Properties Of Microbubbles Research Articles

Nanostructural features on stable microbubbles

Stable, surfactant-coated microbubbles offer an interesting new platform on which to study the nanostructural features of Langmuir monolayers, particularly in regions of high compression and where curvature effects are important. Recent electron and fluorescence microscopy images have revealed a rich array of possible domain shapes. Polygons, dendrites, beans and networks have been observed. Domain formation arises owing to Laplace-pressure-driven compression and may occur through more than one mechanism, such as phase separation or a buckling transition. Highlighted are recent reports on the relationships between surfactant composition, processing history and domain nanostructure. More work is necessary to better understand the origins of nanostructure and the impact on microbubble properties. Such insights will lead to creative and innovative microbubble formulations for biomedical and industrial applications.

A comparative study of microbubble generation by mechanical agitation and sonication

As focus on the potential applications of microbubbles increases, information about the efficiency of generation methods and their effects on the properties and stability of microbubbles is crucial in the selection of an appropriate method to generate microbubbles with the desired properties. This paper evaluates the generation efficiencies of two commonly used methods, mechanical agitation and sonication, in two surfactant systems. The results demonstrated that sonication was more effective than mechanical agitation in the generation of microbubbles in terms of higher gas hold-up, smaller bubble size, and larger interfacial area. Analysis of the changes in bubble size over time revealed that the existence of a critical diameter for the shrinkage of microbubbles. The behavior of microbubbles and the critical diameter depended on the generation method employed and the surfactant used. Microbubble technology has gradually become accepted as a cost-effective and environmentally friendly technology with great potential within almost every field of the food industry. Selection of a suitable method to generate microbubbles with the desired properties is crucial. Mechanical agitation and sonication are two commonly used methods for microbubble generation. However, systematic information on their generation efficiency and effects on the properties of microbubbles is not available. Thus, a comparative study was conducted in this paper.

21215 気泡表面電位がマイクロバブルの合体・収縮過程に及ぼす影響(マイクロバブル・界面現象,一般講演,学術講演)

The electrical properties of microbubbles are important in the interaction between bubbles and other materials, such as solid particles, fiber pulps and oil in oil-in-water emulsion, for technical applications of purification processes. The ζ potential was negative in distilled water and was negatively charged in a wide range of pH conditions. However, the effect of electrical potential of gas-water interface on the behavior and the characteristic of microbubbles have not been completely clarified yet. In this study, the compact and low power microbubble generator has been developed, and the ζ potential was measured by electrophoresis method in the several pH conditions. The coalescence process is observed at the time of interaction between two bubbles under low ζ potential conditions. On the other hand, in the case of a bubble with a high electrical potential, the coalescence does not occur due to the large electrostatic repellent force between two bubbles.

Point:Counterpoint: There is/is not capillary recruitment in active skeletal muscle during exercise

#### Focus. The key issue here is whether resting skeletal muscle is fully perfused. We will make the case that it is not, and thus there exists a reserve of unperfused capillaries (capillary reserve) that are recruited to carry flow not only by muscle contraction, but also by insulin. #### Our

Nanomechanical probing of microbubbles using the atomic force microscope

Atomic force microscopy (AFM) is a versatile mechanical nanosensor that can be used to quantify the mechanical properties of microbubbles (MBs) and the adhesion mechanisms of targeted MBs. Mechanical properties were investigated using AFM tipless cantilevers to microcompress the MBs. The range of compressive stiffness for biSphere ® was found to be between 1 and 10 N m −1 using a cantilever with a spring constant of 0.6 N m −1. This stiffness was shown to decrease with the MB size in a non-linear fashion. It is also possible to calculate a theoretical Young’s modulus of the shell. The adhesion properties of targeted lipid based MBs that use avidin–biotin chemistry for the attachment of targeting ligands were also studied. The MBs were attached to poly- l-lysine treated tipless cantilevers with spring constants ranging from 0.03 to 0.1 N m −1. This system interrogated individual cells with pulling cantilever distance of 15 μm, and scan rate at 0.2 Hz. The depth of contact was not larger than 0.4 μm. The targeted MBs provided a significantly larger adhesion to the cells compared to control ones. Average adhesion force was dependent on depth of contact. Analysis of the data demonstrated a single distribution of adhesion events with median at 89 pN, which is in agreement with the literature for such interactions. The nanointerrogation of MBs using AFM provides new insight into their mechanical properties, and should be of assistance to MB design and manufacture.

1436 オゾン水生成における気泡電位の影響(S38-2 気泡・粒子,S38 マイクロ・ナノフルイズ)

1436 オゾン水生成における気泡電位の影響(S38-2 気泡・粒子,S38 マイクロ・ナノフルイズ)

High frequency attenuation measurements of lipid encapsulated contrast agents

A number of recent studies have indicated the potential of ultrasound contrast agent imaging at high ultrasound frequencies. However, the acoustic properties of microbubbles at frequencies above 10 MHz remain poorly understood at present. In this study we characterize the high frequency attenuation properties of (1) BR14, (2) BR14 that has been mechanically filtered (1 and 2 μm pore sizes) to exclude larger bubbles, and (3) the micron to submicron agent BG2423. A narrowband pulse-echo substitution method is employed with a series of four transducers covering the frequency range from 2 to 50 MHz. For BR14, attenuation decreases rapidly from 2 to 10 MHz and then more gradually from 10 to 50 MHz. For 2 μm filtration, the attenuation peaks between 10 and 15 MHz. For 1 μm filtration, attenuation continues to rise until 50 MHz. The agent BG2423 exhibits a diffuse attenuation peak in the range of 15–25 MHz and remains high until 50 MHz. These results demonstrate a strong influence of bubble size on high frequency attenuation curves, with bubble diameters of 1–2 μm and below having more pronounced acoustic activity at frequencies above 10 MHz.

Nanointerrogation of ultrasonic contrast agent microbubbles using atomic force microscopy

Predicting the acoustic response of an encapsulated microbubble to ultrasound requires an accurate assessment of the mechanical properties of the microbubble shell. Atomic force microscopy (AFM) provides an unprecedented spatial and force resolution of the order of Angstroms and subnanonewtons, respectively. It is introduced here as a means to interrogate microbubbles manufactured for ultrasonic imaging. The advantage of AFM over scanning electron microscopy (SEM) is that the microbubbles need not be subjected to a low temperature or low-pressure environment. The microbubbles were interrogated in a liquid environment, which could potentially be a simulated physiological environment. AFM was used in tapping mode imaging to reveal topographical detail of biSphere ® microbubbles. Because microbubbles are large objects compared with the overall size of usual AFM tips, a convolution between the AFM tip and the microbubble was typical of the acquired topographies. However, a part of the top half of the bubble was imaged with nanometer resolution, and roughness measurements are reported. Force-distance curves were captured using contact mode AFM. The range of stiffness or effective spring constant of biSphere ® was found to be between 1 and 6 N m –1. In conclusion, the AFM is proposed here for the first time as a tool to image the surface of bubbles at the nanometer range in liquid and to perform reproducible measurements on the mechanical properties of individual microbubbles. (E-mail: Vassilis.Sboros@ed.ac.uk)

Tethering Functional Ligands onto Shell of Ultrasound Active Polymeric Microbubbles

Hollow (air-filled) microparticles, i.e., microbubbles, provide a promising novel vehicle for both local delivery of therapeutic agents and simultaneous diagnostic ultrasound echo investigations. In this paper, we describe the synthetic routes for decorating the polymeric shell of a poly(vinyl alcohol)-based microbubble with low and high molecular weight ligands with pharmacological relevance. Investigations on physical properties of microbubbles and surface chemical coupling with different cargo molecules such as L-cysteine, L-lysine, poly(L-lysine), chitosan, and beta-cyclodextrin were carried out by CD and NMR spectroscopies, confocal laser scanning microscopy, and microcalorimetry. The in vitro cytotoxicity and biocompatibility of the polymer microbubbles have been also determined toward different cell lines. The results are discussed in terms of the features shown by this device, i.e., injectability, long shelf life, ease of preparation, biocompatibility, loading and cargo capacities, and functional properties.

Physical properties of ultrasound contrast agents

It has recently been shown that the new generation of contrast agents has suitable pressure ranges and driving pulse sequences for optimal imaging. Differences in imaging conditions are due to differences in physical properties of microbubbles of the ultrasound contrast agents: mechanical properties of shell materials and diffusion of encapsulated gases. In this study, bubble behaviors of two types of contrast agents were observed using a high-speed camera, and differences in mechanical properties of the shells and diffusion of the encapsulated gases were investigated. A microbubble was exposed to five ultrasound pulses with constant or increasing pressures with a pulse interval of 20 μs, and the bubbles exposed to each pulse were photographed using a high-speed camera. Definity® and Levovist® were used in the experiments. In the case of Definity®, amplitude of bubble oscillation increased with an increase in pulse pressure. In the case of Levovist®, discontinuous expansion of the bubble was observed during exposure to five pulses with increasing pressure, and it is thought that the strong non-linear relationship between oscillation amplitude and ultrasound pressure in the case of Levovist® is caused by the presence of bubble shells, which cannot be treated with a simple elastic model. Furthermore, shrinkage of bubble fragments was observed in the case of Levovist®, and it is thought that diffusion of encapsulated gas is accelerated by exposure to pulsed ultrasound.

Ultrasound contrast imaging research.

This article is a review of the research on ultrasound contrast agents in general imaging. While general imaging contrast agent applications are still undergoing investigation and waiting FDA approval in the United States, they are approved for clinical use in Europe and other countries. The contrast microbubble properties are described, including their nonlinear behavior and destruction properties. Imaging techniques like harmonic imaging, pulse inversion, power pulse inversion, agent detection imaging, microvascular imaging, and flash contrast imaging are explained. A connection is made between the aforementioned imaging techniques and the different contrast agents available. The blood flow appearance of different liver tumors in the presence of contrast agents is demonstrated with examples.

Contrast Echocardiography

Contrast echocardiography is an important technique that can be used to examine the cardiac cavity, vascular structure, intracardiac shunt, and myocardial microcirculation. It uses gas-filled microbubbles and various imaging techniques. The properties of microbubbles and their interaction with ultrasound are important in ultrasound-enhanced contrast imaging. This article will describe microbubble physics and new ultrasound techniques that are necessary to understand the basics of contrast echocardiography. The utility of contrast echocardiography in various clinical scenarios will be also described.

Physical principles of microbubble ultrasound contrast agents

Early contrast agents could not achieve left-sided cardiac opacification because these microbubbles could not traverse the pulmonary circulation and remain intact. The specific shell material and gas used determine the properties of individual microbubbles, including fragility, persistence, and resonance. Persistence, perhaps the most important property of a microbubble, has been achieved by second-generation agents through the use of shells or surfactants and by substituting high-density, high molecular weight gas for air. Today’s agents readily achieve opacification, not only of the cardiac chambers but also of the myocardium. Refinements in contrast agents and in the instrumentation for their detection are primarily responsible for these improvements.

On the design of a capillary flow phantom for the evaluation of ultrasound contrast agents at very low flow velocities

Recently, a new imaging technology has become available that allows the evaluation of tissue perfusion using echo-contrast agents in real-time imaging: power pulse inversion imaging (PPI). Although numerous in vitro phantoms have been designed for different imaging modalities in ultrasound (US), there is a need for a phantom that mimics microcirculation and allows, in particular, the assessment of contrast replenishment kinetics following US-induced destruction of microbubbles using the new method. We, therefore, designed a new capillary flow phantom that takes the requirements of the new US imaging techniques and the physical properties of microbubbles into account and serves flow velocities in the range of microcirculation (1 to 10 mm/s). PPI studies were performed in the newly designed phantom. The contrast agent used was AF0150. We studied homogeneity of contrast distribution within the capillary phantom, constancy of contrast infusion, the dose-effect relationship and, finally, the feasibility of flow assessment using the method of contrast replenishment following US-induced microbubble destruction in a flow velocity range of 2.1 to 9.45 mm/s. Analysis of the replenishment kinetics was performed using the mathematical model f(t) = A(1 − e−βt), with A representing the blood volume and β the microbubble velocity. The new capillary phantom allowed homogeneous contrast opacification within the perfused capillaries independently of the flow. Constancy of signal intensity was achieved over a time period of almost 2 h, indicating constant contrast delivery. A strong linear correlation between the PPI signal and the contrast dose was found (r = 0.998). Analysis of the replenishment parameters revealed a strong linear relationship between parameter β and flow (r = 0.994) as well as A∗β and flow (r = 0.984) in the observed flow range. The newly designed perfusion phantom for the evaluation of echo-contrast replenishment kinetics fulfills, at very low flow velocities, important prerequisites such as constancy of contrast delivery, homogeneity of contrast signals, linear dose-effect relation and minimal attenuation. Thus, the new phantom allows standardized analysis of contrast replenishment kinetics using real-time perfusion imaging techniques at flow velocities comparable to those of the microcirculation. (E-mail: k-tiemann@uni-bonn.de)

Myocardial contrast echocardiography: Basic principles

Myocardial contrast echocardiography (MCE) is a new technique that can be used to examine the myocardial microcirculation. It uses gas-filled microbubbles that behave similarly to red blood cells in the microcirculation. This report describes the parts of the coronary microcirculation visualized by MCE. It also describes the types of microbubbles currently available for research. The properties of microbubbles and their interaction with ultrasound are also described as well as different imaging techniques. This information is necessary to understand the basics of MCE. Copyright © 2001 by W.B. Saunders CompanyProgress in Cardiovascular Diseases, Vol. 44, No. 1, (July/August) 2001: pp 1-11

Local drug and gene delivery through microbubbles

Ultrasound contrast agents (microbubbles) lower the threshold for cavitation by ultrasound energy. Ultrasound microbubbles may be used as cavitation nuclei for drug and gene delivery. By tailoring the physical properties of microbubbles and coating materials, drugs and genetic drugs can be incorporated into ultrasound contrast agents. As the microbubbles enter the region of insonation, the microbubbles cavitate, locally releasing the therapeutic agents. Cavitation also causes a local shockwave that improves cellular uptake of the therapeutic agent. As a result of the human genome project and continuing advances in molecular biology, many therapeutic genes have been discovered. In the cardiovascular system, gene therapy has the potential to improve myocardial vascularization and ameliorate congestive heart failure. For successful development of clinical gene therapy, however, effective gene delivery vectors are needed. Ultrasound contrast agents can be used to develop new, more effective vectors for gene delivery. Transthoracic ultrasound can be focused on the heart so that an intravenous injection of gene-bearing microbubbles will deliver genes relatively selectively to the myocardium. Using this technique, we have produced high levels of transgene expression in the insonated region of the myocardium. This new technology, using microbubbles and ultrasound for drug and gene delivery, merits further study and development. Copyright © 2001 by W.B. Saunders CompanyProgress in Cardiovascular Diseases, Vol. 44, No. 1, (July/August) 2001: pp 45-54

Gene delivery using ultrasound contrast agents.

With the human genome product and continuing advances in molecular biology many therapeutic genes have been discovered. In the cardiovascular system, gene therapy has the potential to improve myocardial vascularization and ameliorate congestive heart failure. For successful development of clinical gene therapy, however, effective gene delivery vectors are needed. Ultrasound contrast agents can be used to develop new, more effective vectors for gene delivery. Ultrasound contrast agents lower the threshold for cavitation by ultrasound energy. Using physical properties of microbubbles and coating materials, genetic drugs have been incorporated into ultrasound contrast agents. Gene-bearing microbubbles can be injected IV and ultrasound energy applied to the target region. As the microbubbles enter the region of insonation, the microbubbles cavitate, locally releasing DNA. Cavitation also likely causes a local shockwave that improves cellular uptake of DNA. With transthoracic ultrasound, using commercially available diagnostic ultrasound system and an IV injection of gene-bearing microbubbles, high levels of transgene expression are observed in the insonated region of the myocardium. This new technology using microbubbles and ultrasound for gene delivery merits further study and development.

Study on the lifetime and attenuation properties of microbubbles coated with carboxylic acid salts

Four kinds of surfactants, sodium laurate, sodium myristate, sodium palmitate and sodium oleate were used to study the effects of surfactant coatings on the lifetime and attenuation of microbubbles. The changes in the size distribution of microbubbles prepared with these surfactants in saline were measured with a Coulter Multisizer (Coulter Electronics Ltd., Luton, UK). Frequency characteristics of ultrasonic attenuation of the microbubble suspensions were measured between 400 kHz and 6 MHz. From the changes in attenuation in the microbubble suspensions over time, it was found that the lifetime of microbubbles in a suspension also depends on the frequency of the irradiating ultrasound. The effect of surfactants on the frequency characteristics of attenuation was also studied, and characteristics of the surfactant coating, including shell elasticity and shell friction parameters were calculated from the measurement results. Microbubbles produced with sodium palmitate had the longest lifetime and the smallest average size. The shell had very little effect on the ultrasonic properties of microbubbles produced with sodium palmitate, suggesting that the sodium palmitate microbubbles behaved ultrasonically as free microbubbles.

Ultrasonic characterization of the nonlinear properties of contrast microbubbles

The nonlinear properties of microbubble contrast agents have been used to create contrast-specific imaging modalities such as harmonic imaging and subharmonic imaging. Thus, a better understanding of the nonlinear performance of contrast microbubbles may enhance the diagnostic capabilities of medical ultrasound (US) imaging. The first and second harmonic, the 1/2 order subharmonic and the 3/2 order ultraharmonic components in spectra of scattered signals from Optison microbubbles insonified at 2 and 4 MHz have been investigated using an in vitro laboratory pulse-echo system. The development of these signal components over time is quite different for 2-MHz insonification compared to 4-MHz insonification. Scattered subharmonic and ultraharmonic signals are much more time-dependent than first and second harmonic echoes. The dependence of the first and second harmonic, subharmonic and ultraharmonic components on acoustic pressure for 2-MHz insonification is similar to that for 4-MHz insonification. The first and second harmonic components increase linearly with acoustic pressure (in double logarithmic scales) and the subharmonic and ultraharmonic amplitudes undergo rapid growths in the intermediate acoustic pressure range and much slower increases at both lower and higher acoustic pressures.

Reactor Design Issues for Synthesis-Gas Fermentations.

Synthesis gas is readily obtained by gasifying coal, oil, biomass, or waste organics and represents an abundant, potentially inexpensive, feedstock for bioprocessing. The primary components of synthesis gas, carbon monoxide and hydrogen, can be converted into methane, organic acids, and alcohols via anaerobic fermentations. Bioconversion of synthesis gas is an attractive alternative to catalytic processing because the biological catalysts are highly specific and often more tolerant of sulfur contaminants than inorganic catalysts. However, because the aqueous solubilities of carbon monoxide and hydrogen are low, synthesis-gas fermentations are typically limited by the rate of gas-to-liquid mass transfer. Consequently, a major engineering challenge in commercial development of synthesis-gas fermentations is to provide sufficient gas mass transfer in an energy-efficient manner. This paper reviews recent progress in the development of synthesis-gas fermentations, with emphasis on efforts to increase the efficiency of gas mass transfer. Metabolic properties of several microbes able to ferment synthesis gas are described. Results of synthesis-gas fermentations conducted in various bioreactor configurations are summarized. Recent results showing enhancement of synthesis-gas fermentations using microbubble dispersions are presented, and studies of the mass-transfer and coalescence properties of microbubbles are described.