Control of Oxygen Levels in Cell Chips by Oxygen Expulsion via Tubing

초록

Cell chips are small devices imitating the in vivo environment and a useful tool for studying physiological and pathological processes using cells, tissues or organoids. The oxygen concentration inside a cell chip must be controlled to mimic the oxygen concentration in vivo, and hypoxic conditions play a significant role in many processes, including cancer development and stem cell differentiation. Several methods have been proposed to reproduce hypoxic conditions inside cell chips. However, they require large-scale equipment, can only be used in closed environments, or are cytotoxic, making them inapplicable in practice. Therefore, new methods are needed to overcome these issues. In this study, oxygen-permeable tubing was contacted with a solution of sodium sulfite, an oxygen scavenger, to remove oxygen indirectly and completely from the medium flowing through the tubing. A 0% oxygen concentration was maintained over a flow rate range from as little as 10 μL/min up to 100 μL/min. By mixing with deoxygenated medium, an oxygen concentration of 3%, which is equivalent to the hypoxic environment in vivo, was continuously set and maintained up to about 44 hours without replacement of the oxygen scavenger. In addition, by mixing deoxygenated medium with non-deoxygenated medium in a certain ratio, the oxygen concentration (0% to 21%) inside the cell chip can be adjusted proportionally to the flow rate.