Dynamics of fragmentation of a multicharge fullerene ion

We have studied the process of fragmentation of a molecular ion of C₆₀ fullerene, which takes place as a result of the loss of five electrons in collision with a 64-keV Ar⁶⁺ ion. The spectrum of kinetic energies of the fragment ions with a given mass, as well as the number of such ions, were determined from the shapes of lines in the mass spectrum measured using a time-of-flight analyzer. It is established that, in addition to the capture of electrons by the projectile ion, an important role in the formation of a multicharge molecular C₆₀ ion is played by additional ionization of the target molecule. It is shown for the first time that the fragmentation of fullerene molecular ions is not a single-stage process. The kinetic energies and the mass spectrum of fragment ions are determined both by the Coulomb repulsion in a multicharge fullerene ion and by the subsequent additional decay of heavy fragment ions in the course of expansion.     

Radial modulation of single microbubbles

Radial modulation imaging is a new promising technique to improve contrast-enhanced ultrasound images. The method is based on dual-frequency insonation of contrast agent microbubbles. A low-frequency (LF) pulse is used to modulate the responses of the microbubbles to a high-frequency (HF) imaging pulse. Inverting the LF pulse induces amplitude and phase differences in the HF response of contrast agent microbubbles, which can be detected using Doppler techniques. Although the technique has been successfully implemented, no consensus persists on parameter choice and resulting effects. In a separate study, "compression-only" behavior of coated microbubbles was observed. Compression-only behavior could be beneficial for radial modulation imaging. This was investigated using high-speed camera recordings and simulations. We recorded the vibrations of 78 single microbubbles in a dual-frequency ultrasound field. The results showed that the LF pulse induced significant compression-only behavior, which for microbubble sizes below and at HF resonance resulted in high radial amplitude modulation. It, however, also appeared that, for radial modulation imaging, microbubble size is more important than resonance and compression-only effects.     

Detecting microbubbles in transformer oil

The growth of microbubbles under the action of a negative pressure wave in transformer oil (TO) has been studied. It is established that microbubbles in TO grow to a detectable size of 100–200 μm. According to the results of calculations, these bubbles can develop from the nuclei of micron and submicron dimensions.     

Multiple emulsion microbubbles for ultrasound imaging

In order to improve the sensitivity of ultrasound imaging, the contrast agents, a powerful non-invasive and real-time medical imaging technique, are used. However, air or N₂ or perfluorocarbon only encapsulated microbubbles which are currently used have lower efficiency and short imaging time. So the novel contrast agents with a higher efficiency are required. To achieve this objective, the strategy that we have explored involves the use of superparamagnetic iron oxide (SPIO) Fe₃O₄ nanoparticles multilayer emulsion microbubbles. This multilayer structure consists of three layers. The core is poly-d, l-lactide (PLA) encapsulated N₂ nanobubble with the SPIO nanoparticles forming oil-in-water (W/O) layer. The outermost is water-in-oil-in-water ((W/O)/W) emulsion layer with PVA solution. Herein we describe the synthesis and characterization of ultrasound imaging microstructure with an overall diameter of around 2μm-8μm. On the one hand, the stable gas encapsulated microstructure can provide a high scattering intensity resulting in high echogenicity, On the other hand, SPIO nanoparticles have shown the potential of high-resolution sonography. So the multiple emulsion microbubbles with SPIO can have double action to enhance the ultrasound imaging. Besides, because SPIO can also serve as magnetic resonance imaging (MRI) contrast agents, such microstructure may be useful for multimodality imaging studies in ultrasound imaging and MRI.     

The influence of blood on targeted microbubbles

The ability to successfully target the delivery of drugs and other therapeutic molecules has been a key goal of biomedical research for many decades. Despite highly promising in vitro results, however, successful translation of targeted drug delivery into clinical use has been extremely limited. This study investigates the significance of the characteristics of whole blood, which are rarely accounted for in vitro assays, as a possible explanation for the poor correlation between in vitro and in vivo experiments. It is shown using two separate model systems employing either biochemical or magnetic targeting that blood causes a substantial reduction in targeting efficiency relative to saline under the same flow conditions. This finding has important implications for the design of targeted drug delivery systems and the assays used in their development.     

Shielding and fragmentation studies

Radiation dosimetry for manned spaced missions depends on the ability to adequately describe the process of high-energy ion transport through many materials. Since the types of possible nuclear interactions are many and complex, transport models are used which depend upon a reliable source of experimental data. To expand the heavy ion database used in the models we have been measuring charge-changing cross sections and fragment production cross sections from heavy-ion interactions in various elementa targets. These include materials flown on space missions such as carbon and aluminium, as well as those important in radiation dosimetry such as hydrogen, nitrogen and water. Measuring heavy-ion fragmentation through these targets also gives us the ability to determine the effectiveness of new materials proposed for shielding such as graphite composites and polyethylene hybrids. Measurement without a target present gives an indication of the level of contamination of the primary beam, which is also important in radiobiology experiments.     

Optical and acoustic detection of laser-generated microbubbles in single cells

Acoustically monitored laser-induced optical breakdown (LIOB) has potential as an important tool to diagnose and treat living cells. Laser-induced intracellular microbubbles are readily detectable using high-frequency ultrasound, and LIOB can be controlled to operate within two distinct regimes. In the nondestructive regime, a single, short-lived bubble can be generated within a cell, without affecting its immediate viability. In the destructive regime, the induced photodisruption quickly can kill a targeted cell. To generate and monitor this range of bioeffects in real time, we have developed a system integrating an ultrafast laser source with optical and acoustic microscopy. Experiments were performed on monolayers of Chinese hamster ovary (CHO) cells. A 793 nm, 100 fs laser pulsed at 3.8 kHz was tightly focused within each cell to produce the photodisruption, and a 50 MHz ultrasonic transducer monitored the resultant bubble via continuous pulse-echo recordings. Photodisruption was also observed using bright field microscopy, and cell viability was assessed following laser exposure with a trypan blue assay. By controlling laser pulse fluence and exposure duration, either nondestructive or destructive LIOB could be produced. The intracellular position of the laser focus was also varied to demonstrate that cell viability was affected by the specific location of material breakdown.     

Self-activated fragmentation

We explore the consequences of a point of view stating that fracture in strained brittle solids results from the action of mechanically activated random fluctuations. As opposed to thermally activated fracture, the energy reservoir feeding the crack progression is given by the mean elastic energy stored in the cracked region, itself a sub-sample of the strained material. The crack and the material bulk exchange self-consistently energy and momentum via random elastic waves, which are themselves produced by the fracture progression. The statistics of the fluctuating energy, and of the random force directing the fracture are derived, as well as the corresponding Langevin dynamics of the crack position. The role of pre-existing defects in the material is shown to be secondary. We examine in particular the case of a bent beam, for which we determine the distributions of breakup times, fragments number and lengths as a function of its initial deformation and of the material elastic and cohesion properties. The corrections due to plasticity, the effect of a transiently applied load, and the special case of liquids are discussed as well.     

Preparation and antitumor activity of bFGF-mediated active targeting doxorubicin microbubbles

Characterization and antitumor activity of basic fibroblast growth factor-mediated active targeting doxorubicin microbubbles (bFGF-DOX-MB) were investigated. Pluronic F68 with chemical conjugation of doxorubicin (DOX-P) and peptide KRTGQYKLC-conjugated DSPE–PEG2000 were prepared. bFGF-DOX-MB had a normal distribution of particle size, with average particle size of 2.7 μm. Using A549 mouse model, bFGF-DOX-MB combined ultrasound showed the best inhibition effect on tumor volume growth among all the test groups. Similar conclusion was obtained from experimental measurements of tumor weight change and blood cell count. From the results, chemotherapeutic drug inhibition on tumor growth could be enhanced by local ultrasound combined with active targeting bFGF-DOX-MB, which might provide a potential application for ultrasound-mediated chemotherapy.     

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.     

Review of shell models for contrast agent microbubbles

Micrometer-scale encapsulated gas bubbles, known as ultrasound contrast agents, are used in ultrasound medical diagnostics for enhancing blood-tissue contrast during an ultrasonic examination. They are also employed in therapy as an activator of drug incorporation or extravasation. Adequate modeling of the effect of encapsulation is of primary importance because it is the encapsulating shell that determines many of the functional properties of contrast agents. In this review, existing approaches to the modeling of the radial motion of an encapsulated bubble are discussed and comparative analysis of available shell models is conducted. The capabilities of the shell models are evaluated in the context of recent experimental observations, such as compression-only behavior and the dependence of shell material properties on initial bubble radius. It is shown that for early shell models, the main problem is that the behavior of encapsulation is described by linear elastic and viscous laws, whereas recent experimental data attest to complicated rheological properties inherent in shell materials. Currently, a trend toward models involving nonlinear laws for shell elasticity and viscosity is observed. In particular, nonlinear models have been proposed that allow one to reproduce compression-only behavior. However, the problem of the radius dependence of shell material parameters remains unsolved.     

Ultrasound-induced gas release from contrast agent microbubbles

We investigated gas release from two hardshelled ultrasound contrast agents by subjecting them to high-mechanical index (MI) ultrasound and simultaneously capturing high-speed photographs. At an insonifying frequency of 1.7 MHz, a larger percentage of contrast bubbles is seen to crack than at 0.5 MHz. Most of the released gas bubbles have equilibrium diameters between 1.25 and 1.75 microm. Their disappearance was observed optically. Free gas bubbles have equilibrium diameters smaller than the bubbles from which they have been released. Coalescence may account for the long dissolution times acoustically observed and published in previous studies. After sonic cracking, the cracked bubbles stay acoustically active.     

Gas-storage ice grown from water containing microbubbles

Gas-storage ice is the ice that contains various functional gas pores, and can be produced by freezing water in which a desired gas is dissolved. In this conventional method, however, the gas content in the ice is limited by the gas solubility in water. To overcome this limitation, we developed a method to produce gas-storage ice from water in which microbubbles of a desired gas are dispersed, and then obtained images of the structural features of pores formed in the ice prepared using this microbubble method. The images clarified the interaction between a microbubble arriving at an ice–water interface and an existing pore already formed in the ice. The air content in ice prepared using the microbubble method was higher than that prepared using the conventional method, and was about three times higher than the solubility of air in water.     

Simulations and measurements of optical images of insonified ultrasound contrast microbubbles

Ultrasound contrast agents (UCAs) are used in a clinical setting to enhance the backscattered signal from the blood pool to estimate perfusion and blood flow. The UCAs consist of encapsulated microbubbles, measuring 1-10 /spl mu/m in diameter. Acoustic characterization of UCAs is generally carried out from an ensemble of bubbles. The measured signal is a complicated summation of all signals from the individual microbubbles. Hence, characterization of a single bubble from acoustic measurements is complex. In this study, 583 optical observations of freely flowing, oscillating, individual microbubbles from an experimental UCA were analyzed. The excursions during ultrasound exposure were observed through a microscope. Images were recorded with a high frame rate camera operating at 3 MHz. Microbubbles on these images were measured offline, and maximal excursions were determined. A technique is described to determine the diameters of the bubbles observed. We compared the maximal excursions of microbubbles of the same initial size in an ultrasound field with a 500 kHz center frequency at acoustic amplitudes ranging from 0.06 MPa to 0.85 MPa. It was concluded that maximal excursions of identical bubbles can differ by 150% at low acoustic pressures (mechanical index or MI<0.2). At a high acoustic pressure (MI=1.2) an image sequence was recorded on which a bubble collapsed, but an apparently identical bubble survived.     

Radial modulation of microbubbles for ultrasound contrast imaging

Over the past few years, extensive research has been carried out in the field of ultrasound contrast imaging. In addition to the development of new types of ultrasound contrast agents, various imaging methods dedicated to contrast agents have been introduced, and some of them are now commercially available. In this study, we present results of an imaging technique that is capable of detecting echoes from microbubbles and eliminating those emanating from nonoscillating structures (tissue), thereby enhancing contrast imaging. The method is based on mixing a low frequency (LF) modulator signal and a high frequency (HF) imaging signal to effectively modulate the size of the contrast microbubble through its volumetric oscillations using the LF signal and to probe the radial motion using the HF imaging signal. To evaluate the performances and limitations of the method, high-speed optical observations and acoustic measurements were carried out on soft-shelled microbubbles. The results showed that, by incorporating the modulator signal, the bubbles respond differently compared to the HF excitation alone. The decorrelation between the signals obtained at the compression and expansion phase of the modulator signal is significantly high to be used as a parameter to detect contrast microbubbles and discriminate them from tissue. The echo received from a solid reflector shows identical responses during the compression and rarefaction phase of the LF signal. In conclusion, these results demonstrate the feasibility of this fully linear approach for improving the contrast detection.     

Stable and transient subharmonic emissions from isolated contrast agent microbubbles

Ultrasound contrast agents (UCAs) have been widely studied in recent years in order to improve and develop new, sophisticated imaging techniques for clinical applications. In order to improve the understanding of microbubble-ultrasound interactions, an acoustic dynamic characterization of UCA microbubble behavior was performed in this work using a high frame-rate acquiring and processing system. This equipment is connected to a commercial scanner that provides RF beam-formed data with a frame-rate of 30 Hz. Acquired RF sequences allows us to follow the dynamics of cavitation mechanisms in its temporal evolution during different insonifying conditions. The experimental setup allowed us to keep the bubbles free in a spatial region of the supporting medium, thus avoiding boundary effects that can alter the ultrasound field and the scattered echo from bubbles. The work focuses on the study of subharmonic emission from an isolated bubble of contrast agent. In particular, the acoustic pressure threshold for a subharmonic stable emission was evaluated for a subset of 50 microbubbles at 3.3 MHz and at 5 MHz of insonation frequencies. An unexpected second pressure threshold, which caused the stand still of the subharmonic emission, was detected at 3.3 MHz and 5 MHz excitation frequencies. A transient subharmonic emission, which is hypothesized as being related to the formation of new free gas bubbles, was detected during the ultrasound-induced destruction of microbubbles. An experimental procedure was devised in order to investigate these behaviors and several sequences of RF echo signals and the related spectra, acquired from an isolated bubble in different insonation conditions, are presented and discussed in this paper.     

Mechanics of fibre fragmentation

A fragmentation specimen consists of a single fibre embedded along the axis of a long narrow resin block. When the fibre is broken by a tensile load, either a lateral crack runs outwards into the resin, initiated by the break, or a debond (or equivalently a cylindrical crack in the resin) propagates along the fibre. Debonding always occurs with thin fibres. Strain energy release rates have now been calculated, analytically for long debonds and by FEA for short ones. The force to propagate a debond is found to increase as the debond grows, reaching a final value, termed pull-out force, that is higher for softer fibres. If this force exceeds the strength of the fibre, then the fibre breaks again. This is the proposed mechanism of fibre fragmentation. For weakly-bonded, stiff fibres, the inferred minimum distance between breaks, i.e. the critical fragment length, is deduced to be of the order of the geometric mean of the radii of fibre and resin block, about 0.1–0.5 mm for typical fragmentation specimens, and it increases as the ratio of fibre stiffness to resin block stiffness increases, in agreement with observation.     

陶瓷微孔膜管制造微气泡的研究

气浮工艺中气泡的大小是衡量气泡制造技术的关键.研究了陶瓷微孔膜管产生微气泡的条件,并对两种不同材质的微孔膜管产生微气泡的结果进行了比较,从气泡形成机理上分析了影响气泡粒径分布的因素.实验采用静态显微摄像技术和图像分析系统时气泡粒径分布进行了表征.实验结果表明,利用陶瓷微孔膜管产生的气泡粒径主要集中在15～50 μm之间,平均粒径在25.7～44.2 μm之间.微孔膜管的孔径大小、表面性能,气体流量,剪切流流速,液体表面张力,黏度是影响气泡粒径分布的主要因素.