Transport-Reaction-Signal Coupling in Lateral Flow Assays for Next-Generation Point-of-Care Diagnostics

Lateral flow assays (LFAs) remain central to point-of-care diagnostics because they combine low cost, portability, and operational simplicity. Emerging diagnostic demands, including low-abundance biomarkers, complex sample matrices, quantitative readout, and multiplexed analysis, increasingly expose limitations that cannot be solved by signal-label enhancement alone. This Review examines recent LFA advances through a three-phase framework that couples porous-material mass transfer, interfacial reaction engineering, and signal transduction. The framework clarifies how membrane and flow design regulate analyte delivery and residence time, how antibody orientation, reaction amplification, and hook-effect mitigation improve capture efficiency and dynamic range, and how advanced nanolabels, integrated readers, multiplexed formats, and AI/ML-supported design and analysis expand performance across the assay workflow. By distinguishing intrinsic performance gains from strategies that transfer complexity to reagents, devices, or software, this Review provides design principles for sensitive, quantitative, and translation-oriented LFA systems.