Cavitation-threshold Determination and Rheological-parameters Estimation of Albumin-stabilized Nanobubbles

Abstract

Nanobubbles (NBs) are of high interest for ultrasound (US) imaging as contrast agents and therapy as cavitation nuclei. Because of their instability (Laplace pressure bubble catastrophe) and low sensitivity to US, reducing the size of commonly used microbubbles to submicron-size is not trivial. We introduce stabilized NBs in the 100–250-nm size range, manufactured by agitating human serum albumin and perfluoro-propane. These NBs were exposed to 3.34- and 5.39-MHz US, and their sensitivity to US was proven by detecting inertial cavitation. The cavitation-threshold information was used to run a numerical parametric study based on a modified Rayleigh-Plesset equation (with a Newtonian rheology model). The determined values of surface tension ranged from 0 N/m to 0.06 N/m. The corresponding values of dilatational viscosity ranged from 5.10−10 Ns/m to 1.10−9 Ns/m. These parameters were reported to be 0.6 N/m and 1.10−8 Ns/m for the reference microbubble contrast agent. This result suggests the possibility of using albumin as a stabilizer for the nanobubbles that could be maintained in circulation and presenting satisfying US sensitivity, even in the 3–5-MHz range.

Nanobubble Mediated Gene Delivery in Conjunction With a Hand-Held Ultrasound Scanner

“…Histologic analysis showed that NBs were retained in tumor tissue to a greater extent compared with MBs. Lafond et al (2018) recently demonstrated that their in-house fabricated albumin-based NBs, which is 100 to 250 nm in diameter were sensitive to specific acoustic pressures and could become efficient cavitation nuclei in the 3 to 5-MHz US frequency range. Acoustic passive cavitation detectors indicated that inertial cavitation threshold was lower than the commercially available MB US contrast agents.…”

“…Secondly, human serum albumin based NBs were prepared according to a previous study reported elsewhere (Lafond et al, 2018). Briefly, the air in a plastic container tube (height, 30 mm, outer diameter, 25 mm) was replaced with 15 ml of perfluoropropane (C3F8; Takachiho Chemical Industrial, Tokyo, JP) gas using a 23-gauge needle inserted through a small opening in a custom made cap.…”

Echographic and physical characterization of albumin-stabilized nanobubbles

“…It is suggested that a similar cell killing or disruption phenomenon occurred in our experiments using albumin NBs. Furthermore, we previously reported that similar sized albumin-stabilized NBs (100–250 nm) were sensitive to irradiated ultrasound and were excited easily to low acoustic pressure at frequency range from 3 to 5 MHz [10]. Inertial cavitation was observed by analyzing the noise emission from the albumin NBs where the level of scattered inertial cavitation noise was greater than that of conventional microbubble ultrasound contrast agent Sonazoid®.…”

“…We recently reported on the cavitation-threshold and rheological parameters of albumin stabilized bubbles in the nanoscale range [10]. It was suggested that these nanobubbles (NBs) could be used as efficient cavitation nuclei with low intensity ultrasound.…”

Cavitation in soft matter

“…Despite the extensive applications of AIC, the rheological applications of AIC are relatively unexplored. In contrast to NIC and LIC, AIC produces a cavitation cloud consisting of microbubbles; thus, collective characteristics of AIC, such as a threshold of the cloud cavitation (86), are preferentially introduced instead of the cavity dynamics of a single bubble.…”