A microfluidic chip with single-sided herringbone microstructure has been developed to isolate circulating tumor cells (CTCs) from blood samples of cancer patients. Here, we describe a new double-sided herringbone chip in which staggered herringbone micromixers are placed on both top and bottom surfaces of microchannels. The double-sided herringbone structure enables a high CTC capture efficiency of whole blood samples without depletion of red blood cells because of the effects of leukocyte margination and plasma skimming. However, compared with the traditional single-sided herringbone chip, the double-sided herringbone chip has more complicated geometrical design, leading to a difficulty in experimental optimization of geometrical parameters. In this study, we developed an analytical model to geometrically optimize the herringbone chip by investigating the interactions between cells and antibody-immobilized device surfaces for enhancing CTC capture efficiency. On-chip cell capture experiments for validating modeling results were performed by spiking cultured EpCAM-positive tumor cells into blood samples from healthy donors. Based on the geometrical parameters optimized from the single-sided herringbone chip, the geometrically optimized double-sided herringbone chip enables a capture efficiency of 94 ± 4% of rare tumor cells directly from whole blood.

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具有双面人字形微结构的微流控芯片，用于增强对稀有肿瘤细胞的捕获

已开发出具有单侧人字形微结构的微流控芯片，以从癌症患者的血液样本中分离循环肿瘤细胞（CTC）。在这里，我们描述了一种新的双面人字形芯片，其中交错的人字形微混合器放置在微通道的顶表面和底表面上。由于白血球边缘化和血浆撇除的影响，双面人字形结构可实现全血样本的高CTC捕获效率，而不会耗尽红血球。但是，与传统的单面人字形芯片相比，双面人字形芯片的几何设计更为复杂，导致几何参数的实验优化困难。在这项研究中，我们通过研究细胞与抗体固定的设备表面之间的相互作用来提高CTC捕获效率，开发了一种分析模型以几何优化人字形芯片。通过将培养的EpCAM阳性肿瘤细胞掺入健康供体的血液样本中，进行芯片上细胞捕获实验以验证建模结果。基于从单面人字形芯片优化的几何参数，经几何优化的双面人字形芯片可直接从全血中捕获94±4％的稀有肿瘤细胞。通过将培养的EpCAM阳性肿瘤细胞掺入健康供体的血液样本中，进行芯片上细胞捕获实验以验证建模结果。基于从单面人字形芯片优化的几何参数，经几何优化的双面人字形芯片可直接从全血中捕获94±4％的稀有肿瘤细胞。通过将培养的EpCAM阳性肿瘤细胞掺入健康供体的血液样本中，进行芯片上细胞捕获实验以验证建模结果。基于从单面人字形芯片优化的几何参数，经几何优化的双面人字形芯片可直接从全血中捕获94±4％的稀有肿瘤细胞。