Effect of non-acoustic parameters on heterogeneous sonoporation mediated by single-pulse ultrasound and microbubbles

Sonoporation—transient plasma membrane perforation elicited by the interaction of ultrasound waves with microbubbles—has shown great potential for drug delivery and gene therapy. However, the heterogeneity of sonoporation introduces complexities and challenges in the realization of controllable and predictable drug delivery. The aim of this investigation was to understand how non-acoustic parameters (bubble related and bubble-cell interaction parameters) affect sonoporation. Using a customized ultrasound-exposure and fluorescence-imaging platform, we observed sonoporation dynamics at the single-cell level and quantified exogenous molecular uptake levels to characterize the degree of sonoporation. Sonovue microbubbles were introduced to passively regulate microbubble-to-cell distance and number, and bubble size. 1 MHz ultrasound with 10-cycle pulse duration and 0.6 MPa peak negative pressure were applied to trigger the inertial collapse of microbubbles. Our data revealed the impact of non-acoustic parameters on the heterogeneity of sonoporation. (i) The localized collapse of relatively small bubbles (diameter, D < 5.5 μm) led to predictable sonoporation, the degree of which depended on the bubble-to-cell distance (d). No sonoporation was observed when d/D > 1, whereas reversible sonoporation occurred when d/D < 1. (ii) Large bubbles (D > 5.5 μm) exhibited translational movement over large distances, resulting in unpredictable sonoporation. Translation towards the cell surface led to variable reversible sonoporation or irreversible sonoporation, and translation away from the cell caused either no or reversible sonoporation. (iii) The number of bubbles correlated positively with the degree of sonoporation when D < 5.5 μm and d/D < 1. Localized collapse of two to three bubbles mainly resulted in reversible sonoporation, whereas irreversible sonoporation was more likely following the collapse of four or more bubbles. These findings offer useful insight into the relationship between non-acoustic parameters and the degree of sonoporation.     

Combining COMSOL modeling with acoustic pressure maps to design sono-reactors

Scaled-up and economically viable sonochemical systems are critical for increased use of ultrasound in environmental and chemical processing applications. In this study, computational simulations and acoustic pressure maps were used to design a larger-scale sono-reactor containing a multi-stepped ultrasonic horn. Simulations in COMSOL Multiphysics showed ultrasonic waves emitted from the horn neck and tip, generating multiple regions of high acoustic pressure. The volume of these regions surrounding the horn neck were larger compared with those below the horn tip. The simulated acoustic field was verified by acoustic pressure contour maps generated from hydrophone measurements in a plexiglass box filled with water. These acoustic pressure contour maps revealed an asymmetric and discrete distribution of acoustic pressure due to acoustic cavitation, wave interaction, and water movement by ultrasonic irradiation. The acoustic pressure contour maps were consistent with simulation results in terms of the effective scale of cavitation zones (∼10 cm and <5 cm above and below horn tip, respectively). With the mapped acoustic field and identified cavitation location, a cylindrically-shaped sono-reactor with a conical bottom was designed to evaluate the treatment capacity (∼5 L) for the multi-stepped horn using COMSOL simulations. In this study, verification of simulation results with experiments demonstrates that coupling of COMSOL simulations with hydrophone measurements is a simple, effective and reliable scientific method to evaluate reactor designs of ultrasonic systems.     

Acoustic properties of micro-perforated panel absorber having arbitrary cross-sectional perforations

Micro-perforated panel absorber is used in many noise control applications as a next-generation absorbing material. Perforation shapes of micro-perforated panel studied are usually circular in the past. However, in practice, the perforations are often non-circular or irregular shape due to manufacturing techniques. Sound absorption coefficient and absorption bandwidth of the micro-perforated panel absorber may be further improved, when the perforations in shape are changed. In view of the existing exact solutions of sound propagation in tubes, the simple formulas of specific acoustic impedances of the tubes for triangle and square cross-sectional perforations are derived. Mass reactance end correction of the micro-perforated panel is obtained based on the sound radiation of a shaped piston. The specific acoustic impedance ratio of the micro-perforated panel absorber is calculated and analyzed, which can predict its sound absorption bandwidth. Finally, for closed perforations, the influences of the perforations in shape (including triangle, circle, square and irregular circle) on sound absorption of the MPP absorber are discussed in collaboration with FE simulations.     

Optimization of the three-dimensional electric f ield in IH-DTL

The tuning process of the three-dimensional electric field near the beam axis is very important in the optimization of the Interdigital H-mode Drift Tube Linac (IH-DTL). The tuning of the longitudinal field distribution, the Kilpatrik (Kp) factor, and the transverse dipole field have been discussed in detail, combined with the radio-frequency tuning process of the 53.667 MHz short IH-DTL cavity, which was designed to accelerate ²³⁸U³⁴⁺ from 0.143 MeV/u to 0.289 MeV/u in the SSC-Linac injector project at the Institute of Modern Physics. The flatness criterion and the tube tuning method are discussed in order to meet the beam dynamics requirements. In the tube tuning process, the energy gain error in the cells should be reduced to less than ±2%, and the Kp factor should be reduced to 1.6. The transverse dipole field and the method that uses a "plunger" to dismiss this dipole field are evaluated. The experience gained from the first cavity optimization benefits the tuning process of the three remaining IH-DTL cavities in the SSC-Linac project.     

十字形银纳米结构的表面等离子体光子学性质

本文应用离散偶极子近似方法计算了十字形银纳米结构的消光光谱及其近场电场强度分布. 研究表明相比于单根纳米棒, 十字形纳米结构能够提供更强的表面电场; 由于相邻凸起间的电场耦合作用, 当入射光的偏振方向改变时, 在十字形纳米结构的侧表面总能激发出较强的电场.另外, 本文还系统地研究了十字形纳米结构的形貌参数对其表面等离子体共振峰的影响. 这些结果将会指导十字形纳米结构的制备, 以满足其在表面增强拉曼散射中的应用.     

Design of undercuts and dipole stabilizer rods for the CPHS RFQ accelerator

As part of the design and machining of the RFQ accelerator in the Compact Pulsed Hadron Source (CPHS) project at Tsinghua University, the design process of the undercuts and dipole stabilizer rods is presented in this paper. In particular, the relationship between the inter-vane voltage slope and the local frequency of the undercut section is described quantitatively. With the identification of modes existing in the cavity, the specific parameters are optimized by the SUPERFISH and MAFIA codes. In addition, the water-cooling requirement of the dipole stabilizer rods is briefly discussed.     

Reconstruction of the acoustic impedance profile in a plate using an inverse spectral procedure

An inverse spectral procedure was applied to reconstruct the acoustic impedance profile along the thickness direction of a plate using its thickness resonance frequencies, density and thickness. For a successful reconstruction, the material-property profile must be symmetric about the mid-plane of the plate. Several cases of numerical simulations, including plates with a few layers and with a high number of layers are described. The calculated resonance frequencies were used to reconstruct the acoustic impedance profile, a process that was successful for all cases. We assume that a plate with a high number of layers, each with a different but constant acoustic impedance, simulates a plate with a smoothly varying acoustic impedance profile. It can be concluded that such a plate, which generates small, virtually undetectable, internally reflected waves, can also be reconstructed. In the special case of a plate of unknown thickness and unknown but constant density, the method is still useful, because a relative variation of the material property can be reconstructed using only the resonance frequencies. An experiment using a resonance-mode electromagnetic acoustic transducer (resonance-mode EMAT) is also described. EMAT is a non-contact ultrasonic method that can measure thickness resonance frequencies, making it appropriate for this method. Some examples of applications are measurement of the temperature profile inside a rolled metal sheet, measurement of a clad metal plate, and monitoring of a metal casting.     

用于储罐底板缺陷检测的超声兰姆波模式研究

从超声兰姆波的声场方程出发,得到板材表面离面位移(法向位移)为零的条件,即当超声兰姆波的相速度等于板材介质的纵波声速时,在板材表面的离面位移为零。在给定适当频厚积的条件下,分别数值模拟了仅有切向位移而无离面位移的A1、S1、A2和S2兰姆波模式在有液体负载的单层钢板中的传播情形。结果表明:离面位移为零的S2模式频散较小且对板中缺陷更为敏感。     

随机分布黑碳-硅酸盐混合凝聚粒子的消光特性研究

基于分形理论,采用蒙特卡罗方法对随机分布的混合凝聚粒子的空间结构进行了仿真模拟。利用Bruggeman有效介质理论得到了占有不同体积份额黑碳的内混合凝聚粒子的等效复折射率。采用离散偶极子近似方法对随机分布混合凝聚粒子在内外混合状态下的吸收、散射和消光效率因子等消光特性参量进行了数值计算,深入探讨了混合方式、容积含量、入射波长以及基本粒子粒径和数量对混合凝聚粒子消光特性的影响规律。通过将所得数值结果与T矩阵方法的数值结果进行比较发现,两种数值方法计算的结果非常相近。结果表明,随机分布混合凝聚粒子的散射效率因子对混合方式非常敏感,消光效率因子对混合方式较敏感,而吸收效率因子对混合方式不敏感。随着凝聚粒子尺度参数的增大,混合方式对散射和消光效率因子的影响逐渐显著。内外混合方式下,随着黑碳体积比的增大随机分布混合凝聚粒子的吸收、散射和消光效率因子均近似线性增大,并且增大的幅度随着粒子尺度参数的增大而增大。     

电涡流传感器所受电磁力研究

本文研究电涡流传感器的探测线圈与电涡流之间的电磁作用力。理论计算与测量结果表明,对于某些应用电涡流传感器的灵敏装置而言,这个力的影响是不能忽略的。