Microstreaming velocity field and shear stress created by an oscillating encapsulated microbubble near a cell membrane

Sonoporation mediated by microbubbles is being extensively studied as a promising technology to facilitate gene/drug delivery to cells. However, the theoretical study regarding the mechanisms involved in sonoporation is still in its infancy.Microstreaming generated by pulsating microbubble near the cell membrane is regarded as one of the most important mechanisms in the sonoporation process. Here, based on an encapsulated microbubble dynamic model with considering nonlinear rheological effects of both shell elasticity and viscosity, the microstreaming velocity field and shear stress generated by an oscillating microbubble near the cell membrane are theoretically simulated. Some factors that might affect the behaviors of microstreaming are thoroughly investigated, including the distance between the bubble center and cell membrane（d）, shell elasticity（χ）, and shell viscosity（κ）. The results show that（i） the presence of cell membrane can result in asymmetric microstreaming velocity field, while the constrained effect of the membrane wall decays with increasing the bubble-cell distance;（ii） the bubble resonance frequency increases with the increase in d and χ, and the decrease in κ,although it is more dominated by the variation of shell elasticity; and（iii） the maximal microstreaming shear stress on the cell membrane increases rapidly with reducing the d, χ, and κ. The results suggest that microbubbles with softer and less viscous shell materials might be preferred to achieve more efficient sonoporation outcomes, and it is better to have bubbles located in the immediate vicinity of the cell membrane.

Microflow-induced shear stress on biomaterial wall by ultrasound-induced encapsulated microbubble oscillation

A model of an ultrasound-driven encapsulated microbubble（EMB） oscillation near biomaterial wall is presented and used for describing the microflow-induced shear stress on the wall by means of a numerical method. The characteristic of the model lies in the explicit treatment of different types of wall for the EMB responses. The simulation results show that the radius-time change trends obtained by our model are consistent with the existing models and experimental results. In addition, the effect of the elastic wall on the acoustic EMB response is stronger than that of the rigid wall, and the shear stress on the elastic wall is larger than that of the rigid wall. The closer the EMB to the wall, the greater the shear stress on the wall. The substantial shear stress on the wall surface occurs inside a circular zone with a radius about two-thirds of the bubble radius. This paper may be of interest in the study of potential damage mechanisms to the microvessel for drug and gene delivery due to sonoporation.

Finite element modeling of acoustic scattering from an encapsulated microbubble near rigid boundary

This article proposes a finite element model （FEM） for predicting the acoustic scattering from an encapsulated microbubble near rigid boundary. The validity of the model is first examined by comparing the acoustic nonlinear response of a free microbubble with that obtained by the Church model. Then this model is used to investigate the effect of the rigid boundary on acoustic scattering signals from microbubble. The results indicate that the resonance frequency decreases while the oscillation amplitude increases as the microbubble approaches the rigid boundary. In addition, the fundamental component of the acoustic scattering signal is enhanced compared with that of the free microbubble.

Dynamical model of encapsulated gas microbubble under ultrasound based on elastic mechanics

Based on the theory of elastic mechanics, a dynamical model of an encapsulated gas microbubble under ultrasound is presented.The dynamical motion of the microbubble is divided into three states: buckled, elastic, and ruptured. The model describes the compression-only behavior appropriately and derives the transient variation of the resonance frequency of the damped oscillation and the relation between the critical rupture radius and initial outer radius. The normal stress in the tangential direction plays the principal role in the rupture and buckling of the encapsulating shell, resulting in likely rupture for a larger microbubble and resistance to rupture for a thicker-shell microbubble. Comparison of proposed dynamical model with Marmottant's model has been given. The dynamical model can be employed in ultrasound medical diagnostics and therapy of drug incorporation or extravasation through further understanding the influence of the encapsulating shell.