非线性光学显微镜的研究
|
摘要
非线性共焦显微镜，如双光子荧光(TPF)和多光子荧光(MPF)共焦显微镜、二次谐波(SHG)和三次谐波(THG)共焦显微镜、相干反斯托克斯散射(CARS)共焦显微镜等，是基于非线性光学效应的高分辨率成像技术。非线性效应能导致其成像焦斑比激发光的焦斑更小，从而突破了经典衍射极限，极大地改善了共焦显微镜的空间分辨率，从而实现超分辨率三维成像。非线性显微镜具有空间分辨率高、层析成像、穿透深度大等优点，因而在生物医学、生命科学、材料科学等领域具有变革性的应用潜力。近二十年来，非线性共焦显微镜的理论和实验研究取得了许多突破性进展，已成为光学及其交叉学科中最诱人、最活跃的研究领域之一。而拉曼感生克尔效应光谱(RIKES)是一种三阶非线性相干拉曼光谱学过程，大多数文献只是对如何提高RIKES检测的灵敏度做了理论和实验研究，但能否用RIKES光谱来进行显微成像，目前还没有文献做过系统的理论分析。
RIKES成像不同于单光束成像模式，它需要采用两束光进行成像：即泵浦光和探测光，强的泵浦光会对弱的探测光(成像光束)产生很强的非线性调制作用，当泵浦光与探测光的频率差刚好等于样品的某个拉曼模的频率时，强的泵浦光不仅会引起成像光束的锐化，还会引起成像光束偏振态的改变。因此，RIKES成像除了具有非线性共焦显微镜的上述优点外，包含了更多物质内部的结构信息，如：分子的振动模、振动取向以及光克尔效应等信息，其次，RIKES成像是特征成像，那么，对分子某些特征的振动模式进行成像，能够实现分子的特征识别，因此，在分子影像和单分子检测方面具有重要意义。
本文提出了基于拉曼感生克尔效应光谱(RIKES)的非线性共焦显微镜的和微分共焦显微镜的成像模式，从理论上论证了RIKES成像的可行性，研究了RIKES非线性共焦显微镜的三维成像特性，结果表明：RIKES成像具有内在的光学层析成像能力和特征成像能力，可以突破经典衍射极限，实现超分辨率特征成像，有望发展成为一种新型的可与目前其它的非线性成像模式相媲美的非线性成像技术。本文的主要内容包括：
第一、研究了RIKES的物理机制，提出利用RIKES光谱进行显微成像的新型的成像模式，在理论上验证了该成像模式的可行性，系统地研究了拉曼感生克尔效应光谱成像的特点。
第二、利用傅立叶光学成像理论和非线性原理，研究了RIKES共焦显微镜的成像理论。在此基础上，分析了RIKES非线性共焦显微镜的三维成像特性，最后推导了RIKES共焦显微镜的光学传递函数。
第三、推导了高斯光束非线性拉曼共焦显微镜的成像理论。同时，与点光源描述的非线性拉曼共焦显微镜的点扩散函数相比，两者具有内在的一致性。在此基础上，研究了泵浦光对探测光的空间调制机制，分析了不同束腰尺寸的泵浦光和探测光对非线性拉曼共焦显微镜空间分辨率的影响。
第四、提出了一种利用时间分辨技术结合共焦扫描实现微分共焦显微镜的新的方法，推导了微分共焦显微镜的成像理论。结果表明，微分共焦显微镜，可以突破经典衍射极限，极大地改善共焦显微镜的横向分辨率，从而实现超分辨率微分成像。
Nonlinear confocal microscopy, such as two-photon fluorescence (TPF) and multi-photon fluorescence (MPF), second-harmonic generation (SHG) and third-harmonic generation (THG), Coherent anti-Stoke Raman Scattering (CARS) microscopy, has been demonstrated the potential applications in biomedicine, biology and material science et al. As a powerful optical imaging technique, nonlinear confocal microscopy intrinsically provides three-dimensional (3-D) imaging capability and potentially produces image contrast with chemical and physical specificity inside scattering samples. However, is it feasible to utilize Raman induced Kerr effect spectroscopy (RIKES) imaging? No person studies it systematically.
In RIKES imaging, a strong circularly polarized pump beam at frequencyω_1 and a weak, y-polarized bean at frequencyω_s are employed. The pump beam modulated nonlinearly on the probe beam, i.e., the imaging beam. When the frequency differenceω_l-ω_s is tuned to match the frequency of a Raman modeω_R, i.e.,ω_l-ω_s=ω_R, the pump beam can induce an enhanced circular birefringence, which consequently causes a polarization rotation of the linearly polarized probe beam, termed Raman induced Kerr effect spectroscopy (RIKES). Beside the above advantages of nonlinear confocal microscopy, RIKES imaging is capable to characterize inherent structural features, such as vibration mode, vibration orientation, and optically-induced molecular reorientation et al. Considering that Raman spectrum is the fingerprint of the molecular structure, So RIKES imaging on the vibration mode can provide the basis for molecular identification, which is significant in molecular imaging and single molecular detection.
If RIKES imaging is utilized instead of two-photon fluorescence, SHG and CARS imaging, it has potential to provide a novel sub-diffraction limit characteristic imaging method comparable to the existing imaging techniques based on other nonlinear optical processes, such as two-photon fluorescence, SHG and CARS.
In this paper, a novel nonlinear confocal microscopy that utilizing Raman induced Kerr effect spectroscopy (RIKES) is presented. The imaging theory of RIKES confocal microscopy is derived. The imaging properties of RIKES confocal microscopy has been analyzed in detail. The main contents are as follows:
Firstly, the physical mechanism of RIKES generation is discussed. A novel nonlinear imaging utilizing RIKES is presented. The characteristic of RIKES imaging is analyzed in detail.
Secondly, according to Fourier imaging theory and nonlinear optical principle, the imaging theory of RIKES nonlinear confocal microscopy is derived. With the imaging theory, the impact of nonlinear property of RIKES on the spatial resolution and imaging properties of confocal microscopy has been analyzed in detail. Aditionally, the three-dimensional optical transfer function (OTF) of RIKES nonlinear confocal microscopy is calculated.
Thirdly, considering the Gaussian distribution of source function, the three-dimensional point spread function of RIKES confocal microscopy is derived. The spatial modulation mechanism of pump beam on the probe beam is discussed.
Finally, a novel differential confocal microscopy is developed based on a time-resolved technique and confocal scanning technique. The imaging theory of differential confocal microscopy is derived. The three-dimensional point spread function of differential confocal microscopy is derived. It is shown the differential confocal imaging technique can break through the classic diffraction limit and achieve high-resolution imaging.
RIKES成像不同于单光束成像模式，它需要采用两束光进行成像：即泵浦光和探测光，强的泵浦光会对弱的探测光(成像光束)产生很强的非线性调制作用，当泵浦光与探测光的频率差刚好等于样品的某个拉曼模的频率时，强的泵浦光不仅会引起成像光束的锐化，还会引起成像光束偏振态的改变。因此，RIKES成像除了具有非线性共焦显微镜的上述优点外，包含了更多物质内部的结构信息，如：分子的振动模、振动取向以及光克尔效应等信息，其次，RIKES成像是特征成像，那么，对分子某些特征的振动模式进行成像，能够实现分子的特征识别，因此，在分子影像和单分子检测方面具有重要意义。
本文提出了基于拉曼感生克尔效应光谱(RIKES)的非线性共焦显微镜的和微分共焦显微镜的成像模式，从理论上论证了RIKES成像的可行性，研究了RIKES非线性共焦显微镜的三维成像特性，结果表明：RIKES成像具有内在的光学层析成像能力和特征成像能力，可以突破经典衍射极限，实现超分辨率特征成像，有望发展成为一种新型的可与目前其它的非线性成像模式相媲美的非线性成像技术。本文的主要内容包括：
第一、研究了RIKES的物理机制，提出利用RIKES光谱进行显微成像的新型的成像模式，在理论上验证了该成像模式的可行性，系统地研究了拉曼感生克尔效应光谱成像的特点。
第二、利用傅立叶光学成像理论和非线性原理，研究了RIKES共焦显微镜的成像理论。在此基础上，分析了RIKES非线性共焦显微镜的三维成像特性，最后推导了RIKES共焦显微镜的光学传递函数。
第三、推导了高斯光束非线性拉曼共焦显微镜的成像理论。同时，与点光源描述的非线性拉曼共焦显微镜的点扩散函数相比，两者具有内在的一致性。在此基础上，研究了泵浦光对探测光的空间调制机制，分析了不同束腰尺寸的泵浦光和探测光对非线性拉曼共焦显微镜空间分辨率的影响。
第四、提出了一种利用时间分辨技术结合共焦扫描实现微分共焦显微镜的新的方法，推导了微分共焦显微镜的成像理论。结果表明，微分共焦显微镜，可以突破经典衍射极限，极大地改善共焦显微镜的横向分辨率，从而实现超分辨率微分成像。
Nonlinear confocal microscopy, such as two-photon fluorescence (TPF) and multi-photon fluorescence (MPF), second-harmonic generation (SHG) and third-harmonic generation (THG), Coherent anti-Stoke Raman Scattering (CARS) microscopy, has been demonstrated the potential applications in biomedicine, biology and material science et al. As a powerful optical imaging technique, nonlinear confocal microscopy intrinsically provides three-dimensional (3-D) imaging capability and potentially produces image contrast with chemical and physical specificity inside scattering samples. However, is it feasible to utilize Raman induced Kerr effect spectroscopy (RIKES) imaging? No person studies it systematically.
In RIKES imaging, a strong circularly polarized pump beam at frequencyω_1 and a weak, y-polarized bean at frequencyω_s are employed. The pump beam modulated nonlinearly on the probe beam, i.e., the imaging beam. When the frequency differenceω_l-ω_s is tuned to match the frequency of a Raman modeω_R, i.e.,ω_l-ω_s=ω_R, the pump beam can induce an enhanced circular birefringence, which consequently causes a polarization rotation of the linearly polarized probe beam, termed Raman induced Kerr effect spectroscopy (RIKES). Beside the above advantages of nonlinear confocal microscopy, RIKES imaging is capable to characterize inherent structural features, such as vibration mode, vibration orientation, and optically-induced molecular reorientation et al. Considering that Raman spectrum is the fingerprint of the molecular structure, So RIKES imaging on the vibration mode can provide the basis for molecular identification, which is significant in molecular imaging and single molecular detection.
If RIKES imaging is utilized instead of two-photon fluorescence, SHG and CARS imaging, it has potential to provide a novel sub-diffraction limit characteristic imaging method comparable to the existing imaging techniques based on other nonlinear optical processes, such as two-photon fluorescence, SHG and CARS.
In this paper, a novel nonlinear confocal microscopy that utilizing Raman induced Kerr effect spectroscopy (RIKES) is presented. The imaging theory of RIKES confocal microscopy is derived. The imaging properties of RIKES confocal microscopy has been analyzed in detail. The main contents are as follows:
Firstly, the physical mechanism of RIKES generation is discussed. A novel nonlinear imaging utilizing RIKES is presented. The characteristic of RIKES imaging is analyzed in detail.
Secondly, according to Fourier imaging theory and nonlinear optical principle, the imaging theory of RIKES nonlinear confocal microscopy is derived. With the imaging theory, the impact of nonlinear property of RIKES on the spatial resolution and imaging properties of confocal microscopy has been analyzed in detail. Aditionally, the three-dimensional optical transfer function (OTF) of RIKES nonlinear confocal microscopy is calculated.
Thirdly, considering the Gaussian distribution of source function, the three-dimensional point spread function of RIKES confocal microscopy is derived. The spatial modulation mechanism of pump beam on the probe beam is discussed.
Finally, a novel differential confocal microscopy is developed based on a time-resolved technique and confocal scanning technique. The imaging theory of differential confocal microscopy is derived. The three-dimensional point spread function of differential confocal microscopy is derived. It is shown the differential confocal imaging technique can break through the classic diffraction limit and achieve high-resolution imaging.
引文
[1]. Nana Rezai, Taking the Confusion out of Confocal Microscopy, Bio. Teach. Journal, 2003, 1, 75-80
[2]. A. D. Dinsmore, Eric R. Weeks, Vikram Prasad, et al., Three-dimensional confocal microscopy of colloids, Appl. Opt., 2001, 40(24), 4152-4159
[3]. Martin M. Knight, Susan R. Roberts, David A. Lee, et al., Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death, Am J Physiol Cell Physiol, 2003, 284, C1083-C1089
[4]. Barry R. Masters and Peter T. C. So, Confocal microscopy and multi-photon excitation microscopy of human skin in vivo, Opt. Exp., 2001, 8(1), 2-10
[5]. C. J. R. Sheppard and D. M. Shotton, Confocal laser scanning microscopy (BIOS Scientific Publishers Limited, Oxford, UK, 1997)
[6]．陈文霞，肖繁荣，刘力等，利用受激发射损耗(STED)显微术突破远场衍射极限，激光与光电子学进展，2005，42(10)，51-56
[7]．唐志列，黄佐华，梁瑞生等，共焦显微镜的纵向分辨率极限及其判据，量子电子学报，2000，17(3)，199-204
[8]．邢达，周俊初，于彦华等，利用激光共聚焦扫描显微镜的绿色荧光蛋白荧光成像．光学学报，1999，19(10)，1439-1440
[9]．刘力，邓小强，王桂英等，改善共焦系统轴向分辨率的位相型光瞳滤波器，物理学报，2001，50(1)，48-51
[10]．王永红等，多光束并行共焦探测系统特性的研究，计量学报，2004，25(2)，100-103
[11]．邵宏伟等，激光共焦显微镜，计量学报，2004，25(2)，104-106
[12]．张平等，荧光共焦扫描系统成像特性的优化，光学学报，1997，17(3)，308-313。
[13]．丁志华，包正康，刘昱等，共焦扫描显微术中影响轴向分辨率的因素分析，中国激光2000，27(6)，531-536
[14]．余飞鸿等，无扫描光源调制层析成像显微镜理论，光子学报，2001，30(12)，1509-1515
[15]. C. H. Lee, W. C. Lin, and J. E Wang, Using differential confocal microscopy to detect the phase transition of lipid vesicle membranes, Opt. Eng., 2001, 40 (10), 2077-2083
[16]. Chau-Hwang Lee, Hui-Yu Chiang, and Hong-Yao Mong, Sub-diffraction-limit imaging based on the topographic contrast of differential confocal microscopy, Opt. Lett., 2003, 28(19), 1772-1774
[17]. Lisong Yang, Li Liu, Guiying Wang, et alo, Noninterferometric measurement of lead zirconate titanate inverse piezoelectric extension, Opt. Eng., 2001, 40(6), 909-913
[18]. Liu Li, Deng Xiaoqiang, Yang Lisong, et alo, Differential Confocal Microscopy with Annular Pupil Filter, Proc. SPIE, 2000, 4224, 73-77
[19]. Tan Jiubin, et al, Theoretical analysis and property study of optical focus detection based on differential confocal microscopy, Measurement Science and Technology, 2002, 13(8), 1289-1293
[20]. Jiubin Tan, et al., Differential confocal optical system using gradient-index lenses, Opt. Eng., 2003, 42 (10), 2868-2871
[21]. S. H. Cody, S. D. Xiang, M. J. Layton, et al., A simple method allowing DIC imaging in conjunction with confocal microscopy, J. Microsc., 2005, 217, 265-274
[22]. Squier J, Muller M. High resolution nonlinear microscopy: A review of sources and methods for achieving optical imaging. Rev. Sci. Instrum., 2001, 72(7), 2855-2867
[23]. W. Rudolph, E Dorn, X. Liu, et al, Microscopy with femtosecond laser pulses: applications in engineering, physics and biomedicine. Applied Surface Science, 2003, 208-209, 327-332
[24]. Jerome Mertz, Nonlinear microscopy: new techniques and applications, Current Opinion in Neurobiology, 2004, 14, 610-618
[25]. Martin Oheim, Darren J. Michael, Matthias Geisbauer, et al., Principles of two-photon excitation fluorescence microscopy and other nonlinear imaging approaches, Advanced Drug Delivery Reviews 2006, 58, 788-808
[26]. Zipfel W. R., Nonlinear magic: Mutiphoton microscopy in the bioscienceso Nat. Biotechnol., 2003, 21, 1369-1377.
[27]. Helmchen F., Denk W., New developments in multiphoton microscopy, Curr. Opin. Neurobiol., 2002, 12, 593-601
[28]. W. Denk, J. H. Strickler, and W. W. Webb, Two-photon laser scanning fluorescence microscopy, Science, 1990, 248 (4951), 73-76
[29]. Woksin D L et al, Characterization of a range of Fura dyes with two-photon excitation. Biophys. J., 2004, 86, 1726-1738
[30]. Marandi N, et al., Two-photon chloride imaging in neurons of brain slices, Pflugers. Arch., 2002, 445, 357-365
[31]．唐志列，梁瑞生，常鸿森，双光子和多光子共焦显微镜的成像理论，物理学报，2000，49(6)，1076-1080
[32]. Bewersdorf J., Pick R., Hell S. W., Multifocal multiphoton microscopy, Opt. Lett., 1998, 23, 655-657
[33]. Yici Guo, P. P. Ho, Feng Liu, et al., Noninvasive two-photon-excitation imaging of tryptophan distribution in highly scattering biological tissues, Opt. Commun., 1998, 154, 383-389
[34]．邢岐荣，魏赫颖，王明伟等，飞秒激光HpD双光子荧光法诊断癌症，中国激光，2000，27(8)，765-767
[35]. Paul, J. C., Andrew C. M., Mark, T. et al., Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissue. Biophys. J., 2002, 81(1), 493-508
[36]. Guo Y., et al., Second-harmonic tomography of tissue, Opt. Lett., 1997, 22(17), 1323-1325
[37]．唐志列，邢达，刘颂豪，非线性二次谐波和三次谐波共焦显微镜的成像理论，中国科学：G辑，2003，33(3)，212-218
[38]. J. A. Squier, M. Miiller and G. J. Brakenhoff, et al., Third harmonic generation microscopy, Opt. Exp., 1998, 3(9), 315-324
[39]. Gauderon R., Lukins P. B., Sheppard C. J. R., Simultaneous multichannal nonlinear imaging: combined two-photon excited fluorescence and second-harmonic generation microscopy. Micron., 2001, 32, 685-689
[40]. D. Yelin et al., Phase-matched third-harmonic generation in a nematic liquid crystal cell, Phys. Rev. Lett. 1999, 82, 3046-3049
[41]. Volkmer A., Vibrational imaging and microspectroscopies based on coherent anti-Stokes Raman scattering microscopy, J. Phys. D, 2005, 38, 59-81
[42]. Ji-xin Cheng, Eric O. Potma, Sunney X. Xie, Recent advances on Coherent Anti-Stokes Raman Scattering (CARS) Microscopy, Proc. SPIE., 2002, 4620, 248-258
[43]．袁景和，肖繁荣，王桂英等，CARS显微术的基本原理及其进展，激光与光电子学进展，2004，41(7)，17-23
[44]. Yakovlev V. V., Broadband cost-effective nonlinear Raman microscopy, Proc. SPIE, 2004, 5323, 214-220
[45]. M. D. Duncan, J. Reintjes, T. J. Manuccia, Scanning coherent anti-Stokes Raman microscope, Opt. Lett., 1982, 7, 350-352
[46]. Zumbusch A., Holtom G. R., Xie X. S., Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering, Phys. Rev. Lett., 1999, 82(20), 4142—4144
[47]. Cheng Jixin, Volkmer A., Book L. D., et al., An epi-detected coherent anti-Stokes Raman scattering (E-CARS) microscope with high special resolution and high sensitivity, Phys. Chem. B, 2001, 105(7), 1277-1280
[48]. J. -X. Cheng, A. Volkmer, and X. S. Xie, Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy, J. Opt. Soc. Am. B, 2002, 19, 1363-1375
[49]. J. -X. Cheng, L. D. Book, and X. S. Xie, "Polarization coherent anti-Stokes Raman scattering microscopy," Opt. Lett. 26, 1341-1343 (2001)
[50]. Cheng Jixin, Jia Y K, Zheng Gengfeng et al., Laser-scanning coherent anti-Stokes Raman scattering microscopy and applications to cell biology, Biophysical J., 2002, 83, 502-509
[51]. Wurpel G. W. H., Schins J. M., Muller M., Chemical specificity in three-dimensional imaging with mutiplex coherent anti-Stokes Raman scattering microscopy, Opt. Lett., 2002, 27(13), 1093-1095
[52]. Dudovich N., Oron D., Silberberg Y., Single-pulse coherently controlled nonlinear Raman spectroscopy and microscopy, Letter. Nature, 2002, 418(8), 512-514
[53]. H. Kano, H. Hamaguchi, Near-infrared coherent anti-Stokes Raman scattering microscopy using supercontinuum generated from a photonic crystal fiber, Appl. Phys. B, 2005, 80, 243-246
[54]. S. W. Hell and J. Wichmann, Breaking the diffraction resolution limit by stimulated emission: stimulated emission depletion microscopy, Opt. Lett., 1994, 19, 780-782
[55]. Mats G. L. Gustafsson, Nonlinear structured-illumination microscopy: Wide-field fluorescence imaging with theoretically unlimited resolution, PNAS, 2005, 102(37), 13081-13086
[56]. V. Westphal, J. Seeger, T. Salditt, et al., Stimulated emission depletion microscopy on lithographic nanostructures, J. Phys. B, 2005, 38, S695
[57]. Westphal V., Kastrup L., Hell S. W., Lateral resolution of 28 nm (λ/25) in far-field fluorescence microscopy, Appl. Phys. B., 2003, 77, 377-380
[58]. Marcus Dyba and Stefan W. Hell, Focal spots of size λ/23 open up far-field florescence microscopy at 33 nm axial resolution, Phy. Rev. Lett., 2002 88, 163901-4
[59]. Hongki Yoo, Incheon Song, Taehoon Kim, et al, Effects of a pupil filter on Stimulated Emission Depletion Microscopy, Proc. SPIE, 6090, 2006, 60900X-6
[60]. Yasui T., Minoshima K., Abraham E., et al., Microscopic time-resolved two-dimensional imaging with a femtosecond amplifying optical Kerr gate, Appl. Opt., 2002, 41(24), 5191-5194
[61]. Potma E. O., Boeij W. P. de, Wiersma D. A., Femtosecond dynamics of intracellular water probed with nonlinear optical Kerr effect microspectroscopy, Biophys. J., 2001, 80(6), 3019-3024
[62]. C. Egami, Naoki Kobayashi, Yoshimasa Kawata, et al., Confocal nonlinear optical microscopy for high-resolution measurement of absorptive objects, Opt. Lett., 2006, 31(6), 784-786 46
[2]. D. Heiman, R. W. Hellwarth, M. D. Levenson, et al, Raman-induced Kerr effect, Phys. Rev. Lett., 1976, 36, 189-192
[3]．钱士雄，王恭明编著，非线性光学：原理与进展，上海：复旦大学出版社，2001
[4]．石顺祥，陈国夫，赵卫等编著，非线性光学，西安：西安电子科技大学出版社，2003
[5]．喻远琴，周晓国，林柯等，CH_4分子v_1模拉曼诱导克尔效应谱与受激拉曼光声光谱峰形的比较，物理学报，2006，55(6)，2740-2745
[6]. Y. R. Shen, The Principles of Nonlinear Optics, Wiley, New York, 1984, p. 47
[7]. Jinghe Yuan et al, The intensity distributions of collected signal in coherent anti-Stokes Raman scattering microscopy, Colloids and Surfaces A, 2005, 257-258, 525-527
[8]. X. L. Xie and J. D. Simon, Picosecond time-resolved circular dichroism spectroscopy: experimental details and applications, 1989, 60(8), 2614-2627
[9]. R. C. Jones, Anew calculus for the treatment of optical systems. Ⅱ. Properties of the N-Matrices, J. Opt. Soc. Am. A, 1948, 38(8), 671-685
[10]．(日)堀江一之，(日)牛木秀治，(加)F．M．威尼克(Francoise M．Winnik)著，张镇西译，分子光子学：原理及应用，北京：科学出版社，2004，178-197
[1]．Marc D．Levensan著，腾家炽，林礼煌，李秀春译，非线性激光光谱学导论，北京：宇航出版社，1988
[2]. Bhatia P. S., Keto J. W., Pressure and power dependence of the optically heterodyne Raman-induced Kerr effect line shape, Phys. Rev. A, 1999, 59(5), 4045-4051
[3]. Giraud G., Karolin J., Wynne K., Low-frequency modes of peptides and globular proteins in solution observed by ultrafast OHD-RIKES spectroscopy, Biophy., 2003, 85, 1903-1913
[4]. Tang Z. L., Xing D., and Liu S. H., Imaging theory of nonlinear second harmonic and third harmonic generations in confocal microscopy, Sci. China Ser. G, 2004, 47(1), 8-16
[5]. J. J. Song, G. L. Eesley, and M. D. Levenson, Background suppression in coherent Raman spectroscopy, Appl. Phys. Lett., 1976, 20, 567
[6]. Heiman D., Hellwarth R. W., Levenson M. D., et al., Raman-induced Kerr effect. Phys. Rev. Lett., 1976, 36(4), 189-192
[7]. Tang Z. L., Yang C. P., Pei H. J., Liang R. S., and Liu S. H., Imaging theory and resolution improvement of two-photon confocal microscopy, Sci. China Ser. A, 2002, 45(11), 1468-1478
[1]. M. Born, E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light, 7th ed., Cambridge University Press, 2001
[2]．唐志列，邢达，刘颂豪，非线性二次谐波和三次谐波共焦显微镜的成像理论，中国科学：G辑，2003，33(3)，212-218
[3]．唐志列，杨初平，裴红津，等，双光子共焦电子显微镜的三维成像理论及其分辨率的改善，中国科学：A辑，2002 32(6)，538-547
[4]．唐志列，梁瑞生，常鸿森，双光子和多光子共焦显微镜的成像理论，物理学报，2000，9(6)，1076-1080
[5]．古德曼(Joseph W．Goodman)著，傅立叶光学导论，秦克诚等译，北京：电子工业出版社，2006
[6]．杨初平，吴燕山，李海等，高斯光束对荧光共焦显微镜分辨率的影响，华南师范大学学报(自然科学版)，2004，No．3，66-71
[1]. C. H. Lee, W. C. Lin, and J. P. Wang, Using differential confocal microscopy to detect the phase transition of lipid vesicle membranes, Opt. Eng., 2001, 40 (10), 2077-2083
[2]. Lisong Yang, Li Liu, Guiying Wang, et al, Noninterferometric measurement of lead zirconate titanate inverse piezoelectric extension, Opt. Eng., 2001, 40(6), 909-913
[3]. Jiubin Tan, et al., Differential confocal optical system using gradient-index lenses, Opt. Eng., 2003, 42 (10), 2868-2871.
[4]. M. R. Amison, K. G. Larkin, C. J. R. Sheppard, et al., Linear phase imaging using differential interference contrast Microscopy, J. Microsc. 214, 2004, 7-12
[5]. Chrysanthe Prezay, Donald L. Snydery, Jose-Angel Conchello, Imaging models for three-dimensional transmitted-light DIC microscopy, SPIE, 1996, 1-13
[6]. C. J. R. Sheppard and C. J. Cogswell, Image formation in video-enhanced and confocal DIC microscopy, SPIE, 1846, 64-71
[7]. L. Guo, Z. Tang, Y. He, et al., Characterization of a derivative photoacoustic spectrometer, Rev. Sci. Instrum., 2007, 78, 023104
[2]. A. D. Dinsmore, Eric R. Weeks, Vikram Prasad, et al., Three-dimensional confocal microscopy of colloids, Appl. Opt., 2001, 40(24), 4152-4159
[3]. Martin M. Knight, Susan R. Roberts, David A. Lee, et al., Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death, Am J Physiol Cell Physiol, 2003, 284, C1083-C1089
[4]. Barry R. Masters and Peter T. C. So, Confocal microscopy and multi-photon excitation microscopy of human skin in vivo, Opt. Exp., 2001, 8(1), 2-10
[5]. C. J. R. Sheppard and D. M. Shotton, Confocal laser scanning microscopy (BIOS Scientific Publishers Limited, Oxford, UK, 1997)
[6]．陈文霞，肖繁荣，刘力等，利用受激发射损耗(STED)显微术突破远场衍射极限，激光与光电子学进展，2005，42(10)，51-56
[7]．唐志列，黄佐华，梁瑞生等，共焦显微镜的纵向分辨率极限及其判据，量子电子学报，2000，17(3)，199-204
[8]．邢达，周俊初，于彦华等，利用激光共聚焦扫描显微镜的绿色荧光蛋白荧光成像．光学学报，1999，19(10)，1439-1440
[9]．刘力，邓小强，王桂英等，改善共焦系统轴向分辨率的位相型光瞳滤波器，物理学报，2001，50(1)，48-51
[10]．王永红等，多光束并行共焦探测系统特性的研究，计量学报，2004，25(2)，100-103
[11]．邵宏伟等，激光共焦显微镜，计量学报，2004，25(2)，104-106
[12]．张平等，荧光共焦扫描系统成像特性的优化，光学学报，1997，17(3)，308-313。
[13]．丁志华，包正康，刘昱等，共焦扫描显微术中影响轴向分辨率的因素分析，中国激光2000，27(6)，531-536
[14]．余飞鸿等，无扫描光源调制层析成像显微镜理论，光子学报，2001，30(12)，1509-1515
[15]. C. H. Lee, W. C. Lin, and J. E Wang, Using differential confocal microscopy to detect the phase transition of lipid vesicle membranes, Opt. Eng., 2001, 40 (10), 2077-2083
[16]. Chau-Hwang Lee, Hui-Yu Chiang, and Hong-Yao Mong, Sub-diffraction-limit imaging based on the topographic contrast of differential confocal microscopy, Opt. Lett., 2003, 28(19), 1772-1774
[17]. Lisong Yang, Li Liu, Guiying Wang, et alo, Noninterferometric measurement of lead zirconate titanate inverse piezoelectric extension, Opt. Eng., 2001, 40(6), 909-913
[18]. Liu Li, Deng Xiaoqiang, Yang Lisong, et alo, Differential Confocal Microscopy with Annular Pupil Filter, Proc. SPIE, 2000, 4224, 73-77
[19]. Tan Jiubin, et al, Theoretical analysis and property study of optical focus detection based on differential confocal microscopy, Measurement Science and Technology, 2002, 13(8), 1289-1293
[20]. Jiubin Tan, et al., Differential confocal optical system using gradient-index lenses, Opt. Eng., 2003, 42 (10), 2868-2871
[21]. S. H. Cody, S. D. Xiang, M. J. Layton, et al., A simple method allowing DIC imaging in conjunction with confocal microscopy, J. Microsc., 2005, 217, 265-274
[22]. Squier J, Muller M. High resolution nonlinear microscopy: A review of sources and methods for achieving optical imaging. Rev. Sci. Instrum., 2001, 72(7), 2855-2867
[23]. W. Rudolph, E Dorn, X. Liu, et al, Microscopy with femtosecond laser pulses: applications in engineering, physics and biomedicine. Applied Surface Science, 2003, 208-209, 327-332
[24]. Jerome Mertz, Nonlinear microscopy: new techniques and applications, Current Opinion in Neurobiology, 2004, 14, 610-618
[25]. Martin Oheim, Darren J. Michael, Matthias Geisbauer, et al., Principles of two-photon excitation fluorescence microscopy and other nonlinear imaging approaches, Advanced Drug Delivery Reviews 2006, 58, 788-808
[26]. Zipfel W. R., Nonlinear magic: Mutiphoton microscopy in the bioscienceso Nat. Biotechnol., 2003, 21, 1369-1377.
[27]. Helmchen F., Denk W., New developments in multiphoton microscopy, Curr. Opin. Neurobiol., 2002, 12, 593-601
[28]. W. Denk, J. H. Strickler, and W. W. Webb, Two-photon laser scanning fluorescence microscopy, Science, 1990, 248 (4951), 73-76
[29]. Woksin D L et al, Characterization of a range of Fura dyes with two-photon excitation. Biophys. J., 2004, 86, 1726-1738
[30]. Marandi N, et al., Two-photon chloride imaging in neurons of brain slices, Pflugers. Arch., 2002, 445, 357-365
[31]．唐志列，梁瑞生，常鸿森，双光子和多光子共焦显微镜的成像理论，物理学报，2000，49(6)，1076-1080
[32]. Bewersdorf J., Pick R., Hell S. W., Multifocal multiphoton microscopy, Opt. Lett., 1998, 23, 655-657
[33]. Yici Guo, P. P. Ho, Feng Liu, et al., Noninvasive two-photon-excitation imaging of tryptophan distribution in highly scattering biological tissues, Opt. Commun., 1998, 154, 383-389
[34]．邢岐荣，魏赫颖，王明伟等，飞秒激光HpD双光子荧光法诊断癌症，中国激光，2000，27(8)，765-767
[35]. Paul, J. C., Andrew C. M., Mark, T. et al., Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissue. Biophys. J., 2002, 81(1), 493-508
[36]. Guo Y., et al., Second-harmonic tomography of tissue, Opt. Lett., 1997, 22(17), 1323-1325
[37]．唐志列，邢达，刘颂豪，非线性二次谐波和三次谐波共焦显微镜的成像理论，中国科学：G辑，2003，33(3)，212-218
[38]. J. A. Squier, M. Miiller and G. J. Brakenhoff, et al., Third harmonic generation microscopy, Opt. Exp., 1998, 3(9), 315-324
[39]. Gauderon R., Lukins P. B., Sheppard C. J. R., Simultaneous multichannal nonlinear imaging: combined two-photon excited fluorescence and second-harmonic generation microscopy. Micron., 2001, 32, 685-689
[40]. D. Yelin et al., Phase-matched third-harmonic generation in a nematic liquid crystal cell, Phys. Rev. Lett. 1999, 82, 3046-3049
[41]. Volkmer A., Vibrational imaging and microspectroscopies based on coherent anti-Stokes Raman scattering microscopy, J. Phys. D, 2005, 38, 59-81
[42]. Ji-xin Cheng, Eric O. Potma, Sunney X. Xie, Recent advances on Coherent Anti-Stokes Raman Scattering (CARS) Microscopy, Proc. SPIE., 2002, 4620, 248-258
[43]．袁景和，肖繁荣，王桂英等，CARS显微术的基本原理及其进展，激光与光电子学进展，2004，41(7)，17-23
[44]. Yakovlev V. V., Broadband cost-effective nonlinear Raman microscopy, Proc. SPIE, 2004, 5323, 214-220
[45]. M. D. Duncan, J. Reintjes, T. J. Manuccia, Scanning coherent anti-Stokes Raman microscope, Opt. Lett., 1982, 7, 350-352
[46]. Zumbusch A., Holtom G. R., Xie X. S., Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering, Phys. Rev. Lett., 1999, 82(20), 4142—4144
[47]. Cheng Jixin, Volkmer A., Book L. D., et al., An epi-detected coherent anti-Stokes Raman scattering (E-CARS) microscope with high special resolution and high sensitivity, Phys. Chem. B, 2001, 105(7), 1277-1280
[48]. J. -X. Cheng, A. Volkmer, and X. S. Xie, Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy, J. Opt. Soc. Am. B, 2002, 19, 1363-1375
[49]. J. -X. Cheng, L. D. Book, and X. S. Xie, "Polarization coherent anti-Stokes Raman scattering microscopy," Opt. Lett. 26, 1341-1343 (2001)
[50]. Cheng Jixin, Jia Y K, Zheng Gengfeng et al., Laser-scanning coherent anti-Stokes Raman scattering microscopy and applications to cell biology, Biophysical J., 2002, 83, 502-509
[51]. Wurpel G. W. H., Schins J. M., Muller M., Chemical specificity in three-dimensional imaging with mutiplex coherent anti-Stokes Raman scattering microscopy, Opt. Lett., 2002, 27(13), 1093-1095
[52]. Dudovich N., Oron D., Silberberg Y., Single-pulse coherently controlled nonlinear Raman spectroscopy and microscopy, Letter. Nature, 2002, 418(8), 512-514
[53]. H. Kano, H. Hamaguchi, Near-infrared coherent anti-Stokes Raman scattering microscopy using supercontinuum generated from a photonic crystal fiber, Appl. Phys. B, 2005, 80, 243-246
[54]. S. W. Hell and J. Wichmann, Breaking the diffraction resolution limit by stimulated emission: stimulated emission depletion microscopy, Opt. Lett., 1994, 19, 780-782
[55]. Mats G. L. Gustafsson, Nonlinear structured-illumination microscopy: Wide-field fluorescence imaging with theoretically unlimited resolution, PNAS, 2005, 102(37), 13081-13086
[56]. V. Westphal, J. Seeger, T. Salditt, et al., Stimulated emission depletion microscopy on lithographic nanostructures, J. Phys. B, 2005, 38, S695
[57]. Westphal V., Kastrup L., Hell S. W., Lateral resolution of 28 nm (λ/25) in far-field fluorescence microscopy, Appl. Phys. B., 2003, 77, 377-380
[58]. Marcus Dyba and Stefan W. Hell, Focal spots of size λ/23 open up far-field florescence microscopy at 33 nm axial resolution, Phy. Rev. Lett., 2002 88, 163901-4
[59]. Hongki Yoo, Incheon Song, Taehoon Kim, et al, Effects of a pupil filter on Stimulated Emission Depletion Microscopy, Proc. SPIE, 6090, 2006, 60900X-6
[60]. Yasui T., Minoshima K., Abraham E., et al., Microscopic time-resolved two-dimensional imaging with a femtosecond amplifying optical Kerr gate, Appl. Opt., 2002, 41(24), 5191-5194
[61]. Potma E. O., Boeij W. P. de, Wiersma D. A., Femtosecond dynamics of intracellular water probed with nonlinear optical Kerr effect microspectroscopy, Biophys. J., 2001, 80(6), 3019-3024
[62]. C. Egami, Naoki Kobayashi, Yoshimasa Kawata, et al., Confocal nonlinear optical microscopy for high-resolution measurement of absorptive objects, Opt. Lett., 2006, 31(6), 784-786 46
[2]. D. Heiman, R. W. Hellwarth, M. D. Levenson, et al, Raman-induced Kerr effect, Phys. Rev. Lett., 1976, 36, 189-192
[3]．钱士雄，王恭明编著，非线性光学：原理与进展，上海：复旦大学出版社，2001
[4]．石顺祥，陈国夫，赵卫等编著，非线性光学，西安：西安电子科技大学出版社，2003
[5]．喻远琴，周晓国，林柯等，CH_4分子v_1模拉曼诱导克尔效应谱与受激拉曼光声光谱峰形的比较，物理学报，2006，55(6)，2740-2745
[6]. Y. R. Shen, The Principles of Nonlinear Optics, Wiley, New York, 1984, p. 47
[7]. Jinghe Yuan et al, The intensity distributions of collected signal in coherent anti-Stokes Raman scattering microscopy, Colloids and Surfaces A, 2005, 257-258, 525-527
[8]. X. L. Xie and J. D. Simon, Picosecond time-resolved circular dichroism spectroscopy: experimental details and applications, 1989, 60(8), 2614-2627
[9]. R. C. Jones, Anew calculus for the treatment of optical systems. Ⅱ. Properties of the N-Matrices, J. Opt. Soc. Am. A, 1948, 38(8), 671-685
[10]．(日)堀江一之，(日)牛木秀治，(加)F．M．威尼克(Francoise M．Winnik)著，张镇西译，分子光子学：原理及应用，北京：科学出版社，2004，178-197
[1]．Marc D．Levensan著，腾家炽，林礼煌，李秀春译，非线性激光光谱学导论，北京：宇航出版社，1988
[2]. Bhatia P. S., Keto J. W., Pressure and power dependence of the optically heterodyne Raman-induced Kerr effect line shape, Phys. Rev. A, 1999, 59(5), 4045-4051
[3]. Giraud G., Karolin J., Wynne K., Low-frequency modes of peptides and globular proteins in solution observed by ultrafast OHD-RIKES spectroscopy, Biophy., 2003, 85, 1903-1913
[4]. Tang Z. L., Xing D., and Liu S. H., Imaging theory of nonlinear second harmonic and third harmonic generations in confocal microscopy, Sci. China Ser. G, 2004, 47(1), 8-16
[5]. J. J. Song, G. L. Eesley, and M. D. Levenson, Background suppression in coherent Raman spectroscopy, Appl. Phys. Lett., 1976, 20, 567
[6]. Heiman D., Hellwarth R. W., Levenson M. D., et al., Raman-induced Kerr effect. Phys. Rev. Lett., 1976, 36(4), 189-192
[7]. Tang Z. L., Yang C. P., Pei H. J., Liang R. S., and Liu S. H., Imaging theory and resolution improvement of two-photon confocal microscopy, Sci. China Ser. A, 2002, 45(11), 1468-1478
[1]. M. Born, E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light, 7th ed., Cambridge University Press, 2001
[2]．唐志列，邢达，刘颂豪，非线性二次谐波和三次谐波共焦显微镜的成像理论，中国科学：G辑，2003，33(3)，212-218
[3]．唐志列，杨初平，裴红津，等，双光子共焦电子显微镜的三维成像理论及其分辨率的改善，中国科学：A辑，2002 32(6)，538-547
[4]．唐志列，梁瑞生，常鸿森，双光子和多光子共焦显微镜的成像理论，物理学报，2000，9(6)，1076-1080
[5]．古德曼(Joseph W．Goodman)著，傅立叶光学导论，秦克诚等译，北京：电子工业出版社，2006
[6]．杨初平，吴燕山，李海等，高斯光束对荧光共焦显微镜分辨率的影响，华南师范大学学报(自然科学版)，2004，No．3，66-71
[1]. C. H. Lee, W. C. Lin, and J. P. Wang, Using differential confocal microscopy to detect the phase transition of lipid vesicle membranes, Opt. Eng., 2001, 40 (10), 2077-2083
[2]. Lisong Yang, Li Liu, Guiying Wang, et al, Noninterferometric measurement of lead zirconate titanate inverse piezoelectric extension, Opt. Eng., 2001, 40(6), 909-913
[3]. Jiubin Tan, et al., Differential confocal optical system using gradient-index lenses, Opt. Eng., 2003, 42 (10), 2868-2871.
[4]. M. R. Amison, K. G. Larkin, C. J. R. Sheppard, et al., Linear phase imaging using differential interference contrast Microscopy, J. Microsc. 214, 2004, 7-12
[5]. Chrysanthe Prezay, Donald L. Snydery, Jose-Angel Conchello, Imaging models for three-dimensional transmitted-light DIC microscopy, SPIE, 1996, 1-13
[6]. C. J. R. Sheppard and C. J. Cogswell, Image formation in video-enhanced and confocal DIC microscopy, SPIE, 1846, 64-71
[7]. L. Guo, Z. Tang, Y. He, et al., Characterization of a derivative photoacoustic spectrometer, Rev. Sci. Instrum., 2007, 78, 023104