Direct measurement of circular dichroism by evanescent wave cavity ring-down spectroscopy using rationally designed plasmonic structures

圆二色性是分子手性域对圆偏振光的微分吸收。CD提供了分子构象的重要信息，已广泛用于生物医学和药物样品的定性分析。然而，由于光的波长和分子手性结构域的大小不匹配，CD通常非常小，对定量分析不够敏感。在过去的十年中，等离子体纳米结构在塑造光学近场以增强手性光-物质相互作用方面已经被证明是非常强大的。另一方面，倏逝波腔衰荡光谱（EW-CRDS）已经成为一种成熟的、可实现的通过腔内多次反射增加微弱吸收的方法。因此，等离子体与EW-CRDS的成功结合有望大大提高手性分析的灵敏度。在本研究中，我们计划结合纳米等离子体和ewcrds的增强效应来提高凝聚相手性样品的CD分析灵敏度。目的是研制一种新型、灵敏的等离子体EW-CRDS定量手性分析装置。由于很难保持EW-CRDS腔内光的圆偏振，因此目前还没有使用EW-CRDS对CD进行直接分析。典型的EW-CRDS工作方式为线偏振光学模式。因此，光场不能区分手性域的不同手性。为了解决这一问题，我们提出利用合理设计的等离子体纳米结构将线极化腔模式局部转化为对手性分析的局部场。等离子体纳米结构不仅解决了腔模式的线性极化问题，而且为增强手性光-物质相互作用提供了机会。如果该项目成功，我们可以绕过线偏振光的限制，将EW-CRDS应用于直接灵敏的CD分析。这将是首次使用EW-CRDS进行直接CD分析。研究成功后，基于EW-CRDS的台式CD灵敏定量分析仪器有望问世。本项目的创新之处在于将纳米等离子体学与EW-CRDS相结合，使超灵敏的直接CD分析成为可能。这个项目不仅对基础研究有兴趣，而且对生化分析和药物设计的实际应用也很有兴趣。

Circular dichroism (CD) is the differential absorption of circularly polarized light by molecular chiral domains. CD provides important information of the molecular conformation and has been heavily used for qualitative analysis of biomedical and pharmaceutical samples. However, due to the mismatch of the wavelength of light and the size of molecular chiral domains, CD is typically very small and not sensitive enough for quantitative analysis. In the last decade, plasmonic nanostructures have been demonstrated very powerful in sculpting optical near fields to enhance chiral light-matter interaction. On the other hand, evanescent wave cavity-ring-down spectroscopy (EW-CRDS) has become a matured and realizable method to increase weak absorption by multiple reflection in the cavity. A successful combination of plasmonics and EW-CRDS is therefore expected to greatly improve the sensitivity of chiral analysis. In this proposal, we plan to combine the enhancement effect of nanoplasmonics and EW-CRDS to boost the sensitivity of CD analysis on condense phase chiral samples. The objective is to develop a novel and sensitive plasmonic EW-CRDS apparatus for quantitative chiral analysis. So far, direct CD analysis with EW-CRDS has not been demonstrated due to the difficulty to maintain the circular polarization of light in the cavity of EW-CRDS. Typical EW-CRDS operates with linearly polarized optical modes. Therefore, the optical field cannot discriminate different handedness of chiral domains. To address this issue, we propose using rationally designed plasmonic nanostructures to locally transform the linearly polarized cavity mode into enantioselective local field for chiral analysis. Plasmonic nanostructures not only solve the problem of linear polarization of cavity mode but also offer the opportunity to enhance chiral light-matter interaction. If this project is successful, we can bypass the limitation of linearly polarized light and apply EW-CRDS to direct and sensitive CD analysis. This would be the first demonstration of direct CD analysis using EW-CRDS. Upon the success of the proposed research, new desktop analytical instrument for sensitive and quantitative CD analysis based on EW-CRDS can be anticipated. The innovation of this project is to combine nanoplasmonics with EW-CRDS to make ultrasensitive direct CD analysis possible. This project is not only interesting for fundamental research but also for real applications in biochemical analysis and drug design.