Unveiling the\nCorrelation between Protein, Protein\nCorona, and Target Signal Loss in SERS Detection

The application of surface-enhanced Raman scattering\n(SERS) technology\nis hindered by the protein corona in a protein-rich complex matrix,\nwhich is a hot and important issue that needs consideration. However,\nthe impact of the protein corona on SERS detection has not been fully\nstudied. Herein, we selected three proteins, α-lactalbumin (α-La),\nβ-lactoglobulin (β-Lg), and bovine serum albumin (BSA),\nas models for forming a protein corona, and melamine was employed\nas the target in SERS detection. The results indicate that three proteins\nform a protein corona on gold nanoparticles (AuNPs), leading to a\nsignificant loss of melamine signals. With increasing protein concentration,\nthe degree of loss increases. The protein corona significantly inhibits\ntarget-induced nanoparticle aggregation, increases the distance between\nneighboring nanoparticles, and reduces the formation of “hot-spot”\nregions. Moreover, the adsorption capacity of AuNPs for melamine decreases,\nreducing the number of molecules that can achieve direct chemical\nenhancement. The Raman signal loss caused by different types of proteins,\nvaries, even at the same molecule number, which is related to the\ndeformability of proteins. This deformability determines the density\nof the protein corona formed on the surface of the AuNPs. Our results\nadvance the fundamental understanding of the relationship between\nproteins, protein corona, and target signal loss in SERS detection,\noffering valuable insights for establishing models to predict Raman\nsignal loss in protein-rich samples.