基于宽光谱导模共振成像的生化传感方法研究

Guided mode resonance imaging (GMRI) is an evanescent-wave sensing technique that is highly specific and highly sensitive to biochemical reaction at surface and interface. GMRI is immune to EM interference, capable of in-situ, real-time, label-free and high-throughput detection of chemical and biological species. However, the monochromatic GMRI image can only reflect the on-resonance and off-resonance states of the guided mode and thus it is unsuitable for quantitative detection. This project aims to overcome the above-mentioned key issue and to develop arrayed GMRI sensor for quantitative detection of multiple biochemical targets. The main research contents focus on both the method establishment and the device realization. To establish the method, the following items will be studied: (1) to acquire high-quality resonance color images by using time-resolved broadband imaging method; (2) to create an algorithm of extracting the hue component of the resonance color image; (3) to study the relationships between the hue and the resonance wavelength and between the resonance wavelength and the surface biochemical reaction and finally to establish the quantitative relationship between the hue and the surface coverage of molecular targets. To realize the sensor device, the following contents will be carried out: (1) to design of the arrayed 2D leaky-mode waveguides with the dielectric core and to prepare prototype GMRI sensor; (2) to examine the capability of TE/TM dual polarization resonance color imaging for measuring 2D profiles of monolayer thickness and refractive index; (3) to demonstrate the feasibility of the GMRI sensing technique and to optimize the performance of the GMRI sensor, the device will be investigated by using the persistent organic pollutants such as benzopyrene and polychlorinated biphenyls in water as targets. The implementation of this project will lay a foundation for the development of advanced multi-functional biochemical sensors based on optical resonance imaging.

导模共振成像(GMRI)是一种对表界面生化反应高度专一和高度敏感的消逝波传感技术，具有抗电磁干扰、原位实时、免标记、高通量等优点。单波长GMRI的灰度像只能反映导模共振和非共振两种状态，因此不适合定量检测。本项目针对这一问题开展研究，拟采用时间分辨宽带成像方法，获取高质量导模共振彩像，建立共振彩像的色相提取算法，研究色相与共振波长以及共振波长与表界面生化反应的依赖关系，进而求取色相与待测分子表面覆盖度的定量关系；针对多靶标探测的需求，设计制备漏模光波导阵列传感芯片，研制具有定量、动态、多靶标检测本领的宽光谱GMRI生化传感器，分析传感器的TE/TM正交偏振双模共振成像功能和单分子层厚度与折射率二维分布测定方法，以水中苯并芘、多氯联苯等持久性有机污染物为探测对象，开展传感器的可行性实验验证，取得若干创新成果。本项目的顺利实施将促进我国先进生化传感器研发能力，提升我国生化检测技术水平。

单波长导模共振成像(GMRI)传感技术具有抗电磁干扰、免标记、响应快、高通量等优点，但检测动态范围窄，定量分析难度大。为了解决该问题，本项目研究了宽光谱GMRI传感方法，分析了导模共振波长灵敏度，建立了RGB共振彩像的色相提取算法，获得了共振波长与色相的依赖关系，实现了基于色相灵敏度的二维定量检测技术。在此基础上，提出了表面电磁模式共振高光谱成像传感新方法，获重点基金项目资助。本项目取得的主要成果包括：.（1）研制出SPR/GMR光谱检测与彩色成像检测双功能传感装置，实现了基于光谱灵敏度的生化样品定量检测和基于彩色共振图像的可视化分析； .（2）建立了基于RGB共振彩像的色相提取算法，构建了共振彩像的二维色相分布，实现了基于色相灵敏度的微尺度选区苯并芘特异性定量检测，检测下限达0.01μg/L。.（3）提出了一种基于光源辐射度色散曲线的SPR/GMR共振光谱校正方法，提高了SPR/GMR共振波长的测量精度；通过标定光谱测量系统的仪器响应函数曲线，将光谱仪得到的原始光谱转换成光源辐射光谱，进而计算出不依赖于光谱仪系统中任何部件的SPR/GMR相对反射率光谱；.（4）提出了多孔薄膜厚度与孔隙率测量方法，利用自制SPR/GMR光谱检测装置样机实验验证了该方法的可靠性与准确性。针对厚度较大、可支撑多个导模的多孔介质膜，提出并实验验证了单光谱求取其厚度和孔隙率的简化方法。上述方法使SPR/GMR光谱检测装置具备原位无损薄膜表征功能。. 在项目执行期间，课题组在Nature Communications等期刊上发表SCI论文8篇，撰写中文和英文专著各一章，申请发明专利5项，其中2项已授权，完成计算机软件著作权登记1项，在国际国内学术会议上作邀请报告5次，研制出高光谱导模共振成像生化分析装置样机一台，提交该装置验收报告一份，培养在站博士后1名、在读博士生4名、硕士毕业生2名；项目负责人成为“微纳传感技术”创新研究群体项目核心骨干，竞聘为中科院特聘核心岗位研究员，并兼任国科大岗位教授。