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

Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer
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DOI:
10.1002/smll.202207381
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发表时间:
2023-02-17
期刊:
影响因子:
13.3
通讯作者:
Du,Lutao
Du,Lutao
中科院分区:
材料科学1区
文献类型:
--
作者:
Li,Peilong;Chen,Jiaci;Du,Lutao

文献摘要

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外泌体具有丰富的生物指纹和高度的稳定性,是一种很有前途的结直肠癌诊断新生物标志物。然而,具有特异性表面受体的外泌体的准确检测仅限于临床应用。在此,构建了一个三维多孔海绵微流控芯片上的外泌体富集平台,该芯片的外泌体捕获效率为90%左右。此外,深度质谱分析后的多水平表达筛选揭示了CRC特异性外泌体膜蛋白(SORL 1)。进一步设计了通过特定量子点标记检测SORL 1的方法,并通过从64个补丁的荧光图像中提取特征来建立总体分类系统。重要的是,使用该系统的曲线下面积(AUC)为0.99,其显著高于(p< 0.001)使用常规生物标志物(癌胚抗原(CEA),AUC为0.71)的曲线下面积。上述系统显示出类似的诊断性能,处理早期CRC、年轻CRC和CEA阴性CRC患者。
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.