On the thermodynamics and kinetics of superheated fluorocarbon phase-change agents.

Superheated nanodrops are a new class of submicron-diameter liquid emulsion particles comprising perfluoropropane (C3F8), perfluorobutane (C4F10) and perfluoropentane (C5F12) that are being developed for ultrasound imaging and therapy. They can be formed by condensation of precursor lipid-coated, gas-filled microbubbles. Application of ultrasound or laser energy triggers the phase transformation back to a vapor bubble, and this process can be exploited for certain biomedical applications. The nanodrops are remarkably metastable in the liquid state under physiological conditions, even though they are highly superheated. In prior work, it was suggested that a high Laplace pressure in the lipid-coated nanodrop is responsible for its stability in the superheated state. Recent work by our group, however, points to the energy barrier for homogeneous nucleation as a more likely explanation. The purpose of this article is to review and discuss this mechanism in greater detail. We start with a brief description of basic fluorocarbon intermolecular forces. We then use the van der Waals equation of state to construct equilibrium phase diagrams and saturation curves. The effect of droplet Laplace pressure is superimposed onto these curves and compared to experimental data, where a poor correlation is observed. It is also shown that nanodrops with Laplace pressure are unstable to dissolution. The mechanism of homogeneous nucleation is then offered as an alternative explanation for the metastability of superheated nanodrops, with calculations that show good agreement with experimental data.