Insights of Surface-Enhanced Raman Spectroscopy Detection by Guiding Molecules into Nanostructures to Activate Hot Spots

A misunderstanding of how target molecules enter hot spot nanostructures has significantly hindered the advancement of surface-enhanced Raman spectroscopy (SERS) detection methods in recent years. The challenge lies in finding convenient ways to transport target molecules to various nanostructures. In this work, we discovered that filling the gaps in empty nanostructures with water is often difficult, as metal surfaces are not well wetted. Additionally, the adsorption of pollutants from the air reduces the water wettability within the nanogaps, severely restricting the diffusion of molecules in the hot spots. This study proposes a method that uses a binary solvent mixture of ethanol and water (EtOH–H₂O) to effectively guide target molecules into the nanostructures containing numerous hot spots. By utilizing the tunable surface tension gradient of this binary solvent mixture, we can control solvent transport within the nanostructures, significantly enhancing the activity of the hot spots and increasing the efficiency of SERS detection. The detection limit of this simple and rapid binary solvent mixing method is improved by 2–3 orders of magnitude compared to traditional methods that use only water or ethanol as solvents while also demonstrating high reproducibility. This method can be widely applied to various nanostructures for different types of molecules, maximizing the efficient use of intrinsic hot spots. This innovative approach provides new momentum for the advancement of SERS technology and lays a solid foundation for its widespread adoption in various analytical applications.