Acoustic bubble sorting of ultrasound contrast agents

Abstract

Ultrasound contrast agents are coated microbubbles with radii ranging from 1 to 10 ?m. Medical transducers typically operate at a single frequency, therefore only a small selection of bubbles will contribute to the nonlinear contrast through resonance. Thus, the sensitivity of contrast-enhanced ultrasound can be improved by narrowing down the size distribution. Monodisperse bubble can be formed in a flow-focusing geometry. However, it requires extensive skills in microfluidics technology and in surface chemistry. Here, we present a simple lab-on-a-chip technique to sort microbubbles on-line in a traveling ultrasound wave. A broad range of the parameter space of bubble size and frequency has been characterized to provide physical input parameters for a simple force balance model. We find good agreement for the modeled displacement as a function of the bubble radius for a range of sizes in the unbounded fluid. Within the confinement of the sorting chip we find good agreement for the resonance behavior and overall with a smaller displacement than predicted as a result of bubble-wall interactions.This novel sorting strategy may lead to an overall improvement of the sensitivity of contrast echo of at least one order of magnitude.