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Miniaturized video-rate epi-third-harmonic-generation fiber-microscopeShih-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
Shih-Hsuan Chia,1
Che-Hang Yu,1
Chih-Han Lin,1
Nai-Chia Cheng,1
Tzu-Ming Liu,2
Ming-Che Chan,1
I-Hsiu Chen,1
and Chi-Kuang Sun1,3,*
1Graduate Inst. of Photonics and Optoelectronics and Department of Electrical Engineering, Natl. Taiwan Univ., Taipei 10617, Taiwan 2Inst. of Biomedical Engineering, Natl. Taiwan Univ., Taipei 10617, Taiwan 3Research Center for Applied Sciences, Academia Sinica, Taipei 115, Taiwan *Corresponding author: sun@cc.ee.ntu.edu.tw |
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/oe/abstract.cfm?URI=oe-18-16-17382
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- 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]
- 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]
- 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]
- J. Sawinski and W. Denk, “Miniature random-access fiber scanner for in vivo multiphoton imaging,” J. Appl. Phys. 102(3), 034701 (2007). [CrossRef]
- 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]
- 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]
- 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]
- 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]
- 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]
- H. Bao and M. Gu, “A 0.4-mm-diameter probe for nonlinear optical imaging,” Opt. Express 17(12), 10098–10104 (2009). [CrossRef] [PubMed]
- 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]
- D. Bird and M. Gu, “Two-photon fluorescence endoscopy with a micro-optic scanning head,” Opt. Lett. 28(17), 1552–1554 (2003). [CrossRef] [PubMed]
- 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]
- 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]
- 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]
- 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]
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- 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]
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Adv. Biochem. Engin, Biotechnol.
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Appl. Opt.
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IEEE J. Sel. Top. Quantum Electron.
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J. Biomed. Opt.
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- 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]
J. Biophoton.
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J. Neurophysiol.
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Micron
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Nat. Biotechnol.
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Opt. Commun.
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Opt. Express
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Proc. SPIE
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Other
- http://www.imaginis.com/biopsy/biopsy_risks.asp
2010, Chen, IEEE J. Sel. Top. Quantum Electron.
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- 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]
- 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]
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- 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]
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- C.-K. Sun, “Higher harmonic generation microscopy,” Adv. Biochem. Engin, Biotechnol. 95, 17–56 (2005).
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
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