Department of Mechanical Engineering, Sharif University of Technology, Tehran, Iran.
Sci Rep. 2021 Jan 21;11(1):1939. doi: 10.1038/s41598-021-81661-2.
Isolation of rare cancer cells is one of the important and valuable stages of cancer research. Regarding the rarity of cancer cells in blood samples, it is important to invent an efficient separation device for cell enrichment. In this study, two centrifugal microfluidic devices were designed and fabricated for the isolation of rare cancer cells. The first design (passive plan) employs a contraction-expansion array (CEA) microchannel which is connected to a bifurcation region. This device is able to isolate the target cells through inertial effects and bifurcation law. The second design (hybrid plan) also utilizes a CEA microchannel, but instead of using the bifurcation region, it is reinforced by a stack of two permanent magnets to capture the magnetically labeled target cells at the end of the microchannel. These designs were optimized by numerical simulations and tested experimentally for isolation of MCF-7 human breast cancer cells from the population of mouse fibroblast L929 cells. In order to use the hybrid design, magnetite nanoparticles were attached to the MCF-7 cells through specific Ep-CAM antibodies, and two permanent magnets of 0.34 T were utilized at the downstream of the CEA microchannel. These devices were tested at different disk rotational speeds and it was found that the passive design can isolate MCF-7 cells with a recovery rate of 76% for the rotational speed of 2100 rpm while its hybrid counterpart is able to separate the target cells with a recovery rate of 85% for the rotational speed of 1200 rpm. Although the hybrid design of separator has a better separation efficiency and higher purity, the passive one has no need for a time-consuming process of cell labeling, occupies less space on the disk, and does not impose additional costs and complexity.
稀有癌细胞的分离是癌症研究的重要且有价值的阶段之一。由于血液样本中癌细胞的稀有性，发明一种用于细胞富集的高效分离装置非常重要。在这项研究中，设计并制造了两种用于分离稀有癌细胞的离心微流控装置。第一种设计（被动式设计）采用收缩-扩张阵列（CEA）微通道，该微通道连接到一个分叉区域。该装置能够通过惯性效应和分叉定律分离目标细胞。第二种设计（混合式设计）也利用 CEA 微通道，但不是使用分叉区域，而是通过堆叠两个永磁体来增强微通道的末端，以捕获标记有磁性的目标细胞。这些设计通过数值模拟进行了优化，并通过实验测试了从 L929 细胞群体中分离 MCF-7 人乳腺癌细胞的性能。为了使用混合设计，通过特定的 Ep-CAM 抗体将磁铁矿纳米颗粒附着到 MCF-7 细胞上，并在 CEA 微通道的下游使用两个 0.34T 的永磁体。这些装置在不同的磁盘转速下进行了测试，结果发现被动式设计在 2100rpm 的转速下可以分离出 76%的 MCF-7 细胞，而其混合式设计在 1200rpm 的转速下可以分离出 85%的目标细胞。尽管分离装置的混合式设计具有更好的分离效率和更高的纯度，但被动式设计不需要耗时的细胞标记过程，在磁盘上占用的空间更小，并且不会增加额外的成本和复杂性。
