Response of chemically crosslinked microbubble clusters in an ultrasound field

Abstract

The purpose of this study is to introduce a new concept of chemically cross-linked microbubble clusters (CCMCs), demonstrate a facile means of their production, and describe how they can potentially be used in biomedical applications. Currently, ultrasound contrast agents (UCAs- also known as microbubbles) are thought of as single gas bubbles stabilized by a biocompatible shell with sizes ranging from 1–10 μm. By tethering UCAs together into CCMCs, we propose that novel methods of ultrasound-mediated imaging and therapy can be developed through unique inter-bubble interactions in an ultrasound field. One of the major challenges in generating CCMCs is maintaining stability to Ostwald Ripening and coalescence. In this study, we demonstrate that chemically cross-linked microbubble clusters can produce small (<10 μm) quasi-stable complexes that slowly fuse into bubbles with individual gas cores. Furthermore, we demonstrate that this process can be driven with low-intensity ultrasound pulses, enabling a rapid fusion of clusters which could potentially be used to generate novel acoustics. The development of novel microbubble clusters here presents a simple yet robust process for generating novel UCAs with a design that could allow for more versatility in contrast-enhanced ultrasound (CEUS), molecular imaging, and drug delivery applications.The purpose of this study is to introduce a new concept of chemically cross-linked microbubble clusters (CCMCs), demonstrate a facile means of their production, and describe how they can potentially be used in biomedical applications. Currently, ultrasound contrast agents (UCAs- also known as microbubbles) are thought of as single gas bubbles stabilized by a biocompatible shell with sizes ranging from 1–10 μm. By tethering UCAs together into CCMCs, we propose that novel methods of ultrasound-mediated imaging and therapy can be developed through unique inter-bubble interactions in an ultrasound field. One of the major challenges in generating CCMCs is maintaining stability to Ostwald Ripening and coalescence. In this study, we demonstrate that chemically cross-linked microbubble clusters can produce small (<10 μm) quasi-stable complexes that slowly fuse into bubbles with individual gas cores. Furthermore, we demonstrate that this process can be driven with low-intensity ultrasound pulses, enabling a rapi...