Abstract

Third-order sum frequency generation (TSFG) is one of the third-order nonlinear optical processes, and has the generation mechanism analogous to third harmonic generation (THG). By using a white-light supercontinuum, we can obtain broadband multiplex TSFG spectra. In the present study, we developed an electronically resonant TSFG spectrometer, and applied it to obtain TSFG spectra of hemoproteins. Analyzed TSFG ratio spectra clearly showed the resonant enhancement attributable to the electronic state of hemoproteins. This is a promising method for the imaging of electronic states of molecules inside living cells or tissues.

© 2014 Optical Society of America

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References

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    [CrossRef] [PubMed]
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2013 (1)

2012 (1)

2010 (1)

C.-F. Chang, C.-H. Yu, C.-K. Sun, “Multi-photon resonance enhancement of third harmonic generation in human oxyhemoglobin and deoxyhemoglobin,” J. Biophotonics 3(10-11), 678–685 (2010).
[CrossRef] [PubMed]

2009 (1)

L. Gebicka, E. Banasiak, “Flavonoids as reductants of ferryl hemoglobin,” Acta Biochim. Pol. 56(3), 509–513 (2009).
[PubMed]

2008 (1)

2006 (3)

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

G. O. Clay, A. C. Millard, C. B. Schaffer, J. Aus-der-Au, P. S. Tsai, J. A. Squier, D. Kleinfeld, “Spectroscopy of third-harmonic generation: evidence for resonances in model compounds and ligated hemoglobin,” J. Opt. Soc. Am. B 23(5), 932–950 (2006).
[CrossRef]

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, W. A. Mohler, “Characterization of the Myosin-Based Source for Second-Harmonic Generation from Muscle Sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[CrossRef] [PubMed]

2003 (3)

P. J. Campagnola, L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003).
[CrossRef] [PubMed]

2002 (3)

G. Veres, S. Matsumoto, Y. Nabekawa, K. Midorikawa, “Enhancement of third-harmonic generation in absorbing media,” Appl. Phys. Lett. 81(20), 3714–3716 (2002).
[CrossRef]

A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, W. A. Mohler, “Three-Dimensional High-Resolution Second-Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues,” Biophys. J. 82(1), 493–508 (2002).
[CrossRef] [PubMed]

2001 (1)

2000 (1)

R. D. Schaller, J. C. Johnson, R. J. Saykally, “Nonlinear Chemical Imaging Microscopy: Near-Field Third Harmonic Generation Imaging of Human Red Blood Cells,” Anal. Chem. 72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

1999 (1)

1997 (1)

Y. Barad, H. Eisenberg, M. Horowitz, Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[CrossRef]

1996 (1)

A. Mathy, K. Ueberhofen, R. Schenk, H. Gregorius, R. Garay, K. Müllen, C. Bubeck, “Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers,” Phys. Rev. B Condens. Matter 53(8), 4367–4376 (1996).
[CrossRef] [PubMed]

1964 (1)

R. Benesch, R. E. Benesch, G. MacDuff, “Spectra of Deoxygenated Hemoglobin in the Soret Region,” Science 144(3614), 68–69 (1964).
[CrossRef] [PubMed]

Aus-der-Au, J.

Banasiak, E.

L. Gebicka, E. Banasiak, “Flavonoids as reductants of ferryl hemoglobin,” Acta Biochim. Pol. 56(3), 509–513 (2009).
[PubMed]

Barad, Y.

Y. Barad, H. Eisenberg, M. Horowitz, Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[CrossRef]

Barille, R.

Beaurepaire, E.

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

Benesch, R.

R. Benesch, R. E. Benesch, G. MacDuff, “Spectra of Deoxygenated Hemoglobin in the Soret Region,” Science 144(3614), 68–69 (1964).
[CrossRef] [PubMed]

Benesch, R. E.

R. Benesch, R. E. Benesch, G. MacDuff, “Spectra of Deoxygenated Hemoglobin in the Soret Region,” Science 144(3614), 68–69 (1964).
[CrossRef] [PubMed]

Boucher, Y.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003).
[CrossRef] [PubMed]

Brown, E.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003).
[CrossRef] [PubMed]

Bubeck, C.

A. Mathy, K. Ueberhofen, R. Schenk, H. Gregorius, R. Garay, K. Müllen, C. Bubeck, “Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers,” Phys. Rev. B Condens. Matter 53(8), 4367–4376 (1996).
[CrossRef] [PubMed]

Campagnola, P. J.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, W. A. Mohler, “Characterization of the Myosin-Based Source for Second-Harmonic Generation from Muscle Sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[CrossRef] [PubMed]

P. J. Campagnola, L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, W. A. Mohler, “Three-Dimensional High-Resolution Second-Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues,” Biophys. J. 82(1), 493–508 (2002).
[CrossRef] [PubMed]

Canioni, L.

Chan, Y.-F.

Chang, C.-F.

C.-F. Chang, C.-H. Yu, C.-K. Sun, “Multi-photon resonance enhancement of third harmonic generation in human oxyhemoglobin and deoxyhemoglobin,” J. Biophotonics 3(10-11), 678–685 (2010).
[CrossRef] [PubMed]

Clay, G. O.

Combettes, L.

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

Couderc, V.

Débarre, D.

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

diTomaso, E.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003).
[CrossRef] [PubMed]

Dombeck, D. A.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

Eisenberg, H.

Y. Barad, H. Eisenberg, M. Horowitz, Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[CrossRef]

Fabre, A.

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

Fukutake, N.

Garay, R.

A. Mathy, K. Ueberhofen, R. Schenk, H. Gregorius, R. Garay, K. Müllen, C. Bubeck, “Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers,” Phys. Rev. B Condens. Matter 53(8), 4367–4376 (1996).
[CrossRef] [PubMed]

Gebicka, L.

L. Gebicka, E. Banasiak, “Flavonoids as reductants of ferryl hemoglobin,” Acta Biochim. Pol. 56(3), 509–513 (2009).
[PubMed]

Gregorius, H.

A. Mathy, K. Ueberhofen, R. Schenk, H. Gregorius, R. Garay, K. Müllen, C. Bubeck, “Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers,” Phys. Rev. B Condens. Matter 53(8), 4367–4376 (1996).
[CrossRef] [PubMed]

Hamaguchi, H.-O.

Hoppe, P. E.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, W. A. Mohler, “Three-Dimensional High-Resolution Second-Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues,” Biophys. J. 82(1), 493–508 (2002).
[CrossRef] [PubMed]

Horowitz, M.

Y. Barad, H. Eisenberg, M. Horowitz, Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[CrossRef]

Hyman, B. T.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

Ingelsson, M.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

Jain, R. K.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003).
[CrossRef] [PubMed]

Johnson, J. C.

R. D. Schaller, J. C. Johnson, R. J. Saykally, “Nonlinear Chemical Imaging Microscopy: Near-Field Third Harmonic Generation Imaging of Human Red Blood Cells,” Anal. Chem. 72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

Kano, H.

Kasischke, K. A.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

Kleinfeld, D.

Kung, C.-T.

Lee, W.-J.

Leproux, P.

Liu, H.-L.

Loew, L. M.

P. J. Campagnola, L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

Lyu, J.-Y.

MacDuff, G.

R. Benesch, R. E. Benesch, G. MacDuff, “Spectra of Deoxygenated Hemoglobin in the Soret Region,” Science 144(3614), 68–69 (1964).
[CrossRef] [PubMed]

Malone, C. J.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, W. A. Mohler, “Three-Dimensional High-Resolution Second-Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues,” Biophys. J. 82(1), 493–508 (2002).
[CrossRef] [PubMed]

Mathy, A.

A. Mathy, K. Ueberhofen, R. Schenk, H. Gregorius, R. Garay, K. Müllen, C. Bubeck, “Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers,” Phys. Rev. B Condens. Matter 53(8), 4367–4376 (1996).
[CrossRef] [PubMed]

Matsumoto, S.

G. Veres, S. Matsumoto, Y. Nabekawa, K. Midorikawa, “Enhancement of third-harmonic generation in absorbing media,” Appl. Phys. Lett. 81(20), 3714–3716 (2002).
[CrossRef]

McKee, T.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003).
[CrossRef] [PubMed]

Midorikawa, K.

G. Veres, S. Matsumoto, Y. Nabekawa, K. Midorikawa, “Enhancement of third-harmonic generation in absorbing media,” Appl. Phys. Lett. 81(20), 3714–3716 (2002).
[CrossRef]

Millard, A. C.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, W. A. Mohler, “Characterization of the Myosin-Based Source for Second-Harmonic Generation from Muscle Sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[CrossRef] [PubMed]

G. O. Clay, A. C. Millard, C. B. Schaffer, J. Aus-der-Au, P. S. Tsai, J. A. Squier, D. Kleinfeld, “Spectroscopy of third-harmonic generation: evidence for resonances in model compounds and ligated hemoglobin,” J. Opt. Soc. Am. B 23(5), 932–950 (2006).
[CrossRef]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, W. A. Mohler, “Three-Dimensional High-Resolution Second-Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues,” Biophys. J. 82(1), 493–508 (2002).
[CrossRef] [PubMed]

Mohler, W. A.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, W. A. Mohler, “Characterization of the Myosin-Based Source for Second-Harmonic Generation from Muscle Sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[CrossRef] [PubMed]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, W. A. Mohler, “Three-Dimensional High-Resolution Second-Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues,” Biophys. J. 82(1), 493–508 (2002).
[CrossRef] [PubMed]

Müllen, K.

A. Mathy, K. Ueberhofen, R. Schenk, H. Gregorius, R. Garay, K. Müllen, C. Bubeck, “Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers,” Phys. Rev. B Condens. Matter 53(8), 4367–4376 (1996).
[CrossRef] [PubMed]

Nabekawa, Y.

G. Veres, S. Matsumoto, Y. Nabekawa, K. Midorikawa, “Enhancement of third-harmonic generation in absorbing media,” Appl. Phys. Lett. 81(20), 3714–3716 (2002).
[CrossRef]

Okuno, M.

Pena, A. M.

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

Plotnikov, S. V.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, W. A. Mohler, “Characterization of the Myosin-Based Source for Second-Harmonic Generation from Muscle Sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[CrossRef] [PubMed]

Pluen, A.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003).
[CrossRef] [PubMed]

Rivet, S.

Sarger, L.

Saykally, R. J.

R. D. Schaller, J. C. Johnson, R. J. Saykally, “Nonlinear Chemical Imaging Microscopy: Near-Field Third Harmonic Generation Imaging of Human Red Blood Cells,” Anal. Chem. 72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

Schaffer, C. B.

Schaller, R. D.

R. D. Schaller, J. C. Johnson, R. J. Saykally, “Nonlinear Chemical Imaging Microscopy: Near-Field Third Harmonic Generation Imaging of Human Red Blood Cells,” Anal. Chem. 72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

Schanne-Klein, M. C.

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

Schenk, R.

A. Mathy, K. Ueberhofen, R. Schenk, H. Gregorius, R. Garay, K. Müllen, C. Bubeck, “Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers,” Phys. Rev. B Condens. Matter 53(8), 4367–4376 (1996).
[CrossRef] [PubMed]

Seed, B.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003).
[CrossRef] [PubMed]

Segawa, H.

Silberberg, Y.

D. Yelin, Y. Silberberg, “Laser scanning third-harmonic-generation microscopy in biology,” Opt. Express 5(8), 169–175 (1999).
[CrossRef] [PubMed]

Y. Barad, H. Eisenberg, M. Horowitz, Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[CrossRef]

Squier, J. A.

Sun, C.-K.

C.-F. Chang, C.-H. Yu, C.-K. Sun, “Multi-photon resonance enhancement of third harmonic generation in human oxyhemoglobin and deoxyhemoglobin,” J. Biophotonics 3(10-11), 678–685 (2010).
[CrossRef] [PubMed]

C.-H. Yu, S.-P. Tai, C.-T. Kung, W.-J. Lee, Y.-F. Chan, H.-L. Liu, J.-Y. Lyu, C.-K. Sun, “Molecular third-harmonic-generation microscopy through resonance enhancement with absorbing dye,” Opt. Lett. 33(4), 387–389 (2008).
[CrossRef] [PubMed]

Supatto, W.

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

Tai, S.-P.

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P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, W. A. Mohler, “Three-Dimensional High-Resolution Second-Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues,” Biophys. J. 82(1), 493–508 (2002).
[CrossRef] [PubMed]

Tordjmann, T.

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

Tromberg, B. J.

A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

Tsai, P. S.

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A. Mathy, K. Ueberhofen, R. Schenk, H. Gregorius, R. Garay, K. Müllen, C. Bubeck, “Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers,” Phys. Rev. B Condens. Matter 53(8), 4367–4376 (1996).
[CrossRef] [PubMed]

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G. Veres, S. Matsumoto, Y. Nabekawa, K. Midorikawa, “Enhancement of third-harmonic generation in absorbing media,” Appl. Phys. Lett. 81(20), 3714–3716 (2002).
[CrossRef]

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D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

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D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

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A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

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C.-F. Chang, C.-H. Yu, C.-K. Sun, “Multi-photon resonance enhancement of third harmonic generation in human oxyhemoglobin and deoxyhemoglobin,” J. Biophotonics 3(10-11), 678–685 (2010).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

Acta Biochim. Pol. (1)

L. Gebicka, E. Banasiak, “Flavonoids as reductants of ferryl hemoglobin,” Acta Biochim. Pol. 56(3), 509–513 (2009).
[PubMed]

Anal. Chem. (1)

R. D. Schaller, J. C. Johnson, R. J. Saykally, “Nonlinear Chemical Imaging Microscopy: Near-Field Third Harmonic Generation Imaging of Human Red Blood Cells,” Anal. Chem. 72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

Appl. Phys. Lett. (2)

Y. Barad, H. Eisenberg, M. Horowitz, Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[CrossRef]

G. Veres, S. Matsumoto, Y. Nabekawa, K. Midorikawa, “Enhancement of third-harmonic generation in absorbing media,” Appl. Phys. Lett. 81(20), 3714–3716 (2002).
[CrossRef]

Biophys. J. (2)

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, W. A. Mohler, “Three-Dimensional High-Resolution Second-Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues,” Biophys. J. 82(1), 493–508 (2002).
[CrossRef] [PubMed]

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, W. A. Mohler, “Characterization of the Myosin-Based Source for Second-Harmonic Generation from Muscle Sarcomeres,” Biophys. J. 90(2), 693–703 (2006).
[CrossRef] [PubMed]

J. Biophotonics (1)

C.-F. Chang, C.-H. Yu, C.-K. Sun, “Multi-photon resonance enhancement of third harmonic generation in human oxyhemoglobin and deoxyhemoglobin,” J. Biophotonics 3(10-11), 678–685 (2010).
[CrossRef] [PubMed]

J. Opt. Soc. Am. B (2)

Nat. Biotechnol. (1)

P. J. Campagnola, L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

Nat. Med. (1)

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, R. K. Jain, “Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation,” Nat. Med. 9(6), 796–801 (2003).
[CrossRef] [PubMed]

Nat. Methods (1)

D. Débarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods 3(1), 47–53 (2006).
[CrossRef] [PubMed]

Opt. Express (2)

Opt. Lett. (2)

Phys. Rev. B Condens. Matter (1)

A. Mathy, K. Ueberhofen, R. Schenk, H. Gregorius, R. Garay, K. Müllen, C. Bubeck, “Third-harmonic-generation spectroscopy of poly(p-phenylenevinylene): A comparison with oligomers and scaling laws for conjugated polymers,” Phys. Rev. B Condens. Matter 53(8), 4367–4376 (1996).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (2)

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

Science (1)

R. Benesch, R. E. Benesch, G. MacDuff, “Spectra of Deoxygenated Hemoglobin in the Soret Region,” Science 144(3614), 68–69 (1964).
[CrossRef] [PubMed]

Other (1)

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Figures (9)

Fig. 1
Fig. 1

Schematic diagrams of THG and TSFG.

Fig. 2
Fig. 2

Absorption spectra of sample solutions. (a) Absorption spectrum of cyt c dissolved into PBS. (b) Absorption spectra of two Hbs and albumin. Orange one is the spectrum of lyophilized powder sample solution, green corresponds to hemoglobin A0, Ferrous Stabilized human. The blue spectrum corresponds to albumin solution.

Fig. 3
Fig. 3

Experimental setup: (a) TSFG miscrocpectroscopic system. (b) Schematics at the sample position. To obtain TSFG signal from interfaces, the preparation placed on the piezo electric stage was scanned in z, axial direction.

Fig. 4
Fig. 4

Results of cyt c solution. (a) Cross-sectional image of TSFG. (b) Intensity profile of the axial direction scanning. The inset is the enlarged view of this profile. (c) TSFG spectra from the upper glass/solution interface. Left and right curves correspond to the averaged spectra of PBS (purple) and cyt c (red). (d) Corrected TSFG spectra of PBS (purple) and cyt c (red). For comparison, the absorption spectrum of cyt c solution is also shown. (e) Calculated ratio spectrum obtained by dividing the corrected TSFG spectrum of cyt c solution by that of PBS.

Fig. 5
Fig. 5

(a) Intensity-corrected TSFG spectra of Hb solutions. Each plot corresponds to PBS (purple), oxidized Hb (orange), reduced Hb (green) and albumin (blue), respectively. For comparison, absorption spectra of oxidized and reduced Hb solutions are shown by solid lines. (b) Calculated ratio spectra of oxidized (orange) and reduced (green) Hb solutions.

Fig. 6
Fig. 6

Simulated TSFG ratio spectra of Hbs. In this calculation, ωres of oxidized Hb is 405 nm, and that of reduced Hb is 414 nm, corresponding to peak positions of absorption spectra in Fig. 2(b). For comparison, the experimental results are also shown.

Fig. 7
Fig. 7

Contribution of each section in ASF of THG (CARS) microscopy to the THG (CARS) signal. Arrows indicate complex numbers in complex plane. The summations of the contribution of each section for the upper and lower parts are shown.

Fig. 8
Fig. 8

Schematic of destructive buildup of THG signal. The top figures illustrate the ASFs of THG microscopy and the ideal planes. The middle figures describe the buildup of THG signal generated from the part above the ideal plane, representing the sum of the THG complex amplitudes that correspond to the arrows in Fig. 7. The bottom figures depict the buildup of THG signal generated from the part below the ideal plane. The leftmost figures show the case where the ideal plane is located in the center of the ASF.

Fig. 9
Fig. 9

The THG intensity and the THG complex amplitude acquired by scanning the interface in z direction.

Equations (18)

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χ TSFG (3) = χ resonant (3) + χ nonresonant (3) .
χ resonant (3) = A res ω res ω TSFG i Γ res ,
χ nonresonant (3) =C e iθ ,
I( ω TSFG )= | A res ω res ω TSFG i Γ res +C e iθ | 2 .
A(x', y', z')= χ (3) (xx', yy', zz')ASF(x, y, z) dxdydz,
χ step (3) (x,y,z)= χ 0 (3) u(z)={ 0 (z<0) χ 0 (3) (z0) ,
A step (z')= χ step (3) (xx', yy', zz')ASF(x, y, z) dxdydz = χ 0 (3) F(z')
F(z')= z' ASF(x, y, z) dxdydz= z=z' α(z)Δz
α(z)Δz= z z+Δz ASF(x, y, z) dxdydz,
U( f x , f y , f z )= 1 2 δ( f x )δ( f y ){ δ( f z )+ i π f z },
F(z')= 1 2 CTF( f x , f y , f z ) δ( f x )δ( f y ) { δ( f z )+ i π f z } ×exp[ i2π( f x x'+ f y y'+ f z z') ]d f x d f y d f z = 1 2 CTF(0, 0, f z ) { δ( f z )+ i π f z }exp[ i2π f z z' ]df.
F'(z')= z' ASF(x, y, z) dxdydz.
U'( f x , f y , f z )= 1 2 δ( f x )δ( f y ){ δ( f z ) i π f z }.
F'(z')= 1 2 CTF(0, 0, f z ) { δ( f z ) i π f z }exp[ i2π f z z' ]d f z .
F(0)= 1 2 CTF(0, 0, f z ) { δ( f z )+ i π f z }d f z .
A homo = χ 0 (3) ASF(x, y, z) dxdydz = χ 0 (3) { F(z')+F'(z') } = χ 0 (3) { F(0)+F'(0) } = χ 0 (3) { F(0)+ F * (0) }.
F THG (z')= 1 2 0 i π f z CTF(0, 0, f z ) exp[ i2π f z z' ]d f z .
F THG ' (z')= 1 2 0 i π f z CTF(0, 0, f z ) exp[ i2π f z z' ]d f z .

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