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用于先进生物医学应用的细胞外囊泡的微流控辅助分析

Microfluidic-assisted analysis of extracellular vesicles for advanced biomedical applications.

作者信息

Li Dezhong, Zhao Yueyue, Nie Zhun, Tang Jingshi, Wang Rui, Lu Jiaxiang, Xing Yanlong, Yu Fabiao

机构信息

Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, School of Pharmacy, The Second Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China.

Engineering Research Centre for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China.

出版信息

Chem Commun (Camb). 2025 Aug 21. doi: 10.1039/d5cc02460a.

DOI:10.1039/d5cc02460a
PMID:40838375
Abstract

Extracellular vesicles are lipid bilayer-enclosed nanoparticles that play a crucial role in intercellular communication by transporting bioactive molecules across cells, tissues, and even organisms. Although certain aspects of EV biogenesis, function, and metabolic pathways are yet to be fully elucidated, their distinctive features such as cargo protection, structural stability, and the capacity to cross biological barriers render them highly promising for medical applications, especially as novel biomarkers for disease diagnosis. However, the ultrasmall size and complex surface properties pose substantial challenges to their analysis. Microfluidic technology has emerged as a powerful tool for EV isolation and analysis. It offers remarkable advantages, including high throughput, efficiency, and minimal sample consumption, providing innovative solutions for isolating and analyzing EVs with unparalleled precision. Moreover, the integration of artificial intelligence and advanced digital analytics with microfluidic platforms has opened new avenues for enhanced data processing and diagnostic accuracy. In this review, we comprehensively summarize recent advances in EV research, beginning with an in-depth analysis of EVs' biogenesis mechanisms and the formation of disease-specific biomarkers. Then EV-mediated pathological processes with diagnostic significance are discussed, followed by a comprehensive evaluation of microfluidic-based approaches for isolation, purification, and single-vesicle analysis of EVs. The clinical diagnostic potential of EVs is assessed across major disease categories including cancers, cardiovascular disorders, neurological conditions, infectious diseases, and autoimmune pathologies, highlighting their emerging role as next-generation biomarkers. Finally, the current advances in EV-based diagnostics are discussed, along with the future perspectives on microfluidic-based EV analysis towards various biomedical applications and clinical translation.

摘要

细胞外囊泡是由脂质双分子层包裹的纳米颗粒,通过在细胞、组织甚至生物体之间运输生物活性分子,在细胞间通讯中发挥关键作用。尽管细胞外囊泡的生物发生、功能和代谢途径的某些方面尚未完全阐明,但其独特的特征,如货物保护、结构稳定性以及跨越生物屏障的能力,使其在医学应用中极具前景,尤其是作为疾病诊断的新型生物标志物。然而,其超小尺寸和复杂的表面性质给分析带来了巨大挑战。微流控技术已成为用于细胞外囊泡分离和分析的强大工具。它具有显著优势,包括高通量、高效率和最小化样品消耗,为以无与伦比的精度分离和分析细胞外囊泡提供了创新解决方案。此外,人工智能和先进数字分析与微流控平台的整合为增强数据处理和诊断准确性开辟了新途径。在本综述中,我们全面总结了细胞外囊泡研究的最新进展,首先深入分析细胞外囊泡的生物发生机制以及疾病特异性生物标志物的形成。然后讨论具有诊断意义的细胞外囊泡介导的病理过程,接着全面评估基于微流控的细胞外囊泡分离、纯化和单囊泡分析方法。在包括癌症、心血管疾病、神经疾病、传染病和自身免疫性疾病在内的主要疾病类别中评估了细胞外囊泡的临床诊断潜力,突出了它们作为下一代生物标志物的新兴作用。最后,讨论了基于细胞外囊泡的诊断的当前进展,以及基于微流控的细胞外囊泡分析在各种生物医学应用和临床转化方面的未来前景。

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