一种靶向蛋白质超声微泡的制备及表征

以氟碳气体为超声造影剂,通过接枝纳米磁性颗粒-RGD多肽,构建靶向蛋白质超声微泡,制备一种可同时用于超声造影和磁共振成像(MRI)的双模态造影增强剂。通过显微镜对磁性蛋白超声微泡形貌进行观察,利用红外光谱、分光光度法分析纳米磁性颗粒接枝牛血清蛋白的接枝率,并通过细胞实验评价磁性蛋白微泡的生物相容性。     

Computational modeling of microbubble coalescence and breakup using large eddy simulation and Lagrangian tracking

The flow of dispersed microbubbles was studied with an Eulerian–Lagrangian technique using large eddy simulation to predict the continuous liquid flow and Lagrangian tracking to compute bubble trajectories. The model fully accounts for bubble coalescence and breakup and was applied to horizontal and vertical channel flows. With low levels of turbulence, gravity in horizontal, and lift in vertical, channel flows govern the bubble spatial and collision distribution. When turbulence is sufficiently high to, at least partially, oppose bubble preferential concentration, more uniform collision and coalescence distributions are found, although these remain peaked near the wall in both configurations. Almost 100% coalescence efficiency was always found, due to bubbles colliding along similar trajectories, with breakup only recorded in a flow of low surface tension refrigerant R134a. Models like this can provide the required quantitative understanding of the microbubbles complex behavior, as well as supporting the development of more macroscopic modeling closures.     

Increasing the nonlinear character of microbubble oscillations at low acoustic pressures

The nonlinear response of gas bubbles to acoustic excitation is an important phenomenon in both the biomedical and engineering sciences. In medical ultrasound imaging, for example, microbubbles are used as contrast agents on account of their ability to scatter ultrasound nonlinearly. Increasing the degree of nonlinearity, however, normally requires an increase in the amplitude of excitation, which may also result in violent behaviour such as inertial cavitation and bubble fragmentation. These effects may be highly undesirable, particularly in biomedical applications, and the aim of this work was to investigate alternative means of enhancing nonlinear behaviour. In this preliminary report, it is shown through theoretical simulation and experimental verification that depositing nanoparticles on the surface of a bubble increases the nonlinear character of its response significantly at low excitation amplitudes. This is due to the fact that close packing of the nanoparticles restricts bubble compression.     

Pumping,spraying, and mixing of fluids by electric fields

The mechanism of electrostatic spraying of insulating fluids, such as air or organic solvents, into relatively conductive fluids, such as water, is investigated in this work. Experiments with air sprayed into water through an electrified capillary showed that the pressure inside the capillary increases, reaches a maximum, and then decreases as the applied voltage is increased. The initial pressure increase is due to the electric stress on the fluid interface, while the decrease is due to the Coulombic electrohydrodynamic flow generated near the end of the capillary. It is shown that electric fields can cause simultaneous pumping, spraying, and mixing of fluids. This phenomenon is demonstrated for air and kerosene in water.     

Ultrasound-Triggered Enzymatic Gelation

Hydrogels are formed using various triggers, including light irradiation, pH adjustment, heating, cooling, or chemical addition. Here, a new method for forming hydrogels is introduced: ultrasound-triggered enzymatic gelation. Specifically, ultrasound is used as a stimulus to liberate liposomal calcium ions, which then trigger the enzymatic activity of transglutaminase. The activated enzyme catalyzes the formation of fibrinogen hydrogels through covalent intermolecular crosslinking. The catalysis and gelation processes are monitored in real time and both the enzyme kinetics and final hydrogel properties are controlled by varying the initial ultrasound exposure time. This technology is extended to microbubble–liposome conjugates, which exhibit a stronger response to the applied acoustic field and are also used for ultrasound-triggered enzymatic hydrogelation. To the best of the knowledge, these results are the first instance in which ultrasound is used as a trigger for either enzyme catalysis or enzymatic hydrogelation. This approach is highly versatile and can be readily applied to different ion-dependent enzymes or gelation systems. Moreover, this work paves the way for the use of ultrasound as a remote trigger for in vivo hydrogelation.     

Chemical hydrodynamics of a downward microbubble flow for intensification of gas‐fed bioreactors

Bioreactors are of interest for value‐upgrading of stranded or waste industrial gases. Reactor intensification requires development of low cost bioreactors with fast gas–liquid mass transfer rate. Here we assess published reactor technology in comparison with a novel downward bubble flow created by a micro‐jet array. Compared to known technology, the advanced design achieves higher volumetric gas transfer efficiency (k_La per power density) and can operate at higher k_La. We measure the effect of four reactor heights (height‐to‐diameter ratios of 12, 9, 6, and 3) on the gas transfer coefficient k_L, total interfacial area a, liquid residence time distribution, energy consumption, and turbulent hydrodynamics. Leading models for predicting k_L and a are appraised with experimental data. The results show k_L is governed by “entrance effects” due to Higbie penetration dominate at short distances below the micro‐jet array, while turbulence dominates at intermediate distances, and finally terminal rise velocity dominates at large distances. © 2017 American Institute of Chemical Engineers AIChE J, 64: 1399–1411, 2018     

生物医学诊疗用磁性微纳材料

磁性微气泡是由包膜微气泡和磁性纳米粒子组成的微纳复合结构,由于其具有超声对比剂和核磁共振对比剂的双重特性,已被应用于双模造影领域。声致穿孔现象（Sonoporation）使得磁性微气泡能介导多种生物学效应,使其在药物输运和基因转染等方面有潜在的应用价值,而磁性微气泡与各种生物分子（抗体、肿瘤标记物等）的偶联,又扩展了磁性微气泡的应用领域,可用于分子影像诊断和靶向治疗肿瘤等方面,可以说磁性微气泡是新一代的生物医学诊疗用磁性微纳材料。总结了磁性微气泡的制备方法,磁性纳米颗粒与微气泡的结合方式,磁性微气泡的功能扩展,以及磁性微气泡在生物医学诊疗领域的实验研究,最后对磁性微气泡在未来的发展方向提出了一些构想,展望了磁性微气泡在诊疗学上广阔的应用前景。     

生物医学诊疗用磁性微纳材料

磁性微气泡是由包膜微气泡和磁性纳米粒子组成的微纳复合结构,由于其具有超声对比剂和核磁共振对比剂的双重特性,已被应用于双模造影领域。声致穿孔现象（Sonoporation）使得磁性微气泡能介导多种生物学效应,使其在药物输运和基因转染等方面有潜在的应用价值,而磁性微气泡与各种生物分子（抗体、肿瘤标记物等）的偶联,又扩展了磁性微气泡的应用领域,可用于分子影像诊断和靶向治疗肿瘤等方面,可以说磁性微气泡是新一代的生物医学诊疗用磁性微纳材料。总结了磁性微气泡的制备方法,磁性纳米颗粒与微气泡的结合方式,磁性微气泡的功能扩展,以及磁性微气泡在生物医学诊疗领域的实验研究,最后对磁性微气泡在未来的发展方向提出了一些构想,展望了磁性微气泡在诊疗学上广阔的应用前景。     

Phospholipid-based ultrasonic microbubbles for loading protein and ultrasound-triggered release

Background: Ultrasonic microbubbles are used as ultrasound-triggered delivery carriers for protein drugs. Aim: This work was to prepare stabilized protein-loaded phospholipid-based ultrasonic microbubbles (PUM) and to determine its value as a protein delivery system. Method: Bovine serum albumin (BSA) was used as a model protein drug. BSA-containing PUM were prepared by dissolving lyophilized PUM powder in BSA solution. The particle size and microbubble concentration of BSA-containing PUM were measured. The BSA encapsulation efficiency as a function of BSA concentration was determined. Contrast enhancement of BSA-containing PUM in vivo was detected. The release profile of BSA from PUM was also investigated. Results: The mean particle size and microbubble concentration of PUM were unchanged by the presence of BSA for at least 30 minutes after preparation. The net amount of BSA entrapped in PUM was maintained unchanged with increasing BSA concentration. BSA-containing PUM were shown easily to be visible in in vivo rabbit kidney. There was no difference in echogenicity between the loaded and unloaded PUM. Ultrasound duration had a positive relationship with BSA release. Ultrasound of 30 seconds stimulated 94.1% and 93.3% of BSA release from PUM solutions containing 0.3% and 1.5% BSA, respectively. Conclusions: Protein-loaded PUM exhibited satisfactory physical characteristics and were potent for using in ultrasound-triggered delivery.