Lu Chang, Zhang Hongyi, Yu Alfred C H, Qin Peng
School of Automation and Intelligent Sensing, Shanghai Jiao Tong University, Shanghai 200240, China.
Schlegel Research Institute for Aging, University of Waterloo, Waterloo, ON N2L3G1, Canada.
J Colloid Interface Sci. 2025 Dec;699(Pt 1):138123. doi: 10.1016/j.jcis.2025.138123. Epub 2025 Jun 8.
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.
微泡的声学响应强烈依赖于壳层的粘弹性。准确表征粘弹性特性对于为超声成像和治疗定制磷脂至关重要。然而，目前对非线性表面积相关的壳层粘弹性的理解有限。我们使用流动聚焦微流体技术制备了具有不同磷脂壳层的单分散微泡（MDMBs）。通过分析共振频率随时间的变化，评估MDMBs的壳层是否已接近最终机械压缩状态。基于测量的压力相关半径，通过将线性化振荡模型拟合到测量的压力相关衰减光谱来表征表面积相关的粘弹性特性。对于所有类型的MDMBs，在膨胀时，壳层弹性略有增加，随后迅速降至几乎为零；粘度最初下降，然后增加；表面张力（ST）逐渐增加到周围介质的表面张力。在压缩时，弹性和粘度分别持续下降和增加；ST降至几乎为零。对于不同类型的MDMBs，弹性与气泡半径无关，而粘度随气泡半径增加。弹性主要取决于主要脂质，与脂质乳化剂无关。基于DSPC的MDMBs比基于DPPC的MDMBs表现出更高的弹性。当在主要脂质和乳化剂中使用相同的酰基链长度时，酰基链壳层较短的气泡中初始ST低于20 mN/m，数值更小。这些为微泡壳层粘弹性的标准化表征提供了指导，并有助于为设计先进的微泡定制磷脂。
