Surface-enhanced femtosecond stimulated Raman spectroscopy for detection of trace chemicals in mixtures
Analytical Chemistry
Optics, Quantum Optics and Physics of Atoms, Molecules and Plasmas
Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
Final Report Abstract
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 was to assess the possible use of a combination of surface-enhanced (SERS) 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, in principle, be increased by several orders of magnitude compared to the enhancement usually found in SERS. This additional enhancement was expected to give a dramatic increase in sensitivity. The first experiments were conducted on two different commercially available SERS substrates, one consisting of regular inverted pyramids with a well defined plasmonic resonance, the other of randomly dispersed gold nanospheres of various sizes showing a very broad plasmon absorption over the entire visible and near-infrared spectral range. Despite a SERS enhancement factor that was several orders of magnitude above that of the pyramids, the nanoparticle substrate did not show any SE-FSRS signal. We could relate this result to the coherent superposition of scattered light waves, which is effective in a stimulated nonlinear optical process, such as FSRS, and causes the signal to average out over an inhomogeneous SERS substrate. In contrast, SERS is an incoherent process where only intensities are integrated. Thus, a first result was that the geometry of the substrate matters. The major obstacle for a clear demonstration of SE-FSRS on solid SERS substrates was the high peak intensity associated with the ultrashort laser pulses of FSRS, which required a reduction of average power by more than three orders of magnitude. Unfortunately, the 1-kHz repetition rate of the laser system could not yield a sufficient signal-to-noise ratio for this kind of measurement. The second result, therefore, was that SE-FSRS requires high-repetition rate laser systems (several hundred kHz to MHz) as used for FSRS microscopy, for instance. During this project, alternative approaches for SE-FSRS could be identified and demonstrated theoretically: cavity enhanced FSRS in planar metal-dielectric microcavities especially for thin polymer films with thicknesses on the order of a few hundred nanometers, and surface-plasmon enhanced FSRS in an attenuated total reflection geometry using a prism and a thin metal film. Both approaches are conceptionally simple, easy to fabricate and well suited for coherent optical processes such as FSRS. Theoretical enhancement factors on the order of 104 – 105 are predicted.
Publications
- Molecular Orientation and Optical Properties of 3,3’- Diethylthiatricarbocyanine Iodide Adsorbed to Gold Surfaces: Consequences for Surface- Enhanced Resonance Raman Spectroscopy, J. Phys. Chem. C 119, 9980-9987 (2015)
D. R. Dietze and R. A. Mathies
(See online at https://doi.org/10.1021/acs.jpcc.5b02686) - Femtosecond Stimulated Raman Spectroscopy, ChemPhysChem 17, 1224-1251 (2016)
D. R. Dietze and R. A. Mathies
(See online at https://doi.org/10.1002/cphc.201600104)
