Multivalent Antibody-Nanoparticle Conjugates To Enhance the Sensitivity of Surface-Enhanced Raman Scattering-Based Immunoassays

Multivalent immunoprobes can improve the sensitivity of biosensors because increased valency can strengthen the binding affinity between the receptor and target biomolecules. Here, we report surface-enhanced Raman scattering (SERS)-based immunoassays using multivalent antibody-conjugated nanoparticles (NPs) for the first time. Multivalent antibodies were generated through the ligation of Fab fragments fused with Fc-binding peptides to immunoglobulin G. This fabrication method is easy and fast because of the elimination of heterologous protein expression, high degrees of antibody modifications, and covalent chemical ligation steps. We constructed multivalent antibody-NP conjugates (MANCs) and employed them as SERS immunoprobes. MANCs improved the sensitivity of SERS-based immunoassays by 100 times compared to standard antibody-NP conjugates. MANCs will increase the feasibility of practical SERS-based immunoassays.