Methods to study the tumor microenvironment under controlled oxygen conditions

• Hypoxia, low levels of oxygen concentration, affects cell behavior and fate.
• Real-time cell behavior studies in hypoxia are difficult with conventional methods.
• Advanced microfluidic platforms allow for precise control over oxygen concentration.
• Microfluidic platforms enable real-time imaging of cell behavior under hypoxia.

The tumor microenvironment (TME) is a complex heterogeneous assembly composed of a variety of cell types and physical features. One such feature, hypoxia, is associated with metabolic reprogramming, the epithelial–mesenchymal transition, and therapeutic resistance. Many questions remain regarding the effects of hypoxia on these outcomes; however, only a few experimental methods enable both precise control over oxygen concentration and real-time imaging of cell behavior. Recent efforts with microfluidic platforms offer a promising solution to these limitations. In this review, we discuss conventional methods and tools used to control oxygen concentration for cell studies, and then highlight recent advances in microfluidic-based approaches for controlling oxygen in engineered platforms.