Continuous separation of breast cancer cells from blood samples using multi-orifice flow fractionation (MOFF) and dielectrophoresis (DEP)

TLDR

Circulating tumor cells are strongly linked to cancer invasiveness, making their isolation and quantification critical for prognosis and drug‑response monitoring. The study develops a microfluidic device that separates circulating tumor cells from blood cells by exploiting their physical properties. The device combines high‑flow multi‑orifice flow fractionation to filter blood cells with dielectrophoresis for precise post‑processing, enabling high‑speed, label‑free continuous separation. The system achieved a 162‑fold enrichment of MCF‑7 breast cancer cells at 126 µL min⁻¹, removed red and white blood cells with 99.24 % and 94.23 % efficiencies, and shows promise for CTC separation in biomedical applications.

Abstract

Circulating tumor cells (CTCs) are highly correlated with the invasive behavior of cancer, so their isolations and quantifications are important for biomedical applications such as cancer prognosis and measuring the responses to drug treatments. In this paper, we present the development of a microfluidic device for the separation of CTCs from blood cells based on the physical properties of cells. For use as a CTC model, we successfully separated human breast cancer cells (MCF-7) from a spiked blood cell sample by combining multi-orifice flow fractionation (MOFF) and dielectrophoretic (DEP) cell separation technique. Hydrodynamic separation takes advantage of the massive and high-throughput filtration of blood cells as it can accommodate a very high flow rate. DEP separation plays a role in precise post-processing to enhance the efficiency of the separation. The serial combination of these two different sorting techniques enabled high-speed continuous flow-through separation without labeling. We observed up to a 162-fold increase in MCF-7 cells at a 126 µL min−1 flow rate. Red and white blood cells were efficiently removed with separation efficiencies of 99.24% and 94.23% respectively. Therefore, we suggest that our system could be used for separation and detection of CTCs from blood cells for biomedical applications.