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行政院國家科學委員會補助國內專家學者出席國際學術會議 報告

報告人:孫啟光教授 國立台灣大學光電工程研究所

會議名稱:Conference on Lasers and Electro-Optics/Quantum Electronics and Laser Science Conference/Conference on Photonic Applications, Systems, and Technologies

會議時間:西元 2007 年 5 月 6 日至 5 月 11 日

會議地點:Baltimore Convention Center, Baltimore, Maryland, USA

2007 年 Conference on Lasers and Electro-Optics (CLEO)仍循慣例在五月於 Baltimore Convention Center 舉辦,由 OSA、APS、及 IEEE/LEOS 三大學會共同 主辦。會議同時與 Quantum Electronics and Laser Science Conference (QELS)及 Conference on Photonic Applications, Systems, and Technologies(PhAST)合辦,兼具 光電物理、工程、與產業,是瞭解光電相關未來發展的重要會議。今年會議兩個 Plenary Session,共有四位 Plenary speaker。兩位代表 CLEO 會議,ㄧ位代表 QELS 會議、ㄧ位代表 QELS 會議。演講者包含諾貝爾獎得主 Alan Heeger,主題橫跨 電子(塑膠電子、spin electronics)、生醫、光通信、與物理研究(metamaterials、

negative refraction),相當廣泛。筆者於會議首日到達,並於會議結束日當晚起成 返台,期間與許多國內外同人互動,收穫極多。筆者發表一篇邀請論文,同時也 獲邀參加 2008CLEO 會議之 Program committee member。筆者所發表的邀請論文 題目與作者資訊如下:

C.-K. Sun, “In vivo Imaging Using Harmonic Generation Microscopy,” paper JThE3.

Baltimore, MD, USA (2007).

筆者所指導之研究室,在此次會議中另有 8 篇論文發表。其作者序、論文題 目、與文章編號如下

1. T.-F. Kao, H.-P. Chen, and C.-K. Sun, “Design and Analysis of Surface Plasmon-Enhanced Metal-Semiconductor-Metal Traveling Wave Photodetectors,”

paperJThD59.

2. H.-W. Chen, J.-Y. Lu, L.-J. Chen, P.-J. Chiang, H.-C. Chang, Y.-T. Li, C.-L. Pan, and C.-K. Sun, “THz Fiber Directional Coupler,” paper CThLL7.

3. H.-W. Chen, J.-Y. Lu, L.-J. Chen, Y.-T. Li, C.-L. Pan, and C.-K. Sun, “Spectral Loss Characteristics of Subwavelength THz Fibers,” paper CJWA107.

4. S.-P. Tai, C.-H. Yu, C.-Y. Chen, F.-H. Chang, and C.-K. Sun, “Molecular Imaging Using CdSe/ZnS/Lipid Quantum Dots as Contrast Agents of Third Harmonic Generation Microscopy,” paper CMCC4.

5. C.-T. Kung, C.-C. Chuang, Y.-K. Huang, H.-J. Tsai, and C.-K. Sun, “In Vivo Continuous Observation of Vertebrate Cardiac Valve for Congenital Heart Disease Study and Drug Screening Using Third Harmonic Generation Microscopy,” paper CTuP4.

6. J.-Y. Lu, C.-P. Yu, H.-C. Chang, H.-W. Chen, Y.-T. Li, C.-L. Pan, and C.-K. Sun,

“Air-core microstructure fiber for terahertz radiation waveguiding,” paper CThLL5.

7. C.-S. Hsieh, S.-U. Chen, Y.-S. Yang, and C.-K. Sun, “Noninvasive long term observation and evaluation of mammal oocytes and embryos with a 3D subcellular spatial resolution,” paper CTuP5.

8. S.-P. Tai, C.-H. Yu, T.-M. Liu, Y.-C. Wen, and C.-K. Sun, “In vivo Molecular-Resonant Third Harmonic Generation Microscopy of Hemoglobin,”

paper CTuF4.

由於上傳空間有限,僅將個人邀請論文之摘要檢附於後。

In vivo Imaging Using Harmonic Generation Microscopy

Chi-Kuang Sun

Graduate Institute of Electro-Optical Engineering and Department of Electrical Engineering, National Taiwan University, Taipei,10617 TAIWAN, and Research Center for Applied Sciences, Academia Sinica, Taipei 115, TAIWAN, R.O.C.

[email protected]

Abstract: With a virtual-transition characteristic, harmonic generation microscopy provides high-penetration non-invasive intravital optical images with a submicron 3D resolution, ideal for in vivo disease diagnoses and longterm live animal studies.

@2007 Optical Society of America

OCIS codes: (170.3880) Medical and biological imaging, (190.4160) Multiharmonic generation, (170.6900) Three-dimensional microscopy

Optical higher harmonic generations, including second-harmonic-generation (SHG) and third-harmonic-generation (THG) processes are known to leave no energy deposition to the interacted matters due to the virtual-transition characteristic [1]. In contrast to the absorption-induced-fluorescence processes that require energy deposition and electron transitions, the higher harmonic generation processes provide the optical noninvasive nature desired for microscopy applications, especially for long-term observation of the dynamic changes of live samples, including small animals and clinical patients [2,3]. Different from single-photon and multi-photon fluorescence, no cell damage and photobleaching effect is expected from the optical harmonic-generation process due to the fact that there is no real electron-transition involved and the total generated harmonic photon energy has to be equal to the total annihilated photon energy. With a nonlinear nature similar to the multi-photon excited fluorescence, the generated SHG intensity depends on the square of the incident light intensity, while the generated THG intensity depends on the third power of the incident light intensity. These nonlinear dependencies allow localized excitations to enable intrinsic optical sectioning and a high three-dimensional resolution similar or better than that of the two-photon fluorescence microscopy. Combining with a Cr:forsterite laser operating in the biological penetration window [2], harmonic generation microscopy is ideal fir longterm in vivo imaging with high cell viability, high 3D spatial resolution, and high penetration capability [2,3]. In this presentation, we review our recent development of harmonic generation microscopy, which provide high-penetration non-invasive intravital optical microscopic images. Contrast mechanisms of higher harmonic generation microscopy will be discussed [1], with a focus on intravital imaging. Examples of longterm small animal imaging, including noninvasive embryonic studies and virtual biopsy, will be presented.

Molecular imaging capability based on nanoparticles and acetic acid will be demonstrated.

Fiber-optical endoscopic system development will also be discussed.

This research is sponsored by National health Research Institute of Taiwan and NTU Center for Genomic Medicine.

Reference

[1] C.-K. Sun, “Higher Harmonic Generation Microscopy” in Series in Advances in Biochemical Engineering/Biotechnology, Special Volume 95: Microscopic Techniques, J. Rietdorf Ed., (SPRINGER-VERLAG, Berlin, 2005).

[2] C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, “Higher harmonic generation microscopy for developmental biology,” Journal of Structural Biology 147, 19-30 (2004).

[3] 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,” Optics Express 14, 6178-6187 (2006).

行政院國家科學委員會補助國內專家學者出席國際學術會議 報告

報告人:孫啟光教授 國立台灣大學光電工程研究所

會議名稱:Conference on Lasers and Electro-Optics/Quantum Electronics and Laser Science Conference/Conference on Photonic Applications, Systems, and Technologies

會議時間:西元 2007 年 5 月 6 日至 5 月 11 日

會議地點:Baltimore Convention Center, Baltimore, Maryland, USA

2007 年 Conference on Lasers and Electro-Optics (CLEO)仍循慣例在五月於 Baltimore Convention Center 舉辦,由 OSA、APS、及 IEEE/LEOS 三大學會共同 主辦。會議同時與 Quantum Electronics and Laser Science Conference (QELS)及 Conference on Photonic Applications, Systems, and Technologies(PhAST)合辦,兼具 光電物理、工程、與產業,是瞭解光電相關未來發展的重要會議。今年會議兩個 Plenary Session,共有四位 Plenary speaker。兩位代表 CLEO 會議,ㄧ位代表 QELS 會議、ㄧ位代表 QELS 會議。演講者包含諾貝爾獎得主 Alan Heeger,主題橫跨 電子(塑膠電子、spin electronics)、生醫、光通信、與物理研究(metamaterials、

negative refraction),相當廣泛。筆者於會議首日到達,並於會議結束日當晚起成 返台,期間與許多國內外同人互動,收穫極多。筆者發表一篇邀請論文,同時也 獲邀參加 2008CLEO 會議之 Program committee member。筆者所發表的邀請論文 題目與作者資訊如下:

C.-K. Sun, “In vivo Imaging Using Harmonic Generation Microscopy,” paper JThE3.

Baltimore, MD, USA (2007).

筆者所指導之研究室,在此次會議中另有 8 篇論文發表。其作者序、論文題 目、與文章編號如下

1. T.-F. Kao, H.-P. Chen, and C.-K. Sun, “Design and Analysis of Surface Plasmon-Enhanced Metal-Semiconductor-Metal Traveling Wave Photodetectors,”

paperJThD59.

2. H.-W. Chen, J.-Y. Lu, L.-J. Chen, P.-J. Chiang, H.-C. Chang, Y.-T. Li, C.-L. Pan, and C.-K. Sun, “THz Fiber Directional Coupler,” paper CThLL7.

3. H.-W. Chen, J.-Y. Lu, L.-J. Chen, Y.-T. Li, C.-L. Pan, and C.-K. Sun, “Spectral Loss Characteristics of Subwavelength THz Fibers,” paper CJWA107.

4. S.-P. Tai, C.-H. Yu, C.-Y. Chen, F.-H. Chang, and C.-K. Sun, “Molecular Imaging Using CdSe/ZnS/Lipid Quantum Dots as Contrast Agents of Third Harmonic Generation Microscopy,” paper CMCC4.

5. C.-T. Kung, C.-C. Chuang, Y.-K. Huang, H.-J. Tsai, and C.-K. Sun, “In Vivo Continuous Observation of Vertebrate Cardiac Valve for Congenital Heart Disease Study and Drug Screening Using Third Harmonic Generation Microscopy,” paper CTuP4.

6. J.-Y. Lu, C.-P. Yu, H.-C. Chang, H.-W. Chen, Y.-T. Li, C.-L. Pan, and C.-K. Sun,

“Air-core microstructure fiber for terahertz radiation waveguiding,” paper CThLL5.

7. C.-S. Hsieh, S.-U. Chen, Y.-S. Yang, and C.-K. Sun, “Noninvasive long term observation and evaluation of mammal oocytes and embryos with a 3D subcellular spatial resolution,” paper CTuP5.

8. S.-P. Tai, C.-H. Yu, T.-M. Liu, Y.-C. Wen, and C.-K. Sun, “In vivo Molecular-Resonant Third Harmonic Generation Microscopy of Hemoglobin,”

paper CTuF4.

由於上傳空間有限,僅將個人邀請論文之摘要檢附於後。

In vivo Imaging Using Harmonic Generation Microscopy

Chi-Kuang Sun

Graduate Institute of Electro-Optical Engineering and Department of Electrical Engineering, National Taiwan University, Taipei,10617 TAIWAN, and Research Center for Applied Sciences, Academia Sinica, Taipei 115, TAIWAN, R.O.C.

[email protected]

Abstract: With a virtual-transition characteristic, harmonic generation microscopy provides high-penetration non-invasive intravital optical images with a submicron 3D resolution, ideal for in vivo disease diagnoses and longterm live animal studies.

@2007 Optical Society of America

OCIS codes: (170.3880) Medical and biological imaging, (190.4160) Multiharmonic generation, (170.6900) Three-dimensional microscopy

Optical higher harmonic generations, including second-harmonic-generation (SHG) and third-harmonic-generation (THG) processes are known to leave no energy deposition to the interacted matters due to the virtual-transition characteristic [1]. In contrast to the absorption-induced-fluorescence processes that require energy deposition and electron transitions, the higher harmonic generation processes provide the optical noninvasive nature desired for microscopy applications, especially for long-term observation of the dynamic changes of live samples, including small animals and clinical patients [2,3]. Different from single-photon and multi-photon fluorescence, no cell damage and photobleaching effect is expected from the optical harmonic-generation process due to the fact that there is no real electron-transition involved and the total generated harmonic photon energy has to be equal to the total annihilated photon energy. With a nonlinear nature similar to the multi-photon excited fluorescence, the generated SHG intensity depends on the square of the incident light intensity, while the generated THG intensity depends on the third power of the incident light intensity. These nonlinear dependencies allow localized excitations to enable intrinsic optical sectioning and a high three-dimensional resolution similar or better than that of the two-photon fluorescence microscopy. Combining with a Cr:forsterite laser operating in the biological penetration window [2], harmonic generation microscopy is ideal fir longterm in vivo imaging with high cell viability, high 3D spatial resolution, and high penetration capability [2,3]. In this presentation, we review our recent development of harmonic generation microscopy, which provide high-penetration non-invasive intravital optical microscopic images. Contrast mechanisms of higher harmonic generation microscopy will be discussed [1], with a focus on intravital imaging. Examples of longterm small animal imaging, including noninvasive embryonic studies and virtual biopsy, will be presented.

Molecular imaging capability based on nanoparticles and acetic acid will be demonstrated.

Fiber-optical endoscopic system development will also be discussed.

This research is sponsored by National health Research Institute of Taiwan and NTU Center for Genomic Medicine.

Reference

[1] C.-K. Sun, “Higher Harmonic Generation Microscopy” in Series in Advances in Biochemical Engineering/Biotechnology, Special Volume 95: Microscopic Techniques, J. Rietdorf Ed., (SPRINGER-VERLAG, Berlin, 2005).

[2] C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, “Higher harmonic generation microscopy for developmental biology,” Journal of Structural Biology 147, 19-30 (2004).

[3] 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,” Optics Express 14, 6178-6187 (2006).