In vivo imaging of microfluidic-produced microbubbles

Microfluidics-based production of stable microbubbles for ultrasound contrast enhancement or drug/gene delivery allows for precise control over microbubble diameter but at the cost of a low production rate. In situ microfluidic production of microbubbles directly in the vasculature may eliminate the necessity for high microbubble production rates, long stability, or small diameters. Towards this goal, we investigated whether microfluidic-produced microbubbles directly administered into a mouse tail vein could provide sufficient ultrasound contrast. Microbubbles composed of nitrogen gas and stabilized with 3 % bovine serum albumin and 10 % dextrose were injected for 10 seconds into wild type C57BL/6 mice, via a tail-vein catheter. Short-axis images of the right and left ventricle were acquired at 12.5 MHz and image intensity over time was analyzed. Microbubbles were produced on the order of 105 microbubbles/s and were observed in both the right and left ventricles. The median rise time, duration, and decay time within the right ventricle were 2.9, 21.3, and 14.3 s, respectively. All mice survived the procedure with no observable respiratory or heart rate distress despite microbubble diameters as large as 19 μm.