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基于3D多孔微流控芯片的外泌体SORL1检测平台构建及其在结直肠癌早期诊断中的应用

Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer.

作者信息

Li Peilong, Chen Jiaci, Chen Yuqing, Song Shangling, Huang Xiaowen, Yang Yang, Li Yanru, Tong Yao, Xie Yan, Li Juan, Li Shunxiang, Wang Jiayi, Qian Kun, Wang Chuanxin, Du Lutao

机构信息

Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, 250033, China.

State Key Laboratory of Biobased Material and Green Papermaking, Department of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250300, China.

出版信息

Small. 2023 May;19(20):e2207381. doi: 10.1002/smll.202207381. Epub 2023 Feb 17.

Abstract

Exosomes are promising new biomarkers for colorectal cancer (CRC) diagnosis, due to their rich biological fingerprints and high level of stability. However, the accurate detection of exosomes with specific surface receptors is limited to clinical application. Herein, an exosome enrichment platform on a 3D porous sponge microfluidic chip is constructed and the exosome capture efficiency of this chip is ≈90%. Also, deep mass spectrometry analysis followed by multi-level expression screenings revealed a CRC-specific exosome membrane protein (SORL1). A method of SORL1 detection by specific quantum dot labeling is further designed and the ensemble classification system is established by extracting features from 64-patched fluorescence images. Importantly, the area under the curve (AUC) using this system is 0.99, which is significantly higher (p < 0.001) than that using a conventional biomarker (carcinoembryonic antigen (CEA), AUC of 0.71). The above system showed similar diagnostic performance, dealing with early-stage CRC, young CRC, and CEA-negative CRC patients.

摘要

外泌体因其丰富的生物学特征和高度的稳定性,有望成为结直肠癌(CRC)诊断的新型生物标志物。然而,对具有特定表面受体的外泌体进行准确检测在临床应用中仍受到限制。在此,构建了一种基于三维多孔海绵微流控芯片的外泌体富集平台,该芯片对外泌体的捕获效率约为90%。此外,通过深度质谱分析和多级表达筛选,发现了一种CRC特异性外泌体膜蛋白(SORL1)。进一步设计了一种通过特异性量子点标记检测SORL1的方法,并通过从64个补丁荧光图像中提取特征建立了整体分类系统。重要的是,使用该系统的曲线下面积(AUC)为0.99,显著高于使用传统生物标志物(癌胚抗原(CEA),AUC为0.71)(p < 0.001)。上述系统在处理早期CRC、年轻CRC和CEA阴性CRC患者时表现出相似的诊断性能。

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