Abstract
A hypoxic microenvironment affects cell fate and regulates various physiological and pathological phenomena. A microfluidic device that enables precise control of oxygen tension by supplying gas of a predefined oxygen concentration was designed for three-dimensional cell cultures. Numerical simulations were performed to investigate changes of oxygen tension in the microfluidic device in response to variation of the media and gas flow rates. Oxygen tension created with the appropriate flow rates of gas and media based on the simulation results was validated by using a ruthenium-coated oxygen-sensing glass cover slip. Moreover, usability of the device in cellular experiments was investigated by observing the migration of breast cancer cells under controlled oxygen tension. The computational results revealed that there was an optimum combination of flow rates of media and gas for control of oxygen tension. The results of validation experiment well agreed with the corresponding computational results, showing the establishment of low uniform oxygen tension (<3%) or an oxygen gradient. The cellular experiment using the device showed that there was enhanced migration of breast cancer cells under a hypoxic condition in comparison with a normoxic condition. The present microfluidic device is a useful tool to investigate cellular responses to hypoxia.
