外泌体即时检测技术在肿瘤液体活检中的研究进展OA
Advances in Point-of-Care Testing of Exosomes for Tumor Liquid Biopsy
肿瘤来源外泌体携带母细胞的核酸、蛋白质和脂质等关键信息,能够动态反映肿瘤发生发展及治疗响应,是液体活检的重要标志物.然而,其在体液中丰度低、复杂基质干扰强且分子异质性显著,使床旁快速检测面临富集效率、识别特异性和信号稳定性等多重挑战.本文系统综述肿瘤外泌体即时检测(POCT)技术的研究进展.首先,分析微量样本、复杂基质和非标准操作环境下外泌体 POCT 的核心瓶颈;随后从信号转导机制与平台集成载体两个维度,阐述比色、荧光、表面增强拉曼散射和电化学传感的信号放大原理,以及微流控芯片和纸基分析器件在样本预处理、外泌体富集、反应控制与便携读出中的集成策略,并比较不同技术在检测限、线性范围、检测时间、成本、操作复杂度及适用场景方面的差异.同时,重点讨论多靶点联合检测、逻辑门双重识别及蛋白质-核酸正交验证对提高肿瘤源性外泌体判别特异性的作用.进一步按乳腺癌、肺癌、结直肠癌和胃癌总结临床样本验证进展.最后,分析标准化、芯片量产和前瞻性多中心验证不足等转化障碍,并展望多模态信号融合、人工智能辅助决策、可穿戴与居家检测及单外泌体组学等发展方向,以期为外泌体POCT 的临床转化和肿瘤早筛提供参考.
Tumor-derived exosomes carry nucleic acids,proteins,lipids,and other molecular information inherited from their parental cells,allowing them to dynamically reflected tumor initiation,progression,molecular subtype,and therapeutic response.They were therefore promising biomarkers for noninvasive liquid biopsy.Nevertheless,point-of-care analysis of tumor-derived exosomes remained technically challenging because these vesicles were present at low abundance in body fluids,coexist with abundant proteins,lipoproteins,and cell debris,and exhibit substantial molecular heterogeneity.These features placed stringent requirements on enrichment efficiency,recognition specificity,signal amplification,analytical stability,and operational simplicity.This review summarized recent advances in point-of-care testing(POCT)technologies for tumor exosomes.First,the major analytical bottlenecks imposed by microliter-scale samples,complex biological matrices,and non-standard operating environments were discussed.The available approaches were then organized from two complementary perspectives:signal-transduction mechanisms and device-integration platforms.Colorimetric,fluorescence,surface-enhanced Raman scattering,and electrochemical sensing were reviewed with emphasis on their recognition and amplification principles,whereas microfluidic chips and paper-based analytical devices were discussed as integrated platforms for sample pretreatment,exosome enrichment,reaction control,and portable readout.Their representative performance was further compared in terms of limit of detection,linear range,total assay time,cost,equipment dependence,operational complexity,and intended application.Colorimetric methods were generally suitable for rapid and low-cost screening,whereas fluorescence,electrochemical,and Raman-based approaches provided greater analytical sensitivity and multiplexing capability but often required additional labels or dedicated readers.Microfluidic platforms offered automated fluid handling and high integration,while paper-based devices provide low-cost operation and broad accessibility,particularly in resource-limited settings.Particular attention was paid to multi-target detection,dual-recognition logic gates,spatially encoded assays,and orthogonal protein-nucleic acid validation,which could reduce false-positive results and improve the discrimination of tumor-derived exosomes from vesicles released by normal cells.Clinical validation studies were subsequently reviewed by cancer type,including breast,lung,colorectal,and gastric cancers,highlighting differences in biomarker selection,sample type,sensing strategy,cohort size,and diagnostic performance.Finally,key barriers to clinical translation were discussed,including the lack of standardized isolation and quantification procedures,batch-to-batch variation and mass-production challenges for sensing devices,insufficient prospective multicenter validation,and limited evaluation under real-world clinical conditions.Future directions included multimodal signal fusion,artificial-intelligence-assisted interpretation,wearable and home-based testing,and single-exosome omics.Collectively,these developments might facilitate the transition of exosome POCT from laboratory proof-of-concept studies toward practical tools for cancer screening,molecular stratification,treatment-response assessment,and longitudinal monitoring.
王南;张桂华;朱志
厦门大学 化学化工学院,福建 厦门 361005上海交通大学医学院 分子医学研究院,上海 200127厦门大学 化学化工学院,福建 厦门 361005
化学化工
外泌体即时检测肿瘤液体活检生物传感器微流控芯片
exosomespoint-of-care testing(POCT)tumor liquid biopsybiosensorsmicrofluidic chips
《化学试剂》 2026 (9)
27-41,15
国家自然科学基金项目(22325404)科技部重点研发计划合成生物学重点专项项目(2021YFA0909400).
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