School of Engineering and Computer Science, Washington State University, Vancouver, WA.
Electrophoresis. 2022 Apr;43(7-8):879-891. doi: 10.1002/elps.202100187. Epub 2022 Jan 22.
Circulating tumor cells (CTCs) have been proven to have significant prognostic, diagnostic, and clinical values in early-stage cancer detection and treatment. The efficient separation of CTCs from peripheral blood can ensure intact and viable CTCs and can, thus, give proper genetic characterization and drug innovation. In this study, continuous and high-throughput separation of MDA-231 CTCs from overlapping sized white blood cells (WBCs) is achieved by modifying inertial cell focusing with dielectrophoresis (DEP) in a single-stage microfluidic platform by numeric simulation. The DEP is enabled by embedding interdigitated electrodes with alternating field control on a serpentine microchannel to avoid creating two-stage separation. Rather than using the electrokinetic migration of cells which slows down the throughput, the system leverages the inertial microfluidic flow to achieve high-speed continuous separation. The cell migration and cell positioning characteristics are quantified through coupled physics analyses to evaluate the effects of the applied voltages and Reynolds numbers (Re) on the separation performance. The results indicate that the introduction of DEP successfully migrates WBCs away from CTCs and that separation of MDA-231 CTCs from similar sized WBCs at a high Re of 100 can be achieved with a low voltage of magnitude 4 ×10 V/m. Additionally, the viability of MDA-231 CTCs is expected to be sustained after separation due to the short-term DEP exposure. The developed technique could be exploited to design active microchips for high-throughput separation of mixed cell beads despite their significant size overlap, using DEP-modified inertial focusing controlled simply by adjusting the applied external field.
循环肿瘤细胞(CTCs)已被证明在早期癌症检测和治疗中具有重要的预后、诊断和临床价值。从外周血中有效分离 CTCs 可以确保 CTCs 的完整和存活,从而进行适当的遗传特征分析和药物创新。在本研究中,通过数值模拟,在单个微流控平台中用介电泳(DEP)对惯性细胞聚焦进行改进,实现了从重叠尺寸的白细胞(WBC)中连续、高通量分离 MDA-231 CTCs。DEP 通过在蛇形微通道上嵌入具有交变场控制的叉指电极来实现,以避免创建两阶段分离。该系统利用惯性微流来实现高速连续分离,而不是使用减缓通量的细胞电动迁移,而是利用惯性微流来实现高速连续分离。通过耦合物理分析来量化细胞迁移和细胞定位特性,以评估施加电压和雷诺数(Re)对分离性能的影响。结果表明,DEP 的引入成功地将 WBCs 从 CTCs 中迁移出来,并且可以在高 Re(100)下从相似尺寸的 WBCs 中分离出 MDA-231 CTCs,施加的电压幅度为 4×10 V/m。此外,由于 DEP 的短期暴露,MDA-231 CTCs 的活力有望在分离后得到维持。该技术可以通过用 DEP 修饰的惯性聚焦来设计高通量分离混合细胞珠的主动微芯片,尽管它们的尺寸重叠显著,但可以通过简单地调整施加的外部场来控制。