Theoretical and experimental evaluation of microstreaming created by a single microbubble: Application to sonoporation

Abstract

It is hypothesized that microstreaming might play a role in the sonoporation process, inducing shear stresses which create tension and stretching over the cell membrane and thus lead to its transient permeabilization. In this study, the results of microscopic particle-image velocimetry (PIV) for large bubbles are presented and compared to those obtained using a numerical model. Air bubbles were created in a water solution and then attached to a wall. For each bubble, the microstreaming was measured over a plane located at a distance of 50 µm from the bubble wall. Bubbles were excited using a single element transducer at 28 kHz and 7 kPa. The acoustic microstreaming generated by the air bubble was calculated for the same excitation signal by using a theoretical model based on an analytical solution of the time-averaged Navier-Stokes equation. This approach was also applied to estimate the flow around an encapsulated contrast microbubble using an excitation signal centered at 2.87 MHz with a pressure amplitude of 50 kPa. PIV measurements show that a maximal average velocity of 0.25 mm/s occurs near the bubble resonant size (244 µm diameter bubble). For this bubble, the shear stress is also maximal. Theoretical data are in good qualitative agreement with PIV measurements. Using the contrast agent microbubble model, a maximal flow velocity and shear stress of 4 mm/s and 19 Pa respectively are obtained for a 2.5 µm diameter bubble. The shear stresses are much higher than those produced by normal blood flow (0.5 -2 Pa). These results suggest that bubbles are capable of exerting significant shear stresses on the cell membrane, affecting likely the sonoporation process.

Ultrasound and Microbubbles for Targeted Drug Delivery to the Lung Endothelium in ARDS: Cellular Mechanisms and Therapeutic Opportunities

“…These and several other theoretical and experimental studies showed that acoustic microstreaming may be a major mechanism of sonoporation [105][106][107]. Furthermore, microstreaming flow pattern is strongly dependent on the driving ultrasound frequency, microbubble size, pressure amplitude, properties of surrounding media as well as oscillation mode of microbubbles, which might explain why sonoporation and intracellular delivery of molecules are strongly affected by these parameters, as noted in several other studies [102,[108][109][110].…”

“…Ultrasound-driven, oscillating microbubbles undergoing stable cavitation are known to generate steady vortical flows in the surrounding liquid (i.e., swirling motion of surrounding liquid), frequently referred as acoustic microstreaming [100]. It is suggested that these microstreaming flows induce a shear stress on the nearby cells resulting in tension and stretching of the membrane, thereby inducing transient membrane perforation [101,102]. One of the earliest experimental studies on microstreaming-induced sonoporation was performed with an ultrasonic horn transducer (also known as Mason horn, sonotrode, ultrasonic homogenizer or disintegrator) vibrating at 21.4 kHz inside a Jurkat lymphocyte suspension [103,104].…”

“…Theoretical calculations performed by the same research group indicated that acoustic microstreaming flows generated by microbubbles could induce shear stresses of similar or higher magnitude, thus facilitating sonoporation [101]. Using a combination of particle image velocimetry (PIV) and theoretical analysis, other researchers have shown that the shear stresses induced by acoustic microstreaming flows around microbubbles are significantly higher (~19 Pa) than the shear stresses induced by normal blood flow (~0.5-2 Pa), resulting in sonoporation [102]. These and several other theoretical and experimental studies showed that acoustic microstreaming may be a major mechanism of sonoporation [105][106][107].…”

Ultrasound-enhanced cascade chemodynamic tumor nanotherapy with lactic acid-enabled hydrogen peroxide self-production

“…51 Furthermore, the oscillation and expansion of the microbubble bring shear pressure to bear on the cell membrane for augmenting permeability. 51,52 High-performance tumor treatment has always been the focus of research. Although nanoparticles can gather in tumors via enhanced permeability and retention effect (EPR), [53][54][55] it is not enough to sustain tumor therapy.…”

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

“…[7][8][9] Although the exact mechanism involved in the sonoporation process has not been fully under-stood due to the complexity of US-mediated interactions between cell and microbubbles, it has been hypothesized that shear stress resulting from microstreaming generated near pulsating bubbles may play an important role generating the sonoporation process. [10][11][12][13][14][15][16][17][18] For instance, Doinikov and Bouakaz have calculated the shear stress distribution on the cell membrane generated by an encapsulated bubble detached from the cell, and used this model for bubble-cell interactions to evaluate the number of sonoporated cells in the bubble-cell solution. [18] Microstreaming relies on the large velocity gradient due to small length scales of the oscillating bubble.…”