Microdevice platform recapitulating hypoxic tissue microenvironments

Abstract

Hypoxia plays a central role in cancer progression and resistance to therapy. A microdevice platform is engineered to recapitulate the intratumor oxygen gradients that drive the heterogeneous hypoxic landscapes in solid tumors. The microdevice design features a “tumor section”-like culture by incorporating a cell layer between two diffusion barriers, where an oxygen gradient is established by cellular metabolism and physical constraints. The oxygen gradient is confirmed by numerical simulation and imaging-based oxygen sensor measurement. Spatially-resolved hypoxic signaling in cancer cells is also demonstrated through immunostaining, gene expression assay, and hypoxia-targeted drug treatment. The microdevice platform can accurately generate and control oxygen gradients, eliminates complex microfluidic handling, allows for incorporation of additional tumor components, and is compatible with high-content imaging and high-throughput applications. It is well suited for understanding hypoxia-mediated mechanisms in cancer disease and other biological tissues and processes, and discovery of new therapeutics.

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