Investigation on a cascaded inertial and acoustic microfluidic device for sheathless and label-free separation of circulating tumor cells

Abstract

High-precision and high-purity acquisition of tumor cells from whole blood is vital for early disease detection and diagnosis. Here, we investigated a cascaded inertial and acoustic microfluidic device for sheathless and label-free separation of circulating tumor cells (CTCs) from the blood through numerical methods. We introduced a spiral microfluidics channel in the first stage (1st) for cell focusing and rough sorting to improve chip integration and reduce the dependence on sheath flow and extra syringe pumps. In the 1st, we simulated the spiral microfluidic with a rectangular cross section to determine the key parameters affecting the migration kinetics of blood cells and tumor cells. Under the influence of Dean drag force and inertial lift force, blood cells migrate toward the inner side of the channel, while CTCs flow out close to the outer side. A flow rate of 400 μl/min was optimized for the operating flow rate. To improve and further enhance the 1st sorting efficiency and purity, we introduced tilted angle standing surface acoustic wave (SSAW) in the second stage (2st). Based on the parametric study, the SSAW with 33.3 MHz, tilted angle with 5°, and acoustic pressure amplitude with 0.7 MPa was selected as the operating parameter. The product of the 1st is used as input for the 2st acoustofluidic unit, enabling a more accurate separation process to obtain CTCs. The simulation results show that the inertial microfluidic units arranged in the first stage help to improve throughput and assist in 2st acoustofluidic separation, and the cascaded chip has accomplished a separation performance of nearly 100% in terms of purity and efficiency.