Uncoated Bubbles Research Articles

Dynamics of a particle-laden bubble colliding with an air-liquid interface

The collision, bouncing and potential bursting of air bubbles with air-liquid interfaces are key processes involved in the initial stage of foam formation. While fundamental studies of these processes, especially for gas-liquid-solid froth systems, are very valuable for a better understanding of various chemical engineering separation systems, these are scarce. This paper investigates the dynamics of rising bubbles, without particles attached and with various particle coverages, as they collide with an air-liquid interface. For uncoated bubbles, an increase in distance from the bubble releasing point to the air-liquid interface resulted in higher bubble approach velocities, although with minor changes in the velocity fluctuation frequency. This increase in approach velocity was not observed for bubbles with relatively high particle coverage. For particle-laden bubbles, the collision with the interface is associated with movement of the particles over the surface of the decelerating bubble. This particle motion on the bubble surface, combined with bubble shape pulsation, contributes to the kinetic energy dissipation of the approaching bubble. A damped oscillation model was derived to represent the velocity of the bubble interacting with the interface, which shows that the amplitude of the velocity decreases gradually with the increase in particle coverage. The damping coefficient in the model, introduced to quantify the influence of attached particles, is shown to increase with particle coverage, confirming the key role that particles play in bubble collision dynamics at an air-liquid interface and allowing, for the first time, the prediction of their behavior.

Experimental and numerical evidence of intensified non-linearity at the microscale: The lipid coated acoustic bubble

A lipid coated bubble (LCB) oscillator is a very interesting non-smooth oscillator with many important applications ranging from industry and chemistry to medicine. However, due to the complex behavior of the coating intermixed with the nonlinear behavior of the bubble itself, the dynamics of the LCB are not well understood. In this work, lipid coated Definity® microbubbles (MBs) were sonicated with 25 MHz 30 cycle pulses with pressure amplitudes between 70 and 300 kPa. Here, we report higher order subharmonics in the scattered signals of single MBs at low-amplitude high-frequency ultrasound excitations. Experimental observations reveal the generation of period 2, period 3, and two different period 4 oscillations at low excitation amplitudes. Despite the reduced damping of the uncoated bubble system, such enhanced nonlinear oscillations have not been observed and cannot be theoretically explained for the uncoated bubble. To investigate the mechanism of the enhanced non-linearity, the bifurcation structure of the lipid coated MBs is studied for a wide range of MBs sizes and shell parameters. Consistent with the experimental results, we show that this unique oscillator can exhibit chaotic oscillations and higher order subharmonics at excitation amplitudes considerably below those predicted by the uncoated oscillator. Buckling or rupture of the shell and the dynamic variation of the shell elasticity cause the intensified non-linearity at low excitation pressure amplitudes. The simulated scattered pressure by single MBs is in good agreement with the experimental signals.

Classification of the major nonlinear regimes of oscillations, oscillation properties, and mechanisms of wave energy dissipation in the nonlinear oscillations of coated and uncoated bubbles

Acoustic waves are dissipated when they pass through bubbly media. Dissipation by bubbles takes place through thermal damping (Td), radiation damping (Rd), and damping due to the friction of the liquid (Ld) and friction of the coating (Cd). Knowledge of the contributions of Td, Rd, Ld, and Cd during nonlinear bubble oscillations will help in optimizing bubble and ultrasound exposure parameters for the relevant applications by maximizing a desirable outcome or oscillation pattern. In this work, we investigate the mechanisms of dissipation in bubble oscillations and their contribution to the total damping (Wtotal) in various nonlinear regimes. By using a bifurcation analysis, we have classified nonlinear dynamics of bubbles that are sonicated with their third superharmonic (SuH) and second SuH resonance frequency (fr), pressure dependent resonance frequency (PDfr), fr, subharmonic (SH) resonance (fsh = 2fr), pressure dependent SH resonance (PDfsh), and 1/3 order SH resonance, which are important exposure ranges for various applications. The corresponding Td, Rd, Ld, Cd, Wtotal, scattering to dissipation ratio, maximum wall velocity, and maximum backscattered pressure from non-destructive oscillations of bubbles were calculated and analyzed using the bifurcation diagrams. Universal ultrasound exposure parameter ranges are revealed in which a particular non-destructive bubble related phenomenon (e.g., wall velocity) is enhanced. The enhanced bubble activity is then linked to relevant ultrasound applications. This paper represents the first comprehensive analysis of the nonlinear oscillations regimes, the corresponding damping mechanisms, and the bubble related phenomena.

The role of microparticles on the shape and surface tension of static bubbles

HypothesisSurface tension is a critical parameter in bubbles and foams, yet it is difficult to assess when microparticles are attached at the interface. By considering the interaction force between an air–liquid interface and microparticles, modified equations for sessile bubble tensiometry can be derived to determine the surface tension and shape of static microparticle-laden bubbles. ExperimentsA modified sessile bubble method, in which the forces between microparticles and the air–liquid interface are considered, was developed and used to analyse the surface tension of bubbles fully coated by a monolayer of silica microparticles of different sizes. The results are compared to those obtained using classical sessile bubble tensiometry. The new method is also used to investigate the contours of particle-laden bubbles of varying particle radius and contact angle. FindingsWhile the classical sessile bubble method overestimates the surface tension, results obtained using the modified sessile bubble method show that the surface tension of static microparticle-laden bubbles remains the same as that of uncoated bubbles, with no dependency on the particle size. The discrepancy is due to the fact that microparticles attached to the air–liquid interface deform a bubble in a similar way that changes in surface tension do for uncoated bubbles.

Deformation dynamics of particle-laden bubbles: The effect of surfactant concentration and particle contact angle

The pinch-off dynamics of bubbles coated with silica particles in deionised water and in dodecylamine (DDA) solution, at 0.2 μM and 20.0 μM, was studied using high-speed photography. Surface pressure generated at the deforming particle-laden interface during bubble pinch-off was obtained based on the fitting to a pinch-off model. It was observed that the pinch-off dynamics of these particle-laden bubbles remained almost unchanged at the low DDA concentration of 0.2 μM, while the dynamics slowed down significantly at the DDA concentration of 20.0 μM. Notably, both the 0.2 μM and 20.0 μM DDA concentrations have a negligible effect on the surface tension and pinch-off dynamics of uncoated bubbles. The difference in DDA concentration, however, is known to change the contact angle of silica particles from approximately 27° to 45°. It can be concluded that it is the change in particle contact angle that affects the pinch-off dynamics of particles-laden bubbles. Indeed, at a concentration of 0.2 μM DDA there is no significant change in contact angle of the silica particles with respect to that in DI water only, resulting in similar dynamics. It is suggested that the increase in the particle contact angle changes particle interactions, leading to a change in the surface pressure and apparent surface tension of particle-laden bubbles, which in turn slows down the pinch-off process. The findings in this work are relevant to our understanding of fundamental aspects of deforming particle-laden interfaces, such as those in the coalescence of flotation froths.

The pinch-off dynamics of bubbles coated by microparticles

HypothesisWhile the pinch-off dynamics of bubbles is known to be influenced by changes in surface tension, previous studies have only assessed changes due to liquid properties or surfactant effects at the air–liquid interface but not due to the presence of particles. The current study proposes that particles at the air–liquid interface play an important role in changing the surface tension and thus the pinch-off dynamics of particle-laden bubbles. ExperimentsHigh-speed photography was used to study the pinch-off dynamics of air bubbles coated by a monolayer of silica microparticles. The influence of bubble surface coverage and particle size classes on the bubble pinch-off dynamics were explored. FindingsWe identify that although the scaling exponent of the power law that governs the pinch-off of coated and uncoated bubbles is the same, the pinch-off dynamics is distinctly different when particles are present at the air–liquid interface due to a decrease in surface tension with time in the neck region. We suggest that the surface pressure generated by particle interaction reduces the pinch-off speed by reducing the apparent surface tension. We observe that the apparent surface tension is dependent on particle size but not on the percentage of bubble surface coated by particles.

Nonlinear power loss in the oscillations of coated and uncoated bubbles: Role of thermal, radiation and encapsulating shell damping at various excitation pressures.

This study presents the fundamental equations governing the pressure dependent disipation mechanisms in the oscillations of coated bubbles. A simple generalized model (GM) for coated bubbles accounting for the effect of compressibility of the liquid is presented. The GM was then coupled with nonlinear ODEs that account for the thermal effects. Starting with mass and momentum conservation equations for a bubbly liquid and using the GM, nonlinear pressure dependent terms were derived for power dissipation due to thermal damping (Td), radiation damping (Rd) and dissipation due to the viscosity of liquid (Ld) and coating (Cd). The pressure dependence of the dissipation mechanisms of the coated bubble have been analyzed. The dissipated energies were solved for uncoated and coated 2-20μm in bubbles over a frequency range of 0.25fr-2.5fr (fr is the bubble resonance) and for various acoustic pressures (1kPa-300kPa). Thermal effects were examined for air and C3F8 gas cores. In the case of air bubbles, as pressure increases, the linear thermal model looses accuracy and accurate modeling requires inclusion of the full thermal model. However, for coated C3F8 bubbles of diameter 1-8μm, which are typically used in medical ultrasound, thermal effects maybe neglected even at higher pressures. For uncoated bubbles, when pressure increases, the contributions of Rd grow faster and become the dominant damping mechanism for pressure dependent resonance frequencies (e.g. fundamental and super harmonic resonances). For coated bubbles, Cd is the strongest damping mechanism. As pressure increases, Rd contributes more to damping compared to Ld and Td. For coated bubbles, the often neglected compressibility of the liquid has a strong effect on the oscillations and should be incorporated in models. We show that the scattering to damping ratio (STDR), a measure of the effectiveness of the bubble as contrast agent, is pressure dependent and can be maximized for specific frequency ranges and pressures.

Subwavelength resonances of encapsulated bubbles

The aim of this paper is to derive an original formula for the subwavelength resonance frequency of an encapsulated bubble with arbitrary shape in two dimensions. Using Gohberg-Sigal theory, we derive an asymptotic formula for this resonance frequency, as a perturbation away from the resonance of the uncoated bubble, in terms of the thickness of the coating. The formula is numerically verified in the case of circular bubbles, where the resonance can be efficiently computed using the multipole method. The approach involves the use of a pole-pencil decomposition of the leading order term in the asymptotic expansion of some integral operator in terms of the thickness of the coating, followed by the application of the generalized argument principle to find the characteristic value. This approach is quite general and can be applied to other subwavelength resonators such as coated plasmonic nanoparticles.

The behavior of rising bubbles covered by particles

A systematic investigation of the influence of particle coverage on the dynamics of rising bubbles was carried out using high-speed photography and image analysis techniques to study bubble behavior in terms of changes in velocity and aspect ratio. The buoyancy force and drag force exerted on the bubbles and the effect of particles were calculated to further understand their behavior. Results show that particles attached on the bubbles strongly dampen the oscillations observed in bubble aspect ratio and decrease its velocity and acceleration. The particles also render the bubbles more spherical and slow their velocity. It was found that the overall velocity of a bubble is directly correlated to its aspect ratio and inversely correlated to its particle coverage, while the acceleration and the aspect ratio and its change are inversely correlated. Interestingly, the trend observed in the oscillation and the oscillation period of particle-laden bubbles is similar for different levels of particle coating. A drag modification factor ηp, which quantifies the drag influence of particles on bubble velocity, was identified from force analysis. A modified drag coefficient for uncoated and particle-laden bubbles was introduced, which allows, for the first time, to predict the behavior of rising bubbles in gas-liquid-particle systems.

On oscillations of asymmetrically coalescing bubbles

Asymmetric coalescence behavior of a particle laden bubble with a bare bubble was studied experimentally. A bubble was coated with particles of lower density than the medium, in the size range of 90–300 μm and with a contact angle of 120°, and was allowed to coalesce with an uncoated bubble. On coalescence, the bubble surface showed under damped oscillation behavior. The extent of dampening effect was found to be a function of the amount of particles on the particle laden bubble and is quantified by the damping constant. A new method, Interface Displacement (I.D.) method, has been proposed to calculate the damping coefficient by characterizing the local surface oscillation which was dependent on the extent of the adherence of the particles on the bubble surface. It is found to decrease with an increase in the coated particle size as well as with an increase in the particle surface coverage area. The damping constant of oscillations of the coalesced bubble has also been calculated using Change in Projected Area (C.P.A.) method and compared with the proposed method. Although the damping constant that is calculated from both these methods are in agreement, the ID method, which can be used to show the variation of the damping coefficient along the interface, is more advantageous than CPA method. The analysis shows that the variation of damping coefficient along the interface follows a “ω” shaped trend for all the particle sizes and surface coverage area.

Shape oscillation and stability of an encapsulated microbubble translating in an acoustic wave.

Encapsulated microbubbles (EMBs) are associated with a wide variety of important medical applications, including sonography, drug delivery, and sonoporation. The nonspherical oscillations, or shape modes, of EMBs strongly affect their stability and acoustic signature, and thus are an important factor to consider in the design and utilization of EMBs. Under acoustic forcing, EMBs often translate with significant velocity, which can excite shape modes, yet few studies have addressed the effect of translation on the shape stability of EMBs. In this work, the shape stability of an EMB subject to translation is investigated through development of an axisymmetric model for the case of small deformations. The potential flow in the bulk volume of the external flow is modeled using an asymptotic analysis. Viscous effects within the thin boundary layer at the interface are included, owing to the no-slip boundary condition, using Prosperetti's theory [Q. Appl. Math. 34, 339 (1977)]. In-plane stress and bending moment due to the encapsulation are incorporated into the model through the dynamic boundary condition at the interface. The evolution equations for radial oscillation, translation, and shape oscillation of an EMB are derived, which can be reduced to model an uncoated gas bubble by neglecting the encapsulation properties. These equations are solved numerically to analyze the shape mode stability of an EMB and a gas bubble subject to an acoustic, traveling plane wave. The findings demonstrate the counterintuitive result that translation has a more destabilizing effect on an EMB than on a gas bubble. The no-slip condition at the encapsulating membrane is the main factor responsible for mediating this interfacial instability due to translation.

Role of Surface Tension in Gas Nanobubble Stability Under Ultrasound.

Shell-stabilized gas nanobubbles have recently captured the interest of the research community for their potential application as ultrasound contrast agents for molecular imaging and therapy of cancer. However, the very existence of submicron gas bubbles (especially uncoated bubbles) has been a subject of controversy in part due to their predicted Laplace overpressure reaching several atmospheres, making them supposedly thermodynamically unstable. In addition, the backscatter resulting from ultrasound interactions with nanoparticles is not predicted to be readily detectable at clinically relevant frequencies. Despite this, a number of recent reports have successfully investigated the presence and applications of nanobubbles for ultrasound imaging. The mechanism behind these observations remains unclear but is thought to be, in part, influenced heavily by the biophysical properties of the bubble-stabilizing shell. In this study, we investigated the effects of incorporating the triblock copolymer surfactant, Pluronic, into the lipid monolayer of nanobubbles. The impact of shell composition on membrane equilibrium surface tension was investigated using optical tensiometry, using both pendant drop and rising drop principles. However, these techniques proved to be insufficient in explaining the observed behavior and stability of nanobubbles under ultrasound. Additionally, we sought to investigate changes in membrane surface tension (surface pressure) at different degrees of compression (analogous to the bubble oscillations in the ultrasound field) via Langmuir-Blodgett experiments. Results from this study show a significant decrease ( p < 0.0001) in the nanobubble equilibrium surface tension through the incorporation of Pluronic L10, especially at a ratio of 0.2, where this value decreased by 28%. However, this reduction in surface pressure was seen only for specific compositions and varied with monolayer structure (crystalline phase or liquid-crystalline packing). These results indicate a potential for optimization wherein surface pressure can be maximized for both contraction and expansion phases with the proper lipid to Pluronic balance and microstructure.

The dynamics of rising oil-coated bubbles: experiments and simulations.

Air bubbles rising through an aqueous medium have been studied extensively and are routinely used for the separation of particulates via froth flotation, a key step in many industrial processes. Oil-coated bubbles can be more effective for separating hydrophilic particles with low affinity for the air-water interface, but the rise dynamics of oil-coated bubbles has not yet been explored. In the present work, we report the first systematic study of the shape and rise trajectory of bubbles engulfed in a layer of oil. Results from direct observation of the coated bubbles with a high-speed camera are compared to computer simulations and confirm a pronounced effect of the oil coat on the bubble dynamics. We consistently find that the oil-coated bubbles display a more spherical shape and straighter trajectory, yet slower rise than uncoated bubbles of comparable size. These characteristics may provide practical benefits for flotation separations with oil-coated bubbles.

Stability of Clay Particle-Coated Microbubbles in Alkanes against Dissolution Induced by Heating.

We investigated the dissolution and morphological dynamics of air bubbles in alkanes stabilized by fluorinated colloidal clay particles when subjected to temperature changes. A model for bubble dissolution with time-dependent temperature reveals that increasing the temperature enhances the bubble dissolution rate in alkanes, opposite to the behavior in water, because of the differing trends in gas solubility. Experimental results for uncoated air bubbles in decane and hexadecane confirm this prediction. Clay-coated bubbles in decane and hexadecane are shown to be stable in air-saturated oil at constant temperature, where dissolution is driven mainly by the Laplace pressure. When the temperature increases from ambient, the particle-coated bubbles are prone to dissolution as the oil phase becomes undersaturated. The interfacial layer of particles is observed to undergo buckling and crumpling, without shedding of clay particles. Increasing the concentration of particles is shown to enhance the bubble stability by providing a higher resistance to dissolution. When subjected to complex temperature cycles, for which the effect of time-dependent temperature is dominant, the clay-coated bubbles can resist long-term dissolution in conditions under which uncoated bubbles dissolve completely. These results underpin the design of ultrastable oil foams stabilized by solid particles with improved shelf life under changing environmental conditions.

Shape oscillations of particle-coated bubbles and directional particle expulsion.

Bubbles stabilised by colloidal particles can find applications in advanced materials, catalysis and drug delivery. For applications in controlled release, it is desirable to remove the particles from the interface in a programmable fashion. We have previously shown that ultrasound waves excite volumetric oscillations of particle-coated bubbles, resulting in precisely timed particle expulsion due to interface compression on a ultrafast timescale [Poulichet et al., Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 5932]. We also observed shape oscillations, which were found to drive directional particle expulsion from the antinodes of the non-spherical deformation. In this paper we investigate the mechanisms leading to directional particle expulsion during shape oscillations of particle-coated bubbles driven by ultrasound at 40 kHz. We perform high-speed visualisation of the interface shape and of the particle distribution during ultrafast deformation at a rate of up to 104 s-1. The mode of shape oscillations is found to not depend on the bubble size, in contrast with what has been reported for uncoated bubbles. A decomposition of the non-spherical shape in spatial Fourier modes reveals that the interplay of different modes determines the locations of particle expulsion. The n-fold symmetry of the dominant mode does not always lead to desorption from all 2n antinodes, but only those where there is favourable alignment with the sub-dominant modes. Desorption from the antinodes of the shape oscillations is due to different, concurrent mechanisms. The radial acceleration of the interface at the antinodes can be up to 105-106 ms-2, hence there is a contribution from the inertia of the particles localised at the antinodes. In addition, we found that particles migrate to the antinodes of the shape oscillation, thereby enhancing the contribution from the surface pressure in the monolayer.

Numerical modeling of the 3D dynamics of ultrasound contrast agent microbubbles using the boundary integral method

Ultrasound contrast agents (UCAs) are microbubbles stabilized with a shell typically of lipid, polymer, or protein and are emerging as a unique tool for noninvasive therapies ranging from gene delivery to tumor ablation. While various models have been developed to describe the spherical oscillations of contrast agents, the treatment of nonspherical behavior has received less attention. However, the nonspherical dynamics of contrast agents are thought to play an important role in therapeutic applications, for example, enhancing the uptake of therapeutic agents across cell membranes and tissue interfaces, and causing tissue ablation. In this paper, a model for nonspherical contrast agent dynamics based on the boundary integral method is described. The effects of the encapsulating shell are approximated by adapting Hoff’s model for thin-shell, spherical contrast agents. A high-quality mesh of the bubble surface is maintained by implementing a hybrid approach of the Lagrangian method and elastic mesh technique. The numerical model agrees well with a modified Rayleigh-Plesset equation for encapsulated spherical bubbles. Numerical analyses of the dynamics of UCAs in an infinite liquid and near a rigid wall are performed in parameter regimes of clinical relevance. The oscillation amplitude and period decrease significantly due to the coating. A bubble jet forms when the amplitude of ultrasound is sufficiently large, as occurs for bubbles without a coating; however, the threshold amplitude required to incite jetting increases due to the coating. When a UCA is near a rigid boundary subject to acoustic forcing, the jet is directed towards the wall if the acoustic wave propagates perpendicular to the boundary. When the acoustic wave propagates parallel to the rigid boundary, the jet direction has components both along the wave direction and towards the boundary that depend mainly on the dimensionless standoff distance of the bubble from the boundary. In all cases, the jet directions for the coated and uncoated bubble are similar but the jet width and jet velocity are smaller for a coated bubble. The effects of shell thickness and shell viscosity are analyzed and determined to affect the bubble dynamics, including jet development.

On the Acoustic Properties of Vaporized Submicron Perfluorocarbon Droplets

The acoustic characteristics of microbubbles created from vaporized submicron perfluorocarbon droplets with fluorosurfactant coating are examined. Utilizing ultra-high-speed optical imaging, the acoustic response of individual microbubbles to low-intensity diagnostic ultrasound was observed on clinically relevant time scales of hundreds of milliseconds after vaporization. It was found that the vaporized droplets oscillate non-linearly and exhibit a resonant bubble size shift and increased damping relative to uncoated gas bubbles due to the presence of coating material. Unlike the commercially available lipid-coated ultrasound contrast agents, which may exhibit compression-only behavior, vaporized droplets may exhibit expansion-dominated oscillations. It was further observed that the non-linearity of the acoustic response of the bubbles was comparable to that of SonoVue microbubbles. These results suggest that vaporized submicron perfluorocarbon droplets possess the acoustic characteristics necessary for their potential use as ultrasound contrast agents in clinical practice.

A general derivation of the subharmonic threshold for non-linear bubble oscillations

The paper describes an approximate but rather general derivation of the acoustic threshold for a subharmonic component to be possible in the sound scattered by an insonified gas bubble. The general result is illustrated with several specific models for the mechanical behavior of the surface coating of bubbles used as acoustic contrast agents. The approximate results are found to be in satisfactory agreement with fully non-linear numerical results in the literature. The amplitude of the first harmonic is also found by the same method. A fundamental feature identified by the analysis is that the subharmonic threshold can be considerably lowered with respect to that of an uncoated free bubble if the mechanical response of the coating varies rapidly in the neighborhood of certain specific values of the bubble radius, e.g., because of buckling.

Rapid Shrinkage of Lipid-Coated Bubbles in Pulsed Ultrasound

Many researchers have observed rapid shrinkage of lipid-coated microbubbles subjected to brief, MHz ultrasound pulses. The shrinkage is sometimes, but not always, accompanied by the shedding of visible fragments of the coat. It has been suggested that the shedding of the lipid coat alone is sufficient to explain the rapid shrinkage, as that loss increases bubble surface tension and, thus, internal pressure, increasing gas loss even between pulses. We have determined, however, that the shedding of the coat lipid must also entrain some of the gas content of the bubble, to account for the observed shrinkage rates. The evidence for this is that insonated bubbles typically shrink much faster than the Epstein-Plesset (diffusion) limit for gas dissolution and diffusion, whereas uncoated quiescent bubbles shrink more slowly. We have also modeled the diffusion of gas in the moving liquid surrounding the bubble and find no advective enhancement of diffusive loss of gas from the bubble. Thus, bubble gas loss through diffusion alone is insufficient to account for rapid shrinkage.

Ultrasound-Induced Nanofragmentation of Bubbles with Saturated and Unsaturated Lipid Coats

Micron-sized lipid-coated bubbles are of considerable interest for applications in biomedical imaging and drug delivery. These bubbles have been reported to rapidly shrink when exposed to a series of short (∼3 μs) ultrasound pulses, purportedly through a shedding of the coat during compression. Loss of coat would lead to an increase in surface tension and internal bubble pressure, enhancing diffusive loss of gas from the bubble long after the ultrasound pulse. For this mechanism, a coated bubble in ultrasound could shrink no faster than an uncoated bubble (absent ultrasound), as the shrinkage rate is entirely dominated by diffusive loss between pulses. Remarkably, we find that most insonated lipid-coated bubbles do shrink faster than quiescent uncoated bubbles. For the extra shrinkage observed to occur by enhanced diffusive loss during the 3 μs pulse, the diffusion coefficient of the gas would have to be increased by 100-1000x. If bubbles cannot shrink by diffusive loss of the gas, they must eject gas-entrapping fragments, even though no microscopically visible fragmentation was observed.We have also studied the role of the lipid coat in bubble stability. We (and others) have observed that bubbles with saturated lipid coats shrink to a stable size of about 2 μm in diameter that persists indefinitely. Interestingly, we find that bubbles coated with an unsaturated lipid shrink to the same stable size, but it is short lived and the bubble catastrophically fragments after about 25-200 pulses. The differing fates of bubbles, and the nature of their fragmentation products, may have important consequences for efficacy in ultrasound-mediated drug delivery.(This work was supported by NSF Grant DGE 0549500)