Point-of-Need Test of <i>Cryptococcus</i> Utilizing Aggregation-induced Emission-based Lateral Flow Immunoassay

Cryptococcus is a top-priority fungal pathogen designated by the World Health Organization. It induces pulmonary cryptococcosis and cryptococcal meningitis that are often misdiagnosed or underdiagnosed, owing to inherent limitations of existing detection methodologies, especially in resource-constrained point-of-need (PoN) settings. Although lateral flow immunochromatography (LFIA) is clinically recommended for its rapidity, it frequently lacks adequate sensitivity for the detection of early-stage infections, restricting its utility in PoN settings. Herein, we integrate the aggregation-induced emission (AIE) material TCBPE with LFIA to establish a novel rapid detection platform targeting glucuronoxylomannan (GXM). The TCBPE-PS-COOH (abbreviated as TCBPE-PS) composite was synthesized via swelling-mediated encapsulation of AIE material into carboxyl-modified polystyrene microspheres (PS-COOH), which enhanced the signal stability and fluorescence intensity. The developed AIE-integrated LFIA assay achieved a detection sensitivity of 12.3 ng/mL for GXM, and successfully detected Cryptococcus antigen in clinical serum samples with a DR value (T/C ratio) significantly higher than that of healthy controls. It delivers results within 12 min and exhibits 100% specificity against non- Cryptococcus pathogens, and the sensitivity for clinical samples is 100%. These findings advance the application of AIE materials in fungal point-of-need testing. Moreover, it provides a strategy for developing sensitive, accurate, and user-friendly diagnostic tools with quantified performance.