Detection of simple proteins by direct surface-enhanced Raman scattering based on the Hofmeister ion-specific effect

Surface-enhanced Raman scattering (SERS) spectroscopy has unique advantages in detecting biomolecules, but label-free determination of proteins with low scattering cross-sections remains challenging. In this study, such proteins' SERS signals have been optimized using the Hofmeister effect between protein molecules and CsI so-lution at physiological concentrations (A 100 mmol/L Cesium iodide, CsI). Cs+ as chaotro cation ion has a complex interaction mechanism with protein, can not only deprive hydrated water molecules on the surface of protein but also penetrate into the hydrophobic interior of protein. In addition to the above advantages, I- in excess CsI solution with appropriate concentration can removes the interference of citric acid-based impurities on the surface of silver nanoparticles, and Cs+ in excess CsI solution attracts the aggregation of negatively charged silver nanoparticles and cause local electromagnetic field enhancement to achieve high sensitivity in protein detection. This has been combined with principal component analysis to perform a comprehensive analysis of several proteins. Molecular dynamics simulations have been performed to study the mechanism of interaction between CsI and proteins. In addition, the vibrational peak of water has been used as an internal standard to quantify the protein content, and a good linear relationship between peak intensity and concentration was obtained.