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Dynamic Halbach array magnet integrated microfluidic system for the continuous-flow separation of rare tumor cells

机译：动态Halbach阵列磁体集成微流体系统，用于稀有肿瘤细胞的连续流动分离

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Circulating tumor cells (CTCs), the most representative rare cells in peripheral blood, have received great attention due to their clinical utility in liquid biopsy. The downstream analysis of intact CTCs isolated from peripheral blood provides important clinical information for personalized medicine. However, current CTC isolation and detection methods have been challenged by their extreme rarity and heterogeneity. In this study, we developed a novel microfluidic system with a continuously moving Halbach array magnet (dHAMI microfluidic system) for negative isolation CTCs from whole blood, which aimed to capture non-target white blood cells (WBCs) and elute target CTCs. The dynamic and continuous movement of the Halbach array magnet generated a continuous magnetic force acting on the magnetic bead-labelled WBCs in the continuous-flow fluid to negatively exclude the WBCs from the CTCs. Furthermore, the continuously moving magnetic field effectively eliminated the effect of magnetic bead aggregation on the fluid flow to realize the continuous-flow separation of the CTCs without a sample loading volume limitation. The experimental procedure for CTC negative isolation using the dHAMI microfluidic system could be completed within 40 min. Under the optimized experimental conditions of the dHAMI microfluidic system, including the flow rate and concentration of the immunomagnetic bead, the average CTC capture rate over a range of spiked cell numbers (50-1000 cancer cells per mL) was up to 91.6% at a flow rate of 100 mu L min(-1). Finally, the CTCs were successfully detected in 10 of 10 (100%) blood samples from patients with cancer. Therefore, the dHAMI microfluidic system could effectively isolate intact and heterogeneous CTCs for downstream cellular and molecular analyses, and this robust microfluidic platform with an excellent magnetic manipulation performance also has great application potential for the separation of other rare cells.
机译：循环肿瘤细胞（CTC），最有代表性的罕见外周血中，也由于其临床应用在液体活检受到了极大的关注。从外周血中分离的完整的CTC的下游分析提供了个性化医学重要的临床信息。然而，目前的CTC的分离和检测方法已经被他们的极端稀有性和异质性的挑战。在这项研究中，我们开发了一种新的微流体系统具有用于从全血中负隔离的CTC，其目的是捕获的非靶的白血细胞（白细胞）和洗脱目标的CTC连续移动的Halbach阵列磁体（dHAMI微流体系统）。产生作用于磁珠标记的白细胞在连续磁力Halbach阵列磁体的连续流动流体的动态和连续的运动从所述的CTC的WBC的负排除。此外，连续移动的磁场有效地消除在流体流动磁珠聚集的效果，实现CTC的连续流动分离而不装载样品的体积的限制。使用dHAMI微流体系统CTC负隔离的实验程序，可以在40分钟内完成。下dHAMI微流体系统的最佳工作条件下，包括流量和免疫磁珠的浓度，在一定范围的加标细胞数的平均值CTC捕获率（每毫升50-1000癌细胞）高达91.6％以流的加入100μl分钟（-1）速率。最后，在10（100％）的血液样品10被成功地检测到来自癌症患者的CTC。因此，dHAMI微流体系统能有效地隔离完整和异构的CTC用于下游细胞和分子分析，并具有优异的磁操控性能这健壮微流体平台还具有用于其它稀有细胞的分离极大的应用潜力。

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    《RSC Advances》 |2019年第66期|共9页
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