A Two-Stage Separation of Circulating Tumor Cells Based on Deterministic Lateral Displacement and Dielectrophoresis Techniques

Circulating tumor cells (CTCs) are cancer cells that fall off from cancer lesions and enter the blood of human extracorporeal circulation. They are the early basis of judging cancer metastasis. However, CTCs are extremely rare, there is a great challenge to create an effective platform to isolate these cells. Herein, a two-stage CTCs separation method that combines deterministic lateral displacement (DLD) and dielectrophoresis (DEP) technology based on microfluidic chips was proposed. In order to verify the effectiveness of the proposed method, the human non-small cell lung cancer cells (H322) were spiked into diluted human blood as the samples. Firstly, a designed DLD chip was used, and the overwhelming majority of RBCs and the platelets were removed based on size. However, due to the size overlapping, the separation of WBCs and H322 cells cannot be achieved by DLD technology. In the second stage, a novel DEP chip was used to separate the mixed cells (H322 cells, WBCs and few residual RBCs) according to their difference dielectric properties. The experimental results show that after the two-stage separation, H322 cells with high purity can be obtained. The separation efficiency of H322 cells was 91%, and the purity was 80.7%, and maintains its activity. In addition, the DEP response of H322 cells under various frequencies was investigated. Those findings will provide a useful reference to the separation and enrichment of CTCs in peripheral blood.