Department of Biomedical Engineering, University of California, Irvine, CA, USA.
School of Engineering and Computer Science, Washington State University, Vancouver, WA, USA.
Electrophoresis. 2019 May;40(10):1486-1493. doi: 10.1002/elps.201800459. Epub 2019 Feb 25.
Detection and analysis of circulating tumor cells (CTCs) have emerged as a promising way to diagnose cancer, study its cellular mechanism, and test or develop potential treatments. However, the rarity of CTCs among peripheral blood cells is a big challenge toward CTC detection. In addition, in cases where there is similar size range between certain types of CTCs (e.g. breast cancer cells) and white blood cells (WBCs), high-resolution techniques are needed. In the present work, we propose a deterministic dielectrophoresis (DEP) method that combines the concept of deterministic lateral displacement (DLD) and insulator-based dielectrophoresis (iDEP) techniques that rely on physical markers such as size and dielectric properties to differentiate different type of cells. The proposed deterministic DEP technology takes advantage of frequency-controlled AC electric field for continuous separation of CTCs from peripheral blood cells. Utilizing numerical modeling, different aspects of coupled DLD-DEP design such as the required applied voltages, velocities, and geometrical parameters of DLD arrays of microposts are investigated. Regarding the inevitable difference and uncertainty ranges for the reported crossover frequencies of cells, a comprehensive analysis is conducted on applied electric field frequency as design's determinant factor. Deterministic DEP design provides continuous sorting of CTCs from WBCs even with similar size and has the future potential for high throughput and efficiency.
循环肿瘤细胞（CTC）的检测和分析已经成为诊断癌症、研究其细胞机制以及测试或开发潜在治疗方法的一种有前途的方法。然而，外周血细胞中 CTC 的稀有性是 CTC 检测的一大挑战。此外，在某些类型的 CTC（例如乳腺癌细胞）和白细胞（WBC）之间存在相似的大小范围的情况下，需要使用高分辨率技术。在本工作中，我们提出了一种确定性介电泳（DEP）方法，该方法结合了确定性横向位移（DLD）和基于绝缘体的介电泳（iDEP）技术的概念，这些技术依赖于大小和介电特性等物理标记来区分不同类型的细胞。所提出的确定性 DEP 技术利用频率控制的交流电场从外周血细胞中连续分离 CTC。利用数值模拟，研究了耦合 DLD-DEP 设计的不同方面，例如微柱 DLD 阵列所需的应用电压、速度和几何参数。关于报道的细胞交叉频率的不可避免的差异和不确定性范围，对作为设计决定因素的应用电场频率进行了全面分析。确定性 DEP 设计即使在细胞大小相似的情况下也能连续地从 WBC 中分拣 CTC，并且具有高通量和高效率的未来潜力。
