Extracellular vesicles on demand (EVOD) chip for screening and quantification of cancer-associated extracellular vesicles.

Extracellular vesicles on demand (EVOD) chip for screening and quantification of cancer-associated extracellular vesicles.
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细胞外囊泡随需应变(EVOD)芯片用于癌症相关细胞外囊泡的筛选和定量。

DOI:
10.1016/j.bios.2020.112535
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发表时间:
2020-11-15
影响因子:
12.6
通讯作者:
--
中科院分区:
工程技术1区
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--
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虽然癌症治疗和治疗已经取得了重大进展,但早期疾病检测和诊断对于确保患者的良好结果仍然至关重要。为此,我们提出了一种基于微流体的方法来灵敏地检测一种有趣的癌症生物标志物--细胞外囊泡(EV)。我们的细胞外囊泡按需(EVOD)芯片利用无催化剂的点击化学,快速,特异性地分离感兴趣的EV。这种特异性分离之后,随后释放分离的EV的二硫苏糖醇用于下游功能分析。这种联合分离和释放为筛选和定量感兴趣的EV提供了强大的工具。通过将针对癌症相关表面蛋白的抗体纳入点击化学,我们能够选择性地恢复癌症相关的外泌体,从而对患者疾病有重要的了解。该平台还使用非小细胞肺癌(NSCLC)患者样本进行了测试,其中抗表皮生长因子受体(EGFR)辅助平台能够选择性地从NSCLC患者中分离和释放比健康供体多76%的外泌体。这与先前报告的NSCLC EV中常见的较高EGFR表达相匹配。通过其快速分离动力学和标记靶向的适应性,EVOD设备为临床医生提供了一个高度通用的液体活检平台,用于对抗癌症。
While significant advancements have been made in cancer therapeutics and treatments, early disease detection and diagnosis remains critical to ensuring favorable outcomes for patients. To that end, we propose a microfluidic based approach to the sensitive detection of an intriguing cancer biomarker, extracellular vesicles (EVs). Our extracellular vesicle on demand (EVOD) chip utilizes a catalyst-free click chemistry to rapidly and specifically isolate EVs of interest. This specific isolation is followed by subsequent dithiothreitol release of the isolated EVs for downstream functional analysis. This joint isolation and release provide a powerful tool for the screening and quantification of EVs of interest. By incorporating antibodies against cancer associated surface proteins into the click-chemistry, we were able to selectively recover cancer-associated exosomes, allowing for important insights into patient disease. This platform was also tested using non-small cell lung cancer (NSCLC) patient samples, where anti-epidermal growth factor receptor (EGFR) assisted platform were able to selectively isolate and release 76% more exosomes from NSCLC patients than from healthy donors. This matches the previously reported higher EGFR expression commonly found in NSCLC EVs. Through its rapid isolation kinetics and adaptability in marker targeting, the EVOD device provides a highly versatile liquid biopsy platform for clinicians to use in the fight against cancer.
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