Sonoporation generates downstream cellular impact after membrane resealing

Sonoporation via microbubble-mediated ultrasound exposure has shown potential in drug and gene delivery. However, there is a general lack of mechanistic knowledge on sonoporation-induced cellular impact after membrane resealing, and this issue has made it challenging to apply sonoporation efficiently in practice. Here, we present new evidence on how sonoporation, without endangering immediate cell viability, may disrupt downstream cellular hemostasis in ways that are distinguished from the bioeffects observed in other sonicated and unsonoporated cells. Sonoporation was realized on HL-60 leukemia cells by delivering pulsed ultrasound (1 MHz frequency, 0.50 MPa peak negative pressure; 10% duty cycle; 30 s exposure period; 29.1 J/cm2 acoustic energy density) in the presence of lipid-shelled microbubbles (1:1 cell-to-bubble ratio). Results showed that 54.6% of sonoporated cells, despite remaining initially viable, underwent apoptosis or necrosis at 24 h after sonoporation. Anti-proliferation behavior was also observed in sonoporated cells as their subpopulation size was reduced by 43.8% over 24 h. Preceding these cytotoxic events, the percentages of sonoporated cells in different cell cycle phases were found to be altered by 12 h after exposure. As well, for sonoporated cells, their expressions of cytoprotective genes in the heat shock protein-70 (HSP-70) family were upregulated by at least 4.1 fold at 3 h after exposure. Taken altogether, these findings indicate that sonoporated cells attempted to restore homeostasis after membrane resealing, but many of them ultimately failed to recover. Such mechanistic knowledge should be taken into account to devise more efficient sonoporation-mediated therapeutic protocols.

Edge Fillet Radius Effect on Acoustic Energy in an Ultrasonic Microcontainer for Preparing Nanoemulsion

Nanoemulsion preparation and improvement play a pivotal role in the area of pharmaceuticals, food, mechanical, and chemical engineering. The ultrasonic technique is one of the most commonly used methods in preparing nanoemulsion, related to mechanical and electrical engineering. The present study aimed to evaluate the effect of edge fillet radius in four different layouts of a cubic ultrasonic microcontainer at different frequencies through 36 simulations by using COMSOL Multiphysics software. To this aim, the simulations were performed in three edge fillet radius values of zero, 2.5 and 5 mm, and at the excitation frequencies of 20, 200 and 300 kHz. In this regard, experimental tests were carried out in two modes of: a) regular ultrasonic bath (RUB) and b) filleted-edges ultrasonic bath (FEUB). Based on the simulation and experimental results, the removal of sharp edges has a positive influence on propagating waves, leading to an increase in the acoustic energy density at different frequencies and the effect was more significant at lower frequencies and layouts with more PZTs.

Monte-Carlo Based Sensitivity Analysis of Acoustic Sorting Methods

Separation in microfluidic devices is a crucial enabling step for many industrial, biomedical, clinical or chemical applications. Acoustic methods offer contactless, biocompatible, scalable sorting with high degree of reconfigurability and are therefore favored techniques. The literature reports on various techniques to achieve particle separation, but these do not investigate the sensitivity of these methods or are difficult to compare due to the lack of figures of merit. In this paper, we present analytical and numerical sensitivity analysis of the time-of-flight and a phase-modulated sorting scheme against various extrinsic and intrinsic properties. The results reveal great robustness of the phase-modulated sorting method against variations of the flow rate or acoustic energy density, while the time-of-flight method shows lower efficiency drop against size and density variations. The results presented in this paper provide a better understanding of the two sorting methods and offer advice on the selection of the right technique for a given sorting application.

Structural Source Identification from Acoustic Measurements Using an Energetic Approach

An inverse energy method for the identification of the structural force in high frequency ranges from radiated noise measurements is presented in this paper. The radiation of acoustic energy of the structure coupled to an acoustic cavity is treated using an energetic method called the simplified energy method. The main novelty of this paper consists in using the same energy method to solve inverse structural problem. It consists of localization and quantification of the vibration source through the knowledge of acoustic energy density. Numerical test cases with different measurement points are used for validation purpose. The numerical results show that the proposed method has an excellent performance in detecting the structural force with a few acoustical measurements.

Estimation of Acoustic Energy and Performance Characterization of Acoustic Concentrator

Among many methods of particle concentration in liquid, acoustic concentrator uses ultrasonic standing wave to concentrate microparticles in liquid. In order to determine its performance on particle concentration, estimation of acoustic energy density inside the concentrator is important since energy density is the main contributing factor in calculating the primary acoustic radiation force acting on the particles. The balance between the primary radiation force and hydrodynamic force acting on the particles inside the acoustic concentrator determine the performance of the acoustic concentrator. Therefore, this study focuses on the measurement of acoustic energy density inside the h-shaped acoustic concentrator and characterization of performance of the concentrator. First, energy density is estimated by curve-fitting the experimental particle position in the ultrasonic field with one-dimensional theoretical position. Second, two-dimensional acoustic and hydrodynamic fields are determined using two-dimensional simulation model in COMSOL Multiphysics. Integrating the governing equation for particle motion in the balance of acoustic and hydrodynamic forces result in the particle trajectory and it is compared with the experimental observation. The results would provide deeper insight into the operation of acoustic concentrator and the detailed phenomenon of particle motions inside the concentrator.