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.