Abstract
Lipid-shelled microbubbles (MBs) and echogenic liposomes (ELIPs) have been proposed as acoustofluidic theranostic agents after having been proven to be efficient in diagnostics as ultrasonic contrast agents. Their mechanical properties-such as shell stiffness, friction, and resonance frequency-are critical to their performance, stability, oscillatory dynamics, and response to sonication. A precise characterization of these properties is essential for optimizing their biomedical applications, however the current methods vary significantly in their sensitivity and accuracy. This review examines the experimental and theoretical methodologies used to quantify the mechanical properties of MBs and ELIPs, discusses how each approach estimates shell stiffness and friction, and outlines the strengths and limitations inherent to each technique. Additionally, the effects of parameters such as temperature and lipid composition on MB and ELIP mechanical behavior are examined. Four characterization methods are analyzed, including frequency-dependent attenuation, optical observation, atomic force microscopy (AFM), and laser scattering, their advantages and limitations are critically assessed. Additionally, the factors that influence the mechanical properties of the MBs and ELIPs, such as temperature and lipid composition, are examined. Frequency-dependent attenuation was shown to provide reliable shell elasticity estimates but is influenced by nonlinear oscillations, AFM confirms that microbubble stiffness is size-dependent with smaller bubbles exhibiting higher shell stiffness, and theoretical models such as modified Rayleigh-Plesset equations increasingly incorporate viscoelastic shell properties to improve prediction accuracy. However, many of these models still assume radial symmetry and neglect inter-bubble interactions, which can lead to inaccurate elasticity values when applied to dense suspensions. In such cases, using modified frameworks like the Sarkar model, which incorporates damping and surface tension explicitly, may provide more reliable estimates under nonlinear conditions. Additionally, lipid composition and temperature significantly affect shell mechanics, with higher temperatures generally reducing stiffness. On the other hand, inconsistencies in experimental protocols hinder direct comparison across studies, highlighting the need for standardized characterization methods and improved computational modeling.