The utilization of optically-induced-dielectrophoresis (ODEP)-based virtual cell filters in a microfluidic system for continuous isolation and purification of circulating tumour cells (CTCs) based on their size characteristics

Abstract

High purity isolation of circulating tumor cells (CTCs) is important for their subsequent gene-related analysis. Nevertheless, the conventional CTC isolation schemes might not be able to avoid the contamination of leukocytes in a treated sample. To address this issue, we proposed to integrate the technique of optically induced dielectrophoresis (ODEP)-based cell manipulation, and flow velocity control in a microfluidic system for further isolating CTCs after a conventional CTC isolation process. The working principle was based on the cell size difference between the CTCs and leukocytes. In the ODEP microfluidic system, a four-cascade cell isolation using four optical light-based virtual cell filters was designed. Based on this, four different selection conditions were simultaneously implemented for a higher-resolution cell separation, and thus higher-purity cell isolation. In this work, the ODEP microfluidic system was designed and fabricated. Moreover, the optimal ODEP operating conditions such as light bar width (40μm), gap (80μm), and number (4), as well as the sample flow rate (0.4μlmin−1) were experimentally determined. Results revealed the presented method was able to isolate cancer cells with cell purity as high as 94.9±0.3% (cancer cell recovery rate: 54±7%). Overall, this study has presented an ODEP microfluidic system capable of refining CTC purity after a conventional CTC isolation process.