Formulation of Monodisperse Contrast Agents in Microfluidic Systems for Ultrasonic Imaging

Abstract

We have successfully demonstrated a microfluidic flow-focusing method to produce monodisperse contrast agents with a mean diameter of 4.0 microns, which is optimal for current ultrasonic imaging techniques. Currently available microbubble contrast agents are produced with agitation techniques, and the random nature of this process results in a highly polydisperse size distribution. PDMS-based microfluidic flow-focusing systems are a cost-effective means to easily and rapidly produce bubbles with a diameter of a few microns. Our device uses expanding nozzle geometry, focusing the bubble break-off location to one single point located at the orifice, which enables the formation of monodisperse bubbles. The geometry of the channel junctions in addition to the liquid and gas flow rates are used to control the bubble sizes. Using this technique, the microbubble diameter can be easily tailored to produce contrast agents with a precise size distribution optimized for various ultrasonic imaging applications