Preparation and characterization of perfluorocarbon microbubbles using Shirasu Porous Glass (SPG) membranes

Abstract

Microbubbles are increasingly used in several fields, such as medical imaging for enhanced contrast ultrasound imaging. Theses microbubbles usually consist of a gas core stabilized by surfactant molecules. In this study, a technique using Shirasu Porous Glass (SPG) membranes was used to produce perfluorocarbon microbubbles. The microbubbles obtained were characterized by their size, size distribution, and stability. The effect of several parameters on the microbubble's size was investigated related to the process (transmembrane pressure, ΔP, bubble point pressure, PBP, shear stress, τw), membrane pore size, Dp, and formulation (gas, surfactants in the aqueous phase). The transmembrane pressure nor the shear stress (τw) had influence on the microbubble's size or size distribution for ΔP/PBP <1.5. The decrease of the membrane pore size from 1.1, 0.5, to 0.2 μm led to lower microbubble size 13.3, 6.36, and 4.42 μm, respectively, which was associated with higher size distribution 16%, 24% and 31%, respectively due to the higher Laplace pressure exerted on smaller microbubbles leading to their destabilization. With the 1.1 μm pore size membrane, perfluorocarbon microbubbles were obtained with a diameter of 13.3 μm and coefficient of variation (CV) of 16% when stabilized by sodium dodecyl sulfate (SDS), 15.6 μm with CV% of 23% when stabilized by Tween20, and 16.5 μm with CV% of 26% when stabilized by Polyoxyethylene (40) stearate (PEG40S). These low CV were indication of monodispersity. Perfluorocarbon microbubbles had a smaller size than air microbubbles due to the lower surface tension that decreased the retention force, keeping the microbubbles at the pore opening. The stability study showed that the perfluorocarbon gas greatly increased the lifetime of the microbubbles with a slight increase in size of 1.3 after 90 s compared to 2.2 for air microbubbles. Overall, the membrane technique proved to be an effective, controlled and reproducible method to produce perfluorocarbon microbubbles at a high rate ∼0.6 − 1.5 × 10+10 microbubbles/min. The key factor that determines the microbubbles formation is the adsorption kinetics of the surfactant at the new gas–liquid interface at the pore opening.