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Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics

| EXPLORING THE INTERFACE OF LIGHT AND BIOMEDICINE

  • Editor: Gregory W. Faris
  • Vol. 5, Iss. 12 — Sep. 30, 2010

Miniaturized video-rate epi-third-harmonic-generation fiber-microscope

Shih-Hsuan Chia, Che-Hang Yu, Chih-Han Lin, Nai-Chia Cheng, Tzu-Ming Liu, Ming-Che Chan, I-Hsiu Chen, and Chi-Kuang Sun  »View Author Affiliations


Optics Express, Vol. 18, Issue 16, pp. 17382-17391 (2010)
http://dx.doi.org/10.1364/OE.18.017382


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Abstract

With a micro-electro-mechanical system (MEMS) mirror, we successfully developed a miniaturized epi-third-harmonic-generation (epi-THG) fiber-microscope with a video frame rate (31Hz), which was designed for in vivo optical biopsy of human skin. With a large-mode-area (LMA) photonic crystal fiber (PCF) and a regular microscopic objective, the nonlinear distortion of the ultrafast pulses delivery could be much reduced while still achieving a 0.4μm lateral resolution for epi-THG signals. In vivo real time virtual biopsy of the Asian skin with a video rate (31Hz) and a sub-micron resolution was obtained. The result indicates that this miniaturized system was compact enough for the least invasive hand-held clinical use.

© 2010 OSA

OCIS Codes
(190.2620) Nonlinear optics : Harmonic generation and mixing
(180.4315) Microscopy : Nonlinear microscopy

ToC Category:
Microscopy

History
Original Manuscript: April 26, 2010
Revised Manuscript: June 29, 2010
Manuscript Accepted: July 1, 2010
Published: July 30, 2010

Virtual Issues
Vol. 5, Iss. 12 Virtual Journal for Biomedical Optics

Citation
Shih-Hsuan Chia, Che-Hang Yu, Chih-Han Lin, Nai-Chia Cheng, Tzu-Ming Liu, Ming-Che Chan, I-Hsiu Chen, and Chi-Kuang Sun, "Miniaturized video-rate epi-third-harmonic-generation fiber-microscope," Opt. Express 18, 17382-17391 (2010)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-18-16-17382


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References

  1. http://www.imaginis.com/biopsy/biopsy_risks.asp
  2. D. Yelin and Y. Silberberg, “Laser scanning third-harmonic-generation microscopy in biology,” Opt. Express 5(8), 169–175 (1999). [CrossRef] [PubMed]
  3. C.-K. Sun, “Higher harmonic generation microscopy,” Adv. Biochem. Engin, Biotechnol. 95, 17–56 (2005).
  4. P. J. Campagnola and 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]
  5. T.-H. Tsai, S.-P. Tai, W.-J. Lee, H.-Y. Huang, Y.-H. Liao, and C.-K. Sun, “Optical signal degradation study in fixed human skin using confocal microscopy and higher-harmonic optical microscopy,” Opt. Express 14(2), 749–758 (2006). [CrossRef] [PubMed]
  6. S.-Y. Chen, H.-Y. Wu, and C.-K. Sun, “In vivo harmonic generation biopsy of human skin,” J. Biomed. Opt. 14(6), 060505 (2009). [CrossRef]
  7. S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE J. Sel. Top. Quantum Electron. 16, 478–492 (2010). [CrossRef]
  8. C.-S. Hsieh, S.-U. Chen, Y.-W. Lee, Y.-S. Yang, and C.-K. Sun, “Higher harmonic generation microscopy of in vitro cultured mammal oocytes and embryos,” Opt. Express 16(15), 11574–11588 (2008). [PubMed]
  9. S.-P. Tai, W.-J. Lee, D.-B. Shieh, P.-C. Wu, H.-Y. Huang, C.-H. Yu, and C.-K. Sun, “In vivo optical biopsy of hamster oral cavity with epi-third-harmonic-generation microscopy,” Opt. Express 14(13), 6178–6187 (2006). [CrossRef] [PubMed]
  10. M.-R. Tsai, S.-Y. Chen, D.-B. Shieh, P.-J. Lou, and C.-K. Sun, “In vivo optical virtual biopsy of human oral cavity with harmonic generation microscopy,” Proc. SPIE (to be published).
  11. C.-K. Sun, C.-C. Chen, S.-W. Chu, T.-H. Tsai, Y.-C. Chen, and B.-L. Lin, “Multiharmonic-generation biopsy of skin,” Opt. Lett. 28(24), 2488–2490 (2003). [CrossRef] [PubMed]
  12. S.-P. Tai, T.-H. Tsai, W.-J. Lee, D.-B. Shieh, Y.-H. Liao, H.-Y. Huang, K. Zhang, H.-L. Liu, and C.-K. Sun, “Optical biopsy of fixed human skin with backward-collected optical harmonics signals,” Opt. Express 13(20), 8231–8242 (2005). [CrossRef] [PubMed]
  13. J.-H. Lee, S.-Y. Chen, C.-H. Yu, S.-W. Chu, L.-F. Wang, C. K. Sun, and B. L. Chiang, “Noninvasive in vitro and in vivo assessment of epidermal hyperkeratosis and dermal fibrosis in atopic dermatitis,” J. Biomed. Opt. 14(1), 014008 (2009). [CrossRef] [PubMed]
  14. T. Yasui, Y. Takahashi, M. Ito, S. Fukushima, and T. Araki, “Ex vivo and in vivo second-harmonic-generation imaging of dermal collagen fiber in skin: comparison of imaging characteristics between mode-locked Cr:forsterite and Ti:sapphire lasers,” Appl. Opt. 48(10), D88–D95 (2009). [CrossRef] [PubMed]
  15. L. Fu, A. Jain, H. Xie, C. Cranfield, and M. Gu, “Nonlinear optical endoscopy based on a double-clad photonic crystal fiber and a MEMS mirror,” Opt. Express 14(3), 1027–1032 (2006). [CrossRef] [PubMed]
  16. W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, and M. J. Schnitzer, “Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror,” Opt. Lett. 31(13), 2018–2020 (2006). [CrossRef] [PubMed]
  17. H. J. Shin, M. C. Pierce, D. Lee, H. Ra, O. Solgaard, and R. Richards-Kortum, “Fiber-optic confocal microscope using a MEMS scanner and miniature objective lens,” Opt. Express 15(15), 9113–9122 (2007). [CrossRef] [PubMed]
  18. W. Piyawattanametha, E. D. Cocker, L. D. Burns, R. P. J. Barretto, J. C. Jung, H. Ra, O. Solgaard, and M. J. Schnitzer, “In vivo brain imaging using a portable 2.9 g two-photon microscope based on a microelectromechanical systems scanning mirror,” Opt. Lett. 34(15), 2309–2311 (2009). [CrossRef] [PubMed]
  19. T.-M. Liu, M.-C. Chan, I.-H. Chen, S.-H. Chia, and C.-K. Sun, “Miniaturized multiphoton microscope with a 24Hz frame-rate,” Opt. Express 16(14), 10501–10506 (2008). [CrossRef] [PubMed]
  20. C. L. Hoy, N. J. Durr, P. Chen, W. Piyawattanametha, H. Ra, O. Solgaard, and A. Ben-Yakar, “Miniaturized probe for femtosecond laser microsurgery and two-photon imaging,” Opt. Express 16(13), 9996–10005 (2008). [CrossRef] [PubMed]
  21. B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, and M. J. Schnitzer, “In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microscope,” Opt. Lett. 30(17), 2272–2274 (2005). [CrossRef] [PubMed]
  22. R. Le Harzic, M. Weinigel, I. Riemann, K. König, and B. Messerschmidt, “Nonlinear optical endoscope based on a compact two axes piezo scanner and a miniature objective lens,” Opt. Express 16(25), 20588–20596 (2008). [CrossRef] [PubMed]
  23. R. Le Harzic, I. Riemann, M. Weinigel, K. König, and B. Messerschmidt, “Rigid and high-numerical-aperture two-photon fluorescence endoscope,” Appl. Opt. 48(18), 3396–3400 (2009). [CrossRef] [PubMed]
  24. Y. Wu, Y. Leng, J. Xi, and X. Li, “Scanning all-fiber-optic endomicroscopy system for 3D nonlinear optical imaging of biological tissues,” Opt. Express 17, 7901–7915 (2009). [CrossRef]
  25. C. J. Engelbrecht, R. S. Johnston, E. J. Seibel, and F. Helmchen, “Ultra-compact fiber-optic two-photon microscope for functional fluorescence imaging in vivo,” Opt. Express 16(8), 5556–5564 (2008). [CrossRef] [PubMed]
  26. J. Sawinski and W. Denk, “Miniature random-access fiber scanner for in vivo multiphoton imaging,” J. Appl. Phys. 102(3), 034701 (2007). [CrossRef]
  27. J. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett. 28(11), 902–904 (2003). [CrossRef] [PubMed]
  28. D. Bird and M. Gu, “Two-photon fluorescence endoscopy with a micro-optic scanning head,” Opt. Lett. 28(17), 1552–1554 (2003). [CrossRef] [PubMed]
  29. M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004). [CrossRef]
  30. W. Göbel, J. N. D. Kerr, A. Nimmerjahn, and F. Helmchen, “Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective,” Opt. Lett. 29(21), 2521–2523 (2004). [CrossRef] [PubMed]
  31. H. Bao and M. Gu, “A 0.4-mm-diameter probe for nonlinear optical imaging,” Opt. Express 17(12), 10098–10104 (2009). [CrossRef] [PubMed]
  32. D. Kobat, M. E. Durst, N. Nishimura, A. W. Wong, C. B. Schaffer, and C. Xu, “Deep tissue multiphoton microscopy using longer wavelength excitation,” Opt. Express 17(16), 13354–13364 (2009). [CrossRef] [PubMed]
  33. I.-H. Chen, S.-W. Chu, C.-K. Sun, P.-C. Cheng, and B.-L. Lin, “Wavelength dependent cell damages in multi-photon confocal microscopy,” Opt. Quantum Electron. 34(12), 1251–1266 (2002). [CrossRef]
  34. K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, “Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes,” Opt. Lett. 22(2), 135–136 (1997). [CrossRef] [PubMed]
  35. P.-C. Cheng, B.-L. Lin, F.-J. Kao, M. Gu, M.-G. Xu, X. Gan, M.-K. Huang, and Y.-S. Wang, “Multi-photon fluorescence microscopy--the response of plant cells to high intensity illumination,” Micron 32(7), 661–669 (2001). [CrossRef] [PubMed]
  36. M.-C. Chan, T.-M. Liu, S.-P. Tai, and C.-K. Sun, “Compact fiber-delivered Cr:forsterite laser for nonlinear light microscopy,” J. Biomed. Opt. 10(5), 054006 (2005). [CrossRef] [PubMed]
  37. J. Schutz, W. Hodel, and H. Weber, “Nonlinear pulse distortion at the zero dispersion wavelength of an optical fibre,” Opt. Commun. 95(4-6), 357–365 (1993). [CrossRef]
  38. V. P. Yanovsky and F. W. Wise, “Nonlinear propagation of high-power, sub-100-fs pulses near the zero-dispersion wavelength of an optical fiber,” Opt. Lett. 19(19), 1547–1549 (1994). [CrossRef] [PubMed]
  39. K. G. Jespersen, T. Le, L. Grüner-Nielsen, D. Jakobsen, M. E. V. Pederesen, M. B. Smedemand, S. R. Keiding, and B. Palsdottir, “A higher-order-mode fiber delivery for Ti:Sapphire femtosecond lasers,” Opt. Express 18(8), 7798–7806 (2010). [CrossRef] [PubMed]
  40. C. K. Sun, C. H. Yu, S. P. Tai, C. T. Kung, I. J. Wang, H. C. Yu, H. J. Huang, W. J. Lee, and Y. F. Chan, “In vivo and ex vivo imaging of intra-tissue elastic fibers using third-harmonic-generation microscopy,” Opt. Express 15(18), 11167–11177 (2007). [CrossRef] [PubMed]
  41. C.-H. Yu, S.-P. Tai, C.-T. Kung, W.-J. Lee, Y.-F. Chan, H.-L. Liu, J.-Y. Lyu, and C.-K. Sun, “Molecular third-harmonic-generation microscopy through resonance enhancement with absorbing dye,” Opt. Lett. 33(4), 387–389 (2008). [CrossRef] [PubMed]
  42. C.-F. Chang, H.-C. Chen, M.-J. Chen, W.-R. Liu, W.-F. Hsieh, C.-H. Hsu, C.-Y. Chen, F.-H. Chang, C.-H. Yu, and C.-K. Sun, “Direct backward third-harmonic generation in nanostructures,” Opt. Express 18(7), 7397–7406 (2010). [CrossRef] [PubMed]
  43. C.-F. Chang, C.-Y. Chen, F.-H. Chang, S.-P. Tai, C.-Y. Chen, C.-H. Yu, Y.-B. Tseng, T.-H. Tsai, I.-S. Liu, W.-F. Su, and C.-K. Sun, “Cell tracking and detection of molecular expression in live cells using lipid-enclosed CdSe quantum dots as contrast agents for epi-third harmonic generation microscopy,” Opt. Express 16(13), 9534–9548 (2008). [CrossRef] [PubMed]
  44. C.-F. Chang, C.-H. Yu, and C.-K. Sun, “Multi-photon resonance enhancement of third harmonic generation in human oxyhemoglobin and deoxyhemoglobin,” to be published in J. Biophoton. (2010). [CrossRef]

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