3D dynamic magnetic microfluidic chip for efficient plasma extracellular vesicle enrichment and machine learning–based multiparametric diagnosis of hepatocellular carcinoma

作者：Xiaodan Xi, Kezhen Yi, Lili Xu, Danfei Xu, Xin Hu, Menglu Gao, Junfeng Ren, Fei Long, Wei Zhong, Yue Hu, Si Wu, Xin He, Jia He, Wei‐Hua Huang, Yuan Rong, Min Xie, Fubing Wang, Wei Cui · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03839-4 · 被引用次数：2 · 研究领域：Extracellular vesicles in disease、Hepatocellular Carcinoma Treatment and Prognosis、Advanced biosensing and bioanalysis techniques

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, with early diagnosis critical for improving outcomes. Current diagnostic tools, including serum biomarkers and imaging techniques, exhibit limited sensitivity and specificity. Although extracellular vesicles (EVs) have emerged as a promising source of cancer biomarkers, their clinical utility is hampered by inefficient enrichment technologies.To overcome this limitation, a microfluidic platform was developed to enable rapid and efficient EV capture. RESULTS: The 3D DynaMag-EV capture chip was developed, integrating active and passive micromixing strategies for efficient capture of plasma-derived EVs. This platform employs tentacle-like magnetic particles conjugated with aptamers as the capture matrix, in combination with a 3D porous chip structure and an alternating, non-uniform magnetic field, thereby significantly enhancing EVs-capture substrate interactions and effectively addressing the limitations in collision efficiency and mass transfer. The 3D DynaMag-EV capture chip enabled rapid EV enrichment within 20 minutes, achieving high capture efficiency and purity.Transcriptome analysis of plasma EVs enriched by the developed chip identified two HCC-specific long non-coding RNAs (KCNQ1-AS1 and LINC01785) in HCC, liver cirrhosis or hepatitis patients, and healthy controls. A diagnostic model based on these two markers (EVlncRNA score) demonstrated robust performance,...