Preparation of perfluorocarbon emulsions by premix membrane emulsification for Acoustic Droplet Vaporization (ADV) in bi
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Preparation of perfluorocarbon emulsions by premix membrane emulsification for Acoustic Droplet Vaporization (ADV) in biomedical applications ´ eric ´ Padilla2,3,4 · Catherine Charcosset1 Romain Melich1,2 · Ali Zorgani2 · Fred
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Perfluorocarbon (PFC) droplets are used in acoustic droplet vaporization (ADV), a phenomenon where droplets vaporize into gas microbubbles under exposure to ultrasound. The size and the size distribution of a phase change contrast agent is an important factor in determining the ADV threshold and the biodistribution. Thus, high throughout manufacturing of uniformsized droplets, required to maintain spatial control of the vaporization process, remains challenging. This work describes a parametric evaluation of a novel process using premix membrane emulsification (PME) to produce homogeneous PFC emulsions at high rate with moderate pressure using Shirasu Porous Glass (SPG) membranes. In this study, we investigated the effect of several process parameters on the resulting pressure and droplet size: membrane pore size, flow rate, and dispersed phase type. The functionality of the manufactured emulsions for ADV was also demonstrated. Vaporization of the PFC emulsions was obtained using an imaging ultrasound transducer at 7.813 MHz, and the ADV thresholds were determined. Here, the pressure threshold for ADV was determined to be 1.49 MPa for uniform-sized perfluorohexane (PFHex) droplets with a mean size of 1.51 μm and a sharp distribution (CV and span respectively of 20% and 0.6). Thus, a uniform-sized droplet showed a more homogeneous vaporization with a uniform response in the focal region of the transducer. Indeed, polydispersed droplets had a more diffuse response outside the focal region due to the presence of large droplets that vaporize at lower energies. The ADV threshold of uniform-sized PFC droplets was found to decrease with the droplet diameter and the bulk fluid temperature, and to increase with the boiling temperature of PFC and the presence of an oil layer surrounding the PFC core. Keywords Emulsion · Premix membrane emulsification · Perfluorocarbon · Acoutic droplet vaporization · Homogeneous distribution
1 Introduction Fr´ed´eric Padilla
[email protected] Catherine Charcosset
[email protected] 1
Univ Lyon, Universit´e Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, 43 boulevard du 11 novembre 1918, F-69100, Villeurbanne, France
2
LabTAU, INSERM, Centre L´eon B´erard, Universit´e Lyon 1, Univ-Lyon, F-69003, LYON, France
3
Department of Radiology, University of Virginia School of Medicine, Charlottesville, VA, USA
4
Focused Ultrasound Foundation, 1230 Cedars Court, Suite 206, Charlottesville, VA, USA
In acoustic droplet vaporization (ADV), an emulsion is converted into gas bubbles upon exposure to ultrasound energy beyond a vaporization threshold (Fig. 1) (Kripfgans et al. 2000; Mark T. Burgess and Tyrone M. Porter 2015). Upon ultrasound exposure above the ADV threshol
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