光纤生物传感的动态范围及灵敏度增强效应研究
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摘要
本论文从满足微型生化分析仪器特别是片上实验室对小尺寸、高集成、低成本、高灵敏度、宽动态范围等要求出发，研究了结构简单、成本低廉、抗干扰能力强、方便集成的双锥形光纤折射率传感器，探讨其灵敏度提高的方法，并研究了在无标生物检测方面的应用。论文完成的工作及主要结论如下：
（1）基于均匀光纤中传导模式的特性及存在条件，采用局部模式法分析了双锥形光纤中的模式耦合机制，推导了耦合效率的计算公式。
（2）用二氧化硅纳米小球对双锥形光纤表面进行修饰，利用米氏散射效应与模式传输特性相结合实现了宽动态范围高灵敏度的折射率传感，给出并分析了纳米小球修饰后的光传输模型，得出了与实验结果相一致的结论。
（3）发现并证明了纳米小球的高阶模式过滤效果。从理论上分析了其模式过滤的机理，并设计多个实验进行了验证。高阶模式过滤使纳米小球修饰后光纤对亚甲基兰的检测灵敏度大大降低，说明纳米修饰能够在提高折射率检测灵敏度的同时降低对吸收的敏感性，这在需要从吸收物质中提取折射率信息的场合中将会有重要潜在应用。
（4）利用弯曲锥形光纤的简单结构实现了高灵敏度的折射率传感。分析了这种折射率传感器的原理，并推导了理论计算模型，通过计算说明了锥形包层对高灵敏度的贡献，实验得到了4000nm/RIU的灵敏度。
（5）利用双锥形微纳光纤对多种抗原进行了高灵敏度无标检测。探讨了微纳光纤的导光及物理机械特性，解释了其高灵敏度的内在原因。研究了对不同溶解环境中的不同性质抗原的检测能力，其中由去离子水配制的相思子毒素的检出限达到10pg/mL。最后，通过解离实验探讨了传感器的再生能力。
In order to meet the requirements of small size, high integration, low cost, highsensitivity, and broad dynamic range for micro biochemical analysis systems,particularly lab on a chip, a biconical fiber-optic refractometer (BFOR) is studied. Ithas a simple structure, low cost, strong immunity to electromagnetic interference, andthe feasibility for integration. The schemes to improve the sensitivity have beeninvestigated and the application to label-free biological detections has been studied.The accomplished work and main points in this thesis are as follows:
(1) Based on the properties of bound modes of a uniform optical fiber, the modetransition in a tapered fiber was illustrated by resort to local modes and the formulaefor calculating the coupling efficiencies were derived.
(2) Silica nanospheres were used to modify the BFOR, combination of the Miescattering of nanospheres and multimode propagation in the tapered optical fiber(TOF) contributed to an enhanced sensitivity and a broadened detection range forrefractive index (RI) measurement. The theoretical model of the modified TOF(MTOF) was provided and analyzed, and the theory fitted well with experiments.
(3) The effect of filtering higher-order optical fiber modes was discovered andproofed. The underlying mechanism was theoretically investigated and severalexperiments were designed for support. It was also experimentally-revealed that theMTOF was much less sensitive to methylene blue due to the higher-order mode filtering. Thus, while silica nanospheres improved the sensitivity for RI detection,they reduced the absorbancy sensitivity, which suggested the MOTF was suitable forextracting the RI information from an absorbing medium.
(4) A simple bent TOF was proposed for highly-sensitive RI measurements. Theprinciple was illustrated. The theoretical models were deduced and the contribution oftapered cladding was shown through theory. A high sensitivity of4000nm/RIU wasexperimentally-obtained.
(5) Biconically-tapered optical micro/nano fibers were used to realize label-freebiological recognition of several kinds of antigen dissolved in different solutions. Thelight guiding and mechanical properties of micro/nano fibers were investigated, andthe reasons for high sensitivities were revealed. A detection limit of10pg/mL forabrin in deionized water was obtained. In the end, the release experiments indicatedthe excellent regeneration ability.
（1）基于均匀光纤中传导模式的特性及存在条件，采用局部模式法分析了双锥形光纤中的模式耦合机制，推导了耦合效率的计算公式。
（2）用二氧化硅纳米小球对双锥形光纤表面进行修饰，利用米氏散射效应与模式传输特性相结合实现了宽动态范围高灵敏度的折射率传感，给出并分析了纳米小球修饰后的光传输模型，得出了与实验结果相一致的结论。
（3）发现并证明了纳米小球的高阶模式过滤效果。从理论上分析了其模式过滤的机理，并设计多个实验进行了验证。高阶模式过滤使纳米小球修饰后光纤对亚甲基兰的检测灵敏度大大降低，说明纳米修饰能够在提高折射率检测灵敏度的同时降低对吸收的敏感性，这在需要从吸收物质中提取折射率信息的场合中将会有重要潜在应用。
（4）利用弯曲锥形光纤的简单结构实现了高灵敏度的折射率传感。分析了这种折射率传感器的原理，并推导了理论计算模型，通过计算说明了锥形包层对高灵敏度的贡献，实验得到了4000nm/RIU的灵敏度。
（5）利用双锥形微纳光纤对多种抗原进行了高灵敏度无标检测。探讨了微纳光纤的导光及物理机械特性，解释了其高灵敏度的内在原因。研究了对不同溶解环境中的不同性质抗原的检测能力，其中由去离子水配制的相思子毒素的检出限达到10pg/mL。最后，通过解离实验探讨了传感器的再生能力。
In order to meet the requirements of small size, high integration, low cost, highsensitivity, and broad dynamic range for micro biochemical analysis systems,particularly lab on a chip, a biconical fiber-optic refractometer (BFOR) is studied. Ithas a simple structure, low cost, strong immunity to electromagnetic interference, andthe feasibility for integration. The schemes to improve the sensitivity have beeninvestigated and the application to label-free biological detections has been studied.The accomplished work and main points in this thesis are as follows:
(1) Based on the properties of bound modes of a uniform optical fiber, the modetransition in a tapered fiber was illustrated by resort to local modes and the formulaefor calculating the coupling efficiencies were derived.
(2) Silica nanospheres were used to modify the BFOR, combination of the Miescattering of nanospheres and multimode propagation in the tapered optical fiber(TOF) contributed to an enhanced sensitivity and a broadened detection range forrefractive index (RI) measurement. The theoretical model of the modified TOF(MTOF) was provided and analyzed, and the theory fitted well with experiments.
(3) The effect of filtering higher-order optical fiber modes was discovered andproofed. The underlying mechanism was theoretically investigated and severalexperiments were designed for support. It was also experimentally-revealed that theMTOF was much less sensitive to methylene blue due to the higher-order mode filtering. Thus, while silica nanospheres improved the sensitivity for RI detection,they reduced the absorbancy sensitivity, which suggested the MOTF was suitable forextracting the RI information from an absorbing medium.
(4) A simple bent TOF was proposed for highly-sensitive RI measurements. Theprinciple was illustrated. The theoretical models were deduced and the contribution oftapered cladding was shown through theory. A high sensitivity of4000nm/RIU wasexperimentally-obtained.
(5) Biconically-tapered optical micro/nano fibers were used to realize label-freebiological recognition of several kinds of antigen dissolved in different solutions. Thelight guiding and mechanical properties of micro/nano fibers were investigated, andthe reasons for high sensitivities were revealed. A detection limit of10pg/mL forabrin in deionized water was obtained. In the end, the release experiments indicatedthe excellent regeneration ability.
引文
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