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使用集成微流控装置对全血中的循环肿瘤细胞进行单细胞表型分析。

Single-Cell Phenotypic Profiling of CTCs in Whole Blood Using an Integrated Microfluidic Device.

机构信息

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging, Institute of Molecular and Nano Science , Shandong Normal University , Jinan 250014 , People's Republic of China.

Shandong Provincial Hospital affiliated to Shandong University , Jinan 250021 , People's Republic of China.

出版信息

Anal Chem. 2019 Sep 3;91(17):11078-11084. doi: 10.1021/acs.analchem.9b01647. Epub 2019 Aug 14.

Abstract

Single-cell phenotypic profiling of circulating tumor cells (CTCs) in the blood of cancer patients can reveal vital tumor biology information. Even though various approaches have been provided to enrich and detect CTCs, it remains challenging for consecutive CTC sorting, enumeration, and single-cell characterizations. Here, we report an integrated microfluidic device (IMD) for single-cell phenotypic profiling of CTCs that enables automated CTCs sorting from whole blood following continuous single-cell phenotypic analysis while satisfying the requirements of both high purity (92 ± 3%) of cell sorting and high-throughput processing capacity (5 mL whole blood/3 h). Using this new technique we test the phenotypes of individual CTCs collected from xenograft tumor-bearing mice and colorectal (CRC) patients at different tumor stages. We obtained a correlation between CTC characterization and clinical tumor stage and treatment response. The developed IMD offers a high-throughput, convenient, and rapid strategy to study individual CTCs toward minimally invasive cancer therapy prediction and disease monitoring and has the potential to be translated to clinic for liquid biopsy.

摘要

对癌症患者血液中的循环肿瘤细胞 (CTC) 进行单细胞表型分析可以揭示重要的肿瘤生物学信息。尽管已经提供了各种方法来富集和检测 CTC,但连续的 CTC 分选、计数和单细胞特征分析仍然具有挑战性。在这里,我们报告了一种用于 CTC 单细胞表型分析的集成微流控装置 (IMD),它能够在满足高细胞分选纯度 (92 ± 3%) 和高通量处理能力 (5 mL 全血/3 h) 的要求下,从全血中自动对 CTC 进行分选。使用这项新技术,我们测试了从异种移植肿瘤荷瘤小鼠和结直肠癌 (CRC) 患者不同肿瘤阶段采集的单个 CTC 的表型。我们获得了 CTC 特征与临床肿瘤分期和治疗反应之间的相关性。所开发的 IMD 提供了一种高通量、方便和快速的策略,用于研究单个 CTC,以实现微创癌症治疗预测和疾病监测,并有可能转化为临床液体活检。

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