nonlinear Optics, Second Edition, (Academic Press) 2003.

T. Tukker, "A high repetition rate picosecond infrared light source for a sum frequency vibration spectrometer," Thesis University of Twente, The Netherlands, ISBN 90-365 11860 (1998).

E. M. H. P. van Dijk, "Single Nanoparticles, ultrafast and unltrasensitive detection," Thesis Universiteit Twente, The Netherlands ISBN 90-365-2136-X (2005).

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Figures (4)

Fig. 1.
Fig. 1.

Optical chain for the phase-preserved generation of wavelengths for the CARS process. The inset shows the energy diagram for both paths to the CARS wavelength

Fig. 2.
Fig. 2.

Noise as a function of local oscillator power. The noise is expressed in Noise Equivalent Power (NEP), Root Mean Square (rms) in 1.58Hz bandwidth so that all lines can be compared directly. The dashed lines A and B have a slope of 1/2,1 respectively. Continuous lines are a simulation, symbols represent measured data. Inset shows the detector electronics.

Fig. 3.
Fig. 3.

Noise (NEP, R=1MΩ, BW=1.58Hz) for 2μW of the signal and the total signal output versus OPO pump power (532nm inside the crystal)

Fig. 4.
Fig. 4.

Heterodyne signal and direct detected signal (rms in 1.58Hz BW) versus CARS power. (A) represents the improvement factor (3500) in detection sensitivity between the heterodyne detection and direct (chopper) detection signal for a photodiode. (B) represents the improvement factor (7.5) for detection with a PMT.

Equations (1)

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I detector = LO + CARS + 2 LO CARS HCARS

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