Sophisticated Microbubble Coating Materials for Functional Ultrasound Sensing

Lipid-coated microbubbles are fascinating objects rich in nonlinear dynamics. They are used in medicine as ultrasound contrast agents (UCAs) to visualize organ perfusion. The contrast enhancement results from their ultrasound-driven oscillations, which produce a powerful echo. The echo response is sensitive to ambient pressure and the microbubble surroundings so that bubbles have potential sensing capabilities that reach far beyond their current use as contrast agents. However, UCAs contain microbubbles non-uniform in size (1-10 μm diameter) and in shell properties. The resulting ill-defined echo inhibits game-changing applications such as non-invasive pressure sensing and molecular sensing using functionalized bubbles that bind to diseased cells. Microfluidics allows controlled formation of mono-sized bubbles. However, even the echo response of mono-sized bubbles is heterogeneous due to uncontrolled shell properties.I aim to go beyond size-control and enable the microfluidic formation of functional mono-acoustic bubbles with a tuned and predictable acoustic response. The challenge is to bridge the gaps between fluid dynamics, colloid and interface science, interface rheology, and acoustics to unravel the coupled problem of microfluidic bubble-shell formation and ultrasound-driven bubble dynamics in the bulk and near or targeted to a wall. To reach this goal, we will develop highly controlled lab experiments at the sub-microsecond and sub-micrometer level, together with simulations and theory development. The ultimate goal is a physics-based parametrization of the acoustic bubble response as a function of shell formulation, microfluidic control parameters, diffusive gas exchange effects, and targeted molecular binding of the bubble to a boundary.