Stimulated Raman scattering (SRS) describes a family of techniques first discovered and developed in the 1960s. Whereas the nascent history of the technique is parallel to that of laser light sources, recent advances have spurred a resurgence in its use and development that has spanned across scientific fields and spatial scales. SRS is a nonlinear technique that probes the same vibrational modes of molecules that are seen in spontaneous Raman scattering. While spontaneous Raman scattering is an incoherent technique, SRS is a coherent process, and this fact provides several advantages over conventional Raman techniques, among which are much stronger signals and the ability to time-resolve the vibrational motions. Technological improvements in pulse generation and detection strategies have allowed SRS to probe increasingly smaller volumes and shorter time scales. This has enabled SRS research to move from its original domain, of probing bulk media, to imaging biological tissues and single cells at the micro scale, and, ultimately, to characterizing samples with subdiffraction resolution at the nanoscale. In this Review, we give an overview of the history of the technique, outline its basic properties, and present historical and current uses at multiple length scales to underline the utility of SRS to the molecular sciences.

Surface-enhanced coherent anti-Stokes Raman scattering (SECARS) measurements carried out on individual nanosphere dimer nantennas are presented. The ν-domain and t-domain CARS measurements in the few-molecule limit are contrasted as vibrational autocorrelation and cross-correlation, respectively. We show that in coherent Raman spectroscopies carried out with ultrashort pulses, the effect of surface enhancement is to saturate stimulated steps at very low incident intensities (100 fJ in 100 fs pulses), and the principal consideration in sensitivity is the effective quadratic enhancement of spontaneous emission cross sections, σ* = (EL/Eo)2σ. Through multicolor femtosecond SECARS measurements we show that beside enhancement factors, an effective plasmon mode matching consideration controls the interplay between coherent electronic Raman scattering on the nantenna and vibrational Raman scattering on its molecular load. Through extensive measurements on individual nantennas, we establish the tolerable average and peak intensities that can be used in ultrafast measurements at nanojunctions, and we highlight a variety of plasmon-driven chemical and physical channels of signal and sample degradation.

The enormous advances made in nanotechnology have also intensified the need for tools that can characterize newly synthesized nanoaterials with high sensitivity and with high spatial resolution. Many existing tools with nanoscopic resolution or better, including scanning electron microscopy (SEM), atomic force microscopy (AFM), and scanning tunneling microscopy (STM) methods, can generate highly detailed maps of nanoscopic structures. However, while these approaches provide great views of the morphological properties of nanomaterials, it has proven more challenging to derive chemical information from the corresponding images. To address this issue, attempts have been made to dress existing nanoscopy methods with spectroscopic sensitivity. A powerful approach in this direction is the combination of scan probe techniques with optical illumination, which aims to marry the nanoscopic resolution provided by a sharp tip with the chemical selectivity provided by optical spectroscopy. Examples of this approach include existing techniques such as scattering-type scanning near-field optical microscopy and tip-enhanced Raman spectroscopy. A new and emerging technique in this direction is photoinduced force microscopy (PiFM), which enables spectroscopic probing of materials with a spatial resolution well under 10 nm.In PiFM, the sample is optically excited and the response of the material is probed directly in the near-field by reading out the time-integrated force between the tip and the sample. Because the magnitude of the force is dependent on the photoinduced polarization in the sample, PiFM exhibits spectroscopic sensitivity. The photoinduced forces measured in PiFM are spatially confined on the nanometer scale, which translates into a very high spatial resolution even under ambient conditions. The PiFM approach is compatible with a wide range optical excitation frequencies, from the visible to the mid-infrared, enabling nanoscale imaging contrast based on either electronic or vibrational transitions in the sample. These properties make PiFM an attractive method for the visualization and spectroscopic characterization of a vast variety of nano materials, from semiconducting nanoparticles to polymer thin films to sensitive measurements of single molecules.In this Account, we review the principles of the PiFM technique and discuss the basic components of the photoinduced force microscope. We highlight the imaging properties of the PiFM instrument and demonstrate the inherent spectroscopic sensitivity of the technique. Furthermore, we show that the PiFM approach can be used to probe both the linear and nonlinear optical properties of nano materials. In addition, we provide several examples of PiFM imaging applications.

Point-scanning sum-frequency generation (SFG) microscopy enables the generation of images of collagen I fibers in tissues by tuning into specific vibrational resonances of the polypeptide. It is shown that when collagen-rich tissues are visualized near the 2954 cm–1 stretching vibration of methylene groups, the SFG image contrast is higher compared to the contrast seen in nonresonant second-harmonic generation (SHG) imaging. Polarization and spectrally resolved analysis of the SFG signal as a function of fiber orientation in the CH-stretching range of the vibrational spectrum enabled a comparative characterization of the achiral tensor elements of collagen’s second-order susceptibility. This analysis reveals that selected on-resonance tensor elements are enhanced over other elements, giving rise to a much stronger anisotropy ρ of the signal for SFG (ρ ≈ 15) compared to SHG (ρ ≈ 3). The improved anisotropy of the vibrationally resonant signal contributes to the higher contrast seen in the SFG tissue images.

Ongoing progress in micro- and nano-material fabrication has led to novel devices and new optical properties have emerged. Among these properties are high optical nonlinearities, which can be used for light-based operations such as frequency shifting and optical computing. Optimizing and utilizing optical nonlinearities requires sensitive instruments to study them. Given the miniature sizes of the new materials under study, conventional analysis approaches may be insufficient, thus putting an emphasis on emerging technologies. Four-wave mixing (FWM) microscopy is a budding technique that is poised to become a useful tool in materials science. FWM microscopy provides a fast eye for spotting small structures and uncovering their material properties. The FWM signal derives its selectivity from material-specific electronic resonances and Raman transitions, providing an optical microscope that is attuned to visualizing and studying a broad range of micro- and nano-structured materials. In this article, the basics of FWM microscopy are discussed and the impact of this technique in materials science is highlighted.

First-principles anharmonic calculations are carried out for the IR and Raman spectra of the CH stretching bands in butane. The calculations use the Vibrational Self-Consistent Field (VSCF) algorithm. The results are compared with gas-state experiments. Very good agreement between the computed and experimental results is found. Theory is successful also in computing a weak peak which is caused by combination transitions. The B3LYP potential surface is found superior to MP2, though both methods give good accord with experiment. The theoretical results provide an understanding of the role of different modes in the spectra of hydrocarbons.Graphical abstractComparison of first-principles vibrational calculations with IR and Raman experiments for butane.Highlights► VSCF calculations closely reproduce IR and Raman experiments for butane. ► B3LYP is superior to MP2 for butane by the test of spectroscopy. ► Anharmonic effects in the CH band spectra are very large. ► Vibrational degeneracy effects in butane are washed out by broadening.

Coherent anti-Stokes Raman scattering (CARS) microscopy is combined with spontaneous Raman scattering microspectroscopy and second harmonic generation (SHG) microscopy to interrogate the molecular alignment in dry and hydrated cellulose fibers. Two types of cellulose were investigated: natural cellulose I in cotton fibers and regenerated cellulose II in rayon fibers. On the basis of the orientation of the methylene symmetric stretching vibration, the molecular alignment of cellulose microfibrils is found to be conserved on the micrometer scale. Whereas the molecular orientation in cotton shows modest variability along the fiber, the alignment of the cellulose units in rayon is highly consistent throughout the fiber. The ordered alignment is retained upon fiber hydration. Upon hydration of the cellulose fibers, an anisotropic electronic contribution is observed, which indicates an ordered incorporation of water molecules into the fiber structure. The third-order and second-order electronic polarizability of cellulose I are directed along the axis of the polyglucan chain. No second-order optical response is observed in cellulose II, supporting the antiparallel arrangement of the polyglucan chains in regenerated cellulose.

Dual color four-wave-mixing (FWM) microscopy is used to spatially resolve the third-order optical response from individual carbon nanotubes. Good signal-to-noise is obtained from single-walled carbon nanotubes (SWNT) sitting on substrates, when the excitation beams are resonant with electronic transitions of the nanotube, by detecting the FWM response at the anti-Stokes frequency. Whereas the coherent anti-Stokes (CAS) signal is sensitive to both electronic and vibrational resonances of the material, it is shown that the signal from individual SWNTs is dominated by the electronic response. The CAS signal is strongly polarization dependent, with the highest signals found parallel with the enhanced electronic polarizibility along the long axis of the SWNT.

Focus-engineered coherent anti-Stokes Raman scattering (FE-CARS) microscopy is used to visualize microscopic samples with differential imaging contrast in both longitudinal and lateral directions. Multi-dimensional contrast is achieved by applying a one-dimensional π-phase step in the transverse beam profile of the Stokes beam. The observed longitudinal differential contrast results from fortuitous phase-matching at axial interfaces and is highly sensitive to the resonant part of the third-order susceptibility. Based on phase-sensitive recordings of the vibrational spectrum of dimethyl sulfoxide in the CH3-stretching range, it is shown that FE-CARS uniquely probes the spectral phase of the Raman bands of the sample.

Intrinsic coherent anti-Stokes emission is observed in lithographically patterned gold nanowires. Polarization dependent measurements reveal that the nanostructure’s anti-Stokes response is polarized in the direction of the transverse surface plasmon resonance of the wire. We have used specially fabricated gold nanozigzag wires that are modulated in height between 20 and 80 nm to demonstrate tuning of the plasmon polarizability through control of wire height. Stronger anti-Stokes emission is shown to correlate with structures that support higher plasmon polarizability, underlining the primary role of the transverse plasmon resonance in the generation of anti-Stokes radiation from gold nanostructures. Our results also point out that a potential surface-enhanced coherent anti-Stokes Raman scattering (CARS) assay for detecting the vibrational response of surface-tethered molecules needs to include a mechanism for separating the molecular response from the strong intrinsic anti-Stokes emission of the metallic nanosubstrate.

The two-photon excited luminescence (TPEL) of single gold nanowires was investigated under far-field illumination with picosecond pulses. These nanowires, having a rectangular cross-section, a precisely defined thickness, and millimeter-scale length, were prepared by using the lithographically patterned nanowire electrodepostion (LPNE) technique. The TPEL from these wires was investigated as a function of wire thickness. It is found that the optical properties of the wire are dominated by the transverse surface plasmon resonance, which enhances the two-photon absorption process and subsequent emission in the polarization direction of the plasmon mode. Upon tuning the thickness of the wire from 74 to 25 nm, an enhancement of 3 orders of magnitude in the TPEL was observed. The TPEL tunability is found to be consistent with the geometry-dependent field concentration at the metal surface as predicted by the lightning rod model.

Cholesterol crystals (ChCs) have been identified as a major factor of plaque vulnerability and as a potential biomarker for atherosclerosis. Yet, due to the technical challenge of selectively detecting cholesterol in its native tissue environment, the physiochemical role of ChCs in atherosclerotic progression remains largely unknown. In this work, we demonstrate the utility of hyperspectral stimulated Raman scattering (SRS) microscopy combined with second-harmonic generation (SHG) microscopy to selectively detect ChC. We show that despite the polarization sensitivity of the ChC Raman spectrum, cholesterol monohydrate crystals can be reliably discriminated from aliphatic lipids, from structural proteins of the tissue matrix and from other condensed structures, including cholesteryl esters. We also show that ChCs exhibit a nonvanishing SHG signal, corroborating the noncentrosymmetry of the crystal lattice composed of chiral cholesterol molecules. However, combined hyperspectral SRS and SHG imaging reveals that not all SHG-active structures with solidlike morphologies can be assigned to ChCs. This study exemplifies the merit of combining SRS and SHG microscopy for an enhanced label-free chemical analysis of crystallized structures in diseased tissue.