Institute of Fluid Dynamics

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Acoustic Droplet Vaporization

We investigate the physics of acoustic droplet vaporization to develop safer, more efficient ultrasound-based therapies for drug delivery and embolotherapy.

Enlarged view: Acoustic droplet vaporization.
The nucleation positions (blue dots) are shown overlapped with a snapshot of the pressure field inside a perfluoropentane droplet, at the instant of global minimum pressure, for 2 different sets of experiments. On the left, data for a 9-micrometer droplet sonicated using a 5-MHz High Intensity Focused Ultrasound (HIFU) transducer are presented. The right side presents the data for a 38-micrometer droplet sonicated using a 3.5-MHz HIFU transducer. In both cases, nucleation inception happens at the time t = 0.

Contributors: Samuele Fiorini, Anunay Prasanna

In the past years, there has been a growing interest in investigating ultrasound-based therapies for applications such as embolotherapy and targeted drug delivery. The use of ultrasound-activatable agents such as microbubbles has shown great potential in terms of specificity of the treatment and reduction of the required ultrasound peak pressure. Acoustic droplet vaporization (ADV) is a technique that employs metastable micron- and sub-micron-sized liquid droplets as bubble precursors. The liquid cores present several advantages with respect to their gaseous counterpart, such as an improved in-vivo stability and the possibility to create stable nanodroplets that can naturally extravasate into tumor tissue thanks to the enhanced permeability and retention (EPR) effect. 

The vaporization process can be divided in two main stages – the first being the vapor nucleation and the second the bubble growth. Typically, after the initial nucleation event, the newly formed vapor bubble(s) grow in size, both due to gas diffusion and spontaneous phase change if the droplet is in a superheated state. The vaporization inception is characterized by a threshold, which depends on parameters such as excitation frequency, droplet radius and temperature.

Our research focuses on elucidating the underlying physics of ADV, as well as in characterizing and reducing the acoustic vaporization threshold, which is currently much higher than the pressure required to excite microbubble contrast agents and is therefore, a major safety concern for possible in vivo applications. We have shown that the incoming ultrasound wave, under certain conditions, is focused in the droplet core, and its positive pressure phase can undergo sign inversion, generating extremely localized tension (negative pressure) areas without affecting the surrounding medium. This finding can open the way to the development of safer and more efficient techniques to trigger ADV. More details can be found e.g. in our external page journal publication.

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