Gas-filled microbubbles can be synthesized using a continuous flow chamber and a sonicator. The resulting microbubble solution can be size-sorted for a particular application, such as injection into a patient for gas delivery thereto. The microbubble solution may be concentrated to have greater than 50% volume gas while maintaining microbubble sizes below 10 μm. Control of the microbubble generation process can yield highly stable microbubbles. The microbubbles may retain over half of their original gas payload for over three weeks while exhibiting minimal change in microbubble size. The systems, methods, and devices described herein thus allow for continuous or batch-wise continuous production of gas-filled microbubbles that readily release their gas payload when introduced into an under-saturated or de-saturated solution.