Magnetic assistance highly sensitive protein assay based on surface-enhanced resonance Raman scattering

[Display omitted] ► Development of AgMNPs as protein carrier. ► External magnetic field induced the aggregation of AgMNPs can provide high SERRS enhancement. ► This is a promising potential of applications for quantitatively immunoassays based on SERRS. A simple and effective surface-enhanced Raman scattering (SERS)-based protocol for the detection of protein–small molecule interactions has been developed. We employed silver-coated magnetic particles (AgMNPs), which can provide high SERS activity as a protein carrier to capture a small molecule. Combining magnetic separation and the SERS method for protein detection, highly reproducible SERS spectra of a protein–small molecule complex can be obtained with high sensitivity. This time-saving method employs an external magnetic field to induce the AgMNPs to aggregate to increase the amount of atto610-biotin/avidin complex in a unit area with the SERS enhancement. Because of the contribution of the AgMNP aggregation to the SERS, this protocol has great potential for practical high-throughput detection of the protein–small molecule complex and the antigen–antibody immunocomplex.