Microfluidics systems for formulation of contrast agents for molecular imaging

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DESCRIPTION (provided by applicant): Ultrasound contrast agents are stabilized microbubbles with diameters on the order of 1-10 microns. Because the compressibility of the gas core of these microbubbles, they are substantially more echogenic than the interfaces between different types of tissue that ultrasound is traditionally used to detect. To this date, available microbubble contrast agents are produced with techniques which result in a polydisperse size distribution. Since the resonance frequency of the contrast agent depends on its diameter, an aliquot of current contrast agents has a wide range of resonance frequencies. This variance limits the sensitivity of current ultrasound imaging systems, which have bandwidth limits which permit detection of only a narrow range of resonance frequencies. With this research, we will produce a new type of contrast agent with a small size distribution. Significantly decreasing the polydispersity of the contrast agent will result in an increase in the sensitivity of the imaging system. Through simulations, we have estimated that by reducing the standard deviation in the size distribution from the current average of 1.5 microns to 0.2 microns would increase sensitivity of the imaging system over 500%. Recently, our research group has demonstrated that nearly monodisperse contrast agents can be produced using a technique known as flow-focusing. In this proposal, support is requested for manufacture and testing of a novel type of microfluidic system designed to produce monodisperse, micron-sized, contrast agents. Preliminary studies have demonstrated feasibility of using microfluidic technology for achieving the desired goal. We are able to produce bubbles on the order of 8 microns using a flow-focusing microfluidic device. The further development of this microfluidic system, and resulting production of monodisperse contrast agents, will open several new avenues for high sensitivity targeted ultrasound imaging.