Sorting of circulating tumor cells based on the microfluidic device of a biomimetic splenic interendothelial slit array

Abstract

In this paper, we focused on a microfluidic sorting method based on bionic splenic sinus microstructures to capture circulating tumor cells (CTCs). A dynamic multiphase fluidic model was developed to explore the effects of different flows and the parameters of the spleen-specific structure of the interendothelial slit (IES) on the cell membrane strain, as represented by the interface area between two phases. The results indicated that parameters of the IES and flow velocity strongly influence cell membrane strain. The biomimetic IES structure has more advantages than do circular pores because the slit structure has a lower flow resistance compared to the circle structure. A microfluidic device based on a biomimetic IES with ultrathin (500\xa0nm thick) silicon nitride filters was designed and fabricated for high-throughput enrichment of high-viability CTCs. The silicon nitride filters had areas as large as 36\xa0mm2 (6\u2009×\u20096\xa0mm) and included nearly 18,000 slit units, which was conducive to obtaining a high-throughput device. Moreover, the effects of different parameters, such as velocity, slit width, dilution ratio and solution volume, on the cell capture efficiency and cell viability were explored. The results show that the microfluidic device based on a biomimetic IES has a high potential for preserving viable cells. This study quantitatively explored the effects of different parameters on cell viability during the CTC physical filtration process. Additionally, this study will be helpful for designing high-throughput CTC enrichment devices that capture high-viability cells.