Clinically Accurate Diagnosis of Alzheimer's Disease via Single‐Molecule Bioelectronic Label‐Free Profiling of Multiple Blood Extracellular Vesicle Biomarkers
Abstract
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 (Aβ 1‐40 and Aβ 1‐42 ), total tau (t‐tau), and phosphorylated tau (p‐tau 181 ). 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.
Article Details
Authors (18)
Jintao Zheng
Xiaohong Jiang
Shiyao Bai
School of Medicine The Chinese University of Hong Kong (CUHK) Shenzhen 518172 China
Minchao Lai
Department of Neurology First Affiliated Hospital of Shantou University Medical College Shantou China
Jiacheng Yu
Molecular Medicine Program, The Hospital for Sick Children
Mingxi Chen
Runzhi Zhou
Faculty of Biotechnology and Food Engineering Guangdong Technion‐Israel Institute of Technology (GTIIT) Shantou China
Yue Jia
Department of Biotechnology and Food Engineering Guangdong Technion‐Israel Institute of Technology (GTIIT) Shantou 515063 China
Haoyang Yan
Faculty of Biotechnology and Food Engineering Guangdong Technion‐Israel Institute of Technology (GTIIT) Shantou China
Zheng Liang
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering
Dian Wang
Chuyan Wu
Shantou University Medical College (SUMC) Shantou 515041 China
Shan Liu
Chenzhong Li
School of Medicine The Chinese University of Hong Kong (CUHK) Shenzhen 518172 China
Jinguang Yang
Key Laboratory of Tobacco Pest Monitoring Controlling and Integrated Management Tobacco Research Institute of Chinese Academy of Agricultural Sciences Qingdao 266101 China
Yang Luo
Cheng Jiang
School of Electrical and Electronic Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
Keying Guo
Key Lab for Special Functional Materials of Ministry of Education, National & Local Joint Engineering Research Center for High-efficiency Display and Lighting Technology, School of Nano Science and Materials Engineering, Collaborative Innovation Center of Nano Functional Materials and Applications