Microfluidic shrinking of microbubble contrast agents

We develop a new microfluidic technique to generate lipid-stabilized microbubbles of 1-7 μm diameter. We shrink microbubbles that are initially O(100) μm in diameter by using a vacuum system. We use a polydimethylsiloxane (PDMS) microfluidic device to generate microbubbles in a conventional flow focusing orifice. The bubbles pass through a serpentine channel while under vacuum pressure, and shrink to O(1) μm in diameter. We control a single parameter, the vacuum pressure, in the vacuum channels that are fabricated adjacent to the serpentine channel. We demonstrate that the shrunk microbubbles are stable for at least 75 minutes in atmospheric conditions. We anticipate that this simple approach can be used to generate microbubbles for ultrasound (US) imaging and therapeutic applications by increasing the throughput of the microfluidic microbubble generating system.