1. History of SERS

Raman spectroscopy is an important optical detection method for studying molecular rotation and vibration. Since its vibration mode information is related to specific chemical bonds and molecular symmetry, Raman spectroscopy is commonly used in chemical analysis. Raman spectroscopy has a very narrow "fingerprint" spectrum, which allows simultaneous detection of multiple molecules without labelling. In 1928, C.V. Raman found that the scattering frequency of light changed when light passed through a transparent medium and interacted with molecules, now called Raman scattering. The incident photons interact with molecules and subsequently generate emitting photons under laser irradiation. In the process, most photons are elastically scattered without exchanging energy (Rayleigh scattering), while a small proportion of photons gain or lose energy, thus leading to a change in both the frequency and direction of the photon (Raman scattering). The intensity of Rayleigh scattering is only 10⁻³ of the incident light intensity, and the intensity of Raman scattering is only about 10⁻³ of the intensity of Rayleigh scattering, which is 10⁻⁶ of the incident light intensity. Typically, Raman scattering is weak, so some effective strategies need to be used to enhance the Raman signal for the detection of the molecules. In 1974, Fleischmann and co-workers first reported that the Raman signal of pyridine when in close contact to a rough silver electrode was considerably enhanced. Subsequently, Jeanmaire and Van Duyne discovered that the Raman signal of adsorbed molecules on the surface of a roughened novel metal was significantly enhanced. Since then, the concept of surface-enhanced Raman scattering (SERS) has been proposed and attracted lots of attention.

2. Principles for Raman Enhancement

So far, the SERS enhancement theory has still been a controversial matter and has not been clearly explained. It is generally accepted that electromagnetic enhancement and chemical enhancement make major contributions to SERS enhancements. In the SERS enhancement process, electromagnetic enhancement and chemical enhancement are not mutually exclusive, and the two mechanisms work together.

2.1. Electromagnetic Enhancement

Electromagnetic enhancement is the main contributor to the SERS effect and relies on the resonance between the electrons on the surface of a metallic nanostructure and the incident light, namely, the localized surface plasmon resonances (LSPR). The metals with rich free electrons (mainly gold, silver, copper) can generate surface plasmon resonance under visible light excitation. According to the classical theory of electromagnetic radiation, the Raman scattering intensity of molecules is proportional to the square of the molecular induced dipole moment. Therefore, it can be inferred that the enhancement of Raman scattering intensity is related to the enhancement of the electric field acting on the molecule. The electromagnetic field enhancement mechanism has a long-range effect and is independent of the type of adsorbed molecules. Factors such as the energy of incident photons, the composition, particle size and morphology of metal nanoparticles, have important effects on the enhancement of the local electric field on the surface of the substrate. It has been proven that the enhancement factor for electromagnetic field is approximately proportional to the fourth power of the local electric field intensity generated by metal nanostructures. More importantly, the electromagnetic field around the nanostructures is not uniformly distributed but highly localized in a narrow space called “hot spots”. It should be pointed out that the electric field enhancement generated by surface plasmon resonance has an effective operation distance between 1~10 nm. SERS enhancement declined nearly exponentially with the distance between the interested point and nanostructures, so only the molecules adsorbed on or very near the surface of the nanostructures can be enhanced. Generally, the intensity of local electromagnetic field is greatest in the regions with high local curvature of single nanoparticles and the strongest surface photoelectric field is formed in certain region of aggregations with two or more particles, which is known as “hot spots”. “Hot spots” usually occur in the gaps or sharp vertices of the nanostructures made by noble metals, semiconductors or metal–organic frameworks. Compared with traditional Raman, the SERS signal of molecules near the “hot spots” can be greatly enhanced with an enhancement factor of 10⁶~10⁸, and the density of “hot spots” is proportional to the enhancement effect.

2.2. Chemical Enhancement

Chemical enhancement is attributed to the electronic-transfer processes between the metallic surface and the adsorbed molecules. The distance of the electronic-transfer effect is limited to within 10 nanometers. Once the incident light is matched with the electron transfer energy of the adsorbed molecules, resonance Raman enhancement can be achieved. This effect brings about a change in the molecular polarization, and the Raman signal of the analyte can be enhanced by two to three orders of magnitude. Compared to electromagnetic enhancement, chemical enhancement makes a lower contribution to the total enhancement of a Raman scattering signal. Unlike electromagnetic enhancement, chemical enhancement is closely related to the chemical structures of the molecules. The correlation between the molecular structures of different organothiols and their SERS enhancement factors can be estimated using a simple internal reference method.

3. Applications and Perspectives

The SERS shift only depends on the internal structure of molecules, which can provide a basis for qualitative analysis. The vibration frequencies of different chemical bonds and functional groups in biological macromolecules (such as sugars, proteins, lipids, nucleic acids, etc.) correspond to different SERS shifts. Therefore, SERS can provide the information about the molecular composition, and also is used to analyze biochemical components to explore biological molecular structures. Due to the merits of fast detection, high sensitivity, good selectivity, multiplexing and absence of interference in water, SERS has been widely used in the areas including food science, environmental analysis, materials science, biosensing, catalysis, electrochemistry etc. However, as a new rapid detection technology, SERS detection technology still has many challenges such as poor repeatability of spectra, which may lead to inaccurate data processing and difficulty in obtaining standard spectra. The small differences in SERS cannot be detected with naked eyes, and chemometrics statistical methods such as principal component analysis and hierarchical clustering analysis are often used for SERS spectral data processing. In the future, more efforts should be taken to develop high stability, good reproducibility, and high enhancement factor SERS substrates, and also establish the standard spectral analysis library, thereby SERS technology can be used in practical applications.