Encapsulated microbubbles are used as contrast agents for molecular imaging with ultrasound. Current techniques of producing microbubbles result in a large size variance. Detection of these contrast agents depends on properties related to the microbubble size such as resonant frequency, and current ultrasound imaging systems have bandwidth limits which reduce their sensitivity to a polydisperse contrast agent population. For ultrasonic molecular imaging, where only a limited number of targeted contrast agents may be retained at the site of pathology, it is important to optimize sensitivity of the imaging system to the entire population of contrast agent. In this manuscript, a microfluidics technique was used to produce monodisperse microbubbles having a narrow size distribution specifically for ultrasound molecular imaging. Monodisperse microbubbles within the diameter range of 1-10 microns can be made with a diameter standard deviation on the order of 0.2 microns. These results are in contrast to currently available lipid shelled agents, which we measure to have a standard deviation in diameter on the order of 1 micron. We demonstrate the manufacture of monodisperse functionalized and targeted lipid-shelled microbubble contrast agents for molecular imaging applications, and we demonstrate acoustically that our monodisperse agents demonstrate a higher pulse to pulse echo correlation compared to that of polydisperse microbubbles (0.9 vs. 0.7). Our initial results indicate that optimizing contrast agent distribution has the potential to enhance the sensitivity of contrast imaging.

Extended Abstract Status: Not Uploaded