Neural Engineering and Nanobiosensors Group, Biomedical Engineering Program, Maroun Semaan Faculty of Engineering and Architecture, American University of Beirut, Beirut 1107 2020, Lebanon.
Department of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon.
Lab Chip. 2024 Sep 10;24(18):4264-4274. doi: 10.1039/d4lc00319e.
The spread of metastatic cancer cells poses a significant challenge in cancer treatment, making innovative approaches for early detection and diagnosis essential. Dielectrophoretic impedance spectroscopy (DEPIS), a powerful tool for cell analysis, combines dielectrophoresis (DEP) and impedance spectroscopy (IS) to separate, sort, cells and analyze their dielectric properties. In this study, we developed and built out-of-plane inkjet-printed castellated arrays to map the dielectric properties of MDA-MB-231 breast cancer cell subtypes across their metastatic potential. This was realized modulating the expression of connexin 43 (Cx43), a marker associated with poor breast cancer prognosis and increased metastasis. We employed DEP-based trapping, followed by EIS measurements on bulk cell population, for rapid capture and differentiation of the cancer cells according to their metastatic state. Our results revealed a significant correlation between the various MDA-MB-231 metastatic subtypes and their respective dielectrophoretic and dielectric properties. Notably, cells with the highest metastatic potential exhibited the highest membrane capacitance 16.88 ± 3.24 mF m, followed by the less metastatic cell subtypes with membrane capacitances below 14.3 ± 2.54 mF m. In addition, highly metastatic cells exhibited lower crossover frequency (25 ± 1 kHz) compared to the less metastatic subtypes (≥27 ± 1 kHz), an important characteristic for cell sorting. Finally, EIS measurements showed distinct double layer capacitance () values at 1 kHz between the metastatic subgroups, confirming unique dielectric and dielectrophoretic properties correlated with the metastatic state of the cell. Our findings underscore the potential of DEPIS as a non-invasive and rapid analytical tool, offering insights into cancer biology and facilitating the development of personalized therapeutic interventions tailored to distinct metastatic stages.
转移性癌细胞的扩散是癌症治疗中的一个重大挑战，因此需要创新方法来进行早期检测和诊断。介电泳阻抗谱（DEPIS）是一种用于细胞分析的强大工具，它结合了介电泳（DEP）和阻抗谱（IS）来分离、分选细胞，并分析它们的介电特性。在这项研究中，我们开发并构建了面外喷墨印刷的 castellated 阵列，以绘制 MDA-MB-231 乳腺癌细胞亚型在其转移潜能范围内的介电特性图谱。这是通过调节连接蛋白 43（Cx43）的表达来实现的，Cx43 是与乳腺癌预后不良和转移增加相关的标志物。我们采用基于 DEP 的捕获，然后对细胞群体进行 EIS 测量，根据其转移状态快速捕获和区分癌细胞。我们的结果表明，各种 MDA-MB-231 转移性亚型及其各自的介电泳和介电特性之间存在显著相关性。值得注意的是，具有最高转移潜能的细胞表现出最高的细胞膜电容 16.88 ± 3.24 mF m，其次是转移能力较低的细胞亚型，其细胞膜电容低于 14.3 ± 2.54 mF m。此外，高转移性细胞的交叉频率（25 ± 1 kHz）低于低转移性亚型（≥27 ± 1 kHz），这是细胞分选的一个重要特征。最后，EIS 测量在 1 kHz 时在转移性亚组之间显示出明显的双层电容（）值，证实了与细胞转移状态相关的独特介电和介电泳特性。我们的研究结果强调了 DEPIS 作为一种非侵入性和快速分析工具的潜力，为癌症生物学提供了新的见解，并促进了针对不同转移阶段的个性化治疗干预措施的发展。
