Honey, I shrunk the bubbles: microfluidic vacuum shrinkage of lipid-stabilized microbubbles

We present a microfluidic technique that shrinks lipid-stabilized microbubbles from O(100) to O(1) μm in diameter - the size that is desirable in applications as ultrasound contrast agents. We achieve microbubble shrinkage by utilizing vacuum channels that are adjacent to the microfluidic flow channels to extract air from the microbubbles. We tune a single parameter, the vacuum pressure, to accurately control the final microbubble size. Finally, we demonstrate that the resulting O(1) μm diameter microbubbles have similar stability to microfluidically generated microbubbles that are not exposed to vacuum shrinkage. We anticipate that, with additional scale-up, this simple approach to shrink microbubbles generated microfluidically will be desirable in ultrasound imaging and therapeutic applications.