A hydrodynamic-based microfluidic chip consisted of two function units that could not only separate tumor cells (TCs) from whole blood but also remove residual blood cells was designed. The separation of TCs was achieved by a straight contraction-expansion array (CEA) microchannel on the front end of the chip. The addition of contractive structure brought a micro-vortex like Dean vortex that promoted cell focusing in the channel, while when cells entered the dilated region, the wall-induced lift force generated by the channel wall gave cells a push away from the wall. As the wall-induced lift force is proportional to the third power of the cell diameter, TCs with larger diameter will have a larger lateral migration under the wall-induced lift force, realizing the separation of TCs from blood sample. Fluorescent particles with diameters of 19.3 μm and 4.5 μm were used to simulate TCs and red blood cells, respectively, to verify the separation capacity of the proposed CEA microchannel for particles with different diameter. And a separation efficiency 98.7% for 19.3 μm particles and a removal rate 96.2% for 4.5 μm particles was observed at sample flow rate of 10 μL min and sheath flow rate of 190 μL min. In addition, a separation efficiency about 96.1% for MCF-7 cells (stained with DiI) and removal rates of 96.2% for red blood cells (RBCs) and 98.7% for white blood cells (WBCs) were also obtained under the same condition. However, on account of the large number of blood cells in the blood, there will be a large number of blood cells remained in the isolated TCs, so a purification unit based on hydrodynamic filtration (HDF) was added after the separation microchannel. The purification channel is a size-dictated cell filter that can remove residual blood cells but retain TCs, thus achieving the purification of TCs. Combined the CEA microchannel and the purifier, the microchip facilitates sorting of MCF-7 cells from whole blood with a separation rate about 95.3% and a removal rate over 99.99% for blood cells at a sample flow rate of 10 μL min, sheath flow rate of 190 μL min and washing flow rate of 63 μL min.

中文翻译：

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基于流体动力学的双功能微流控芯片，用于高通量区分肿瘤细胞

设计了一种由两个功能单元组成的基于流体动力学的微流控芯片，该芯片不仅可以从全血中分离肿瘤细胞（TC），还可以去除残留的血细胞。 TC 的分离是通过芯片前端的直收缩-膨胀阵列 (CEA) 微通道实现的。收缩结构的加入带来了类似迪恩涡流的微涡流，促进细胞在通道内聚焦，而当细胞进入扩张区域时，通道壁产生的壁诱导升力将细胞推离壁。由于壁升力与细胞直径的三次方成正比，直径较大的TC在壁升力作用下会产生较大的侧向迁移，实现TC与血样的分离。分别使用直径为19.3 μm和4.5 μm的荧光颗粒模拟TC和红细胞，以验证所提出的CEA微通道对不同直径颗粒的分离能力。在样品流量为 10 μL·min、鞘流流量为 190 μL·min 时，对 19.3 μm 颗粒的分离效率为 98.7%，对 4.5 μm 颗粒的去除率为 96.2%。此外，在相同条件下，MCF-7细胞（用DiI染色）的分离效率约为96.1%，红细胞（RBC）的去除率为96.2%，白细胞（WBC）的去除率为98.7%。但由于血液中含有大量的血细胞，分离出来的TC中会残留大量的血细胞，因此在分离微通道后增加了基于流体动力过滤（HDF）的净化单元。纯化通道是一个尺寸决定的细胞过滤器，可以去除残留的血细胞但保留TC，从而实现TC的纯化。该微芯片结合CEA微通道和净化器，可实现全血中MCF-7细胞的分选，在样品流速10μL/min、鞘流流速下，血细胞分离率约为95.3%，血细胞去除率超过99.99% 190 μL/分钟，洗涤流速为 63 μL/分钟。