A Microfluidic Approach to Examine How the Hemodynamic Environment Alters Circulating Tumor Cell Phenotype

An important step in the metastatic progression of cancer is the migration of cancer cells from a primary tumor to distal location through intravasation, in which cancer cells travel through the bloodstream as circulating tumor cells (CTCs). While in the blood vessels, CTCs experience hemodynamic shear stresses at high levels (5-60 dyn/cm2). Previous studies identified that exposing cancer cells to fluid shear stress (FSS) induced a phenotypic change causing the cells to be more metastatic. While a novel finding, this study was limited in its ability to control the FSS used to challenge the cells and was limited to only final measurements at the end of the experiment. The goal of this project is to address this limitation by developing a microfluidic device to isolate and trap single CTCs and then interrogate them with varying amounts of FSS. The microfluidic traps were designed with a semi-circular geometry with a space in the middle to allow for optimal trapping and testing of FSS-induced cell deformability. COMSOL simulations were performed to optimize the fluid velocity profile of the device to ensure a high trapping efficiency. The simulations also identified the flow profiles needed to produce FSS on the cells that they typically encounter in the bloodstream. These flow profiles were used to test the phenotypic change in MDA-MB-231 cells trapped in the microfluidic device. Preliminary findings demonstrate the ability to efficiently trap single cells in the microfluidic device to explore how increasing the values in fluid shear stress magnitude and duration altered size and shape of the cells allowing for a more accurate determination of cell phenotype. These results will provide new insight into the mechanisms of how CTCs survive in the bloodstream and if changes in FSS results in a more aggressive cancer phenotype.