We present a method of synthesizing albumin-shelled, large diameter (>10 μm), transiently-stable microbubbles using a flow-focusing microfluidic device (FFMD). Microfluidic device production enables microbubbles to be produced immediately prior to insonation, thus relaxing the requirements for stability. Both reconstituted fractionated bovine serum albumin (BSA) and fresh bovine blood plasma were investigated as shell stabilizers. Microbubble coalescence was inhibited by the addition of either dextrose or glycerol and propylene glycol. Microbubbles were observed to have an acoustic half-life of approximately 6 s. Microbubbles generated directly within a vessel phantom containing flowing blood produced a 6.5 dB increase in acoustic signal within the lumen. Microbubbles generated in real-time upstream of in vitro rat aortic smooth muscle cells under physiological flow conditions successfully permeabilized 58 % of the cells upon insonation at a peak negative pressure of 200 kPa. These results demonstrate that transiently-stable microbubbles produced via flow-focusing microfluidic devices are capable of image enhancement and drug delivery. In addition, successful microbubble production with blood plasma suggests the potential to utilize blood as a stabilizing shell.
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