The analysis of circulating tumor cells (CTCs) in blood is a powerful noninvasive alternative to conventional tumor biopsy. Inertial-based separation is a promising high-throughput, marker-free sorting strategy for the enrichment and isolation of CTCs. Here, we present and validate a double spiral microfluidic device that efficiently isolates CTCs with a fine-tunable cut-off value of 9 μm and a separation range of 2 μm. We designed the device based on computer simulations that introduce a novel, customized inertial force term, and provide practical fabrication guidelines. We validated the device using calibration beads, which allowed us to refine the simulations and redesign the device. Then we validated the redesigned device using blood samples and a murine model of metastatic breast cancer. Finally, as a proof of principle, we tested the device using peripheral blood from a patient with hepatocellular carcinoma, isolating more than 17 CTCs/ml, with purity/removal values of 96.03% and 99.99% of white blood cell and red blood cells, respectively. These results confirm highly efficient CTC isolation with a stringent cut-off value and better separation results than the state of the art.

中文翻译：

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用于有效富集血液中循环肿瘤细胞的可调惯性微流体系统的设计和验证

血液中循环肿瘤细胞 (CTC) 的分析是传统肿瘤活检的一种强大的非侵入性替代方法。基于惯性的分离是一种很有前途的高通量、无标记分选策略，用于富集和分离 CTC。在这里，我们展示并验证了一种双螺旋微流体装置，该装置可有效分离 CTC，其可微调的截止值为 9 μm，分离范围为 2 μm。我们基于计算机模拟设计了该设备，该模拟引入了一种新颖的定制惯性力项，并提供了实用的制造指南。我们使用校准珠验证了设备，这使我们能够改进模拟并重新设计设备。然后，我们使用血液样本和转移性乳腺癌小鼠模型验证了重新设计的设备。最后，作为原理证明，我们使用来自一名肝细胞癌患者的外周血对该设备进行了测试，分离出超过 17 个 CTCs/ml，白细胞和红细胞的纯度/去除率分别为 96.03% 和 99.99%。这些结果证实了高效的 CTC 分离，具有严格的截止值和比现有技术更好的分离结果。