Surface-enhanced Raman scattering (SERS) has become a powerful tool in chemical, material and life sciences, owing to its intrinsic features (i.e., fingerprint recognition capabilities and high sensitivity) and to the technological advancements that have lowered the cost of the instruments and improved their sensitivity and user-friendliness. We provide an overview of the most significant aspects of SERS. First, the phenomena at the basis of the SERS amplification are described. Then, the measurement of the enhancement and the key factors that determine it (the materials, the hot spots, and the analyte-surface distance) are discussed. A section is dedicated to the analysis of the relevant factors for the choice of the excitation wavelength in a SERS experiment. Several types of substrates and fabrication methods are illustrated, along with some examples of the coupling of SERS with separation and capturing techniques. Finally, a representative selection of applications in the biomedical field, with direct and indirect protocols, is provided. We intentionally avoided using a highly technical language and, whenever possible, intuitive explanations of the involved phenomena are provided, in order to make this review suitable to scientists with different degrees of specialization in this field.

A SERS sensor based on gold nanostars is described. The size and sharpness of the nanostar spikes are tuned to maximize sensitivity and SERS enhancement, yielding a detection limit of 10 ⁻¹⁵ M and an enhancement factor of 10 ⁹ . The effectiveness of the sensor is proven for both chemisorbed and physisorbed analytes under non-resonant conditions and its multiplexing capability is demonstrated.

Gold nanostars are one of the most fascinating anisotropic nanoparticles. The morphology of a nanostar can be controlled by changing various synthetic parameters; however, the detailed growth mechanism is still not fully understood. Herein, we investigate this process in six-branched nanostars, focusing first on the properties of a single crystalline seed, which evolves to include penta-twinned defects as the gateway to anisotropic growth into the 6-branched morphology. In particular, we report on a high-yield seed-mediated protocol for the synthesis of these particles with high dimensional monodispersity in the presence of Triton-X, ascorbic acid, and AgNO₃. Detailed spectroscopic and microscopic analyses have allowed the identification of several key intermediates in the growth process, revealing that it proceeds via penta-twinned intermediate seeds. Importantly, we report the first experimental evidence tracking the location of silver with sub-nanometer resolution and prove its role as a stabilizing agent in these highly branched nanostructures. Our results indicate that metallic silver on the spikes stabilizes the nanostar morphology and the remaining silver, present when AgNO₃ is added at a high concentration, deposits on the core and between the bases of neighboring spikes. Importantly, we also demonstrate the possibility of achieving dimensional monodispersity, reproducibility, and tunability in colloidal gold nanostars that are substantially higher than those previously reported, which could be leveraged to carry out holistic computational–experimental studies to understand, predict, and tailor their plasmonic response.