Document Type

Article

Publication Date

5-19-2022

Abstract

Shell-stabilized gas microbubbles (MB) and nanobubbles (NB) are frequently used for biomedical ultrasound imaging and therapeutic applications. While it is widely recognized that monodisperse bubbles can be more effective in these applications, the efficient formulation of uniform bubbles at high concentrations is difficult to achieve. Here, it is demonstrated that a standard mini-extruder setup, commonly used to make vesicles or liposomes, can be used to quickly and efficiently generate monodisperse NBs with high yield. In this highly reproducible technique, the NBs obtained have an average diameter of 0.16 ± 0.05 µm and concentration of 6.2 ± 1.8 × 1010 NBs mL−1 compared to 0.32 ± 0.1 µm and 3.2 ± 0.7 × 1011 mL−1 for NBs made using mechanical agitation. Parameters affecting the extrusion and NB generation process including the temperature, concentration of the lipid solution, and the number of passages through the extruder are also examined. Moreover, it is demonstrated that extruded NBs show a strong acoustic response in vitro and a strong and persistent US signal enhancement under nonlinear contrast enhanced ultrasound imaging in mice. The extrusion process is a new, efficient, and scalable technique that can be used to easily produce high yield smaller monodispersed nanobubbles.

Keywords

contrast-enhanced ultrasound, extrusion, monodispersity, nanobubbles

Publication Title

Small

Volume

18

Issue

24

Grant

R01EB028144

Funder

Case-Coulter Translational Research Partnership; Wallace H. Coulter Foundation; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Included in

Radiology Commons

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