This study explored the thermal conditions necessary for the vaporization of superheated perfluorocarbon nanodrops. Droplets C3F8 and C4F10 coated with a homologous series of saturated diacylphosphatidylcholines were formed by condensation of 4 μm diameter microbubbles. These drops were stable at room temperature and atmospheric pressure, but they vaporized back into microbubbles at higher temperatures. The vaporization transition was measured as a function of temperature by laser light extinction. We found that C3F8 and C4F10 drops experienced 90% vaporization at 40 and 75 °C, respectively, near the theoretical superheat limits (80-90% of the critical temperature). We therefore conclude that the metastabilty of these phase-change agents arises not from the droplet Laplace pressure altering the boiling point, as previously reported, but from the metastability of the pure superheated fluid to homogeneous nucleation. The rate of C4F10 drop vaporization was quantified at temperatures ranging from 55 to 75 °C, and an apparent activation energy barrier was calculated from an Arrhenius plot. Interestingly, the activation energy increased linearly with acyl chain length from C14 to C20, indicating that lipid interchain cohesion plays an important role in suppressing the vaporization rate. The vaporized drops (microbubbles) were found to be unstable to dissolution at high temperatures, particularly for C14 and C16. However, proper choice of the fluorocarbon and lipid species provided a nanoemulsion that could undergo at least ten reversible condensation/vaporization cycles. The vaporization properties presented in this study may facilitate the engineering of tunable phase-shift particles for diagnostic imaging, targeted drug delivery, tissue ablation, and other applications.

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The microbubble offers a unique platform to study lung surfactant mechanics at physiologically relevant geometry and length scale. In this study, we compared the response of microbubbles (∼15 μm initial radius) coated with pure dipalmitoyl-phosphatidylcholine (DPPC) versus naturally derived lung surfactant (SURVANTA) when subjected to linearly increasing hydrostatic pressure at different rates (0.5-2.3 kPa/s) at room temperature. The microbubbles contained perfluorobutane gas and were submerged in buffered saline saturated with perfluorobutane at atmospheric pressure. Bright-field microscopy showed that DPPC microbubbles compressed spherically and smoothly, whereas SURVANTA microbubbles exhibited wrinkling and smoothing cycles associated with buckling and collapse. Seismograph analysis showed that the SURVANTA collapse amplitude was constant, but the collapse rate increased with the pressurization rate. An analysis of the pressure-volume curves indicated that the dilatational elasticity increased during compression for both shell types. The initial dilatational elasticity for SURVANTA was nearly twice that of DPPC at higher pressurization rates (>1.5 kPa/s), producing a pressure drop of up to 60 kPa across the film prior to condensation of the perfluorobutane core. The strain-rate dependent stiffening of SURVANTA shells likely arises from their composition and microstructure, which provide enhanced in-plane monolayer rigidity and lateral repulsion from surface-associated collapse structures. Overall, these results provide new insights into lung surfactant mechanics and collapse behavior during compression.

Microbubbles (MBs) are micrometre sized gas spheres comprising a biocompatible shell that provide vascular contrast for diagnostic ultrasound (US) imaging. MBs volumetrically oscillate in an ultrasonic field and scatter acoustic energy over a range of frequencies that can be separated from the tissue response. MBs can also provide organ perfusion rates by imaging their “wash-in” to a region of interest which can be correlated to vascular flow. When driven at higher acoustic pressures, localized biological effects can be induced, including increased tissue permeabilization, thermal effects and localised release of drugs that can be encapsulated in the MBs themselves. Both hydrophobic and hydrophilic drugs can be loaded on to MBs e.g. through the use of liposomal carriers or direct attachment of drug molecules to the bubble shell. Since the early 2000s, MB-based technologies have been well researched, though there was significant regulatory push back starting in 2006 based on a controversial clinical trial. From that point, both physicians and researchers have consistently demonstrated the robust safety of MBs as ultrasound contrast agents and their significant clinical utility. Within the last 5 years, more indications have been approved. A recent first-in-man clinical trial of therapeutic US with MBs reversibly opening the blood brain barrier has also been shown to be safe in amyotrophic lateral sclerosis patients. The following article outlines the coupling of US and MBs as a diagnostic and therapeutic platform with a particular focus on their application to the therapy of surgical diseases.