Fully Inter-restricted Assembly of Aggregation-Induced Emission Luminogens and Polymers Enables Ultra-bright Nanoparticles for Sensitive Point-of-Care Diagnosis

Fluorescent lateral flow immunoassay (LFIA) is recognized as a leading quantitative point-of-care (POC) platform for precise clinical diagnostics. However, conventional fluorescent nanoprobes are hampered by low quantum yield (QY), which constrain the sensitivity of fluorescent LFIA. Herein, we employed a butterfly aggregation-induced emission luminogen (AIEgen) and developed the fully inter-restricted assembly with a polyphenyl polymer poly(maleicanhydride-styrene) (PMPS) to create highly fluorescent homogeneous nanoparticles (ho-AIENPs) with QY over 91%. Compared to conventional fluorescent nanoparticles with a core–shell heterostructure (he-AIENPs), ho-AIENPs demonstrate a homogeneous structure with AIEgens uniformly dispersed in the PMPS matrix nanoparticles. The robust and broad intermolecular interaction (e.g., π–π interactions) between PMPS and AIEgens effectively restricts the molecular motion of AIEgens, producing a 30% increase in the QY of ho-AIENPs than he-AIENPs. Ho-AIENPs exhibit a 5-fold and 80-fold improved sensitivity compared to traditional he-AIENP-based fluorescent LFIAs and AuNP-based colorimetric LFIAs. Owing to the excellent optical properties of ho-AIENPs, we developed ho-AIENP-based multiplex LFIAs, which can simultaneously detect lung cancer biomarkers with exceptionally high sensitivity. In contrast to the conventional core–shell assembly and physical encapsulation strategies, the fully inter-restricted assembly strategy is promising, versatile, and efficient in enhancing the polymer matrix-derived fluorescent particles and sensitizing the immunoassays.