Optically-induced-dielectrophoresis (ODEP)-based cell manipulation in a microfluidic system for high-purity isolation of integral circulating tumor cell (CTC) clusters based on their size characteristics

Circulating tumor cell (CTC) clusters play a more critical role in cancer metastasis than single CTCs. The study of CTC clusters might therefore provide more biologically meaningful information for a clear understanding of cancer metastasis. To achieve this goal, the isolation of high-purity, and integral CTC clusters from the blood samples of cancer patients is required. We herein propose to integrate optically-induced-dielectrophoresis (ODEP)-based cell manipulation with a microfluidic system for isolating cancer cell clusters based on their size characteristics. In this work, a two-step ODEP-based cell manipulation was designed. A dynamic square light image array was designed for the preliminary isolation of cancer cell clusters, followed by the utilization of another ODEP-based cell manipulation to refine the purity of the cancer cell clusters harvested in the first step. In this study, the optimal ODEP operating conditions for cell isolation process were experimentally determined. Moreover, the performance of cell isolation was experimentally evaluated for the isolation of CTC clusters with a cell purity and recovery rate of 91.5 ± 5.6%, and 70.5 ± 5.2%, respectively, without compromising the integrity of cancer cell clusters. Overall, this study presents a method and device capable of isolating high-purity and integral cancer cell clusters.