NER: Surface-enhanced hyper-Raman scattering for biosensing and bioimaging

本建议书是应NSF 04-043纳米科学与工程计划(NSF 04-043，NER)而提出的。我们将探讨表面增强超拉曼光谱(SEHRS)的非线性技术在生物分析传感和成像方面的可能应用。线性模拟表面增强拉曼光谱(SERS)是一种广为人知的技术，被广泛应用于在低浓度下获得分析物的振动光谱，在某些情况下甚至可以精确到单分子水平。SERS在包括细胞内检测在内的生物传感应用中是有价值的，但它的局限性包括基于拉曼的方法通常对荧光干扰和样品光降解的敏感性。利用红光或近红外激光激发产生近紫外光到可见光的拉曼散射的SEHRS具有许多潜在的优点，包括对荧光的敏感性较低，样品光损害较小，对感兴趣的分析物的选择性更高，成像应用中的空间分辨率更高，以及由于激发频率和检测频率之间的巨大差异而能够使用更简单的检测系统。主要的缺点是效果通常很弱。这项研究的目的是确定通过将拉曼显微镜的小焦点体积与金属纳米粒子表面增强相结合来缓解这种情况的程度，该表面增强来自固有的超拉曼活性发色团的入射和/或散射电磁场。

0507960KelleyThis proposal was received in response to Nanoscale Science and Engineering initiative, NSF 04-043, category NER.The nonlinear technique of surface-enhanced hyper-Raman spectroscopy (SEHRS) will be explored for its possible applications to bioanalytical sensing and imaging. The linear analog, surface-enhanced Raman spectroscopy (SERS) is a well-known technique widely applied for obtaining vibrational spectra of analytes at low concentrations, in some cases down to the single-molecule level. SERS is proving valuable for biological sensing applications including intracellular detection, but its limitations include the usual sensitivity of Raman-based methods to interference from fluorescence and sample photodegradation. SEHRS, in which red or nearinfrared laser excitation produces Raman scattering in the near-uv to visible, has a number of potential advantages including less sensitivity to fluorescence, less sample photodamage, greater selectivity for the analyte of interest, better spatial resolution in imaging applications, and the ability to use a simpler detection system because of the large difference between the excitation and detection frequencies. The main disadvantage is the usual weakness of the effect. The goal of this research is to determine the extent to which this can be mitigated by combining the small focal volume of a Raman microscope with metallic nanoparticle surface enhancement of the incident and/or scattered electromagnetic fields from intrinsically hyper-Raman-active chromophores.