The Effect of Different PEG Chain Conformations on the Stability and Shell Elasticity of Monodisperse Microbubbles

The acoustic-induced oscillation and stability of microbubbles are mainly governed by the physicochemical characteristics of their encapsulating shells. Addressing how shell compositions influence both the stability and shell elasticity of microbubbles is essential for improving ultrasound-based diagnostic and therapeutic strategies. In this study, monodisperse lipid-coated microbubbles with varying molar ratios of a primary lipid and a pegylated-lipid were generated using a flow-focusing microfluidic device . The density of lipid packing on the shell was modulated by adjusting the surrounding ambient pressure. The measured temporal change of pressure-dependent resonance-frequency profiles during bubble dissolution was used to evaluate the microbubble stability. Shell elasticity, as a function of surface area, was calculated by fitting a theoretical oscillation model to experimentally obtained pressure-dependent acoustic attenuation spectra. Results showed that reducing the molar proportion of pegylated-lipid accelerated the transition rate of microbubbles, indicative of reduced bubble stability. Microbubbles with 5%– 10% pegylated-lipid exhibited significantly lower elasticity compared to those with 1%–2%, while the elasticity of microbubbles with above or below 5% had no significant difference. The methodology presented here offers a robust framework for dissecting the relationships between shell composition, stability, and viscoelasticity, and guide the design of microbubbles for ultrasound-base medical applications.