Controllable Formation of Monodisperse Polymer Microbubbles as Ultrasound Contrast Agents

Microbubbles have been widely used as ultrasound contrast agents in clinical diagnosis and hold great potential for ultrasound-mediated therapy. However, polydispersed population and short half-life time (<10 min) of the microbubbles still limit their applications in imaging and therapy. To tackle these problems, we develop a microfluidic flow-focusing approach to produce monodisperse microbubbles stabilized by Poly(lactic-co-glycolic acid) (PLGA) as the polymer shell. The size of PLGA microbubbles can be tightly controlled from ∼600 nm to ∼7 μm with a coefficient of variation less than 4% in size distribution for ensuring highly homogeneous echogenic behavior of PLGA polymer microbubbles in ultrasound fields. Both in vitro and in vivo experiments showed that the monodisperse PLGA microbubbles had excellent echogenicity and elongated sonographic duration time (>3 times) for ultrasound imaging in comparison with the commercial lipid microbubbles.