Acoustic interrogation and optical visualization of ultrasound contrast agents within microcapsules

The effectiveness of localized drug delivery as a treatment for breast cancer requires sufficiently high therapeutic dose, as well as an ability to image the drug for proper spatial targeting. To balance treatment potential and imaging capabilities, we have begun to design a novel drug reservoir using microcapsules that are large in size (> 30 µm) but functionalized with microbubbles or ultrasound contrast agents (UCAs). We term these carriers as 'Acoustically Sensitive Microcapsules' (ASMs). In previous work, we have demonstrated preparation of ASM carriers and their structural changes under therapeutic ultrasound by imaging static changes. In this paper, we describe a combined optical-acoustic setup coupled with a microfluidic device to trap these carriers for imaging and sonication. Using the setup, continuous wave ultrasound (180 kPa, 2.25 MHz, 3 s) produced an average displacement of 3.5 µm in UCAs near the ASM boundary, and exhibited displacement as high as 90 µm near the center of the microcapsule. Longer exposure time and higher acoustic pressure increased UCA displacement within an ASM. These two parameters can be carefully optimized in the future to cause these UCAs to travel to the membrane boundary to help in the drug elution process.