新型光学微腔和微腔激光器生物传感效应研究

【作者】 李皓；

【导师】 徐雷；

【作者基本信息】 复旦大学 ， 光学， 2011， 博士

【摘要】 无标记光学生物传感器是利用光学的手段探测在自然状态下生物分析物的传感器,具有高灵敏度、低探测极限、分析物前处理简单、多通道信号传输、不受电磁干扰、可远程控制、可实时监控等特点,可用于生物医学研究、医疗保健、环境监测和国防等方面。在各种结构中,光学微腔是一种非常合适的传感元件。光学微腔在束缚光场至微米量级的同时,保持很高的Q值(104～109),传感性能优异,理论上甚至可达到单蛋白质分子探测。另外,其传感功能区域小,利于集成和多分析物同步探测,极具实用价值。本论文在光微流谐振环生物传感器优化、基于耦合腔单频激光器的微腔生物传感器的设计与实现方面开展了系列研究,主要创新点是：1.分析并测量了光微流谐振环无标记生物传感器在接近探测极限情况下的体折射率探测和生物小分子表面物质密度无标记探测能力。体折射率和表面物质密度的等噪声探测极限分别为3.8×10-8和0.18 pg/mm2,均突破了多数生物传感器遇到的10-7RIU和1 pg/mm2探测极限瓶颈。这些结果代表了当时微腔生物传感器的最好表现,设定了微腔生物传感器传感的极限基准,也为微腔传感器之间以及与其它技术性能的衡量比较提供了实验依据。2.理论分析了一种三维光场限制的光微流谐振环无标记生物传感器对水中和空气中单纳米颗粒探测的能力。通过各个参数的优化,我们得到了其灵敏度与微球生物传感器相比至少提高10倍。结合目前报道的最低噪声水平,其最小可探测单纳米颗粒半径小于10纳米,已接近单个蛋白质分子水平。3.设计并实现了一种新型的基于耦合腔单频激光器的无标记生物传感器。证明了分析物表面附着会影响耦合条件并引起单频激光的跳模。通过检测跳模过程来进行生物传感,我们利用更加简单的装置得到了80 pg/mL的BSA蛋白质最低探测浓度,这与超高Q值的传统生物传感器的探测极限相当。这些结果首次证明了微腔激光器作为超高灵敏度生物传感器的可行性。更多还原

【Abstract】 Label-free optical biosensors use optical ways to detect biological analytes in their natural forms. These high-sensitive and low-detection-limit biosensors are easy in pre-processing, immune to electromagnetic interference, capable of real time monitoring, remote control and multi-channel detection. They have vast applications in fundamental biomedical researches, health care, environmental monitoring and homeland security.Among all the optical sensors, optical microcavity is one of the most promising sensing structures. Optical microcavities confine the light in a micro-scale area, meanwhile maintain the high Q feature (104～109). They have superb sensing ability, theoretically, even are capable of single molecule detection. Also, the sensing area of microcavity is tiny, which allows optical integration and simultaneous multi-specie detection and makes them very favorable in real application.In this thesis we will systemically characterize and optimize optofluidic ring resonator biosensor, and design and realize a novel biosensing structure based on single-mode coupled microcavity laser.The thesis focuses on the following aspects:1. I investigated the ultimate sensing capability of optofluidic ring resonators in bulk refractive index (RI) detection and label-free small molecule surface mass density detection in the region close to the detection limit. The noise equivalent detection limit of bulk refractive index and surface mass density are 3.8×10-8 RIU and 0.18 pg/mm2, respectively, which break the barriers of 10-7 RIU and 1 pg/mm2 typically encountered in many optical label-free biosensors. These results represent the best sensing performance of microcavity biosensors and set the benchmark for microcavity biosensors and for comparisons with other label-free optical biosensors.2. I theoretically analyzed the ability of 3-dimensionally confined optofluidic ring resonators (OFRRs) for detection of a single nanoparticle in water and in air. Through optimization, the sensitivity is enhanced at lest 10 times, as compared to that of a solid microsphere biosensor. Combined with the lowest reported noise level, the smallest detectable nanoparticle is estimated to be less than 10 nm in radius, which is close to the size of a single protein molecule.3. I designed and experimentally realized a novel label-free optical biosensor based on single mode coupled microcavity laser. We demonstrated that the surface adsorption of bio analyte changes the coupling condition and leads to single mode laser hopping. By applying the sensing scheme based on mode hopping process monitoring, the lowest detectable concentration of BAS protein solution about 80 pg/mm2 is experimentally achieved, which is comparable to that of ultrahigh Q passive microcavity biosensors, but with much simplified experimental setup. Our results for the first time show the possibility of using a microcavity laser to achieve ultra-sensitive optical sensing.更多还原