(275g) Selective Vaporization of Superheated Nanodroplets for Rapid, Sensitive Acoustic Biosensing

This work describes a simple, scalable ultrasound imaging detection method in which aggregation of superheated droplets allows detection of small concentrations of biomolecules without the need to wash out excess reagent. While many contrast agents can be functionalized with ligands that can bind membrane-bound targets, fewer agents are able to sense small quantities of soluble, nonreactive biomarkers and relay their location using a modality capable of deep-tissue imaging. The mechanism of biosensing in this work derives from the discovery that biomolecule-specific aggregation of superheated nanodroplets greatly changes their ability to be vaporized into microbubbles. While in their liquid form the nanodroplets possess poor acoustic contrast properties owing to their incompressibility, these superheated nanodroplets can be vaporized using High Intensity Focused Ultrasound (HIFU), resulting in the generation of high-contrast microbubbles in situ. We show that even small-order aggregates of droplets joined via biotin-streptavidin interactions can specifically be vaporized using HIFU, thus allowing sensing of analytes with a dynamic range of 100 fM to 100 nM. Because of the bulk droplet aggregation mechanism of detection, full activation of signal can be achieved within 10 min. Finally, this work provides evidence of a mechanism for aggregation-based droplet vaporization that will aid the design of future ultrasound contrast agents and biosensors for in vivo imaging.