Abstract

A coaxial thermal lens microscope was used to generate images based on both the absorbance and thermal diffusivity of histological samples. A pump beam was modulated at frequencies ranging from 50kHz to 5MHz using an acousto-optic modulator. The pump and a CW probe beam were combined with a dichroic mirror, directed into an inverted microscope, and focused onto the specimen. The change in the transmitted probe beam’s center intensity was detected with a photodiode. The photodiode’s signal and a reference signal from the modulator were sent to a high-speed lock-in amplifier. The in-phase and quadrature signals were recorded as a sample was translated through the focused beams and used to generate images based on the amplitude and phase of the lock-in amplifier’s signal. The amplitude is related to the absorbance and the phase is related to the thermal diffusivity of the sample. Thin sections of stained liver and bone tissues were imaged; the contrast and signal-to-noise ratio of the phase image was highest at frequencies from 0.11MHz and dropped at higher frequencies. The spatial resolution was 2.5μm for both amplitude and phase images, limited by the pump beam spot size.

© 2011 Optical Society of America

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  1. J. R. Whinnery, “Laser measurement of optical-absorption in liquids,” Acc. Chem. Res. 7, 225–231 (1974).
    [CrossRef]
  2. N. J. Dovichi, “Thermo-optical spectrophotometries in analytical chemistry,” CRC Crit. Rev. Anal. Chem. 17, 357–424(1987).
    [CrossRef]
  3. S. E. Bialkowski, Photothermal Spectroscopic Method for Chemical Analysis (Wiley1996).
  4. N. J. Dovichi and J. M. Harris, “Laser-induced thermal lens effect for calorimetric trace analysis,” Anal. Chem. 53, 106–109 (1981).
    [CrossRef]
  5. T. G. Nolan, B. K. Hart, and N. J. Dovichi, “Photothermal refraction as a microbore liquid-chromatography detector in femtomole amino-acid determination,” Anal. Chem. 57, 2703–2705 (1985).
    [CrossRef]
  6. S. Hiki, K. Mawatari, A. Hibara, M. Tokeshi, and T. Kitamori, “UV excitation thermal lens microscope for sensitive and nonlabeled detection of nonfluorescent molecules,” Anal. Chem. 78, 2859–2863 (2006).
    [CrossRef] [PubMed]
  7. D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297, 1160–1163 (2002).
    [CrossRef] [PubMed]
  8. W. A. Weimer and N. J. Dovichi, “Simple-model for the time-dependence of the periodically excited crossed-beam thermal lens,” J. Appl. Phys. 59, 225–230 (1986).
    [CrossRef]
  9. T. I. Chen and M. D. Morris, “Photothermal deflection densitometer for thin-layer chromatography,” Anal. Chem. 56, 19–21 (1984).
    [CrossRef]
  10. D. S. Burgi, T. G. Nolan, J. A. Risfelt, and N. J. Dovichi, “Photothermal refraction for scanning laser microscopy,” Opt. Eng. 23, 756–758 (1984).
  11. D. S. Burgi and N. J. Dovichi, “Submicrometer resolution images of absorbency and thermal-diffusivity with the photothermal microscope,” Appl. Opt. 26, 4665–4669(1987).
    [CrossRef] [PubMed]
  12. D. Lapotko, G. Kuchinsky, M. Potapnev, and D. Pechkovsky, “Photothermal image cytometry of human neutrophils,” Cytometry 24, 198–203 (1996).
    [CrossRef] [PubMed]
  13. J. Zheng, T. Odake, T. Kitamori, and T. Sawada, “Miniaturized ultrathin slab gel electrophoresis with thermal lens microscope detection and its application to fast genetic diagnosis,” Anal. Chem. 71, 5003–5008 (1999).
    [CrossRef] [PubMed]
  14. H. Kimura, K. Sekiguchi, T. Kitamori, T. Sawada, and M. Mukaida, “Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances,” Anal. Chem. 73, 4333–4337 (2001).
    [CrossRef] [PubMed]
  15. E. Tamaki, K. Sato, M. Tokeshi, K. Sato, M. Aihara, and T. Kitamori, “Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process,” Anal. Chem. 74, 1560–1564 (2002).
    [CrossRef] [PubMed]
  16. B. Bertussi, J. V. Natoli, and M. Commandré, “High-resolution photothermal microscope: a sensitive tool for the detection of isolated absorbing defects in optical coatings,” Appl. Opt. 45, 1410–1415 (2006).
    [CrossRef] [PubMed]
  17. S. J. Lu, W. Min, S. Chong, G. R. Holtom, and X. S. Xie, “Label-free imaging of heme proteins with two-photon excited photothermal lens microscopy,” Appl. Phys. Lett. 96, 113701(2010).
    [CrossRef]
  18. W. A. Weimer and N. J. Dovichi, “Time-resolved crossed-beam thermal lens measurement as a nonintrusive probe of flow velocity,” Appl. Opt. 24, 2981–2986 (1985).
    [CrossRef] [PubMed]
  19. R. McLaren and N. J. Dovichi, “Spatially resolved differential resistance of bulk superconductors by laser-induced heating,” J. Appl. Phys. 68, 4882–4884 (1990).
    [CrossRef]
  20. S. Wu and N. J. Dovichi, “Fresnel diffraction theory for steady-state thermal lens measurements in thin-films,” Appl. Phys. 67, 1170–1182 (1990).
    [CrossRef]
  21. J. P. Gordon, R. C. C. Leite, R. S. Moore, S. P. S. Porto, and J. R. Whinnery, “Long-transient effects in lasers with inserted liquid samples,” J. Appl. Phys. 36, 3–8 (1965).
    [CrossRef]
  22. F. Oberhettinger, Tabellen Zur Fourier Transformation (Springer-Verlag, 1957).
  23. D. J. Doss, J. D. Humphrey, and N. T. Wright, “Measurement of thermal diffusivity of bovine aorta subject to finite deformation,” Ann. NY Acad. Sci. 858, 88–97 (1998).
    [CrossRef]
  24. S. Biyikli, M. F. Modest, and R. Tarr, “Measurements of thermal properties for human femora,” J. Biomed. Mater. Res. 20, 1335–1345 (1986).
    [CrossRef] [PubMed]
  25. C. Haisch, “Quantitative analysis in medicine using photoacoustic tomography,” Anal. Bioanal. Chem. 393, 473–479(2009).
    [CrossRef]
  26. M. H. Xu and V. H. V. Wang, “Photoacoustic imaging in biomedicine,” Rev. Sci. Instrum. 77, 041101 (2006).
    [CrossRef]
  27. N. Tabatabaei, A. Mandelis, and B. T. Amaechi, “Thermal-wave radar: a novel subsurface imaging modality with extended depth-resolution dynamic range,” J. Biomed. Opt. 16, 071402 (2011).
    [CrossRef] [PubMed]

2011 (1)

N. Tabatabaei, A. Mandelis, and B. T. Amaechi, “Thermal-wave radar: a novel subsurface imaging modality with extended depth-resolution dynamic range,” J. Biomed. Opt. 16, 071402 (2011).
[CrossRef] [PubMed]

2010 (1)

S. J. Lu, W. Min, S. Chong, G. R. Holtom, and X. S. Xie, “Label-free imaging of heme proteins with two-photon excited photothermal lens microscopy,” Appl. Phys. Lett. 96, 113701(2010).
[CrossRef]

2009 (1)

C. Haisch, “Quantitative analysis in medicine using photoacoustic tomography,” Anal. Bioanal. Chem. 393, 473–479(2009).
[CrossRef]

2006 (3)

M. H. Xu and V. H. V. Wang, “Photoacoustic imaging in biomedicine,” Rev. Sci. Instrum. 77, 041101 (2006).
[CrossRef]

S. Hiki, K. Mawatari, A. Hibara, M. Tokeshi, and T. Kitamori, “UV excitation thermal lens microscope for sensitive and nonlabeled detection of nonfluorescent molecules,” Anal. Chem. 78, 2859–2863 (2006).
[CrossRef] [PubMed]

B. Bertussi, J. V. Natoli, and M. Commandré, “High-resolution photothermal microscope: a sensitive tool for the detection of isolated absorbing defects in optical coatings,” Appl. Opt. 45, 1410–1415 (2006).
[CrossRef] [PubMed]

2002 (2)

E. Tamaki, K. Sato, M. Tokeshi, K. Sato, M. Aihara, and T. Kitamori, “Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process,” Anal. Chem. 74, 1560–1564 (2002).
[CrossRef] [PubMed]

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297, 1160–1163 (2002).
[CrossRef] [PubMed]

2001 (1)

H. Kimura, K. Sekiguchi, T. Kitamori, T. Sawada, and M. Mukaida, “Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances,” Anal. Chem. 73, 4333–4337 (2001).
[CrossRef] [PubMed]

1999 (1)

J. Zheng, T. Odake, T. Kitamori, and T. Sawada, “Miniaturized ultrathin slab gel electrophoresis with thermal lens microscope detection and its application to fast genetic diagnosis,” Anal. Chem. 71, 5003–5008 (1999).
[CrossRef] [PubMed]

1998 (1)

D. J. Doss, J. D. Humphrey, and N. T. Wright, “Measurement of thermal diffusivity of bovine aorta subject to finite deformation,” Ann. NY Acad. Sci. 858, 88–97 (1998).
[CrossRef]

1996 (1)

D. Lapotko, G. Kuchinsky, M. Potapnev, and D. Pechkovsky, “Photothermal image cytometry of human neutrophils,” Cytometry 24, 198–203 (1996).
[CrossRef] [PubMed]

1990 (2)

R. McLaren and N. J. Dovichi, “Spatially resolved differential resistance of bulk superconductors by laser-induced heating,” J. Appl. Phys. 68, 4882–4884 (1990).
[CrossRef]

S. Wu and N. J. Dovichi, “Fresnel diffraction theory for steady-state thermal lens measurements in thin-films,” Appl. Phys. 67, 1170–1182 (1990).
[CrossRef]

1987 (2)

1986 (2)

W. A. Weimer and N. J. Dovichi, “Simple-model for the time-dependence of the periodically excited crossed-beam thermal lens,” J. Appl. Phys. 59, 225–230 (1986).
[CrossRef]

S. Biyikli, M. F. Modest, and R. Tarr, “Measurements of thermal properties for human femora,” J. Biomed. Mater. Res. 20, 1335–1345 (1986).
[CrossRef] [PubMed]

1985 (2)

T. G. Nolan, B. K. Hart, and N. J. Dovichi, “Photothermal refraction as a microbore liquid-chromatography detector in femtomole amino-acid determination,” Anal. Chem. 57, 2703–2705 (1985).
[CrossRef]

W. A. Weimer and N. J. Dovichi, “Time-resolved crossed-beam thermal lens measurement as a nonintrusive probe of flow velocity,” Appl. Opt. 24, 2981–2986 (1985).
[CrossRef] [PubMed]

1984 (2)

T. I. Chen and M. D. Morris, “Photothermal deflection densitometer for thin-layer chromatography,” Anal. Chem. 56, 19–21 (1984).
[CrossRef]

D. S. Burgi, T. G. Nolan, J. A. Risfelt, and N. J. Dovichi, “Photothermal refraction for scanning laser microscopy,” Opt. Eng. 23, 756–758 (1984).

1981 (1)

N. J. Dovichi and J. M. Harris, “Laser-induced thermal lens effect for calorimetric trace analysis,” Anal. Chem. 53, 106–109 (1981).
[CrossRef]

1974 (1)

J. R. Whinnery, “Laser measurement of optical-absorption in liquids,” Acc. Chem. Res. 7, 225–231 (1974).
[CrossRef]

1965 (1)

J. P. Gordon, R. C. C. Leite, R. S. Moore, S. P. S. Porto, and J. R. Whinnery, “Long-transient effects in lasers with inserted liquid samples,” J. Appl. Phys. 36, 3–8 (1965).
[CrossRef]

Aihara, M.

E. Tamaki, K. Sato, M. Tokeshi, K. Sato, M. Aihara, and T. Kitamori, “Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process,” Anal. Chem. 74, 1560–1564 (2002).
[CrossRef] [PubMed]

Amaechi, B. T.

N. Tabatabaei, A. Mandelis, and B. T. Amaechi, “Thermal-wave radar: a novel subsurface imaging modality with extended depth-resolution dynamic range,” J. Biomed. Opt. 16, 071402 (2011).
[CrossRef] [PubMed]

Bertussi, B.

Bialkowski, S. E.

S. E. Bialkowski, Photothermal Spectroscopic Method for Chemical Analysis (Wiley1996).

Biyikli, S.

S. Biyikli, M. F. Modest, and R. Tarr, “Measurements of thermal properties for human femora,” J. Biomed. Mater. Res. 20, 1335–1345 (1986).
[CrossRef] [PubMed]

Boyer, D.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297, 1160–1163 (2002).
[CrossRef] [PubMed]

Burgi, D. S.

D. S. Burgi and N. J. Dovichi, “Submicrometer resolution images of absorbency and thermal-diffusivity with the photothermal microscope,” Appl. Opt. 26, 4665–4669(1987).
[CrossRef] [PubMed]

D. S. Burgi, T. G. Nolan, J. A. Risfelt, and N. J. Dovichi, “Photothermal refraction for scanning laser microscopy,” Opt. Eng. 23, 756–758 (1984).

Chen, T. I.

T. I. Chen and M. D. Morris, “Photothermal deflection densitometer for thin-layer chromatography,” Anal. Chem. 56, 19–21 (1984).
[CrossRef]

Chong, S.

S. J. Lu, W. Min, S. Chong, G. R. Holtom, and X. S. Xie, “Label-free imaging of heme proteins with two-photon excited photothermal lens microscopy,” Appl. Phys. Lett. 96, 113701(2010).
[CrossRef]

Commandré, M.

Doss, D. J.

D. J. Doss, J. D. Humphrey, and N. T. Wright, “Measurement of thermal diffusivity of bovine aorta subject to finite deformation,” Ann. NY Acad. Sci. 858, 88–97 (1998).
[CrossRef]

Dovichi, N. J.

R. McLaren and N. J. Dovichi, “Spatially resolved differential resistance of bulk superconductors by laser-induced heating,” J. Appl. Phys. 68, 4882–4884 (1990).
[CrossRef]

S. Wu and N. J. Dovichi, “Fresnel diffraction theory for steady-state thermal lens measurements in thin-films,” Appl. Phys. 67, 1170–1182 (1990).
[CrossRef]

N. J. Dovichi, “Thermo-optical spectrophotometries in analytical chemistry,” CRC Crit. Rev. Anal. Chem. 17, 357–424(1987).
[CrossRef]

D. S. Burgi and N. J. Dovichi, “Submicrometer resolution images of absorbency and thermal-diffusivity with the photothermal microscope,” Appl. Opt. 26, 4665–4669(1987).
[CrossRef] [PubMed]

W. A. Weimer and N. J. Dovichi, “Simple-model for the time-dependence of the periodically excited crossed-beam thermal lens,” J. Appl. Phys. 59, 225–230 (1986).
[CrossRef]

T. G. Nolan, B. K. Hart, and N. J. Dovichi, “Photothermal refraction as a microbore liquid-chromatography detector in femtomole amino-acid determination,” Anal. Chem. 57, 2703–2705 (1985).
[CrossRef]

W. A. Weimer and N. J. Dovichi, “Time-resolved crossed-beam thermal lens measurement as a nonintrusive probe of flow velocity,” Appl. Opt. 24, 2981–2986 (1985).
[CrossRef] [PubMed]

D. S. Burgi, T. G. Nolan, J. A. Risfelt, and N. J. Dovichi, “Photothermal refraction for scanning laser microscopy,” Opt. Eng. 23, 756–758 (1984).

N. J. Dovichi and J. M. Harris, “Laser-induced thermal lens effect for calorimetric trace analysis,” Anal. Chem. 53, 106–109 (1981).
[CrossRef]

Gordon, J. P.

J. P. Gordon, R. C. C. Leite, R. S. Moore, S. P. S. Porto, and J. R. Whinnery, “Long-transient effects in lasers with inserted liquid samples,” J. Appl. Phys. 36, 3–8 (1965).
[CrossRef]

Haisch, C.

C. Haisch, “Quantitative analysis in medicine using photoacoustic tomography,” Anal. Bioanal. Chem. 393, 473–479(2009).
[CrossRef]

Harris, J. M.

N. J. Dovichi and J. M. Harris, “Laser-induced thermal lens effect for calorimetric trace analysis,” Anal. Chem. 53, 106–109 (1981).
[CrossRef]

Hart, B. K.

T. G. Nolan, B. K. Hart, and N. J. Dovichi, “Photothermal refraction as a microbore liquid-chromatography detector in femtomole amino-acid determination,” Anal. Chem. 57, 2703–2705 (1985).
[CrossRef]

Hibara, A.

S. Hiki, K. Mawatari, A. Hibara, M. Tokeshi, and T. Kitamori, “UV excitation thermal lens microscope for sensitive and nonlabeled detection of nonfluorescent molecules,” Anal. Chem. 78, 2859–2863 (2006).
[CrossRef] [PubMed]

Hiki, S.

S. Hiki, K. Mawatari, A. Hibara, M. Tokeshi, and T. Kitamori, “UV excitation thermal lens microscope for sensitive and nonlabeled detection of nonfluorescent molecules,” Anal. Chem. 78, 2859–2863 (2006).
[CrossRef] [PubMed]

Holtom, G. R.

S. J. Lu, W. Min, S. Chong, G. R. Holtom, and X. S. Xie, “Label-free imaging of heme proteins with two-photon excited photothermal lens microscopy,” Appl. Phys. Lett. 96, 113701(2010).
[CrossRef]

Humphrey, J. D.

D. J. Doss, J. D. Humphrey, and N. T. Wright, “Measurement of thermal diffusivity of bovine aorta subject to finite deformation,” Ann. NY Acad. Sci. 858, 88–97 (1998).
[CrossRef]

Kimura, H.

H. Kimura, K. Sekiguchi, T. Kitamori, T. Sawada, and M. Mukaida, “Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances,” Anal. Chem. 73, 4333–4337 (2001).
[CrossRef] [PubMed]

Kitamori, T.

S. Hiki, K. Mawatari, A. Hibara, M. Tokeshi, and T. Kitamori, “UV excitation thermal lens microscope for sensitive and nonlabeled detection of nonfluorescent molecules,” Anal. Chem. 78, 2859–2863 (2006).
[CrossRef] [PubMed]

E. Tamaki, K. Sato, M. Tokeshi, K. Sato, M. Aihara, and T. Kitamori, “Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process,” Anal. Chem. 74, 1560–1564 (2002).
[CrossRef] [PubMed]

H. Kimura, K. Sekiguchi, T. Kitamori, T. Sawada, and M. Mukaida, “Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances,” Anal. Chem. 73, 4333–4337 (2001).
[CrossRef] [PubMed]

J. Zheng, T. Odake, T. Kitamori, and T. Sawada, “Miniaturized ultrathin slab gel electrophoresis with thermal lens microscope detection and its application to fast genetic diagnosis,” Anal. Chem. 71, 5003–5008 (1999).
[CrossRef] [PubMed]

Kuchinsky, G.

D. Lapotko, G. Kuchinsky, M. Potapnev, and D. Pechkovsky, “Photothermal image cytometry of human neutrophils,” Cytometry 24, 198–203 (1996).
[CrossRef] [PubMed]

Lapotko, D.

D. Lapotko, G. Kuchinsky, M. Potapnev, and D. Pechkovsky, “Photothermal image cytometry of human neutrophils,” Cytometry 24, 198–203 (1996).
[CrossRef] [PubMed]

Leite, R. C. C.

J. P. Gordon, R. C. C. Leite, R. S. Moore, S. P. S. Porto, and J. R. Whinnery, “Long-transient effects in lasers with inserted liquid samples,” J. Appl. Phys. 36, 3–8 (1965).
[CrossRef]

Lounis, B.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297, 1160–1163 (2002).
[CrossRef] [PubMed]

Lu, S. J.

S. J. Lu, W. Min, S. Chong, G. R. Holtom, and X. S. Xie, “Label-free imaging of heme proteins with two-photon excited photothermal lens microscopy,” Appl. Phys. Lett. 96, 113701(2010).
[CrossRef]

Maali, A.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297, 1160–1163 (2002).
[CrossRef] [PubMed]

Mandelis, A.

N. Tabatabaei, A. Mandelis, and B. T. Amaechi, “Thermal-wave radar: a novel subsurface imaging modality with extended depth-resolution dynamic range,” J. Biomed. Opt. 16, 071402 (2011).
[CrossRef] [PubMed]

Mawatari, K.

S. Hiki, K. Mawatari, A. Hibara, M. Tokeshi, and T. Kitamori, “UV excitation thermal lens microscope for sensitive and nonlabeled detection of nonfluorescent molecules,” Anal. Chem. 78, 2859–2863 (2006).
[CrossRef] [PubMed]

McLaren, R.

R. McLaren and N. J. Dovichi, “Spatially resolved differential resistance of bulk superconductors by laser-induced heating,” J. Appl. Phys. 68, 4882–4884 (1990).
[CrossRef]

Min, W.

S. J. Lu, W. Min, S. Chong, G. R. Holtom, and X. S. Xie, “Label-free imaging of heme proteins with two-photon excited photothermal lens microscopy,” Appl. Phys. Lett. 96, 113701(2010).
[CrossRef]

Modest, M. F.

S. Biyikli, M. F. Modest, and R. Tarr, “Measurements of thermal properties for human femora,” J. Biomed. Mater. Res. 20, 1335–1345 (1986).
[CrossRef] [PubMed]

Moore, R. S.

J. P. Gordon, R. C. C. Leite, R. S. Moore, S. P. S. Porto, and J. R. Whinnery, “Long-transient effects in lasers with inserted liquid samples,” J. Appl. Phys. 36, 3–8 (1965).
[CrossRef]

Morris, M. D.

T. I. Chen and M. D. Morris, “Photothermal deflection densitometer for thin-layer chromatography,” Anal. Chem. 56, 19–21 (1984).
[CrossRef]

Mukaida, M.

H. Kimura, K. Sekiguchi, T. Kitamori, T. Sawada, and M. Mukaida, “Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances,” Anal. Chem. 73, 4333–4337 (2001).
[CrossRef] [PubMed]

Natoli, J. V.

Nolan, T. G.

T. G. Nolan, B. K. Hart, and N. J. Dovichi, “Photothermal refraction as a microbore liquid-chromatography detector in femtomole amino-acid determination,” Anal. Chem. 57, 2703–2705 (1985).
[CrossRef]

D. S. Burgi, T. G. Nolan, J. A. Risfelt, and N. J. Dovichi, “Photothermal refraction for scanning laser microscopy,” Opt. Eng. 23, 756–758 (1984).

Oberhettinger, F.

F. Oberhettinger, Tabellen Zur Fourier Transformation (Springer-Verlag, 1957).

Odake, T.

J. Zheng, T. Odake, T. Kitamori, and T. Sawada, “Miniaturized ultrathin slab gel electrophoresis with thermal lens microscope detection and its application to fast genetic diagnosis,” Anal. Chem. 71, 5003–5008 (1999).
[CrossRef] [PubMed]

Orrit, M.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297, 1160–1163 (2002).
[CrossRef] [PubMed]

Pechkovsky, D.

D. Lapotko, G. Kuchinsky, M. Potapnev, and D. Pechkovsky, “Photothermal image cytometry of human neutrophils,” Cytometry 24, 198–203 (1996).
[CrossRef] [PubMed]

Porto, S. P. S.

J. P. Gordon, R. C. C. Leite, R. S. Moore, S. P. S. Porto, and J. R. Whinnery, “Long-transient effects in lasers with inserted liquid samples,” J. Appl. Phys. 36, 3–8 (1965).
[CrossRef]

Potapnev, M.

D. Lapotko, G. Kuchinsky, M. Potapnev, and D. Pechkovsky, “Photothermal image cytometry of human neutrophils,” Cytometry 24, 198–203 (1996).
[CrossRef] [PubMed]

Risfelt, J. A.

D. S. Burgi, T. G. Nolan, J. A. Risfelt, and N. J. Dovichi, “Photothermal refraction for scanning laser microscopy,” Opt. Eng. 23, 756–758 (1984).

Sato, K.

E. Tamaki, K. Sato, M. Tokeshi, K. Sato, M. Aihara, and T. Kitamori, “Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process,” Anal. Chem. 74, 1560–1564 (2002).
[CrossRef] [PubMed]

E. Tamaki, K. Sato, M. Tokeshi, K. Sato, M. Aihara, and T. Kitamori, “Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process,” Anal. Chem. 74, 1560–1564 (2002).
[CrossRef] [PubMed]

Sawada, T.

H. Kimura, K. Sekiguchi, T. Kitamori, T. Sawada, and M. Mukaida, “Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances,” Anal. Chem. 73, 4333–4337 (2001).
[CrossRef] [PubMed]

J. Zheng, T. Odake, T. Kitamori, and T. Sawada, “Miniaturized ultrathin slab gel electrophoresis with thermal lens microscope detection and its application to fast genetic diagnosis,” Anal. Chem. 71, 5003–5008 (1999).
[CrossRef] [PubMed]

Sekiguchi, K.

H. Kimura, K. Sekiguchi, T. Kitamori, T. Sawada, and M. Mukaida, “Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances,” Anal. Chem. 73, 4333–4337 (2001).
[CrossRef] [PubMed]

Tabatabaei, N.

N. Tabatabaei, A. Mandelis, and B. T. Amaechi, “Thermal-wave radar: a novel subsurface imaging modality with extended depth-resolution dynamic range,” J. Biomed. Opt. 16, 071402 (2011).
[CrossRef] [PubMed]

Tamaki, E.

E. Tamaki, K. Sato, M. Tokeshi, K. Sato, M. Aihara, and T. Kitamori, “Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process,” Anal. Chem. 74, 1560–1564 (2002).
[CrossRef] [PubMed]

Tamarat, P.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297, 1160–1163 (2002).
[CrossRef] [PubMed]

Tarr, R.

S. Biyikli, M. F. Modest, and R. Tarr, “Measurements of thermal properties for human femora,” J. Biomed. Mater. Res. 20, 1335–1345 (1986).
[CrossRef] [PubMed]

Tokeshi, M.

S. Hiki, K. Mawatari, A. Hibara, M. Tokeshi, and T. Kitamori, “UV excitation thermal lens microscope for sensitive and nonlabeled detection of nonfluorescent molecules,” Anal. Chem. 78, 2859–2863 (2006).
[CrossRef] [PubMed]

E. Tamaki, K. Sato, M. Tokeshi, K. Sato, M. Aihara, and T. Kitamori, “Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process,” Anal. Chem. 74, 1560–1564 (2002).
[CrossRef] [PubMed]

Wang, V. H. V.

M. H. Xu and V. H. V. Wang, “Photoacoustic imaging in biomedicine,” Rev. Sci. Instrum. 77, 041101 (2006).
[CrossRef]

Weimer, W. A.

W. A. Weimer and N. J. Dovichi, “Simple-model for the time-dependence of the periodically excited crossed-beam thermal lens,” J. Appl. Phys. 59, 225–230 (1986).
[CrossRef]

W. A. Weimer and N. J. Dovichi, “Time-resolved crossed-beam thermal lens measurement as a nonintrusive probe of flow velocity,” Appl. Opt. 24, 2981–2986 (1985).
[CrossRef] [PubMed]

Whinnery, J. R.

J. R. Whinnery, “Laser measurement of optical-absorption in liquids,” Acc. Chem. Res. 7, 225–231 (1974).
[CrossRef]

J. P. Gordon, R. C. C. Leite, R. S. Moore, S. P. S. Porto, and J. R. Whinnery, “Long-transient effects in lasers with inserted liquid samples,” J. Appl. Phys. 36, 3–8 (1965).
[CrossRef]

Wright, N. T.

D. J. Doss, J. D. Humphrey, and N. T. Wright, “Measurement of thermal diffusivity of bovine aorta subject to finite deformation,” Ann. NY Acad. Sci. 858, 88–97 (1998).
[CrossRef]

Wu, S.

S. Wu and N. J. Dovichi, “Fresnel diffraction theory for steady-state thermal lens measurements in thin-films,” Appl. Phys. 67, 1170–1182 (1990).
[CrossRef]

Xie, X. S.

S. J. Lu, W. Min, S. Chong, G. R. Holtom, and X. S. Xie, “Label-free imaging of heme proteins with two-photon excited photothermal lens microscopy,” Appl. Phys. Lett. 96, 113701(2010).
[CrossRef]

Xu, M. H.

M. H. Xu and V. H. V. Wang, “Photoacoustic imaging in biomedicine,” Rev. Sci. Instrum. 77, 041101 (2006).
[CrossRef]

Zheng, J.

J. Zheng, T. Odake, T. Kitamori, and T. Sawada, “Miniaturized ultrathin slab gel electrophoresis with thermal lens microscope detection and its application to fast genetic diagnosis,” Anal. Chem. 71, 5003–5008 (1999).
[CrossRef] [PubMed]

Acc. Chem. Res. (1)

J. R. Whinnery, “Laser measurement of optical-absorption in liquids,” Acc. Chem. Res. 7, 225–231 (1974).
[CrossRef]

Anal. Bioanal. Chem. (1)

C. Haisch, “Quantitative analysis in medicine using photoacoustic tomography,” Anal. Bioanal. Chem. 393, 473–479(2009).
[CrossRef]

Anal. Chem. (7)

T. I. Chen and M. D. Morris, “Photothermal deflection densitometer for thin-layer chromatography,” Anal. Chem. 56, 19–21 (1984).
[CrossRef]

N. J. Dovichi and J. M. Harris, “Laser-induced thermal lens effect for calorimetric trace analysis,” Anal. Chem. 53, 106–109 (1981).
[CrossRef]

T. G. Nolan, B. K. Hart, and N. J. Dovichi, “Photothermal refraction as a microbore liquid-chromatography detector in femtomole amino-acid determination,” Anal. Chem. 57, 2703–2705 (1985).
[CrossRef]

S. Hiki, K. Mawatari, A. Hibara, M. Tokeshi, and T. Kitamori, “UV excitation thermal lens microscope for sensitive and nonlabeled detection of nonfluorescent molecules,” Anal. Chem. 78, 2859–2863 (2006).
[CrossRef] [PubMed]

J. Zheng, T. Odake, T. Kitamori, and T. Sawada, “Miniaturized ultrathin slab gel electrophoresis with thermal lens microscope detection and its application to fast genetic diagnosis,” Anal. Chem. 71, 5003–5008 (1999).
[CrossRef] [PubMed]

H. Kimura, K. Sekiguchi, T. Kitamori, T. Sawada, and M. Mukaida, “Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances,” Anal. Chem. 73, 4333–4337 (2001).
[CrossRef] [PubMed]

E. Tamaki, K. Sato, M. Tokeshi, K. Sato, M. Aihara, and T. Kitamori, “Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process,” Anal. Chem. 74, 1560–1564 (2002).
[CrossRef] [PubMed]

Ann. NY Acad. Sci. (1)

D. J. Doss, J. D. Humphrey, and N. T. Wright, “Measurement of thermal diffusivity of bovine aorta subject to finite deformation,” Ann. NY Acad. Sci. 858, 88–97 (1998).
[CrossRef]

Appl. Opt. (3)

Appl. Phys. (1)

S. Wu and N. J. Dovichi, “Fresnel diffraction theory for steady-state thermal lens measurements in thin-films,” Appl. Phys. 67, 1170–1182 (1990).
[CrossRef]

Appl. Phys. Lett. (1)

S. J. Lu, W. Min, S. Chong, G. R. Holtom, and X. S. Xie, “Label-free imaging of heme proteins with two-photon excited photothermal lens microscopy,” Appl. Phys. Lett. 96, 113701(2010).
[CrossRef]

CRC Crit. Rev. Anal. Chem. (1)

N. J. Dovichi, “Thermo-optical spectrophotometries in analytical chemistry,” CRC Crit. Rev. Anal. Chem. 17, 357–424(1987).
[CrossRef]

Cytometry (1)

D. Lapotko, G. Kuchinsky, M. Potapnev, and D. Pechkovsky, “Photothermal image cytometry of human neutrophils,” Cytometry 24, 198–203 (1996).
[CrossRef] [PubMed]

J. Appl. Phys. (3)

J. P. Gordon, R. C. C. Leite, R. S. Moore, S. P. S. Porto, and J. R. Whinnery, “Long-transient effects in lasers with inserted liquid samples,” J. Appl. Phys. 36, 3–8 (1965).
[CrossRef]

W. A. Weimer and N. J. Dovichi, “Simple-model for the time-dependence of the periodically excited crossed-beam thermal lens,” J. Appl. Phys. 59, 225–230 (1986).
[CrossRef]

R. McLaren and N. J. Dovichi, “Spatially resolved differential resistance of bulk superconductors by laser-induced heating,” J. Appl. Phys. 68, 4882–4884 (1990).
[CrossRef]

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S. Biyikli, M. F. Modest, and R. Tarr, “Measurements of thermal properties for human femora,” J. Biomed. Mater. Res. 20, 1335–1345 (1986).
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J. Biomed. Opt. (1)

N. Tabatabaei, A. Mandelis, and B. T. Amaechi, “Thermal-wave radar: a novel subsurface imaging modality with extended depth-resolution dynamic range,” J. Biomed. Opt. 16, 071402 (2011).
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Opt. Eng. (1)

D. S. Burgi, T. G. Nolan, J. A. Risfelt, and N. J. Dovichi, “Photothermal refraction for scanning laser microscopy,” Opt. Eng. 23, 756–758 (1984).

Rev. Sci. Instrum. (1)

M. H. Xu and V. H. V. Wang, “Photoacoustic imaging in biomedicine,” Rev. Sci. Instrum. 77, 041101 (2006).
[CrossRef]

Science (1)

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science 297, 1160–1163 (2002).
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F. Oberhettinger, Tabellen Zur Fourier Transformation (Springer-Verlag, 1957).

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Figures (10)

Fig. 1
Fig. 1

Bode plots for the response of the thermal lens signal [Eqs. (5a, 5b)] for t. A—Amplitude response. B—phase response. The insert presents the difference in-phase versus reduced frequency.

Fig. 2
Fig. 2

Apparatus setup: The coaxial wave pump and probe beams are focused into the sample using a high numerical aperture objective. The incident beams are expanded and overfill the objective lens to produce a diffraction limited spot size. The transmitted beams are collected with a second objective that acts as a condenser to deliver the probe beam center to a GRIN-lens-coupled fiber optic. Light emitted from the distal end of the fiber is collimated, passed through a laser line filter centered at the probe laser wavelength, and focused onto a fast photodiode. A lock-in amplifier is phase-referenced to the acousto-optic modulator and the in-phase and quadrature signals are recorded.

Fig. 3
Fig. 3

Time-resolved thermal lens signals obtained from a liver tissue. The green traces are the digitized signal and the blue curves are the least-squares fit of the convolution of the impulse response function of Eq. (1) with a square wave consisting of ten transients. A—transient generated in fatty tissue ( t c = 19.9 μs ). B—transient generated in normal tissue ( t c = 12.1 μs ). Residuals are plotted in red on the same scale as the signals.

Fig. 4
Fig. 4

Log–log plot of the thermal lens amplitude as a function of modulation frequency (plus sign) for the nonfatty region of the liver sample used in Fig. 2. The smooth curve is the amplitude of the Fourier transform of the impulse response function [Eq. (5a)] with t c = 50 μs and the amplitude adjusted to bring the curves into alignment. The bottom trace is the residual (linear Y scale).

Fig. 5
Fig. 5

Thermal lens amplitude microscope image of a thin liver section generated at a pump beam modulation frequency of 50 kHz , 500 kHz , and 4 MHz . In addition, a conventional transmission micrograph is shown using the same false color scheme. Distances are shown in micrometers. Dashed lines are the traces used to estimate spatial resolution in Fig. 6.

Fig. 6
Fig. 6

Thermal lens phase microscope image of a thin liver section generated at a pump beam modulation frequency of 50 kHz , 500 kHz , and 4 MHz . In addition, a conventional transmission micrograph is shown. Distances are in micrometers. Dashed lines are the traces used to estimate spatial resolution in Fig. 6.

Fig. 7
Fig. 7

Overexposed version of the 50 kHz phase image in Fig. 6.

Fig. 8
Fig. 8

Traces taken from the 50 kHz images in Figs. 4, 5. Smooth curves are the least-squares regression fits of an offset error function to the transition near 30 μm in both axes.

Fig. 9
Fig. 9

Thermal lens microscope image of a compact bone section generated at 1 MHz . Left: thermal lens amplitude image. Center: conventional transmission image. Right: thermal lens phase image. Distances are in micrometers.

Fig. 10
Fig. 10

The photothermal phase image of Fig. 9 is overexposed and the contrast is stretched to show subtle features in the compact bone tissue. Image is 200 μm × 200 μm .

Equations (7)

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Δ I I ( t ) = 4.606 E A d n / d T Z 1 π k ω 2 ( 1 + t / t c ) 2 = Θ ( 1 + t / t c ) 2 ,
t c = ω 2 / 4 D T ,
D T = k / ρ C p .
real ( ν 0 ) = Θ t c ν 0 [ cos ( ν 0 + π ) si ( ν 0 ) sin ( ν 0 + π ) Ci ( ν 0 ) ] ,
imaginary ( ν 0 ) = Θ t c ν 0 [ cos ( ν 0 + π ) Ci ( ν 0 ) + sin ( ν 0 + π ) si ( ν 0 ) ] ,
amplitude = real 2 + imaginary 2 ,
phase = arctan ( real imaginary ) .

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