Sonoporation of Cells by a Parallel Stable Cavitation Microbubble Array

Abstract

Sonoporation is a targeted drug delivery technique that employs cavitation microbubbles to generate transient pores in the cell membrane, allowing foreign substances to enter cells by passing through the pores. Due to the broad size distribution of microbubbles, cavitation events appear to be a random process, making it difficult to achieve controllable and efficient sonoporation. In this work a technique is reported using a microfluidic device that enables in parallel modulation of membrane permeability by an oscillating microbubble array. Multirectangular channels of uniform size are created at the sidewall to generate an array of monodispersed microbubbles, which oscillate with almost the same amplitude and resonant frequency, ensuring homogeneous sonoporation with high efficacy. Stable harmonic and high harmonic signals emitted by individual oscillating microbubbles are detected by a laser Doppler vibrometer, which indicates stable cavitation occurred. Under the influence of the acoustic radiation forces induced by the oscillating microbubble, single cells can be trapped at an oscillating microbubble surface. The sonoporation of single cells is directly influenced by the individual oscillating microbubble. The parallel sonoporation of multiple cells is achieved with an efficiency of 96.6 ± 1.74% at an acoustic pressure as low as 41.7 kPa.

Cell Lysis Based on an Oscillating Microbubble Array

“…Moreover, from Kumar and Kuloor (1970) study, we obtain that orifice size and material-dependent surface wettability as equipment variables affect bubble formation [32]. The resonant frequency of the microbubble was approximately 107 kHz and a more detailed calculation can be found in previous work [20]. The signal amplified by a power amplifier (100A400A, Amplifier Research, Souderton, PA, USA) was applied to PZT to excite the microbubble vibration.…”

“…A microfluidic channel was fabricated using the standard replica molding technique [20,29,30]. The geometry of the device is shown in Figure 1.…”

“…Additionally, from Figure 3, we obtain that the ultrasound energy is uniform on the microchannel by LDV. We can estimate the magnitude of shear stress for cell lysis by the following Equation [20,35,36]: When input voltage is applied to PZT, the cells can be trapped on the surface of oscillating bubbles within seconds, as shown in Video S1. The trapping mechanism was mainly based on two primary forces applied to cells induced by the vibrated bubble.…”

“…We can estimate the magnitude of shear stress for cell lysis by the following Equation [20,35,36]: We can estimate the magnitude of shear stress for cell lysis by the following Equation [20,35,36]: Figure 4.…”

“…According to different dynamic behaviors of bubbles, cavitation effect can be divided into inertial cavitation (formerly called transient cavitation) and stable cavitation (also called non-inertial cavitation) [18]. Compared to inertial cavitation, the acoustic pressure required for stable cavitation is not too high, and the process of stable cavitation is more controllable [19][20][21][22]. However, cavitation seems to be a random process, and it is difficult to break the cells completely.…”