Low
oxygen tensions experienced in various pathological and physiological conditions are a major stimulus for angiogenesis. Hypoxic conditions play a critical role in regulating cellular behaviour including migration, proliferation and differentiation. This study introduces the use of a
microfluidic device that allows for the control of
oxygen tension for the study of different three-dimensional (3D) cell cultures for various applications. The device has a central 3D gel region acting as an external cellular matrix, flanked by media channels. On each side, there is a peripheral gas channel through which suitable gas mixtures are supplied to establish a uniform
oxygen tension or gradient within the device. The effects of various parameters, such as gas and media flow rates, device thickness, and diffusion coefficients of
oxygen were examined using numerical simulations to determine the characteristics of the
microfluidic device. A
polycarbonate (PC) film with a low
oxygen diffusion coefficient was embedded in the device in proximity above the channels to prevent
oxygen diffusion from the incubator environment into the
polydimethylsiloxane (PDMS) device. The
oxygen tension in the device was then validated experimentally using a
ruthenium-coated (Ru-coated)
oxygen-sensing glass cover slip which confirmed the establishment of low uniform
oxygen tensions (<3%) or an
oxygen gradient across the gel region. To demonstrate the utility of the
microfluidic device for cellular experiments under hypoxic conditions, migratory studies of MDA-MB-231 human
breast cancer cells were performed. The
microfluidic device allowed for imaging cellular migration with high-resolution, exhibiting an enhanced migration in
hypoxia in comparison to normoxia. This
microfluidic device presents itself as a promising platform for the investigation of cellular behaviour in a 3D gel scaffold under varying hypoxic conditions.