Intensity Fluctuations in Single Molecule Surface-Enhanced Raman Scattering

表面增强拉曼散射(SERS)是一种高灵敏度的振动光谱技术，能够提供独特的分子指纹信息。表面增强拉曼光谱观察到吸附在纳米结构金属表面某些区域的分子，称为表面增强拉曼散射热点。在热点上的紧密聚焦的光甚至可以通过拉曼散射来检测单个分子。实验上，单分子信号由强烈的依赖于时间(或空间)的SERS强度起伏(SIF)组成。虽然单分子表面增强拉曼散射(SM-SERS)现象早在20多年前就已被证实，但实际使用SM-SERS来获取热点环境的基本信息或用于化学应用的例子很少，例如在分析化学中。 我们发现计划的长期目标是将SERS领域引向一个新的方向，考虑到单粒子、单分子甚至单光子事件的统计数据。这一新方法将带来几个有趣的新见解和潜在的新应用。为了实现这一长期目标，我们建议应用一种新的技术来研究高空间和时间分辨率的SIF。在短期内，这种新的方法将被用来跟踪热点上的动态过程，这些过程由于在常规SERS测量中通常使用的低采集率(~1 Hz)而被隐藏。实验将在不同的温度下进行，例如，允许量化基本过程的能量学，例如热点区域的金属团簇重建。一些因素的作用，如金属的性质，热点区域纳米环境的几何特征，以及分子对金属表面的亲和力，将被系统地研究。短期内的总体目标将是提取以前无法访问的热点上的金属-分子相互作用的基本信息。 对快速波动频率的分析将被用来产生SERS量化的另一种方法。尽管SERS是一种非常灵敏的方法，但其在分析化学中的应用受到固有强度波动的阻碍，这些波动会导致分析校准曲线的巨大误差。我们认为，对于非常低的浓度，SIF频率可能与给定分析物在溶液中的浓度有很好的相关性(变化较小)。最后，我们将能够结合SM-SERS测量和高速采集来研究单分子发射的单光子。

Surface-enhanced Raman scattering (SERS) is a highly sensitive vibrational spectroscopy technique capable of providing unique molecular fingerprinting information. SERS is observed for molecules adsorbed on certain areas of nanostructured metallic surfaces known as SERS hotspots. The tightly focussed light at the hotspots allows even the detection of single individual molecules by Raman scattering. Experimentally, the single molecule signature consists of strong time- (or space-) dependent SERS intensity fluctuations (SIFs). Although the phenomenon of single-molecule SERS (SM-SERS) has been demonstrated more than 20 years ago, there were very few examples of actual uses of SM-SERS to either acquire fundamental information about the hotspot environment or for chemical applications, such as in analytical chemistry. The long term goal of our Discovery program is to lead the SERS field to a new direction that takes into consideration the statistics of single particle, single molecule and even single photon events. This new approach will lead to several interesting new insights and potential new applications. In order to achieve this long term goal, we propose the application of a new technology for the study of SIFs with high spatial and time resolution. In the short term, this new method will be used to follow dynamic processes at the hotspot that have remained hidden due to the notorious low acquisition rate (~ 1 Hz) typically used in a regular SERS measurements. Experiments will be realized at different temperatures, allowing, for instance, the quantification of the energetics of fundamental processes, such as metallic cluster reconstruction at the hotspot area. A systematic investigation of the role of several factors, such as the nature of the metal, the geometric characteristics of the nanometric environment at the hotspot region, and the molecular affinity to the metallic surface, will be investigated. The overall goal in the short term will be to extract fundamental information about the metal-molecule interaction at the hotspot that was not accessible before. The analysis of the frequencies of the fast fluctuations will be used to generate an alternative approach in SERS quantification. Although SERS is a very sensitive method, its application in analytical chemistry has been hampered by intrinsic intensity fluctuations that translate into large errors in analytical calibration curves. We suggest that, for very low concentrations, SIF frequencies might correlate well (less variations) with the concentration of a given analyte in solution. Finally, we will be able to combine SM-SERS measurements with high-speed acquisition to investigate single photons emitted by single molecules.