化学
核酸酶
细胞外
生物标志物
膜
生物标志物发现
脂质双层
核糖核酸
膜蛋白
脂筏
小泡
计算生物学
生物物理学
细胞生物学
DNA
生物化学
蛋白质组学
基因
生物
作者
Ping Li,Jie Wang,Mengqiu Gao,Jue Wang,Yi Ma,Yueqing Gu
标识
DOI:10.1021/acs.analchem.1c01712
摘要
Extracellular vesicles (EVs) have recently emerged as a promising tumor biomarker, and EV phenotyping offers many benefits for cancer diagnosis. However, the practicality of EV assays remains a challenge due to macromolecule disturbances, biomarker heterogeneities, and EV abundance limitations. Here, we demonstrate a membrane-based biosensor for precise and sensitive EV identification. The sensor synergistically integrates EV capture and detection by virtue of EV membrane features (membrane protein and lipid bilayer), comprising antibody-conjugated magnetic beads (AbMBs) and duplex-specific nuclease (DSN)-mediated amplification cycles. Bivalent cholesterol (biChol)-modified RNA–DNA duplexes are designed to insert into the EV membrane, transforming EV signals into RNA signals and initiating the signal amplification. The membrane-based signal production pattern eliminates protein interference. By employing four antibodies specific to PCa-related membrane proteins, the AbMB–biChol platform enables the successful differentiation and monitoring of PCa-related EVs and distinguishes PCa patients from healthy donors with improved efficacy, exhibiting superior efficiency over the analyses based on clinically used biomarker CA19-9 and PCa-related proteins. As such, the developed system has great potential for clinical PCa diagnosis.
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