Analytical Chemistry · Apr 28, 2026

Integrating Acridinium Ester with a Soluble Macromolecular Amplification Carrier for Ultrasensitive Detection of Aβ1-42 in Plasma

By Guo C, Liu M, An Z et al.

The research presents the development of a novel ultrasensitive immunoassay for the detection of amyloid-β 1-42 (Aβ1-42) in plasma, a key biomarker for Alzheimer's disease, through the integration of a soluble signal amplification platform (Ficoll400-SA) with an acridinium ester (AE) direct chemiluminescence system. The synthesis of Ficoll400-SA was optimized to maximize the loading of AE molecules by adjusting cross-linker activation ratios and AE labeling density, achieving an approximately 35-fold enhancement of signal intensity relative to conventional streptavidin-AE conjugates. The immunoassay protocol was further refined to improve sensitivity and specificity, resulting in a limit of detection (LoD) of 0.15 pg·mL⁻¹ and a lower limit of quantitation (LLoQ) of 0.31 pg·mL⁻¹. The assay exhibited excellent specificity, with negligible cross-reactivity (<0.5%) to other amyloid isoforms, high precision indicated by coefficients of variation below 8%, and robust reagent stability under both accelerated and onboard conditions. Analysis of clinical samples demonstrated strong correlation (Spearman's ρ = 0.983) and minimal bias compared to a commercial reference method, confirming the assay's reliability. Collectively, this study successfully expanded the application of the Ficoll400-SA signal amplification carrier from enzymatic chemiluminescence assays to the AE direct chemiluminescence platform. Moreover, these findings validate the Ficoll400-SA platform as a versatile, highly sensitive, and automatable approach for detecting low-abundance biomarkers, with significant potential to advance the early diagnosis of Alzheimer's disease and biomarker research.

doi.org/10.1021/acs.analchem.6c00193PubMed 42047375Biomarkers