“…However, accurate and real-time detection of cytokines remains challenging, because of their low trace amount, highly dynamic secretion, and short half-lives. , The commonly used enzyme-linked immunosorbent assay (ELISA) requires labor-intensive sample handling, labeling, and washing processes, falling short of meeting the urgent demands for sensitive, dynamic cytokine monitoring. In contrast, label-free biosensing circumvents the need for secondary tagging by providing direct physical signals upon target binding, rendering them a consolidated approach for high-speed diagnosis. − Among the various transduction mechanisms of optical, , electrical, , and mechanical , sensors, nanoplasmonic biosensors have shown great promise in the compact, simple, and rapid detection of protein biomarkers. − By utilizing the localized surface plasmon resonance (LSPR), nanoplasmonic biosensing allows remote transduction of biomolecular binding in a highly localized environment (∼20–60 nm) around the plasmonic nanoparticle (NP) surface, , presenting excellent sensing performance to detect small target analytes such as cytokines. Despite the great potential, the limit of detection (LOD) of label-free LSPR immunoassay is reaching its theoretical limit of ∼10 pg/mL due to fundamental constraints in the quality (Q)-factor and sensing volume of the plasmonic NPs, and the binding affinity and mass ratio of the antibody–antigen pairs .…”