Metal–Organic Framework@Gold Nanoparticles Enables Point-of-Care Diagnostics To Have Comparable Analytical Performance to Chemiluminescent Immunoassays

Lateral flow immunoassay (LFIA) is a vital point-of-care testing (POCT) technique that is widely used for on-site detection and in vitro diagnosis. Many diseases, particularly cardiovascular diseases (CVDs), require the quantitative detection of multiple biomarkers across a broad dynamic range. Recurrent viral infections like COVID-19 elevate CVDs risk, necessitating early warning and prognostic monitoring, especially based on POCT of multiple blood biomarkers of D-dimer, NT-proBNP, and cTnI across a broad range from pg/mL to μg/mL. Traditional LFIAs lack ultrasensitivity and broad-range quantification. We design the surface chemistry-mediated template-free assembly of metal-aggregation-induced emission luminogens (AIEgen) framework@gold nanoparticles (MAF@AuNPs) for developing ultrasensitive and dynamic dual-quantitative LFIA (ddLFIA). The template-free self-assembled MAF@AuNPs have strong fluorescent and plasmonic properties, avoiding complicated synthesis, chemical modifications, and covalent conjugations, thus leading to highly convenient and versatile visual POCT. MAF@AuNPs ddLFIA achieves a normal detection at ng/mL using chromogenic AuNPs and ultrasensitive detection at pg/mL using fluorogenic MAFs, for which the fluorescence signal is 10²–10³ times more sensitive than the color signal. MAFs and AuNPs are functionally complementary to form a dynamic, broad-range quantification system covering over 5 orders of magnitude, at the same time having a naked eye sensitivity near 1 pg/mL. The visual POCT using MAF@AuNPs ddLFIA aligns well with clinical chemiluminescent assays. MAF@AuNPs ddLFIA perfectly matches ultrasensitive and broad-range multiple biomarker detections for clinical CVDs diagnosis.