基于界面结构增强的高灵敏、无标记OIRD免疫微阵列芯片

斜入射光反射差（oblique-incidence reflectivity difference, OIRD）是一种新型的无标记实时探测技术，具有可兼容任意载体的突出优点，但灵敏度不足极大限制了其在微阵列芯片等生物检测方面的应用。理论分析和预研工作表明：芯片界面结构对OIRD灵敏度具有决定性影响，通过合理结构设计，激活干涉增强效应和有效介电常数效应，是大幅提高OIRD检测灵敏度的有效途径。基于此，本项目拟通过构建具有特定微结构的三维传感层，利用干涉增强效应和有效介电常数效应，提高OIRD灵敏度；定量研究三维传感层各结构参数对OIRD信号的影响规律，揭示光学增强机制；在此基础上建立灵敏OIRD微阵列免疫芯片，用于无标识免疫分析和生物大分子相互作用研究。本项目的实施，将是对OIRD这一先进探测技术在芯片检测应用上的重要革新；同时，也有望进一步拓展OIRD技术在细胞、组织层次研究中的应用。

Oblique-incidence reflectivity difference (OIRD) is a powerful technique to monitor the interface/surface change by measuring the difference in the fractional reflectivity change between p- and s-polarized lights. Due to its intrinsic advantages of being label-free, real-time, non-destructive, and compatible with arbitrary substrates, OIRD demonstrates great promise for detection of high-throughput microarray chips. Its broad applications however, are severely restricted by its limited sensitivity. In pursuit of sensitive OIRD-based immunoassay chips, our theoretical analysis and preliminary results indicate the ultimate importance of interfacial structure of the chip; it is found that the OIRD sensitivity could be dramatically enhanced by generating the interference enhancement effect and effective dielectric constant effect via rational design of chip architecture. We therefore propose in this project to essentially improve the sensitivity of OIRD-based immunoassay microarray chips by constructing a rationally designed three-dimensional sensing layer, which is able to trigger and take advantage of the interference enhancement effect and effective dielectric constant effect. In details, a batch of microarray chips with micro/nanostructured sensing architecture will be fabricated for label-free OIRD detection of targets and the effect of the structural parameters on the OIRD signal will be systematically investigated to reveal the detailed optical mechanism of sensitivity enhancement by combining necessary theoretical simulations. Highly sensitive OIRD microarray chips will be further developed for label-free, real-time and high-throughput immunoassay and biomolecular interaction study. This project will help deepen our understanding on interfacial engineering-enhanced OIRD chip and may also pave the conceptually new way to facilitate the OIRD applications in a broad variety of research areas beyond immunoassay such as cell-tissue level biomolecular interaction investigations.