Nanoparticles as SERS substrates: recent progress in hormone sensing

Abstract Surface-enhanced Raman spectroscopy (SERS) has enabled the, ultrasensitive, and real-time monitoring of clinically significant hormones and related health abnormalities such as diabetes, thyroid dysfunction, infertility, stress etc. Plasmonic nanoparticles (PNPs) specifically, silver (Ag) and gold (Au), provide the foundation for signal enhancement due to their localized surface plasmon resonance (LSPR) and tunable shapes (e.g. spherical, rod, wire, triangle etc.). Recent studies have demonstrated the potential applications of non-plasmonic NPs (Silicon and graphene) and their composites in sensitive detection of hormones in complex biological matrices. Together, the SERS, can detect a wide range of hormones such as insulin, cortisol, dopamine (DA), serotonin (ST), progesterone (P4), etc. at nanomolar (nM) to attomolar (aM) concentrations in complex biological fluids [saliva, blood plasma, serum, sweat (transdermal), cell lysate) and cells. Bimetallic NPs (Ag@Au, Au@Ag), nanocomposites (Si@Ag, Si@Au) have been strategically fabricated to generate high-density electromagnetic hotspots. Further, coupling these substrates with molecularly imprinted polymers (MIPs), antibodies (Ab), aptamers, Raman reporter molecules (RRM) and flexible supports (silicon wafers, paper, PVC/SEBS, PDMS, electrodes) have improved specificity, biocompatibility, and point-of-care (POC) utility of SERS. Thus, the current review evaluates the future diagnostic potential of NPs as SERS substrates for hormone biosensing, highlighting rational nanostructure design, selective surface functionalization, validation in complex matrices and quantitative comparison, reference standards, and clinically translatable SERS platforms across studies.