Magnetic sorting of circulating tumor cells based on different-level antibody expression using a divergent serpentine microchannel

Abstract

The privilege of early cancer detection is entangled with many people's lives. Thus, providing an efficient tool to analyze circulating tumor cells (CTCs) would be an immense asset. In this study, a CTC sorting mechanism is introduced by classifying CTCs based on their EpCAM (epithelial cell adhesion molecule) level, a cell surface marker applicable to cancer staging. For this purpose, an integrated microfluidic chip was designed to focus and separate CTCs from blood cells in a divergent serpentine microchannel, and simultaneously, sort CTCs into three categories [low-EpCAM (N1 = 406), medium-EpCAM (N2 = 693), and high-EpCAM (N3 = 1693)] using a magnetic field. The velocity optimizations, using finite element method (FEM), provided a focusing efficiency above ∼95% (for different cell lines) and a CTC separation efficiency above 92%, validated with our experimental results in the passive section. Furthermore, by optimizing the characteristics of the magnet (through several simulations), three optimum designs were achieved, featuring microchannel lengths of 5, 15, and 30 mm in the active section. The innovative approach introduced in this study integrates microfluidic chips, enabling a one-time, high-throughput process with a recovery rate exceeding 99%. This not only reduces costs and runtime but also enhances sorting efficiency for monitoring the stage of cancer progression.