biostudies-literatureZheng PBeckman Coulter FoundationNIBIB NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHSNational Institute of Biomedical Imaging and Bioengineeringe2200090https://www.ebi.ac.uk/biostudies/studies/S-EPMC9302383biostudies-literatureUnknown18(18)Small molecules play a pivotal role in regulating physiological processes and serve as biomarkers to uncover pathological conditions and the effects of therapeutic treatments. However, it remains a significant challenge to detect small molecules given the size as compared to macromolecules. Recently, the newly emerging plasmonic immunoassays based on surface-enhanced Raman scattering (SERS) offer great promise to deliver extraordinary sensitivity. Nevertheless, they are limited by the intrinsic SERS intensity fluctuations associated with the SERS uncertainty principle. The single transducer that relies on the intensity change is also prone to false signals. Additionally, the prevailing sandwich immunoassay format proves less effective towards detecting small molecules. To circumvent these Small (Weinheim an der Bergstrasse, Germany)A Dual-Modal Single-Antibody Plasmonic Spectro-Immunoassay for Detection of Small Molecules.PMC9302383DP2 GM1281982-P41-EB015871-31DP2GM128198P41 EB0158712‐P41‐EB015871−31Barman IWu LHanson WARaj PZheng PSzabo MMizutani TfalseA Dual-Modal Single-Antibody Plasmonic Spectro-Immunoassay for Detection of Small Molecules.Small molecules play a pivotal role in regulating physiological processes and serve as biomarkers to uncover pathological conditions and the effects of therapeutic treatments. However, it remains a significant challenge to detect small molecules given the size as compared to macromolecules. Recently, the newly emerging plasmonic immunoassays based on surface-enhanced Raman scattering (SERS) offer great promise to deliver extraordinary sensitivity. Nevertheless, they are limited by the intrinsic SERS intensity fluctuations associated with the SERS uncertainty principle. The single transducer that relies on the intensity change is also prone to false signals. Additionally, the prevailing sandwich immunoassay format proves less effective towards detecting small molecules. To circumvent these 2022-01-01T00:00:00Z2022 May2025-04-19T08:10:04.456Z2025-04-19T08:10:04.456ZS-EPMC93023833537350410.1002/smll.202200090