Clinically Accurate Diagnosis of Alzheimer's Disease via Single‐Molecule Bioelectronic Label‐Free Profiling of Multiple Blood Extracellular Vesicle Biomarkers

IF 27.4 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Advanced Materials Pub Date : 2025-06-27 DOI:10.1002/adma.202505262

Jintao Zheng, Xiaohong Jiang, Shiyao Bai, Minchao Lai, Jiacheng Yu, Mingxi Chen, Runzhi Zhou, Yue Jia, Haoyang Yan, Zheng Liang, Dian Wang, Chuyan Wu, Shan Liu, Chenzhong Li, Jinguang Yang, Yang Luo, Cheng Jiang, Keying Guo

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引用次数: 0

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no cure, making early diagnosis critical for mitigating its impact. Blood extracellular vesicles (EVs) hold promises as biomarkers for AD diagnosis, but current detection technologies lack the sensitivity and multiplexing capabilities needed for efficient diagnosis. Here, a novel label‐free bioelectronic platform is presented based on an organic electrochemical transistor (OECT) integrated with a microelectrode array (MEA) for ultrasensitive detection of AD biomarkers in blood EVs, including amyloid‐β (Aβ1‐40 and Aβ1‐42), total tau (t‐tau), and phosphorylated tau (p‐tau181). This platform achieves a detection limit as low as the zeptomolar (zM) level, enabling the detection of single‐molecule targets. It provides a comprehensive multiplexed diagnostic model capable of delivering results within 20 min. Notably, the systematic integration of multiple AD biomarkers in blood EVs is demonstrated to significantly enhance diagnostic accuracy. This study presents a novel EVs‐based multiplexed diagnostic model for AD, correctly classifying all clinical samples (n = 40), far exceeding the accuracy of a single biomarker. With its high sensitivity and rapid turnaround, this platform enables reliable AD diagnosis and holds the potential for tracking disease progression, offering a transformative tool to combat the societal burden of AD.

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通过多种血液细胞外囊泡生物标志物的单分子生物电子无标签分析，临床准确诊断阿尔茨海默病

阿尔茨海默病（AD）是一种无法治愈的进行性神经退行性疾病，因此早期诊断对于减轻其影响至关重要。血液细胞外囊泡（EVs）有望成为AD诊断的生物标志物，但目前的检测技术缺乏有效诊断所需的灵敏度和多路复用能力。本文提出了一种基于有机电化学晶体管（OECT）和微电极阵列（MEA）集成的新型无标签生物电子平台，用于超灵敏检测血液EVs中的AD生物标志物，包括淀粉样蛋白β (a β1‐40和a β1‐42)，总tau （t‐tau）和磷酸化tau （p‐tau181）。该平台的检测限低至zeptomolar （zM）水平，能够检测单分子靶标。它提供了一个全面的多路诊断模型，能够在20分钟内提供结果。值得注意的是，血液EVs中多种AD生物标志物的系统集成被证明可以显着提高诊断准确性。本研究提出了一种新的基于ev的AD多路诊断模型，正确分类所有临床样本（n = 40），远远超过单一生物标志物的准确性。凭借其高灵敏度和快速周转，该平台能够实现可靠的阿尔茨海默病诊断，并具有跟踪疾病进展的潜力，为对抗阿尔茨海默病的社会负担提供了一种变革性工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advanced Materials 工程技术-材料科学：综合

CiteScore

43.00

自引率

4.10%

发文量

2182

审稿时长

2 months

期刊介绍： Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.