This study presents a novel hybrid microfluidic device that integrates pinched-flow fractionation (PFF) with an acoustofluidic design for efficient and label-free separation of circulating tumor cells (CTCs) from blood using numerical simulations. In the first stage, a pinched microchannel operating at a total flow rate of 100 μl/min was employed for cell focusing and rough sorting. Parametric studies identified the flow rate ratio and pinched expansion ratio as key parameters, which were determined to be 10 and 25, respectively. As a key feature of the hybrid design, two intermediate outlets couple the high-throughput PFF stage to the low-flow acoustic region by removing excess fluid and supplying the required 15 μl/min inlet flow to the acoustic section, while maintaining high throughput and enhanced separation performance. At this point, red blood cells were removed, while white blood cells and CTCs entered the acoustic stage with an initial separation distance of 90 μm. In the second stage, a tilted angle standing surface acoustic wave with a concave–convex electrode design was applied. Based on the parametric study, the standing surface acoustic wave with 20.275 MHz, tilted angle with 20°, and applied radio frequency signal amplitudes of 16 V were selected as the operation parameters. In standalone acoustic separation, the maximum separation distance between white blood cells and CTCs was 411 μm, whereas the integrated hybrid design enhanced this distance from 90 μm at the acoustic inlet to 628 μm. Overall, the hybrid design combines high-throughput PFF-based prefocusing with precise acoustofluidic separation, achieving nearly 100% separation efficiency in numerical simulations.
Khorshidian et al. (Sun,) studied this question.