Hybrid Separation of Circulating Tumor Cells in Zigzag and Contraction-Expansion  Microfluidic Channels

Md Sadiqul Islam

doi:10.7273/000005011

Circulating tumor cells (CTCs) are cells that originate from a primary tumor cell and spread into the human body through the bloodstream. CTCs are known to be the primary indicator for early-stage cancer detection, monitoring, and treatment monitoring. Thus, the separation of CTCs is pivotal for cancer diagnosis and prognosis. CTCs can also play a vital role in revealing the mechanism of cancer metastasis. However, CTC separation from blood cells is a challenging task since the number of CTCs found in the blood is extremely low. Therefore, developing an effective, robust, and efficient CTC sorting platform is necessary to isolate CTCs with high purity and throughput. Conventional cell separation methods separate CTCs based on the size difference among the cells which makes those devices vulnerable when the size of CTCs overlap with other cells. To address this issue, we develop a hybrid method for the separation of CTCs from white blood cells (WBCs) coupling Dielectrophoresis (DEP) with inertial microfluidics. The proposed method utilizes the dielectric properties of cells in addition to the cell size. At first, a zigzag microfluidic channel is employed to separate MDA-231 CTC from WBCs which have significant size overlap with the CTCs. The proposed zigzag-shaped channel is coupled with both inertial microfluidics and DEP to isolate MDA-231 CTCs vertically from similar-sized WBCs. Interdigitated planner electrodes are attached to the bottom side of the channel and the proposed technique can achieve high throughput with a Reynolds number of 125. We have also investigated the effect of Reynolds number, voltage, and electrode configuration for enhancing separation efficiency. In the latter work, we propose a contraction-expansion channel with the combination of DEP and inertial forces to separate A549 CTCs from both similar-sized and different-sized WBCs. To get a horizontal DEP force, interdigitated electrodes are attached to the side wall of the channel. The proposed channel can separate CTCs laterally from any sized WBCs with a high separation distance. Moreover, we also analyze the effect of the number of contraction-expansion sections, voltage, and flow rate on cell migration characteristics. The proposed technique can be used for other cell beads by modifying the electric field frequency without changing the channel design.

Hybrid Separation of Circulating Tumor Cells in Zigzag and Contraction-Expansion Microfluidic Channels

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