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基于 SERS 微流控平台的血清细胞外囊泡敏感表型分析用于卵巢癌的早期临床诊断。

Sensitive phenotyping of serum extracellular vesicles on a SERS-microfluidic platform for early-stage clinical diagnosis of ovarian carcinoma.

机构信息

Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, 571199, China; Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, China.

Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, 571199, China; Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, China.

出版信息

Biosens Bioelectron. 2025 Jan 1;267:116724. doi: 10.1016/j.bios.2024.116724. Epub 2024 Sep 7.

DOI:10.1016/j.bios.2024.116724
PMID:39260102
Abstract

Ovarian carcinoma (OvCa) poses a severe threat to women's health due to its high mortality rate and lack of efficient early diagnosis approach. There is evidence to suggest that nanosized small extracellular vesicles (sEVs) which carrying cell-specific components from OvCa can serve as potential diagnostic biomarkers. Herein, we reported a Surface-enhanced Raman Scattering (SERS)-multichannel microchip for sEVs (S-MMEV) assay to investigate the phenotype changes of sEVs. The microchip composed of seven microchannels, which enabled the parallel detection of multiple biomarkers to improve the detection accuracy. Using SERS probes conjugated with antibodies recognizing different biomarkers including ubiquitous EV biomarkers (i.e., tetraspanins; CD9, CD81) and putative OvCa tumor biomarkers (i.e. EpCAM, CD24, CA125, EGFR), we successfully analyzed the phenotypic changes of sEVs and accurately differentiated OvCa patients from healthy controls, even at early stage (I-II), with high sensitivity, high specificity and an area under the curve value of 0.9467. Additionally, the proposed approach exhibited higher sensitivity than conventional methods, demonstrating the efficiency of precise detection from cell culture and clinical samples. Collectively, the developed EV phenotyping approach S-MMEV could serve as a potential tool to achieve the early clinical diagnosis of OvCa for further precise diagnosis and personal treatment monitoring.

摘要

卵巢癌(OvCa)由于其高死亡率和缺乏有效的早期诊断方法,对女性健康构成严重威胁。有证据表明,携带 OvCa 细胞特异性成分的纳米级小细胞外囊泡(sEVs)可以作为潜在的诊断生物标志物。在此,我们报告了一种用于 sEVs(S-MMEV)分析的表面增强拉曼散射(SERS)多通道微芯片,以研究 sEVs 的表型变化。该微芯片由七个微通道组成,可实现多个生物标志物的平行检测,以提高检测准确性。使用与识别不同生物标志物的抗体偶联的 SERS 探针,包括普遍存在的 EV 生物标志物(即四跨膜蛋白;CD9、CD81)和推定的 OvCa 肿瘤生物标志物(即 EpCAM、CD24、CA125、EGFR),我们成功分析了 sEVs 的表型变化,并能够准确地区分 OvCa 患者和健康对照者,甚至在早期(I-II 期)也具有高灵敏度、高特异性和曲线下面积为 0.9467。此外,与传统方法相比,该方法表现出更高的灵敏度,证明了从细胞培养物和临床样本中进行精确检测的效率。总之,所开发的 EV 表型分析方法 S-MMEV 可作为一种潜在的工具,用于实现 OvCa 的早期临床诊断,以进一步进行精确诊断和个性化治疗监测。

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