Design and modeling of tunable microfluidic devices for label-free separation of circulating tumor cells

Abstract

Reliable separation and detection of circulating tumor cells from blood cells are crucial for early cancer diagnosis and prognosis. Many conventional microfluidic platforms take advantage of the size difference between particles for their separation, which renders them impractical for sorting overlapping-sized cells. To address this concern, a hybrid inertial-dielectrophoretic microfluidic chip is proposed in this work for continuous and single-stage separation of lung cancer cell line A549 cells from white blood cells of overlapping size. The working mechanism of the proposed spiral microchannel embedded with planar interdigitated electrodes is validated against the experimental results in the existing literature. A numerical investigation is carried out over a range of flow conditions and electric field intensity to determine the separation efficiency and migration characteristics of the cell mixture. The results demonstrate the unique capability of the proposed microchannel to achieve high-throughput separation of cells (~0.7mL/min) at low applied voltages (~10V) in both vertical and lateral directions. A significant lateral separation distance between the CTCs and the WBCs has been achieved, which allows for high-resolution and effective separation of cells. The separation resolution can be controlled by adjusting the strength of the applied electric field. Furthermore, the results demonstrate that the lateral separation distance is maximum at a voltage termed as the critical voltage, which increases with the increase in the flow rate. Moreover, several electrode configurations have been studied and it was found that better separation can be achieved with higher number of electrodes and also positioning the electrodes towards the beginning of the channel makes them more effective for cell separation. Additionally, the robustness of the system was studied by using a mixture of WBCs containing four main subtypes having different sizes and dielectric properties. The electrode embedded spiral microchannel was successful in separating the CTCs from the mixture of WBCs. The proposed microchannel and the developed technique can provide valuable insight into the development of a tunable and robust point-of-care device for effective and high-throughput separation of cancer cells from the WBCs

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