Surface-area-dependent viscoelastic property characterization of monodisperse microbubbles with different...

The acoustic response of microbubbles is strongly dependent on the viscoelasticity of the shell. Accurately characterizing viscoelastic properties is crucial for tailoring phospholipids for ultrasound imaging and therapy. However, the current understanding of the nonlinear surface-area dependent shell viscoelasticity is limited. We used a flow-focusing microfluidic to fabricate monodisperse microbubbles (MDMBs) with different phospholipid shells. By analyzing the shift in resonance frequency with time, the MDMBs were evaluated if the shells had approached the final mechanical compression state. Based on the measured pressure-dependent radius, the surface-area-dependent viscoelastic properties were characterized by fitting a linearized oscillation model to the measured pressure-dependent attenuation spectra. For all types of MDMBs, upon expansion, the shell elasticity slightly increased, followed by a rapid decrease to almost zero; the viscosity initially decreased before increasing; and the surface tension (ST) gradually increased to that of the surrounding medium. Upon compression, the elasticity and viscosity continuously decreased and increased, respectively; and the ST decreased to almost zero. For different types of MDMBs, the elasticity was independent of bubble radius, whereas the viscosity increased with bubble radius. The elasticity mainly depended on the primary lipid and was independent of the lipid emulsifier. DSPC-based MDMBs exhibited higher elasticity than DPPC-based MDMBs. The initial ST below 20 mN/m was smaller in bubbles with shorter acyl chain shells when the same acyl chain length was used in primary lipid and emulsifier. These provide a guideline for the standardized characterization of shell viscoelasticity of microbubbles, and help tailor phospholipids for designing state-of-art microbubbles.