High-Throughput Microfluidic Labyrinth for the Label-free Isolation of Circulating Tumor Cells

High-Throughput Microfluidic Labyrinth for the Label-free Isolation of Circulating Tumor Cells
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DOI:
10.1016/j.cels.2017.08.012
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发表时间:
2017-09-27
期刊:
影响因子:
9.3
通讯作者:
Nagrath, Sunitha
Nagrath, Sunitha
中科院分区:
生物学1区
文献类型:
--
作者:
Lin, Eric;Rivera-Baez, Lianette;Nagrath, Sunitha

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我们提出了"Labelanth",一种无标记的微流体装置,用于分离循环肿瘤细胞(CTC),使用长环和尖角的组合以2.5 mL/min的高通量聚焦CTC和白色血细胞(WBC)。Labelanth的高产率(> 90%)和纯度(600 WBC/mL)使我们能够分析CTC中的基因表达。作为原理的证明,我们使用先前建立的癌症干细胞基因特征来分析从乳腺癌患者血液中分离的单细胞。我们观察到CTC的异质亚群表达干细胞、上皮细胞、间充质细胞和上皮与间充质之间的细胞过渡的基因。实验室提供了一个不依赖细胞表面标记的单细胞分离平台,用于研究异质性CTC亚群。
We present "Labyrinth,'' a label-free microfluidic device to isolate circulating tumor cells (CTCs) using the combination of long loops and sharp corners to focus both CTCs and white blood cells (WBCs) at a high throughput of 2.5 mL/min. The high yield (>90%) and purity (600 WBCs/mL) of Labyrinth enabled us to profile gene expression in CTCs. As proof of principle, we used previously established cancer stem cell gene signatures to profile single cells isolated from the blood of breast cancer patients. We observed heterogeneous subpopulations of CTCs expressing genes for stem cells, epithelial cells, mesenchymal cells, and cells transitioning between epithelial and mesenchymal. Labyrinth offers a cell-surface marker-independent single-cell isolation platform to study heterogeneous CTC subpopulations.