基于微毛细管的光微流体生物传感器研究
摘要
基于回音壁谐振模式(WGM)的光学微腔生物传感器灵敏度高,体积小,能对微量生物化学分子进行无标记检测,具有重要的研究价值和很好的应用前景。本论文基于微毛细管建立光微流体生物传感器,进行了微管传感模型理论推导,采用时域有限差分算法进行了微环传感器的数值模拟和分析,搭建实验系统进行了微流体传感初步检测实验。完成的主要工作如下:
基于耦合模式理论,研究直波导和微管的耦合性质,建立微管传感的理论模型,得到微管结构的性能参数如谐振波长、自由光谱范围FSR、品质因子Q、峰值半高宽等。
从麦克斯韦方程组出发推导柱坐标下微毛细管中的电磁场分布方程,根据径向电场分布曲线,得出微毛细管内外半径和折射率之间应该满足的关系。推导微管谐振腔的耦合解析模型,为增强透射谱下陷深度,提出三种互耦合结构:在直波导耦合区植入光栅,在微管壁植入光栅以及双管结构。理论分析了光栅和双管的互耦合作用。
利用Fullwave软件对微管谐振器理论模型进行数值模拟,研究各参数变化之间的关系,计算了微腔的径向以及周向电场分布图样。进行了光栅参数以及同心环参数设计和仿真。
利用ZF13棱镜经倏逝场激发微毛细管WGM模式,搭建了微流体生物传感装置,向微毛细管中注入不同浓度的乙醇溶液改变有效折射率,从而使谐振波长发生漂移。通过对不同波段的光波在不同入射角度的实验结果进行分析,得到相应灵敏度。
Opto-fluidic biosensor based on microcapillary, with its unique resonant whispering gallery mode (WGM), which allows high sensing sensitivity, realizes the label-free detection of biological reagents. Also, due to the small size and easy to integrate, this biosensor has very important research value and application prospects. The main point of this paper is to establish a theoretical model of the optic micro fluid biosensor, and to build an experiment system in order to implement the micro fluid sensing detection, combined with the model. The analysis method is that, first, theoretically derivate the relevant parameters of the micro-ring sensing model, then numerically simulate the micro-ring sensor based on the well-known finite-difference time-domain(FDTD) algorithm, finally set up the experiment system to achieve the micro-ring biosensor and analyze the results using the theoretical calculation. The major works completed are as follows:
Based on the coupling mode theory and the FDTD method, the property of the coupling between the straight waveguide and the micro-ring is thoroughly investigated, the theoretical model of the micro-ring resonators are established, and at last get the performance parameters of the micro-ring structure , such as resonant wavelength, free spectral range, quality factor and peak width at half, etc. We deduce the distribution of the electromagnetic field equations under the cylindrical coordinate from Maxwell’s equations, and according to the radial electric field profile, we get the required relationship between the corresponding structure parameters. Enhanced notch depth is demonstrated in micro-ring resonator which is generated either by the nanometer-scaled gratings along the ring sidewalls or by evanescent directional coupling between two concentric rings.
Based on the FDTD algorithm, using the FULLWAVE simulation engine which is a part of the RSoft Photonic Suite simulates the theoretical models of the micro-ring resonators. The relationship between parameters, radial and circumferential electric field pattern observed by simulating. Grating-assisted and concentric micro-ring resonators with different parameters are simulated.
Microcapillary biosensor was established with a prism and a microcapillary. With the prism made from ZF13 material, WGM of the microcapillary is successfully observed by evanescent coupling. The mixture of water and ethanol were used for experiment research on refractive index change sensitivity of microcapillary biosensor. Sensitivity of the biosensor observed in different incident angles.
基于耦合模式理论,研究直波导和微管的耦合性质,建立微管传感的理论模型,得到微管结构的性能参数如谐振波长、自由光谱范围FSR、品质因子Q、峰值半高宽等。
从麦克斯韦方程组出发推导柱坐标下微毛细管中的电磁场分布方程,根据径向电场分布曲线,得出微毛细管内外半径和折射率之间应该满足的关系。推导微管谐振腔的耦合解析模型,为增强透射谱下陷深度,提出三种互耦合结构:在直波导耦合区植入光栅,在微管壁植入光栅以及双管结构。理论分析了光栅和双管的互耦合作用。
利用Fullwave软件对微管谐振器理论模型进行数值模拟,研究各参数变化之间的关系,计算了微腔的径向以及周向电场分布图样。进行了光栅参数以及同心环参数设计和仿真。
利用ZF13棱镜经倏逝场激发微毛细管WGM模式,搭建了微流体生物传感装置,向微毛细管中注入不同浓度的乙醇溶液改变有效折射率,从而使谐振波长发生漂移。通过对不同波段的光波在不同入射角度的实验结果进行分析,得到相应灵敏度。
Opto-fluidic biosensor based on microcapillary, with its unique resonant whispering gallery mode (WGM), which allows high sensing sensitivity, realizes the label-free detection of biological reagents. Also, due to the small size and easy to integrate, this biosensor has very important research value and application prospects. The main point of this paper is to establish a theoretical model of the optic micro fluid biosensor, and to build an experiment system in order to implement the micro fluid sensing detection, combined with the model. The analysis method is that, first, theoretically derivate the relevant parameters of the micro-ring sensing model, then numerically simulate the micro-ring sensor based on the well-known finite-difference time-domain(FDTD) algorithm, finally set up the experiment system to achieve the micro-ring biosensor and analyze the results using the theoretical calculation. The major works completed are as follows:
Based on the coupling mode theory and the FDTD method, the property of the coupling between the straight waveguide and the micro-ring is thoroughly investigated, the theoretical model of the micro-ring resonators are established, and at last get the performance parameters of the micro-ring structure , such as resonant wavelength, free spectral range, quality factor and peak width at half, etc. We deduce the distribution of the electromagnetic field equations under the cylindrical coordinate from Maxwell’s equations, and according to the radial electric field profile, we get the required relationship between the corresponding structure parameters. Enhanced notch depth is demonstrated in micro-ring resonator which is generated either by the nanometer-scaled gratings along the ring sidewalls or by evanescent directional coupling between two concentric rings.
Based on the FDTD algorithm, using the FULLWAVE simulation engine which is a part of the RSoft Photonic Suite simulates the theoretical models of the micro-ring resonators. The relationship between parameters, radial and circumferential electric field pattern observed by simulating. Grating-assisted and concentric micro-ring resonators with different parameters are simulated.
Microcapillary biosensor was established with a prism and a microcapillary. With the prism made from ZF13 material, WGM of the microcapillary is successfully observed by evanescent coupling. The mixture of water and ethanol were used for experiment research on refractive index change sensitivity of microcapillary biosensor. Sensitivity of the biosensor observed in different incident angles.
引文
[1] Rebecca L.Rich, David G.Myszka. Survey of the year 2007 commercial optical literature . Mol. Recgnit .2008, 21:355-400
[2] C.-Y. Chao and L. J. Guo, Biochemical sensors based on polymer microrings with sharp asymmetrical resonance. Appl. Phys. Lett. 2003,83:1527~1529
[3] A. Ksendzov, M. L. Homer, A. M. Manfreda. Integrated optics ring- resonator chemical sensor with polymer transduction layer. Electron. Lett., 2004,40(1)
[4] Liu, A.Q., et al. Label-free detection with micro optical fluidic systems (MOFS): a review. Analytical and Bioanalytical Chemistry, 2008. 391(7): 2443~2452.
[5] Rebecca L.Rich, David G.Myszka. Survey of the year 2006 commerical optical literature . Mol. Recgnit .2007, 20(5):300-366
[6] Fang, Y., Non-invasive optical biosensor for probing cell signaling. Sensors, 2007. 7(10): 2316-2329
[7] P.P.Absil,J.V.Hryniewicz,B.E.Little,et al.Compact microring notch filters.IEEE Photonics Tech. Lett.,2000,12 (4):398~400
[8] Little, B., et al., Microring resonator channel dropping filters. Journal of Lightwave Technology, 1997,15(6): 998-1005.
[9] Khan, M.J., et al., Mode-coupling analysis of multipole symmetric resonant add/drop filters. Ieee Journal of Quantum Electronics, 1999. 35(10): 1451-1460.
[10] Shuichi Suzuki,Yutaka Hatakeyama,Yasuo Kokubun,et al. Precise Control of Wavelength Channel Spacing of Microring Resonator Add-Drop Filter Array.IEEE Journal of Lightwave Tech.,2002,20(4):745~750
[11] Li, Q., et al., Dense wavelength conversion and multicasting in a resonance-split silicon microring. Applied Physics Letters, 2008. 93(8): 08113
[12] Xin Yan,C.-S. Ma,Y.-Z.Xu,et al. Analysis and optimization for a polymer cross-grid array of microring resonant wavelength multiplexers.Opt.Engineering,2005,44(7):075001
[13] V.R.Almeida,C.A.Barrios,R.R.Panepucci,et al. All-optical control of light on a silion chip.Nature,2004,431(10):1081~1083
[14] Xu Q.,Schmidt B.,Pradhan S.,et al. Micrometer-scale silicon electro-optic modulator. Nature,2005,435(7040):325~327
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[16] ]Dominik G.Rabus, Zhixi Bian, Ali Shakouri. A GaInAsP-InP Double-Ring Resonator Coupled Laser. IEEE Photonics technology letters,2005,17(9):1770~1772
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[18] C.K. Madsen, G. Lenz. Optical all-pass filters for phase design with application for dispersion compensation. IEEE Photonics technology letters,1998,10(7):994~996
[19] Hao Shen, Group Delay and Dispersion Analysis of Compound High Order Microring Resonator All-Pass Filter,Optics Communications. 2006,262(2):200~20515
[20] Andrew W.POON, Linjie Zhou,Silicon Photonics Research in Hong Kong: Microresonator Devices and Optical Nonlinearities. Mathematics&Physical Sciences IEICE-Transactions on Electronics. 2007,E91-C(2):156~166
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[22] Fengnian Xia, Lidija Sekaric, Yurii Vlasov. Ultracompact optical buffers on a silicon chip, Nature Photonics1.2006,42:65~71
[23] Xudong Fan, Ian M. White, Hongying Zhu, et al. Overview of novel integrated optical ring resonator bio/chemical sensors
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[32]Teraoka, I. and S. Arnold, Coupled whispering gallery modes in a multilayer-coated microsphere. Optics Letters, 2007. 32(9): 1147-1149.
[33] Teraoka, I. and S. Arnold, Resonance shifts of counterpropagating whispering-gallery modes: degenerate perturbation theory and application to resonator sensors with axial symmetry. Journal of the Optical Society of America B-Optical Physics, 2009. 26(7): 1321-1329.
[34] S.Blair , Y.Chen. Resonant-enhanced evanescent-wave fluorescence biosensing with cylindrical optical cavities. Appl.Opt,2001,40:570~582
[35] R.W.Boyd, J.E.Heebner. Sensitive disk resonator photonic biosensor. Appl,Opt,2001,40:5742~5747
[36] E.Krioukov,D.J.W.Klunder. Intergrated optical microcavities for enhanced evanescent-wave spectroscopy. Opt.Lett,2002,27:1504~1506
[37] D.K. Armani, T.J.Kippenberg, S. M. Spillance, et al., Ultra-high-Q toroid microcavity on a chip .Nature,2003,421:925~928
[38] A. M. Armani, R. P. Kulkarni, S. E. Fraser, et al.,Label-Free, Single-Molecule with Optical Microcavities. Science,2007,317:783~787
[39] C. Y. Chao, L. J. Guo. Biochemical sensors based on polymer microrings with sharp asymmetrical resonance. Appl. Phys. Lett ,2003,83(8),1527~1529
[40] C.Y. Chao, L. J. Guo. Thermal-flow Technique for Reducing Surface Roughness and Controlling Gap Size in Polymer Microring Resonators. Appl. Phys. Lett., 2004, 84(14):2479~2481
[41] C.Y. Chao, W. Fung, L.J. Guo .High Q-Factor Polymer Microring Resonators for Biochemical Sensing Applications. IEEE J. Sel. Top. Quantum Electron., 2006, 12(1):134~142
[42] A. Ksendzov and Y. Lin,. Integrated optics ring-resonator sensors for protein detection. Opt. Lett.,2005,30:3344~3346
[43] Yalcin, A. Popat, K.C. Aldridge, J.C., et al. Optical sensing of biomolecules using microring resonators. IEEE J. Sel. Top. Quantum Electron., 2006,12(1):148~155
[44] Z. Y. Zhang, M. Dainese, L. Wosinski, et al., Resonance-splitting and enhanced notch depth in SOI ring resonators with mutual mode coupling Opt. Express, 2008, 16(7): 4621
[45] X. Li, Z. Zhang, S. Qin, et al., Sensitive label-free and compact biosensor based on concentric silicon-on-insulator microring resonators Appl. Opt., 2009, 48(25):90~94
[46]陈曜,李振宇,周治平等.基于光学微环的化学传感器.光电子激光,2009,20(9):1133~1136
[47] I.M.White, H.Oveys, X.Fan. Liquid Core Optical Ring Resonator Sensors. Opt.Lett, 2006,31:1319~1321
[48] White, I.M., H.Oveys, X.Fan, Integrated multiplexed biosensors based on liquid core optical ring resonators and antiresonant reflecting optical waveguides. Applied Physics Letters, 2006. 89(19):191106
[49] Hongying.Zhu, I.M.White, J.D.Suter, et,al. Opto-?uidic micro-ring resonator for sensitive label-free viral detection. Analyst, 2008. 133(3): 356-360.
[50] Zhu, H.Y., I.M.White, J.D.Suter, et al., Phage-based label-free biomolecule detection in an opto-fluidic ring resonator. Biosensors & Bioelectronics, 2008. 24(3): 461-466.
[51] Suter, J.D., I.M.White, Zhu, H.Y., et al., Label-free quantitative DNA detection using the liquid core optical ring resonator. Biosensors & Bioelectronics, 2008. 23(7): 1003-1009.
[52] V. Zamora, A. Diez, M. V. Andres, et al., Refractometric sensor based on whispering-gallery modes of thin capillarie.Opt. Express, 2007, 15(19):12011~12016
[53] Ling, T. and L.J. Guo, A unique resonance mode observed in a prism-coupled micro-tube resonator sensor with superior index sensitivity. Optics Express, 2007. 15(25): 17424-17432.
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[2] C.-Y. Chao and L. J. Guo, Biochemical sensors based on polymer microrings with sharp asymmetrical resonance. Appl. Phys. Lett. 2003,83:1527~1529
[3] A. Ksendzov, M. L. Homer, A. M. Manfreda. Integrated optics ring- resonator chemical sensor with polymer transduction layer. Electron. Lett., 2004,40(1)
[4] Liu, A.Q., et al. Label-free detection with micro optical fluidic systems (MOFS): a review. Analytical and Bioanalytical Chemistry, 2008. 391(7): 2443~2452.
[5] Rebecca L.Rich, David G.Myszka. Survey of the year 2006 commerical optical literature . Mol. Recgnit .2007, 20(5):300-366
[6] Fang, Y., Non-invasive optical biosensor for probing cell signaling. Sensors, 2007. 7(10): 2316-2329
[7] P.P.Absil,J.V.Hryniewicz,B.E.Little,et al.Compact microring notch filters.IEEE Photonics Tech. Lett.,2000,12 (4):398~400
[8] Little, B., et al., Microring resonator channel dropping filters. Journal of Lightwave Technology, 1997,15(6): 998-1005.
[9] Khan, M.J., et al., Mode-coupling analysis of multipole symmetric resonant add/drop filters. Ieee Journal of Quantum Electronics, 1999. 35(10): 1451-1460.
[10] Shuichi Suzuki,Yutaka Hatakeyama,Yasuo Kokubun,et al. Precise Control of Wavelength Channel Spacing of Microring Resonator Add-Drop Filter Array.IEEE Journal of Lightwave Tech.,2002,20(4):745~750
[11] Li, Q., et al., Dense wavelength conversion and multicasting in a resonance-split silicon microring. Applied Physics Letters, 2008. 93(8): 08113
[12] Xin Yan,C.-S. Ma,Y.-Z.Xu,et al. Analysis and optimization for a polymer cross-grid array of microring resonant wavelength multiplexers.Opt.Engineering,2005,44(7):075001
[13] V.R.Almeida,C.A.Barrios,R.R.Panepucci,et al. All-optical control of light on a silion chip.Nature,2004,431(10):1081~1083
[14] Xu Q.,Schmidt B.,Pradhan S.,et al. Micrometer-scale silicon electro-optic modulator. Nature,2005,435(7040):325~327
[15] R.C.Polson,G.Levin,Z.V.Vardeny,Spectral analysis of polymer microring lasers,Appl.Phys.Lett.,2000,70(26):3858~3860
[16] ]Dominik G.Rabus, Zhixi Bian, Ali Shakouri. A GaInAsP-InP Double-Ring Resonator Coupled Laser. IEEE Photonics technology letters,2005,17(9):1770~1772
[17] Suter, J.D., et al., PDMS embedded opto-fluidic microring resonator lasers.Optics Express, 2008. 16(14): 10248-10253.
[18] C.K. Madsen, G. Lenz. Optical all-pass filters for phase design with application for dispersion compensation. IEEE Photonics technology letters,1998,10(7):994~996
[19] Hao Shen, Group Delay and Dispersion Analysis of Compound High Order Microring Resonator All-Pass Filter,Optics Communications. 2006,262(2):200~20515
[20] Andrew W.POON, Linjie Zhou,Silicon Photonics Research in Hong Kong: Microresonator Devices and Optical Nonlinearities. Mathematics&Physical Sciences IEICE-Transactions on Electronics. 2007,E91-C(2):156~166
[21] Qianfan Xu, Bradley Schmidt, Sammeer Pradhan, et al. Micrometre-scale silicon electro-optic modulator.Nature,2005,435(5):325~327
[22] Fengnian Xia, Lidija Sekaric, Yurii Vlasov. Ultracompact optical buffers on a silicon chip, Nature Photonics1.2006,42:65~71
[23] Xudong Fan, Ian M. White, Hongying Zhu, et al. Overview of novel integrated optical ring resonator bio/chemical sensors
[24] Vollmer, F., et al., Protein detection by optical shift of a resonant microcavity. Applied Physics Letters, 2002. 80(21): 4057-4059.
[25] S. Arnold, M. Khoshsima, I. Teraoka, S. Holler, and F. Vollmer. Shift of whispering-gallery modes in microspheres by protein adsorption. Opt. Lett. ,2003,28(4):272~274
[26] Teraoka, I., S. Arnold, and F. Vollmer, Perturbation approach to resonance shifts of whispering-gallery modes in a dielectric microsphere as a probe of a surrounding medium. Journal of the Optical Society of America B-Optical Physics, 2003. 20(9): 1937-1946.
[27] Teraoka, I. and S. Arnold, Theory of resonance shifts in TE and TM whispering gallery modes by nonradial perturbations for sensing applications. Journal of the Optical Society of America B-Optical Physics, 2006. 23(7): 1381-1389.
[28] Ren, H.C., et al., High-Q microsphere biosensor - analysis for adsorption of rodlike bacteria. Optics Express, 2007. 15(25): 17410-17423.
[29] Vollmer, F., S. Arnold, and D. Keng, Single virus detection from the reactive shift of a whispering-gallery mode. Proceedings of the National Academy of Sciences of the United States of America, 2008. 105(52): 20701-20704.
[30] Teraoka, I. and S. Arnold,. Enhancing the sensitivity of a whispering-gallry mode microsphere sensor by a hight-refractive-index surface layer.Journal of the Optical Society of America B-Optical Physics, 2006. 23(7): 1434-1441.
[31] Gaathon, O., et al., Enhancing sensitivity of a whispering gallery mode biosensor by subwavelength confinement. Applied Physics Letters, 2006. 89(22).
[32]Teraoka, I. and S. Arnold, Coupled whispering gallery modes in a multilayer-coated microsphere. Optics Letters, 2007. 32(9): 1147-1149.
[33] Teraoka, I. and S. Arnold, Resonance shifts of counterpropagating whispering-gallery modes: degenerate perturbation theory and application to resonator sensors with axial symmetry. Journal of the Optical Society of America B-Optical Physics, 2009. 26(7): 1321-1329.
[34] S.Blair , Y.Chen. Resonant-enhanced evanescent-wave fluorescence biosensing with cylindrical optical cavities. Appl.Opt,2001,40:570~582
[35] R.W.Boyd, J.E.Heebner. Sensitive disk resonator photonic biosensor. Appl,Opt,2001,40:5742~5747
[36] E.Krioukov,D.J.W.Klunder. Intergrated optical microcavities for enhanced evanescent-wave spectroscopy. Opt.Lett,2002,27:1504~1506
[37] D.K. Armani, T.J.Kippenberg, S. M. Spillance, et al., Ultra-high-Q toroid microcavity on a chip .Nature,2003,421:925~928
[38] A. M. Armani, R. P. Kulkarni, S. E. Fraser, et al.,Label-Free, Single-Molecule with Optical Microcavities. Science,2007,317:783~787
[39] C. Y. Chao, L. J. Guo. Biochemical sensors based on polymer microrings with sharp asymmetrical resonance. Appl. Phys. Lett ,2003,83(8),1527~1529
[40] C.Y. Chao, L. J. Guo. Thermal-flow Technique for Reducing Surface Roughness and Controlling Gap Size in Polymer Microring Resonators. Appl. Phys. Lett., 2004, 84(14):2479~2481
[41] C.Y. Chao, W. Fung, L.J. Guo .High Q-Factor Polymer Microring Resonators for Biochemical Sensing Applications. IEEE J. Sel. Top. Quantum Electron., 2006, 12(1):134~142
[42] A. Ksendzov and Y. Lin,. Integrated optics ring-resonator sensors for protein detection. Opt. Lett.,2005,30:3344~3346
[43] Yalcin, A. Popat, K.C. Aldridge, J.C., et al. Optical sensing of biomolecules using microring resonators. IEEE J. Sel. Top. Quantum Electron., 2006,12(1):148~155
[44] Z. Y. Zhang, M. Dainese, L. Wosinski, et al., Resonance-splitting and enhanced notch depth in SOI ring resonators with mutual mode coupling Opt. Express, 2008, 16(7): 4621
[45] X. Li, Z. Zhang, S. Qin, et al., Sensitive label-free and compact biosensor based on concentric silicon-on-insulator microring resonators Appl. Opt., 2009, 48(25):90~94
[46]陈曜,李振宇,周治平等.基于光学微环的化学传感器.光电子激光,2009,20(9):1133~1136
[47] I.M.White, H.Oveys, X.Fan. Liquid Core Optical Ring Resonator Sensors. Opt.Lett, 2006,31:1319~1321
[48] White, I.M., H.Oveys, X.Fan, Integrated multiplexed biosensors based on liquid core optical ring resonators and antiresonant reflecting optical waveguides. Applied Physics Letters, 2006. 89(19):191106
[49] Hongying.Zhu, I.M.White, J.D.Suter, et,al. Opto-?uidic micro-ring resonator for sensitive label-free viral detection. Analyst, 2008. 133(3): 356-360.
[50] Zhu, H.Y., I.M.White, J.D.Suter, et al., Phage-based label-free biomolecule detection in an opto-fluidic ring resonator. Biosensors & Bioelectronics, 2008. 24(3): 461-466.
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