面向生物传感的表面等离激元Fano共振增强光微流激光研究

Fluorescent molecules are very useful for tracking biomolecules in biosensing applications. However, fluorescence is caused by spontaneous emission, and the sensitivity is often limited by the relatively weak emission intensity, the broad spectral line width and the photobleaching. Therefore, in order to improve the sensitivity, it is important to enhance the emission intensity and photostability of fluorescent molecules..In this project, we propose to develop an optofluidic laser intra-cavity sensing method based on plasmonic Fano resonance enhanced fluorescence. Compared with that of the conventional sensing method based on fluorescence, it is expected that the output intensity can be significantly amplified by about four orders of magnitudes. This method is also compatible with the existing biosensing platforms, and the sample used can be as little as a few nanoliters. In this work, an optical micro-cavity will be used to realize stimulated emission, and the output laser will be used as the sensing signal. As a result, the signal intensity can be much larger than that of conventional sensing method based on fluorescence. In addition, a metallic nanoparticle - fluorescent molecule hybrid structure is used as the gain medium of the optofluidic laser. The bright and dark modes of Fano resonance are used to enhance fluorescence emission, the gain and stability can be significant improved. Therefore, the laser output intensity can be enhanced, the threshold can be reduced, and the sensitivity can be improved. This project is important for biosensing applications, and can promote the development of biomolecular trace detection.

荧光分子是用于生物传感的重要的示踪材料，然而由自发辐射所形成的荧光发射强度较弱，光谱展宽较大，容易被光漂白，故检测极限受到限制。如何提高荧光分子的发射强度和稳定性是提高检测灵敏度的关键问题。.本项目提出一种基于表面等离激元Fano共振增强荧光的光微流激光腔内检测方法，与传统荧光检测方法相比，输出信号强度有望获得上万倍的提高，这一方法与现有生物检测系统高度兼容，所需样品可低至纳升量级。本研究将采用光学微腔以实现受激辐射，激光取代荧光作为传感信号，输出信号强度可远大于传统基于荧光的生物分子检测方法；同时，金属纳米颗粒−荧光分子杂化体系被用作光微流激光增益介质，利用Fano共振的明态和暗态协同增强荧光分子发射强度，以获得更大增益和稳定性，从而降低激光阈值，增大腔内检测方法激光输出强度，达到进一步提高生物传感灵敏度的目的。本项目的实现对生物传感研究具有重要意义，可推动痕量生物分子检测技术的发展。

本项目针对表面等离激元Fano共振效应、光微流激光的产生以及两者对高灵敏度生物分子的检测特性进行了研究，有望解决基于荧光的传统生物分子检测方法中自发辐射强度相对较弱，限制了其传感灵敏度的问题。研究中为增强纳米尺度光与物质的相互作用，提高生物分子检测灵敏度，设计并制备了由贵金属纳米棒构成的聚合体结构，可大幅度提高多重Fano共振调制深度，同时采用简单的单个劈裂金纳米盘结构即可产生与聚合体结构可比拟的Fano共振效应，简化了相关器件的制备，并可提高系统集成度；为进一步抑制非辐射损耗，提高共振品质因子，项目研究了由电介质纳米颗粒构成的阵列结构中类Fano共振之间的耦合特性，结果表明其共振品质因子高达10^6；项目亦采用高折射率电介质/贵金属杂化体系产生了多重Fano共振效应，能够结合两者优势，提高局域场强及品质因子。在生物传感方面，研究中实验表明由三维贵金属纳米颗粒构成聚合体结构中的Fano共振对颗粒间相对位置非常敏感，可作为三维等离激元标尺用于高灵敏生物传感；研究也表明在电介质纳米腔及分子杂化体系中，类Fano共振与分子激子模式之间耦合可形成Rabi劈裂，依据两者耦合强度更可产生强耦合效应，这为生物传感应用打下了基础。最后研究中采用项目提出的等离激元增强光微流激光的方法，将不同形貌、尺寸、浓度贵金属纳米颗粒与荧光分子杂化体系作为增益介质通入共振微腔中，所产生光微流激光阈值可降低约28.6%；DNA单碱基错配分析实验表明，项目所采用方法可稳定检测高达130个碱基对DNA，这为低成本、快速、大规模基因筛查与诊断提供了一种新的有效手段。以上述成果为基础，在本项目资助下发表SCI论文11篇，投稿中SCI论文3篇，授权国家发明专利2项，申请发明专利6项，培养硕士生13名，博士生3名，其中8名同学取得硕士学位。