A microfabricated platform for establishing oxygen gradients in 3-D constructs.

Oxygen gradients are increasingly implicated in a number of biological processes, including stem cell differentiation and cancer metastasis. Unfortunately, the current in vitro tools designed to mimic conditions found in vivo lack application flexibility, simplicity in operation, and precise spatial control that most researchers require for widespread dissemination. The novel microfluidic-based device presented here addresses all the above concerns, offering a simple platform for enhanced control over the oxygen microenvironment exposed to three-dimensional cell-seeded constructs. The device utilizes an oxygen diffusion membrane approach to establish a gradient across a construct sandwiched between two continually perfused microfluidic networks. The device is capable of forming steady-state gradients at both the conditions tested-0 % to 5 % O₂ and 0 % to 21 % O₂-but a wide variety of profiles within the construct are possible. Cell viability with two model cell lines was also tested, with no adverse effects relative to the control.