Surface-enhanced femtosecond stimulated Raman spectroscopy for detection of trace chemicals in mixtures

及时诊断是成功治疗癌症等疾病的最重要步骤之一。因此，越来越多的努力投入到指示患者癌症状态的潜在生物标志物的分析和检测中。光学方法，如红外吸收或拉曼光谱，已经得到广泛应用。因此，主要的挑战是在几个分子水平上可靠地检测生物标志物，并明确地将光谱特征归因于某些化学物种。虽然前一个条件是通过使用表面增强拉曼散射（Sers）来满足的，但后者是特别苛刻的，因为典型的血液或唾液样品通常包含具有重叠光谱特征的数千种不同分子。该项目的目的是评估表面增强和飞秒受激拉曼光谱（FSRS）的组合用于检测生物标志物的可能性，提高灵敏度和特异性。由于非线性过程的受激性质，与通常在Sers中发现的增强相比，表面增强可以增加几个数量级。这将大大提高灵敏度。此外，FSRS前所未有的时间分辨率（<100 fs）增加了一个额外的标准，用于区分分子，否则表现出类似的拉曼光谱。这是基于这样的想法，即不同的分子对光激发的响应不同，例如对脉冲拉曼散射的响应不同。除了实用方面，表面增强FSRS的研究打开了大门，跟踪单分子水平上的化学反应的动力学。这将对表面和纳米结构上催化反应的研究产生重大影响。

Timely diagnosis is one of the most important steps towards the successful treatment of diseases such as cancer. Therefore, an increasing effort is put into the analysis and detection of potential biomarkers indicative of the cancer state of the patient. Optical methods, such as infrared absorption or Raman spectroscopy, have already found widespread use. The main challenges thereby are posed by the reliable detection of biomarkers on the few molecule level and the unequivocal attribution of spectral features to certain chemical species. While the former condition is met by the use of surface-enhanced Raman scattering (SERS), the latter is especially demanding as typical blood or saliva samples usually contain several thousand different molecules with overlapping spectral features. The aim of this project is to assess the possible use of a combination of surface-enhanced and femtosecond stimulated Raman spectroscopy (FSRS) for the detection of biomarkers with increased sensitivity and specificity. Due to the stimulated nature of the nonlinear process, the surface enhancement can be increased by several orders of magnitude compared to the enhancement usually found in SERS. This will give a dramatic increase in sensitivity. Further, the unprecedented temporal resolution of FSRS (<100fs) adds an additional criterion for discriminating molecules that otherwise exhibit similar Raman spectra. This is based on the idea that different molecules will respond differently to optical excitation, for example, to impulsive Raman scattering. Apart from the practical aspect, the study of surface-enhanced FSRS opens the door to track the dynamics of chemical reactions on the single molecule level. This will have a great impact on the study of catalytic reactions on surfaces and nanostructures.