Co-culture Microdevice with Oxygen Gradient for Tumor Microenvironment Model and Metastasis Imaging

Tu mor hypoxia is a major therapeutic problem since it decreases radiation effects and leads to metastasis. Oxygen is delivered to tumor tissue via abnormal and dysfunctional microvessels, which forms heterogeneity of tissue oxygenation in the tumo r. Mimicking the o xygen gradient fo r cellu lar experiments in vitro is important to clarify the mechanis ms involved in tumor bio logy, but the only method to produce hypoxic conditions at a constant level is using gas-controlled incubators, because there is currently no technique for creating an o xygen gradient using culture dishes. We designed a polydimethylsilo xane (PDMS) microflu idic device integrated with microchannels for cell cultures that enables visualizat ion of cellu lar distribution under a microscope and co -culture to determine interactions between cancer and other cells. Phosphorescence-based partial o xygen measurements quantified the o xygen grad ient, which can be controlled by the gas pressure between the inlet and outlet of the device. A monoculture of end othelial cells with an oxygen gradient in the device showed an increase in cell death in the hypoxic area. In addition, Lewis lung carcino ma cells co -cultured with endothelial cells showed gradient-dependent migration through a membrane pore filter, indicating that the interaction between tumor and endothelial cells under hypo xia is crucial in metastasis. The results suggest that the developed microdevice can be used to study the mechanisms of tu mor metastasis under hypoxic conditions.