Oriented Antibody Functionalized Plasmonic Yolk–Shell-Satellite Nanostructures for Ultrasensitive SERS-Based Lateral Flow Immunoassay

Conventional gold nanoparticle (AuNP)-based lateral flow immunoassays (LFIAs) for detecting matrix metalloproteinase-9 (MMP-9), a biomarker associated with dry eye disease and cancer, often suffer from limited sensitivity. To address this, we developed an ultrasensitive surface-enhanced Raman scattering (SERS)-based LFIA using plasmonic yolk-shell-satellite nanostructures (YSSNs) functionalized with bifunctional 4-mercaptophenylboronic acid (MPBA) as SERS tags. The YSSNs, composed of a gold nanorod core enclosed by a gold nanocage and decorated with satellite nanoparticles, provided strong SERS enhancement. MPBA not only acted as a robust Raman reporter but also improved the orientation of antibodies. The SERS-LFIA achieved a limit of detection of 0.0056 ng·mL-1 in PBS, a 305-fold improvement over conventional AuNP-LFIA, and demonstrated favorable linear detection in biological samples, with limits of 0.051 ng·mL-1 in serum and 0.030 ng·mL-1 in tears. This assay offers a sensitive and reliable platform for MMP-9 detection and has great potential for disease diagnostics.