High-frequency capillary waves excited by oscillating microbubbles

This fluid dynamics video shows high-frequency capillary waves excited by the volumetric oscillations of microbubbles near a free surface. The frequency of the capillary waves is controlled by the oscillation frequency of the microbubbles, which are driven by an ultrasound field. Radial capillary waves produced by single bubbles and interference patterns generated by the superposition of capillary waves from multiple bubbles are shown.Comment: This video is an entry for the 2013 Gallery of Fluid Motion. A high-resolution and a low-resolution video are included as ancillary file

Optical tweezers for the study of microbubble dynamics in ultrasound

2005/2006Optical tweezers enable for non-destructive, contact-free manipulation of ultrasound contrast agent (UCA) microbubbles, which are used in medical imaging for enhancing the echogenicity of the blood pool and to quantify organ perfusion. Understanding the dynamics of ultrasound-driven contrast agent microbubbles from a fundamental physical standpoint is a first step for exploiting their acoustical properties and to develop new diagnostic and therapeutic applications. However, experiments on bubble dynamics presently suffer from a lack of control on bubble position, because of buoyancy, microstreaming and bubble clustering. In this respect, optical tweezers can be used to study UCA microbubbles under controlled and repeatable conditions, by positioning them away from interfaces and from neighboring bubbles. In addition, an ultra-high speed imaging system is required to record the dynamics of UCA microbubbles in ultrasound, as their oscillations occur on the nanoseconds timescale. In this thesis, optical tweezers and an ultra-high speed camera are integrated into an experimental setup to control the boundary conditions and record the oscillations of the microbubbles. Optical tweezers are commonly obtained by focusing a laser beam through a microscope objective, as the high intensity gradient in the focal region causes dielectric microparticles to be attracted in the focus. In the special case of microbubbles, which exhibit a lower refractive index than the surrounding liquid, the opposite situation arises: they are pushed away from the region of maximum intensity. Nevertheless, microbubbles can be trapped in the dark core of a donut-shaped trap, which can be obtained e.g. by focusing a Laguerre-Gaussian beam. In our setup, a Gaussian beam is converted to a Laguerre-Gaussian mode by using diffractive optical elements implemented on a spatial light modulator. This allows to trap and manipulate single or multiple microbubbles, and to control the distance from interfaces as well as the bubbleto- bubble distance. The “Brandaris 128” ultra-high speed camera is used, in combination with the optical tweezers, to recorded the bubble oscillations at a frame rate of 15 million frames per second. The influence of a rigid wall on the resonance frequency and oscillation amplitude was experimentally investigated. An experimental phospholipid-coated agent (BR-14, Bracco Research S.A., Geneva, Switzerland) was used throughout the experiments. A resonance frequency curve was recorded for the same bubble positioned at the wall and at controlled distance from the wall. The experiments show a drop in the resonance frequency for the bubble close to the ii Abstract wall, as expected from the theoretical models. These results are highly relevant for molecular imaging applications, where the response of targeted microbubbles needs to be discriminated from that of freely flowing ones. We also quantify the bubble-to-bubble interaction, in two ways: first, we compare the change of the radial oscillations of one bubble with and without a neighboring bubble. Second, we resolve the change in distance between two bubbles during ultrasonic insonation. This results from an acoustical, generally attractive, interaction force between the bubbles, termed secondary Bjerknes force. To understand this rich two-bubble dynamics, we couple a recent single-bubble model, accounting for both gas and monolayer properties with a model quantifying the mutual interaction of bubbles in their translation and oscillations. Experiments where optical tweezers are used as a force sensor to measure the binding force in an antigen-antibody complex at the single molecule level are also presented. In the future, the possibility of combining optical micromanipulation with the force-sensing capabilities of optical tweezers will open the way to a new class of experiments which will give us a deeper insight into fundamental bubble phenomena and find direct application to new ultrasound-assisted targeting strategies.XIX Ciclo197

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 quasi-steady 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, due to 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 under-saturated. 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 and buckling. When subjected to complex temperature cycles, the clay-coated bubbles can remain stable in conditions for which uncoated bubbles dissolve completely. These results underpin the design of ultra-stable oil foams stabilized by solid particles with improved shelf life under changing environmental conditions

Stability of bubbles in wax-based oleofoams: decoupling the effects of bulk oleogel rheology and interfacial rheology

Oleofoams are dispersions of gas bubbles in a continuous oil phase and can be stabilized by crystals of fatty acids or waxes adsorbing at the oil-air interface. Because excess crystals in the continuous phase form an oleogel, an effect of the bulk rheology of the continuous phase is also expected. Here, we evaluate the contributions of bulk and interfacial rheology below and above the melting point of a wax forming an oleogel in sunflower oil. We study the dissolution behaviour of single bubbles using microscopy on a temperature-controlled stage. We compare the behaviour of a bubble embedded in an oleofoam, which owes its stability to both bulk and interfacial rheology, to that of a bubble extracted from the oleofoam and resuspended in oil, for which the interfacial dilatational rheology alone provides stability. We find that below the melting point of the wax, bubbles in the oleofoam are stable whereas bubbles that are only coated with wax crystals dissolve. Both systems dissolve when heated above the melting point of the wax. These findings are rationalized through independent bulk rheological measurements of the oleogel at different temperatures, as well as measurements of the dilatational rheological properties of a wax-coated oil-air interface

Rapid short-pulse sequences enhance the spatiotemporal uniformity of acoustically driven microbubble activity during flow conditions

Despite the promise of microbubble-mediated focused ultrasound therapies, in vivo findings have revealed over-treated and under-treated regions distributed throughout the focal volume. This poor distribution cannot be improved by conventional pulse shapes and sequences, due to their limited ability to control acoustic cavitation dynamics within the ultrasonic focus. This paper describes the design of a rapid short-pulse (RaSP) sequence which is comprised of short pulses separated by μs off-time intervals. Improved acoustic cavitation distribution was based on the hypothesis that microbubbles can freely move during the pulse off-times. Flowing SonoVue® microbubbles (flow velocity: 10 mm/s) were sonicated with a 0.5 MHz focused ultrasound transducer using RaSP sequences (peak-rarefactional pressures: 146–900 kPa, pulse repetition frequency: 1.25 kHz, and pulse lengths: 5–50 cycles). The distribution of cavitation activity was evaluated using passive acoustic mapping. RaSP sequences generated uniform distributions within the focus in contrast to long pulses (50 000 cycles) that produced non-uniform distributions. Fast microbubble destruction occurred for long pulses, whereas microbubble activity was sustained for longer durations for shorter pulses. High-speed microscopy revealed increased mobility in the direction of flow during RaSP sonication. In conclusion, RaSP sequences produced spatiotemporally uniform cavitation distributions and could result in efficient therapies by spreading cavitation throughout the treatment area

Time-resolved nanoseconds dynamics of ultrasound contrast agent microbubbles

Optical tweezers enable non-destructive, contact-free manipulation of ultrasound contrast agent (UCA) microbubbles, which are used in medical imaging for enhancing the echogenicity of the blood pool and to quantify organ perfusion. The understanding of the fundamental dynamics of ultrasound-driven contrast agent microbubbles is a first step for exploiting their acoustical properties and to develop new diagnostic and therapeutic applications. In this respect, optical tweezers can be used to study UCA microbubbles under controlled and repeatable conditions, by positioning them away from interfaces and from neighboring bubbles. In addition, a high-speed imaging system is required to record the dynamics of UCA microbubbles in ultrasound, as their oscillations occur on the nanoseconds timescale. In this work, we demonstrate the use of an optical tweezers system combined with a high-speed camera capable of 128-frame recordings at up to 25 million frames per second (Mfps), for the study of individual UCA microbubble dynamics as a function of the distance from solid interfaces

Subharmonic Behavior of Phospholipid-coated Ultrasound Contrast Agent Microbubbles

Coated microbubbles, unlike tissue are able to scatter sound subharmonically. Therefore, the subharmonic behavior of coated microbubbles can be used to enhance the contrast in ultrasound contrast imaging. Theoretically, a threshold amplitude of the driving pressure can be calculated above which subharmonic oscillations of microbubbles are initiated. Interestingly, earlier experimental studies on coated microbubbles demonstrated that the threshold for these bubbles is much lower than predicted by the traditional linear viscoelastic shell models. This paper presents an experimental study on the subharmonic behavior of differently sized individual phospholipid coated microbubbles. The radial subharmonic response of the microbubbles was recorded with the Brandaris ultra high-speed camera as a function of both the amplitude and the frequency of the driving pulse. Threshold pressures for subharmonic generation as low as 5 kPa were found near a driving frequency equal to twice the resonance frequency of the bubble. An explanation for this low threshold pressure is provided by the shell buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499–3505 (2005)]. It is shown that the change in the elasticity of the bubble shell as a function of bubble radius as proposed in this model, enhances the subharmonic behavior of the microbubbles

Hydrodynamic mobility of confined polymeric particles, vesicles, and cancer cells in a square microchannel

The transport of deformable objects, including polymer particles, vesicles, and cells, has been a subject of interest for several decades where the majority of experimental and theoretical studies have been focused on circular tubes. Due to advances in microfluidics, there is a need to study the transport of individual deformable particles in rectangular microchannels where corner flows can be important. In this study, we report measurements of hydrodynamic mobility of confined polymeric particles, vesicles, and cancer cells in a linear microchannel with a square cross-section. Our operating conditions are such that the mobility is measured as a function of geometric confinement over the range 0.3 < λ < 1.5 and at specified particle Reynolds numbers that are within 0.1 < Rep < 2.5. The experimental mobility data of each of these systems is compared with the circular-tube theory of Hestroni, Haber, and Wacholder [J. Fluid Mech. 41, 689–705 (1970)] with modifications made for a square cross-section. For polymeric particles, we find that the mobility data agrees well over a large confinement range with the theory but under predicts for vesicles. The mobility of vesicles is higher in a square channel than in a circular tube, and does not depend significantly on membrane mechanical properties. The mobility of cancer cells is in good agreement with the theory up to λ ≈ 0.8, after which it deviates. Comparison of the mobility data of the three systems reveals that cancer cells have higher mobility than rigid particles but lower than vesicles, suggesting that the cell membrane frictional properties are in between a solid-like interface and a fluid bilayer. We explain further the differences in the mobility of the three systems by considering their shape deformation and surface flow on the interface. The results of this study may find potential applications in drug delivery and biomedical diagnostics