The microbubble is a gas-in-liquid emulsion particle of 0.1 to 10 micrometers in diameter that is coated and stabilized by a lipid monolayer shell. Microbubbles are approved as blood pool contrast agents for echocardiography and are under development for use as ultrasound molecular imaging probes, targeted drug/gene delivery vehicles, and blood substitutes. Here, we describe a completely new application, in which it is desired to directly inject oxygen-filled microbubbles into the vein of hypoxic patients in the critical care setting. Design criteria for the microbubble suspension will be discussed. Rational design of the lipid monolayer shell that coats the gas interior is critical. While it is desired to encapsulate as much gas as possible as dispersed microspheres, which requires exceptional stability, it is also desired to have nearly instantaneous oxygen release upon contact with venous blood. The influence of lipid monolayer composition and microstructure on gas encapsulation, stabilization, dissolution and lipid shedding will be discussed. We tested the ability of phase-change monolayers (monolayers that undergo a gel-to-fluid phase transition between room temperature and body temperature) to achieve these dual aims. Results from preliminary experiments performed in vitro will be shown to illustrate this promising technology.