Freeze-dried microfluidic monodisperse microbubbles as a new generation of ultrasound contrast agents

Abstract: In the paper, we succeeded to freeze-dry monodisperse microbubbles without degrading their size and acoustic properties. We used microfluidic technology to generate highly monodisperse (coefficient of variation, CV<5%) microbubbles and optimized their formulation along with a cryoprotectant. By using a specific technique of retrieval of the bubble, we showed that freeze-drying the microbubbles does not alter their size distribution. To compare the fundamental resonance properties of the bubbles, we performed backscattered acoustic characterization measurements. Our experimental results revealed that the freeze-drying process conserved the acoustic properties of the bubbles. The maximum backscattering power amplitude of fresh and freeze-dried monodisperse PVA bubbles was around ten eight times higher than that of SonoVue at a similar concentration in vitro. By solving the question of storage and transportation of monodisperse bubbles, our work facilitates their penetration in the domain of UCAs, for performing new tasks and developing novel non-invasive measurements, such as pressure, unaccessible to the existing commercialized bubbles.