Acoustic droplet vaporization

Abstract

Current tumor chemotherapy is associated with severe side effects caused by adverse effects of the drugs on healthy tissue. A local delivery of the drug has the advantage of a more controlled biodistribution of the therapeutic agent, which will reduce the side-effects, and offers the potential to use a higher concentration which will improve therapeutic efficiency. Recent studies have shown that liquid emulsion microdroplets of a size of 10 μm composed of a low-boiling point perfluorcarbon (PFC) have the potential to be a highly efficient system for local drug delivery. Moreover, nanodroplets of a size of 100 nm can extravasate through the leaky vessels of a tumor and the drug can be released upon triggering with diagnostic ultrasound while an explosive evaporation of the droplet takes place. We use ultra-high speed optical imaging to study, for the first time, acoustic droplet vaporization dynamics at nanoseconds timescales. We develop a simple theoretical model to capture all of the growth dynamics prior to and following the nucleation event at the time scales under study here. We show that on these time scales the evaporation process is limited, not by the kinetic theory of the mass flux, but by the heat transfer from the containing liquid into the vapor bubble required to supply the latent heat for a phase conversion. We also take into account the interaction of the vapor bubble with the applied ultrasound and explain that the phase conversion rate is much more rapid due to rectified heat transfer. And, we recover the driving pressure information from the optical recordings and determine the exact phase of ultrasound when nucleation is initiated. We also explain the long-standing puzzle how ultrasound can physically trigger the vaporization given the large mismatch between the ultrasound wavelength and the microdroplet size. We show that vaporization is preceded by nonlinear propagation of the ultrasound wave generating superharmonics. These high-frequency waves focus efficiently within the droplet, triggering vaporization. ADV shows great potential for advanced medical diagnosis and therapy. Our new understanding allows for further reduction of the required pressure amplitudes, thereby minimizing the adverse effects on healthy tissue.