From sensitivity challenges to nanozyme-driven signal amplification in lateral flow immunoassays for biomarker detection.

Abstract

Disease-related molecular markers are central to early diagnosis, treatment evaluation, and prognostic prediction. Conventional laboratory techniques, such as enzyme-linked immunosorbent assays (ELISA), require multiple incubation and washing steps and depend on specialized instrumentation. These requirements limit their applications in rapid point-of-care testing (POCT). Lateral flow immunoassays (LFIAs) provide a simple, low-cost, and rapid diagnostic platform. However, their sensitivity remains insufficient for detecting low-abundance biomarkers because of the limited signal intensity of conventional labels and interference from complex biological matrices. To address these limitations, nanozymes with enzyme-like catalytic activity offer an effective strategy for signal amplification in LFIAs. Their high catalytic stability, tunable activity, and facile surface modification enable significant enhancement of analytical signal output. In nanozyme-based LFIAs, immune recognition events are converted into amplified colorimetric, chemiluminescent, or multimodal signals, improving both detection sensitivity and quantitative capability. Although nanozyme-enhanced LFIAs develop rapidly in recent years, their clinical translation remains limited, highlighting the need for systematic understanding and rational design strategies. This review summarizes the factors limiting LFIA sensitivity, nanozyme design, and multimodal integration strategies. It also highlights applications in biomarker detection and discusses current challenges and future perspectives for point-of-care testing.