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Point-of-Need Test of Cryptococcus Utilizing Aggregation-induced Emission-based Lateral Flow Immunoassay
Simeng Zhang1,2, Zixuan Wang1,2, Hao Liu1,2
1Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China.
Abstract:
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.
Insights
A new diagnostic test combines aggregation-induced emission (AIE) materials with lateral flow immunochromatography (LFIA) for rapid Cryptococcus detection. This sensitive assay improves early diagnosis of fungal infections at the point-of-need.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Infectious Diseases
Background:
- Cryptococcus is a WHO-priority fungal pathogen causing severe infections.
- Current detection methods for cryptococcosis lack sensitivity, especially in resource-limited settings.
- Lateral flow immunochromatography (LFIA) offers rapid testing but often insufficient sensitivity for early detection.
Purpose of the Study:
- To develop a novel, highly sensitive rapid detection platform for Cryptococcus antigen.
- To integrate aggregation-induced emission (AIE) materials with LFIA for enhanced diagnostic performance.
- To address the limitations of existing point-of-need (PoN) diagnostic tools for fungal infections.
Main Methods:
- Synthesized TCBPE-PS-COOH composite by encapsulating AIE material (TCBPE) into carboxyl-modified polystyrene microspheres (PS-COOH).
- Developed an AIE-integrated LFIA assay targeting glucuronoxylomannan (GXM), a Cryptococcus biomarker.
- Validated the assay using clinical serum samples and non-Cryptococcus pathogens.
Main Results:
- Achieved a detection sensitivity of 12.3 ng/mL for GXM.
- The AIE-LFIA assay successfully detected Cryptococcus antigen in clinical samples with 100% sensitivity.
- Demonstrated 100% specificity against non-Cryptococcus pathogens and provided results within 12 minutes.
Conclusions:
- The AIE-integrated LFIA platform offers a sensitive, accurate, and user-friendly solution for Cryptococcus detection.
- This approach advances the application of AIE materials in point-of-need fungal diagnostics.
- Provides a strategic framework for developing improved diagnostic tools for infectious diseases.
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