Abstract

We demonstrate label-free multi-photon imaging of biological samples using a compact Er3+-doped femtosecond fiber laser mode-locked by a single-walled carbon nanotube (CNT). These compact and low cost lasers have been developed by various groups but they have not been exploited for multiphoton microscopy. Here, it is shown that various multiphoton imaging modalities (e.g. second harmonic generation (SHG), third harmonic generation (THG), two-photon excitation fluorescence (TPEF), and three-photon excitation fluorescence (3PEF)) can be effectively performed on various biological samples using a compact handheld CNT mode-locked femtosecond fiber laser operating in the telecommunication window near 1560nm. We also show for the first time that chlorophyll fluorescence in plant leaves and diatoms can be observed using 1560nm laser excitation via three-photon absorption.

© 2013 Optical Society of America

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2013

E. E. Hoover, J. A. Squier, “Advances in multiphoton microscopy technology,” Nat. Photonics 7(2), 93–101 (2013).
[CrossRef]

2012

2011

T. H. Wu, K. Kieu, N. Peyghambarian, R. J. Jones, “Low noise erbium fiber fs frequency comb based on a tapered-fiber carbon nanotube design,” Opt. Express 19(6), 5313–5318 (2011).
[CrossRef] [PubMed]

K. Kieu, A. Evans, J. Klein, J. Barton, N. Peyghambarian, “Ultrahigh resolution all-reflective OCT system with a compact fiber-based supercontinuum source,” J. Biomed. Opt. 16, 106004 (2011), doi:.
[CrossRef] [PubMed]

K. Murari, Y. Zhang, S. Li, Y. Chen, M. J. Li, X. Li, “Compensation-free, all-fiber-optic, two-photon endomicroscopy at 1.55 μm,” Opt. Lett. 36(7), 1299–1301 (2011).
[CrossRef] [PubMed]

G. Liu, K. Kieu, F. W. Wise, Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J Biophotonics 4(1-2), 34–39 (2011).
[CrossRef] [PubMed]

2010

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, S. Achilefu, “Multiphoton microscopy with near infrared contrast agents,” J. Biomed. Opt. 15(3), 030505 (2010).
[CrossRef] [PubMed]

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, P. Loza-Alvarez, “Third-harmonic generation for the study of Caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15(4), 046020 (2010).
[CrossRef] [PubMed]

K. Kieu, J. Jones, N. Peyghambarian, “Generation of few-cycle pulses from an amplified carbon nanotube mode-locked fiber laser system,” IEEE Photon. Technol. Lett. 22(20), 1521–1523 (2010).
[CrossRef]

2009

T. Hasan, Z. Sun, F. Wang, F. Bonaccorso, P. Tan, A. G. Rozhin, A. C. Ferrari, “Nanotube-polymer composites for ultrafast photonics,” Adv. Mater. 21(38–39), 3874–3899 (2009).
[CrossRef]

D. Kobat, M. E. Durst, N. Nishimura, A. W. Wong, C. B. Schaffer, C. Xu, “Deep tissue multiphoton microscopy using longer wavelength excitation,” Opt. Express 17(16), 13354–13364 (2009).
[CrossRef] [PubMed]

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt. 14(1), 010508 (2009).
[CrossRef] [PubMed]

K. Kieu, B. G. Saar, G. R. Holtom, F. W. Wise, X. S. Xie, “High power all-fiber picosecond laser system for coherent Raman microscopy,” Opt. Lett. 34, 2051–2053 (2009).

2008

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[CrossRef] [PubMed]

G. Androz, M. Bernier, D. Faucher, R. Vallée, “2.3 W single transverse mode thulium-doped ZBLAN fiber laser at 1480 nm,” Opt. Express 16(20), 16019–16031 (2008).
[CrossRef] [PubMed]

2007

2006

2005

F. Helmchen, W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[CrossRef] [PubMed]

2004

S. D. Jackson, “Single-transverse-mode 2.5-W holmium-doped fluoride fiber laser operating at 2.86 microm,” Opt. Lett. 29(4), 334–336 (2004).
[CrossRef] [PubMed]

J.-X. Cheng, X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory and applications,” J. Phys. Chem. B 108(3), 827–840 (2004).
[CrossRef]

2003

W. R. Zipfel, R. M. Williams, W. W. Webb, “Nonlinear magic: Multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[CrossRef] [PubMed]

2002

M. Guina, N. Xiang, O. G. Okhotnikov, “Stretched-pulse fiber lasers based on semiconductor saturable absorber mirrors,” Appl. Phys. B 74(9), S193–S200 (2002).
[CrossRef]

2000

K. König, “Multiphoton microscopy in life sciences,” J. Microsc. 200(2), 83–104 (2000).
[CrossRef] [PubMed]

1999

1995

K. Tamura, E. P. Ippen, H. A. Haus, “Pulse dynamics in stretched-pulse fiber lasers,” Appl. Phys. Lett. 67(2), 158 (1995).
[CrossRef]

1993

1991

G. H. Krause, E. Weis, “Chlorophyll fluorescence and photosynthesis: the basis,” Annu. Rev. Plant Physiol. Plant Mol. Biol. 42(1), 313–349 (1991).
[CrossRef]

1990

W. Denk, J. H. Strickler, W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Abreu-Afonso, J.

Achilefu, S.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, S. Achilefu, “Multiphoton microscopy with near infrared contrast agents,” J. Biomed. Opt. 15(3), 030505 (2010).
[CrossRef] [PubMed]

Akers, W. J.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, S. Achilefu, “Multiphoton microscopy with near infrared contrast agents,” J. Biomed. Opt. 15(3), 030505 (2010).
[CrossRef] [PubMed]

Alonso-Ortega, C.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, P. Loza-Alvarez, “Third-harmonic generation for the study of Caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15(4), 046020 (2010).
[CrossRef] [PubMed]

Androz, G.

Artigas, D.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, P. Loza-Alvarez, “Third-harmonic generation for the study of Caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15(4), 046020 (2010).
[CrossRef] [PubMed]

Aus-der-Au, J.

Aviles-Espinosa, R.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, P. Loza-Alvarez, “Third-harmonic generation for the study of Caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15(4), 046020 (2010).
[CrossRef] [PubMed]

Baldacchini, T.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt. 14(1), 010508 (2009).
[CrossRef] [PubMed]

Balu, M.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt. 14(1), 010508 (2009).
[CrossRef] [PubMed]

Barton, J.

K. Kieu, A. Evans, J. Klein, J. Barton, N. Peyghambarian, “Ultrahigh resolution all-reflective OCT system with a compact fiber-based supercontinuum source,” J. Biomed. Opt. 16, 106004 (2011), doi:.
[CrossRef] [PubMed]

Baumgartl, M.

Berezin, M. Y.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, S. Achilefu, “Multiphoton microscopy with near infrared contrast agents,” J. Biomed. Opt. 15(3), 030505 (2010).
[CrossRef] [PubMed]

Bernier, M.

Bonaccorso, F.

T. Hasan, Z. Sun, F. Wang, F. Bonaccorso, P. Tan, A. G. Rozhin, A. C. Ferrari, “Nanotube-polymer composites for ultrafast photonics,” Adv. Mater. 21(38–39), 3874–3899 (2009).
[CrossRef]

Brodschelm, A.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, P. Loza-Alvarez, “Third-harmonic generation for the study of Caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15(4), 046020 (2010).
[CrossRef] [PubMed]

Bufetov, I. A.

Carter, J.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt. 14(1), 010508 (2009).
[CrossRef] [PubMed]

Chen, Y.

Chen, Z.

G. Liu, K. Kieu, F. W. Wise, Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J Biophotonics 4(1-2), 34–39 (2011).
[CrossRef] [PubMed]

S. Tang, J. Liu, T. B. Krasieva, Z. Chen, B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 0001;14 (3):030508–030508–3.
[CrossRef]

Cheng, J.-X.

J.-X. Cheng, X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory and applications,” J. Phys. Chem. B 108(3), 827–840 (2004).
[CrossRef]

Clay, G. O.

Denk, W.

F. Helmchen, W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Dianov, E. M.

Dietzek, B.

Díez, A.

Durst, M. E.

Evans, A.

K. Kieu, A. Evans, J. Klein, J. Barton, N. Peyghambarian, “Ultrahigh resolution all-reflective OCT system with a compact fiber-based supercontinuum source,” J. Biomed. Opt. 16, 106004 (2011), doi:.
[CrossRef] [PubMed]

Faucher, D.

Fermann, M. E.

Ferrari, A. C.

T. Hasan, Z. Sun, F. Wang, F. Bonaccorso, P. Tan, A. G. Rozhin, A. C. Ferrari, “Nanotube-polymer composites for ultrafast photonics,” Adv. Mater. 21(38–39), 3874–3899 (2009).
[CrossRef]

Firstov, S. V.

Fittinghoff, D. N.

Freudiger, C. W.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[CrossRef] [PubMed]

Fu, D.

Gottschall, T.

Guina, M.

M. Guina, N. Xiang, O. G. Okhotnikov, “Stretched-pulse fiber lasers based on semiconductor saturable absorber mirrors,” Appl. Phys. B 74(9), S193–S200 (2002).
[CrossRef]

Guryanov, A. N.

Hasan, T.

T. Hasan, Z. Sun, F. Wang, F. Bonaccorso, P. Tan, A. G. Rozhin, A. C. Ferrari, “Nanotube-polymer composites for ultrafast photonics,” Adv. Mater. 21(38–39), 3874–3899 (2009).
[CrossRef]

Haus, H. A.

K. Tamura, E. P. Ippen, H. A. Haus, “Pulse dynamics in stretched-pulse fiber lasers,” Appl. Phys. Lett. 67(2), 158 (1995).
[CrossRef]

He, C.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[CrossRef] [PubMed]

Helmchen, F.

F. Helmchen, W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[CrossRef] [PubMed]

Herda, R.

Holtom, G. R.

Hoover, E. E.

E. E. Hoover, J. A. Squier, “Advances in multiphoton microscopy technology,” Nat. Photonics 7(2), 93–101 (2013).
[CrossRef]

Horton, N. G.

Hui, R.

Ippen, E. P.

K. Tamura, E. P. Ippen, H. A. Haus, “Pulse dynamics in stretched-pulse fiber lasers,” Appl. Phys. Lett. 67(2), 158 (1995).
[CrossRef]

Jackson, S. D.

Johnson, C. K.

Jones, J.

K. Kieu, J. Jones, N. Peyghambarian, “Generation of few-cycle pulses from an amplified carbon nanotube mode-locked fiber laser system,” IEEE Photon. Technol. Lett. 22(20), 1521–1523 (2010).
[CrossRef]

Jones, R. J.

Joo, C.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, S. Achilefu, “Multiphoton microscopy with near infrared contrast agents,” J. Biomed. Opt. 15(3), 030505 (2010).
[CrossRef] [PubMed]

Kaenders, W. G.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, P. Loza-Alvarez, “Third-harmonic generation for the study of Caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15(4), 046020 (2010).
[CrossRef] [PubMed]

Kang, J. X.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[CrossRef] [PubMed]

Khopin, V. F.

Kieu, K.

G. Liu, K. Kieu, F. W. Wise, Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J Biophotonics 4(1-2), 34–39 (2011).
[CrossRef] [PubMed]

K. Kieu, A. Evans, J. Klein, J. Barton, N. Peyghambarian, “Ultrahigh resolution all-reflective OCT system with a compact fiber-based supercontinuum source,” J. Biomed. Opt. 16, 106004 (2011), doi:.
[CrossRef] [PubMed]

T. H. Wu, K. Kieu, N. Peyghambarian, R. J. Jones, “Low noise erbium fiber fs frequency comb based on a tapered-fiber carbon nanotube design,” Opt. Express 19(6), 5313–5318 (2011).
[CrossRef] [PubMed]

K. Kieu, J. Jones, N. Peyghambarian, “Generation of few-cycle pulses from an amplified carbon nanotube mode-locked fiber laser system,” IEEE Photon. Technol. Lett. 22(20), 1521–1523 (2010).
[CrossRef]

K. Kieu, B. G. Saar, G. R. Holtom, F. W. Wise, X. S. Xie, “High power all-fiber picosecond laser system for coherent Raman microscopy,” Opt. Lett. 34, 2051–2053 (2009).

K. Kieu, M. Mansuripur, “Femtosecond laser pulse generation with a fiber taper embedded in carbon nanotube/polymer composite,” Opt. Lett. 32(15), 2242–2244 (2007).
[CrossRef] [PubMed]

Klein, J.

K. Kieu, A. Evans, J. Klein, J. Barton, N. Peyghambarian, “Ultrahigh resolution all-reflective OCT system with a compact fiber-based supercontinuum source,” J. Biomed. Opt. 16, 106004 (2011), doi:.
[CrossRef] [PubMed]

Kleinfeld, D.

Kobat, D.

Kong, L.

König, K.

K. König, “Multiphoton microscopy in life sciences,” J. Microsc. 200(2), 83–104 (2000).
[CrossRef] [PubMed]

Krasieva, T. B.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt. 14(1), 010508 (2009).
[CrossRef] [PubMed]

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S. Tang, J. Liu, T. B. Krasieva, Z. Chen, B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 0001;14 (3):030508–030508–3.
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K. Kieu, B. G. Saar, G. R. Holtom, F. W. Wise, X. S. Xie, “High power all-fiber picosecond laser system for coherent Raman microscopy,” Opt. Lett. 34, 2051–2053 (2009).

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
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[CrossRef]

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C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
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T. Hasan, Z. Sun, F. Wang, F. Bonaccorso, P. Tan, A. G. Rozhin, A. C. Ferrari, “Nanotube-polymer composites for ultrafast photonics,” Adv. Mater. 21(38–39), 3874–3899 (2009).
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K. Kieu, B. G. Saar, G. R. Holtom, F. W. Wise, X. S. Xie, “High power all-fiber picosecond laser system for coherent Raman microscopy,” Opt. Lett. 34, 2051–2053 (2009).

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M. Guina, N. Xiang, O. G. Okhotnikov, “Stretched-pulse fiber lasers based on semiconductor saturable absorber mirrors,” Appl. Phys. B 74(9), S193–S200 (2002).
[CrossRef]

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K. Kieu, B. G. Saar, G. R. Holtom, F. W. Wise, X. S. Xie, “High power all-fiber picosecond laser system for coherent Raman microscopy,” Opt. Lett. 34, 2051–2053 (2009).

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
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[CrossRef] [PubMed]

Adv. Mater.

T. Hasan, Z. Sun, F. Wang, F. Bonaccorso, P. Tan, A. G. Rozhin, A. C. Ferrari, “Nanotube-polymer composites for ultrafast photonics,” Adv. Mater. 21(38–39), 3874–3899 (2009).
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Biomed. Opt. Express

IEEE J. Sel. Top. Quantum Electron.

F. W. Wise,, “Femtosecond fiber lasers based on dissipative processes for nonlinear microscopy,” IEEE J. Sel. Top. Quantum Electron. 18, 1412–1421 (2012).
[CrossRef]

IEEE Photon. Technol. Lett.

K. Kieu, J. Jones, N. Peyghambarian, “Generation of few-cycle pulses from an amplified carbon nanotube mode-locked fiber laser system,” IEEE Photon. Technol. Lett. 22(20), 1521–1523 (2010).
[CrossRef]

J Biophotonics

G. Liu, K. Kieu, F. W. Wise, Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J Biophotonics 4(1-2), 34–39 (2011).
[CrossRef] [PubMed]

J. Biomed. Opt.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, S. Achilefu, “Multiphoton microscopy with near infrared contrast agents,” J. Biomed. Opt. 15(3), 030505 (2010).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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[CrossRef]

Nat. Biotechnol.

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Other

M. J. Farrar, F. W. Wise, J. R. Fetcho, and C. B. Schaffer, “In vivo imaging of myelin in the vertebrate central nervous system using third harmonic generation microscopy,” Biophysical Journal 100, 1362–1371, (2011) ISSN 0006–3495, .
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S. Tang, J. Liu, T. B. Krasieva, Z. Chen, B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 0001;14 (3):030508–030508–3.
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N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer & C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Published online: 20 January 2013 | doi:.
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Supplementary Material (4)

» Media 1: AVI (4918 KB)     
» Media 2: AVI (3084 KB)     
» Media 3: AVI (2834 KB)     
» Media 4: AVI (3519 KB)     

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Figures (7)

Fig. 1
Fig. 1

Left: Schematic diagram of the multi-photon microscope. MLL: mode-locked fiber laser with carbon nanotube saturable absorber. VA: variable attenuator. Right: A photograph of the actual microscope, the handheld femtosecond fiber laser is also shown.

Fig. 2
Fig. 2

: Left: THG image of a silicon photonic chip. We observed a strong THG signal from the nano-waveguide coupled to the ring resonator (200x100nm). Right: THG signal profile across the ring resonator showing axial resolution of ~1.1µm. The frame rate was ~3s/frame.

Fig. 3
Fig. 3

Left: Multi-photon image of a fresh leaf from an indoor plant. We observed a strong THG signal (green) from lipid cell layers and a 3PEF signal (red) from chlorophyll. Right: Optical spectrum of the generated light due to the femtosecond laser excitation. Inset: Multi-photon image of a whole mesquite leaf. Mesquite is a desert tree native to Arizona. The image was composed by tiling 56 frames. The frame rate was ~3s/frame.

Fig. 4
Fig. 4

Left: Multi-photon image of living centric diatoms Coscinodiscus wailesii. As with the fresh leaf, we observed strong THG signal (green) from lipid cell layers inside the chloroplasts and 3PEF signal (red) from chlorophyll. Right: 3D view of a 3PEF and THG image of a living non-centric diatom Pyrocystis fusiformis. Inset: Optical image of the non-centric Pyrocystis fusiformis diatom. Media 1 shows the z-sections of diatoms Coscinodiscus wailesii recorded with our multiphoton microscope. Media 2 shows the 3D rendering of the Pyrocystis fusiformis diatom shown on the right. The z-step size is 1µm. The frame rate was ~3s/frame.

Fig. 5
Fig. 5

SHG (red) and THG (green) image of a thin section of a mouse kidney and a thin section of striated muscle tissue. The frame rate was ~8s/frame

Fig. 6
Fig. 6

Left: Optical image of a Drosophila head. Center and Right: 3D reconstruction of a Drosophila head received by tiling 20 separate stacks. We observed strong THG signal (green) as well as SHG signal (red) from different tissue structures. The SHG signal seemed to come from muscle tissues while the THG signal was generated from the other type of tissues including the outer layers which are rich in chitin. Center: The back view and Right: the front view of the head. The thickness of the head is 220µm and the size of the head in the xy-plane is about 1mm × 1mm. Media 3 shows the 3D rendering of the Drosophila head. The frame rate was ~3s/frame.

Fig. 7
Fig. 7

Left: 3D reconstruction of the Zebra fish eye and standard optical image of the fish. The fish embryo was 5 days old and it was fixed in agarose gel for in-vivo imaging. Middle: Examples of images from different depths. Right: The 3D front view (up) and the back view (down) of the eye. We observed strong THG signal (green) from inside the Zebra fish eye. Media 4 shows the 3D rendering of the fish eye. The frame rate was ~8s/frame.

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