Ultra-High-Frequency-Dielectrophoresis Microfluidic Biosensor to Detect the Transformation Potential of Extracellular Vesicles Derived from Cancer Stem Cells.

Cancer stem cells (CSCs) remain challenging to isolate and characterize because of their plastic phenotype. To overcome this issue, we used a microfluidic lab-on-a-chip analysis approach based on ultra-high frequency dielectophoresis (UHF-DEP) to measure the dielectrophoretic signature of colorectal cancer cells. We demonstrated that CSCs exhibit a distinct and lower frequency signature than differentiated cancer cells. Extracellular vesicles (EVs) released by tumor cells are implicated in tumor progression and metastasis. As CSC-derived EVs carry a more aggressive cargo, we hypothesized that treating differentiated colorectal cancer cells with these vesicles might affect their phenotype which would be detected by our lab on a chip. Indeed, the dielectrophoretic signature of cells treated with those EVs was altered in comparison to untreated cells, even in cases where no detectable biological changes were observed. Compared to conventional approaches using biomarkers to characterize CSCs, this UHF-DEP lab on a chip is a label-free method providing rapid and relevant results. Such a method could be useful in the clinic for the early detection of CSCs in the tumor mass, as well as for monitoring CSC-derived EVs in the bloodstream in order to study responses to therapy and prevent relapses.