Microfluidic-based mechanical phenotyping of cells for the validation of epithelial-to-mesenchymal-like transition caused by insufficient heat treatment

Abstract

Radiofrequency ablation (RFA) is widely used for an early stage cancer therapy. However, the insufficient heat treatment enhances the metastatic potential in residual tumor, resulting in recurrence. Here, we present a microfluidic-based cell monitoring chip for detecting the changes in mechanical properties derived by epithelial-to-mesenchymal-like transition (EMT), due to the insufficient hyperthermia. The conventional molecular analysis requires complicated, time-consuming, and irreversible preprocesses. In comparison, the simple and rapid microfluidic-based analysis enables the phenotypical discrimination in a cellular level and permits the further analysis without any chemical damages on cells. We construct five different concentric pressure zones, each consists of four rings, having evenly spaced 10 mu m-wide slots. After exposing cells under 37, 42, and 47 degrees C for an hour, we counted the cells trapped in each zone by inserting cell mixtures into the center of the device. As the exposed temperature increases, the total capture rate decreased by 38.6, 19.2, and 15.3%, showing higher deformability. Moreover, a large portion of heat-treated cells were captured on the low pressure zones, while untreated cells were uniformly distributed. The results suggest that the non-lethal hyperthermia enhances the cell deformability. Thereby, our chip facilitates simple and rapid validation for measuring the efficacy of RFA. (C) 2017 Elsevier B.V. All rights reserved.