Single biomarker detection with interferometric imaging.

Biomarker detection is critical for disease diagnostics, drug development, biomolecular assay design, and personalized medicine. Developing sensitive, multiplexed platforms for point-of-care settings remains a significant challenge. Ensemble techniques such as enzyme-linked immunosorbent assays (ELISAs) and lateral flow assays (LFAs) are widely adopted for point-of-care diagnostics and offer robust, well-established protocols. However, their limitations in sensitivity, dynamic range, and multiplexing capabilities hinder their utility in detecting low-abundance analytes. Emerging optical biosensing platforms overcome these constraints by enabling single-particle resolution and label-free detection. This review critically examines the evolution of the Interferometric Reflectance Imaging Sensor (IRIS) platform, tracing its development from ensemble-based measurements to advanced single-particle interferometric techniques, including Single-Particle IRIS (SP-IRIS) and Polarization-Diversity IRIS (PD-IRIS). Applications of IRIS for detecting a wide spectrum of biomarkers are explored, with emphasis on fluidic integration, plasmonic labeling, and image processing enhancement. Special attention is given to assay strategies that broaden the dynamic range, minimize matrix interference and have implications for next-generation point-of-care diagnostics.