A microfluidic device for label-free separation sensitivity enhancement of circulating tumor cells of various and similar size

Due to the heterogeneity in the size of circulating tumor cells (CTCs), label-free, high-throughput, and efficient separation of CTCs for post-processing analysis is challenging. Recent advances in hybrid microfluidics have demonstrated enormous potential for the separation of complex samples. This paper presents a hybrid microfluidic platform for label-free cell separation that utilizes a cascade deterministic lateral displacement (DLD) array in conjunction with a traveling wave dielectrophoresis (twDEP) system. CTC clusters and red blood cells are separated from the blood sample in the cascade DLD unit. Other white blood cells (WBCs) and CTCs are classified according to their diameters, ranging from 10 to 15 µm, 15 to 20 µm, and 20 to 25 µm. Each category is connected via an outlet to a twDEP unit to separate CTCs from WBCs (even the same size cells). Our proposed structure outperforms conventional designs. Among them are the uniform pressure distribution at the DLD unit's outlets and the cell viability in the twDEP unit. The effect of flow rate and Reynolds number on the separation dynamics of a cascade DLD unit is investigated in this study, as is surveyed the effect of flow rate and variation in the applied voltage to the array of electrodes on the recovery rate of the twDEP units. According to numerical simulations, a recovery rate of nearly 93% for MDA-MB-231 cells spiked into the blood sample is achievable, which is a high recovery rate for systems that can separate cells of the same and different sizes.