State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering , Shanghai Jiao Tong University , Shanghai 200030 , China.
Anal Chem. 2018 Apr 3;90(7):4397-4405. doi: 10.1021/acs.analchem.7b04210. Epub 2018 Mar 20.
Circulating tumor cells (CTCs) are rare cells that detach from a primary or metastasis tumor and flow into the bloodstream. Intact and viable tumor cells are needed for genetic characterization of CTCs, new drug development, and other research. Although separation of CTCs using spiral channel with two outlets has been reported, few literature demonstrated simultaneous isolation of different types of CTCs from human blood using cascaded inertial focusing microfluidic channel. Herein, we introduce a cascaded microfluidic device consisting of two spiral channels and one zigzag channel designed with different fluid fields, including lift force, Dean drag force, and centrifugal force. Both red blood cells (RBCs)-lysed human blood spiked with CTCs and 1:50 diluted human whole blood spiked with CTCs were tested on the presented chip. This chip successfully separated RBCs, white blood cells (WBCs), and two different types of tumor cells (human lung cancer cells (A549) and human breast cancer cells (MCF-7)) simultaneously based on their physical properties. A total of 80.75% of A549 and 73.75% of MCF-7 were faithfully separated from human whole blood. Furthermore, CTCs gathered from outlets could propagate and remained intact. The cell viability of A549 and MCF-7 were 95% and 98%, respectively. The entire separating process for CTCs from blood cells could be finished within 20 min. The cascaded microfluidic device introduced in this study serves as a novel platform for simultaneous isolation of multiple types of CTCs from patient blood.
循环肿瘤细胞 (CTC) 是从原发性或转移性肿瘤上脱落并进入血流的稀有细胞。为了对 CTC 进行基因特征分析、开发新药以及进行其他研究，需要获得完整且有活力的肿瘤细胞。尽管已经有报道使用带有两个出口的螺旋通道来分离 CTC，但很少有文献证明使用级联惯性聚焦微流控通道从人血中同时分离不同类型的 CTC。在这里，我们介绍了一种由两个螺旋通道和一个之字形通道组成的级联微流控装置，该装置设计了不同的流场，包括升力、迪恩拉力和离心力。我们在该芯片上测试了经 RBC 裂解的含 CTC 的人血以及经 1:50 稀释的含 CTC 的人全血。该芯片能够根据其物理特性成功地同时分离 RBC、白细胞 (WBC) 和两种不同类型的肿瘤细胞 (人肺癌细胞 (A549) 和人乳腺癌细胞 (MCF-7))。共有 80.75%的 A549 和 73.75%的 MCF-7 从人全血中被准确地分离出来。此外，从出口收集的 CTC 可以增殖且保持完整。A549 和 MCF-7 的细胞活力分别为 95%和 98%。从血细胞中分离 CTC 的整个过程可以在 20 分钟内完成。本研究中引入的级联微流控装置为从患者血液中同时分离多种类型的 CTC 提供了一个新的平台。
