Preparation of perfluorocarbon emulsions by premix membrane emulsification for Acoustic Droplet Vaporization (ADV) in biomedical applications

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 uniform-sized 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.

Effect of Phase-Change Nanodroplets and Ultrasound on Blood–Brain Barrier Permeability In Vitro

“…During the last several years, several methods of ND preparation have appeared in the literature [ 7 ]. Several reports propose the use of microfluidics [ 11 , 15 ]. In our present study, we adapted a liposome preparation method that yielded nano-size droplets significantly smaller to the ones prepared with microfluidics [ 11 , 16 ].…”

“…The PFC core is the most crucial part of the NDs concerning the cavitation profile [ 17 , 18 ]. Different PFC cores are expected to attribute distinct characteristics to the ADV of the NDs [ 11 , 15 , 19 ]. The differences in the carbon chain, fluorine atoms, and boiling points have a significant role in ADV, cavitation, and, potentially, colloidal stability in biological fluids [ 20 ].…”

Droplet breakup mechanisms in premix membrane emulsification and related microfluidic channels

“…Moreover, for a constant energy input, there is usually a linear relation between final droplet size and membrane pore size, i.e., = [11]. In the preparation of microemulsions, << 0.5 even at low pressures due to self-emulsification, while in case of nanoemulsions and macroemulsions, is typically around 0.7-1.5 [83][84][85]. Nevertheless, < 0.5 is still achievable for nanoemulsions but under specific conditions (i.e., high and suitable membrane properties), as can be seen from the data presented in Table A.1.…”

Fluorinated Ionic Liquids as Task-Specific Materials: An Overview of Current Research

“…These compounds are widespread in consumers life through plastics, fire retardants, dyes, surfactants, polymers, and pharmaceuticals, among others [1][2][3][4][5][6]. Benign PFCs have been used in the development of biomedical applications, such as emulsions, [7,8] imaging agents, [9,10] biocompatible lubricants, [11] oxygen therapeutics, [12] pulmonary delivery agents, [13] and theranostic agents [14]. On the other hand, perfluoroalkyl acids (PFAs) and fluorinated greenhouse gases (F-gases) belong to a class of persistent chemicals, widely used in industrial and commercial products [1,2,5,6].…”