Angew. Chem. Int. Ed. http://doi.org/f3ggns (2015)

Microbubbles, which are typically made up of a lipid or protein shell and contain air or perfluorocarbon in the core, are useful contrast agents in ultrasound imaging because they reflect ultrasound waves differently from soft tissues in the body. Recently, nanobubbles have gained interest because they can traverse smaller capillary networks of organs and potentially be more widely applicable. However, stable nanobubbles are difficult to make. Now, Guojun Liu and colleagues at Queen's University in Canada show that stable and echogenic air nanobubbles can be prepared by lining the inside of the shell with highly hydrophobic fluorinated polymers.

Inspired by the water-repelling properties of perfluorinated coatings on cotton fabrics, the researchers made nanobubbles using a triblock polymer consisting of poly(acrylic acid), poly(2-cinnamoyloxyethyl methacrylate) and poly(2-perfluorooctylethyl methacrylate). As a control, a similar polymer with poly(glyceryl monomethacrylate) and poly(tert-butyl acrylate) replacing poly(acrylic acid) and poly(2-cinnamoyloxyethyl methacrylate), respectively, was made. When injected into a tube filled with water or human blood, the fluorinated nanobubbles could be detected by ultrasound. Further experiments show that their echogenicity is due to the air trapped in the cavity. Nanobubbles that are allowed to age for 4 hours or 3 weeks remain strongly echogenic. Furthermore, their average lifetime before signal decay was about 100 times longer than commercial microbubbles. Transmission electron microscopy showed that the ultrasonicated samples retained their structural integrity, confirming that no air was displaced by water.