Collapse Of Microbubbles Research Articles

Analysis of Microbubble-Blood cell system Oscillation/Cavitation influenced by ultrasound Forces: Conjugate applications of FEM and LBM

Sonoporation is a non-invasive method that uses ultrasound for drug and gene delivery for therapeutic purposes. Here, both Finite Element Method (FEM) and Lattice Boltzmann Method (LBM) are applied to study the interaction physics of microbubble oscillation and collapse near flexible tissue. After validating the Finite Element Method with the nonlinear excited lipid-coated microbubble as well as the Lattice Boltzmann Method with experimental results, we have studied the behavior of a three-dimensional compressible microbubble in the vicinity of tissue. In the FEM phase, the oscillation microbubble with a lipid shell interacts with the boundary. The range of pressure and ultrasound frequency have been considered in the field of therapeutic applications of sonoporation. The viscoelastic and interfacial tension as the coating properties of the microbubble shell have been investigated. The presence of an elastic boundary increases the resonance frequency of the microbubble compared to that of a free microbubble. The increase in pressure leads to an expansion in the range of the microbubble’s motion, the velocity induced in the fluid, and the shear stress on the boundary walls of tissue. An enhancement in the surface tension of the microbubble can influence fluid flow and reduce the shear stress on the boundary. The multi-pseudo-potential interaction LBM is used to reduce thermodynamic inconsistency and high-density ratio in a two-phase system for modeling the cavitation process. The three-dimensional shape of the microbubble during the collapse stages and the counter of pressure are displayed. There is a time difference between the occurrence of maximum velocity and pressure. All results in detail are presented in the article bodies.

The compression-only behavior of coated microbubbles in a wall restricted flow.

The impact that the onset of the compression-only behavior of lipid shelled contrast agents bears on their dynamic interaction with a rigid wall under acoustic disturbances is investigated numerically in the context of axisymmetry. Wall presence is seen to not significantly affect the onset of compression-only since it only reduces the time frame required to trigger the effect. The standoff distance from the wall bears no significant effect on the amplitude threshold except that as it is reduced, it favors asymmetry by altering the compressed buckled shape around which the bubble oscillates. Above the amplitude threshold for parametric shape mode excitation, the onset of compression-only in the vicinity of a rigid wall typically interrupts the process of entrapment by reversing the direction of motion via the positive pressure drug that is generated as a result of the emerging concave upwards buckled shapes. Below this amplitude threshold, symmetric shapes or asymmetric shapes that are concave downwards continue to translate towards the wall where they perform saturated trapped pulsations around nearly spherical flattened or concave downwards buckled shapes. The latter shapes perform compression-only type pulsations and arise on the longer time scale required for the destabilization of the nearly spherical initially trapped shapes. Phase diagrams are constructed identifying regions of trapped pulsations, compression-only response, and microbubble collapse, in the parameter space defined by sound amplitude and shell viscoelastic properties.

Nanoshell Formation at the Electrically Charged Gas-Water Interface of Collapsing Microbubbles: Insights from Atomic Force Microscopy Imaging.

AFM imaging has revealed intriguing features when bulk nanobubbles were deposited on a positively charged substrate. Numerous spherical objects, each less than 20 nm in diameter, were observed on the substrate. These objects were adorned with noticeable, tiny protrusions, each measuring a few nanometers. These findings suggest the presence of solid shells contributing to the stability of the gas bodies. Furthermore, electrically charged microbubbles appear to play a critical role in the formation of these solid shells. The collapse of microbubbles in an electrolyte aqueous solution containing iron ions leads to a condensing ionic cloud, creating conditions necessary for solid nucleation at the interface. At the end of the collapsing process, concurrent multinucleation may result in the deposition of solid material on the interface, forming solid shells with specific structures on the surfaces. This study illuminates the phenomenon of electrically charged gas-water interfaces during microbubble collapse and highlights the generation of stabilized nanoshells in aqueous solutions without the need for chemical stabilizers.

Role of Ultrasonic Microbubbles in Treating Rheumatoid Arthritis: Enhancing the Efficacy of Tocilizumab via Contrast-Enhanced Ultrasound-Monitored, Ultrasound-Targeted Microbubble Destruction.

Our aim was to explore the feasibility of using ultrasound-targeted microbubble destruction (UTMD) to deliver tocilizumab and enhance its efficacy in treating rheumatoid arthritis (RA). Rats with adjuvant-induced arthritis were randomly assigned to one of five treatment groups: group 1, tocilizumab+microbubbles (MBs)+UTMD; group 2, tocilizumab+MBs; group 3, tocilizumab+saline; group 4, MBs+UTMD; group 5, no treatment. We employed a commercially available ultrasound (US) machine capable of performing contrast-enhanced ultrasound (CEUS) and UTMD simultaneously using a single probe. CEUS was performed to monitor the entry and collapse of MBs. After treatment, the rats' left hindlimb paws were harvested for immunohistochemical staining of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). After injection of the mixture of drugs and MBs with UTMD, significant enhancement was seen in the inflamed hindlimb paw regions, which subsided immediately on exposure to low-frequency US beams and re-appeared in the intervals between beam exposures. IL-6 expression was significantly lower in groups 1, 2 and 3 than in groups 4 and 5 (p < 0.01). Group 1 had the lowest level of IL-6 expression (p [G1 vs. G2] < 0.01, p [G1 vs. G3] < 0.01). The levels of TNF-α expression in groups 1, 2, and 3 were significantly lower than those in groups 4 and 5, but no difference was observed in these levels between groups 1-3. UTMD shows promise in enhancing the treatment efficacy of anti-IL-6 drugs for RA treatment.

Development of Microbubbles for Theranostics and Its Application in Brain Targeted Drug Delivery

Theranostics, a new medical term that combines therapeutics and diagnostics is considered an ideal system for medical care. Ultrasound is considered one of the most reasonable energies for the development of theranostics. Additionally, microbubbles, which are ultrasound contrast agents, have received considerable attention for their effectiveness in diagnosis and therapy. Microbubbles are composed of an inner gas and an outer shell composed of proteins or phospholipids. Under ultrasound exposure, the oscillation or collapse of microbubbles is induced depending on the intensity of the ultrasound. These mechanical effects are important for imaging, drug delivery, and ablation therapies. Therefore, it is essential that microbubbles reach the targeted site and induce mechanical effects to achieve effective and efficient diagnosis and therapy. We have previously developed novel microbubbles with high stability by optimizing the outer shell composition. Recently, microbubbles containing distearoylphosphatidyl glycerol showed high stability and prolonged circulation in the blood. These novel microbubbles may be useful for diagnosis and therapy. The combination of microbubbles and ultrasound has received considerable attention for brain-targeted drug delivery applications. We examined whether microbubbles can be used for brain-targeted drug delivery and evaluated the effect of the encapsulated gas on drug delivery. Thus, novel microbubbles combined with ultrasound can deliver molecules to the brain. Microbubbles containing perfluoropropane or perfluorobutane could efficiently deliver molecules to the brain. The novel microbubbles have long-circulating properties in the blood and could deliver molecules to the brain. The combination of novel microbubbles and ultrasound would contribute to the development of efficient thranostic systems.

Microbubble-enhanced cold plasma activation for water decontamination: Degradation dynamics and energy yield in relation to pollutant concentration, total volume and flow rate of water

Necessity to safely dispose effluents from industrial wastewater and also water shortage has motivated the search for novel techniques in water treatment. Cold plasma technology is a green, robust, and flexible approach that can sustainably address concerns about removal of pollutants in water. In this study, hydrodynamic cavitation (HC) in a Venturi tube is combined with plasma activated water (PAW) in a continuous system to treat two common antibiotics (sulfathiazole and norfloxacin) and an azo dye (methylene blue). HC increases mass transfer of active species generated from cold plasma discharge from gas to liquid by formation and collapse of cavitation microbubbles. Effects of initial concentration, total volume of circulating water, and water flow rate are studied. Results show that operating at flow rate of 5 L/min and volume of 500 mL for 30 min, all three pollutants with initial concentration of 8 mg/L or lower can be degraded to >80 %. Energy yield and degradation kinetics of experiments are also elaborated. Thus, the setup ameliorates the hurdle of gas - liquid mass transfer. Finally, larger volume samples (2, 10, and 20 L) were treated to show the applicability of the method for more industrial scale levels. Lower concentrated samples degrade faster compared with more concentrated solutions. Besides, a direct relation is shown between water flow rate and degradation signifying the fact that at higher flow rates the amount of reactive species being able to enter the cavitation chamber are greater. The energy yield is estimated to be the highest as the higher initial concentration with short treatment time. Further studies can focus on optimization and extension of the current setup to other chemicals and other gas atmospheres.

Numerical investigation of ultrasound focusing and bubble collapse

Ultrasound focusing and microbubble collapse are numerically investigated using a level-set interface tracking method for two-phase flows with multiple interfaces. The computations for ultrasound propagating through a spherical lens demonstrate the ultrasound refraction and pressure intensification at the rear of the lens. The focusing of the initial negative pressure wave through the lens induces a converging flow and the focusing of the subsequent positive pressure wave further intensifies the pressure at the lens. Computations are extended to bubble oscillations near the focusing lens and compared with the no-lens case. The lens not only amplifies the bubble expansion and contraction rates significantly but also generates a larger pressure gradient across the bubble. This ultrasound focusing effect contributes to the asymmetric collapse of the bubble and the formation of a liquid jet that penetrates the bubble. The effects of lens size, initial bubble radius and bubble-lens distance on bubble expansion and liquid jet are further investigated.

Ultrasonic Decontamination of Chemical Warfare Agents

Abstract Sonochemistry studies the physical and molecular level changes induced by ultrasonic energy on solutions. Sonochemical degradation of the chemical warfare agents (CWA) may occur due to three successive phenomena based on the principles of acoustic cavitation phenomena: nucleation, growth, and implosive collapse of microbubbles. The sonolytic degradation of CWA was quantified by GC-MS technique, considering the variation of some parameters such as frequency of ultrasonic waves, power control, temperature, and addition of nanoparticles as catalysts to the solution.

Effects of a DMPC molecular film surrounding microbubbles on the sound-pressure threshold for collapse

We investigated the effects of a 1,2-dimyristoyl-sn-glycerol-3-phosphocholine (DMPC) molecular film surrounding microbubbles on their collapse under ultrasound irradiation. We defined the ejection of the internal gas from the microbubble (i.e. “daughter” bubbles) as bubble collapse. In particular, we measured the sound-pressure thresholds for microbubble collapse in water and a DMPC solution. Bubbles with the DMPC film had a smaller resonance size than naked bubbles. The measured contact angles of the bubbles were lower after collapse, implying that DMPC molecules on the bubble surface partially desorbed between the processes of vibration and collapse.

Microbubble collapse near a fiber: Broken symmetry conditions and a planar jet formation

The collapse of microbubbles near a fiber is an example often encountered in water treatment situations and cavitation fibrillation processes. However, due to the broken symmetry conditions, this process has not been studied in detail experimentally or numerically, making it difficult to precisely measure or simulate the rapid bubble evolution during collapse. In this work, we present a novel experimental method, allowing for precisely repeatable cavitation events observation, combined with numerical simulations offering insight into pressure and velocity fields distribution developments in time. Both experimental and numerical works focused on small distances between the bubble and the fiber, where the physical interaction between subjects is the strongest. Four different bubble offsets were considered within the scope of this work, and very good agreement of numerical simulations with experiments was found in all cases. Two modes of bubble collapse were identified, leading to mushroom-shaped bubbles at positions closest to the fiber and a pear-shaped bubble at the farthest position. It is noteworthy that in all four cases, a planar jet formation toward the fiber was observed. The formed jet initially assumes an elongated shape, whereas its stability depends on the mode of bubble collapse. Numerical analysis of the planar jet as the defining feature of the collapse defined lower bounds for the actual values of peak jet velocities, ranging between 250 and 330 m/s, and the resulting impact pressures, which range from 100to 500 MPa.

Cavitation over solid surfaces: microbubble collapse, shock waves, and elastic response

We discuss the interaction of the strongly nonlinear fluid motion induced by the collapse of a vapor microbubble over a planar surface and the elastic dynamics of the underlying solid. The fluid is described using an extension of the Navier-Stokes equations endowed with distributed capillary stresses in the context of a diffuse interface approach. The collapse of the bubble is triggered by overpressure in the liquid and leads to an intense jet that pierces the bubble, changing the bubble topology from spheroidal to toroidal, and impinges the solid wall inducing an intense and strongly localized load. Moreover, at bubble collapse, a compression wave is launched into the liquid surrounding the bubble. By propagating along the solid surface, the compression wave combined with the liquid jet excites the dynamics of the elastic solid, producing a complex system of waves, including, longitudinal, transversal, and Rayleigh waves, propagating in the solid. It is conjectured that the intense deformation of the solid induced by the strongly localized liquid jet may lead to the plastic deformation of the solid producing the surface pitting observed in many applications subject to cavitation-induced material damage.

초음파 압력 펄스에 의한 미세기포와 세포 간의 상호작용에 대한 수치적 연구

The collapse of microbubbles using ultrasonic pressure pulses is accompanied by strong shock waves and jets. This phenomenon is an important topic applied to various environmental and medical fields such as surface cleaning, algae removal, cell poration, and drug delivery. However, a numerical model that can capture the strong bubble collapse, liquid jet, and associated deformation of a cell is lacking in the literature. In this work, numerical simulations are performed for the interaction between the spherical bubble and cell under an ultrasonic pulse condition including the effects of bubble collapsing jet and cell deformation. The cell is treated as a compressible liquid and two distance level-set functions are used for the bubble and cell interfaces. The conservation equations of mass and momentum are solved for compressible two-phase flows. The effects of acoustic amplitude and frequency and initial bubble-cell distance are investigated. The results show that cell deformation increases with increasing acoustic amplitude or decreasing frequency, and the distance between the bubble and cell is observed as an important parameter for cell deformation under the same ultrasound conditions. The present work can contribute to a safer and more efficient use of ultrasound in environmental and medical applications.

A comparative analysis of micro-mixing process in a confined impinging jet reactor with/without applying ultrasound

Studies on the influences of ultrasound-induced cavitation on the micro-mixing process in a confined impinging jet reactor (CIJR) are still lacking. In the present study, experimental and numerical approaches are employed to investigate the effects of ultrasound intensification on the mixing processes in a CIJR. The numerical results are experimentally validated. The model is also coupled with chemical reactions for the first time. It is found that local eddies generated by the collapse of acoustic microbubbles and “turbulence”-like acoustic streaming can significantly reduce the micro-mixing time. In all cases, the micro-mixing efficiency is found to increase with an increase in the power of ultrasound. A reduction of 15–24% in micro-mixing time can be achieved at the inlet velocity of 0.2m/s when the power of ultrasound increases from 122.5W to 175W. It is also found that the effect of ultrasound intensification on the meso-mixing process is larger than that on the micro-mixing process in the vicinity of transducer head. The ratio of micro-mixing time to meso-mixing time in the case of Pultra=175W can be 88% larger than that in the case of Pultra=0W in the front of the transducer head at Rein=5000.

Ultrasound Molecular Imaging for Multiple Biomarkers by Serial Collapse of Targeting Microbubbles with Distinct Acoustic Pressures.

Ultrasound molecular imaging (UMI) has shown promise for assessing the expression levels of biomarkers for the early detection of various diseases. However, it remains difficult to simultaneously image multiple biomarkers in a single systemic administration, which is important for the accurate diagnosis of diseases and for understanding the dynamic intermolecular mechanisms that drive their malignant progression. The authors develop an ultrasound molecular imaging method by serial collapse of targeting microbubbles with distinct acoustic pressures for the simultaneous detection of two biomarkers. To test this, αv β3 -targeting lipid microbubbles (L-MBα ) and VEGFR2-targeting lipid-PLGA microbubbles (LP-MBv ) are fabricated and simultaneously injected into tumor-bearing mice at 7 and 14 days, followed by the low-intensity acoustic collapse of L-MBα and high-intensity acoustic collapse of LP-MBv . The UMI signals of L-MBα and LP-MBv are obtained by subtracting the first post-burst signals from the first pre-burst signals, and subtracting the second post-burst signals from the first post-burst signals, respectively. Interestingly, the signal intensities from UMI agree with the immunohistochemical staining results for αv β3 and VEGFR2. Importantly, they find a better fit for the invasive behavior of MDA-MB-231 breast tumors by analyzing the ratio of αv β3 integrin to VEGFR2, but not the single αv β3 or VEGFR2 levels.

Sonochemistry of actinides: from ions to nanoparticles and beyond

AbstractSonochemistry studies chemical and physical effects in liquids submitted to power ultrasound. These effects arise not from a direct interaction of molecules with sound waves, but rather from the acoustic cavitation: the nucleation, growth, and implosive collapse of microbubbles in liquids submitted to power ultrasound. The violent implosion of bubbles leads to the formation of chemically reactive species. In principle, each cavitation bubble can be considered as a microreactor initiating chemical reactions at mild conditions. In addition, microjets and shock waves accompanied bubble collapse produce fragmentation, dispersion and erosion of solid surfaces or particles. Microbubbles oscillating in liquids also enable nucleation and precipitation of nanosized actinide compounds with specific morphology. This review focuses on the versatile sonochemical processes with actinide ions and particles in homogenous solutions and heterogenous systems. The redox reactions in aqueous solutions, dissolution or precipitation of refractory solids, synthesis of actinide nanoparticles, and ultrasonically driving decontamination are considered. The guideline for further research is also discussed.

Polishing of zirconia ceramics by chemically-induced micro-nano bubbles

This study introduces micro-nano bubbles (MNBs) in the process of polishing zirconia ceramics through sodium borohydride hydrolysis to assist in polishing yttria-stabilized zirconia (YSZ). Compared with conventional silica sol, the material removal rate using this MNB-assisted technology is increased by 261.4%, and a lower surface roughness of 1.28 nm can be obtained. Raman, X-ray diffraction, and X-ray photoelectron spectroscopy are used to study the structural changes and phase stability of the YSZ during different polishing periods. The results show that MNBs are the key factor promoting the transformation from the tetragonal phase to the monoclinic phase on the surface of the YSZ during polishing. The H2O molecules (or OH− ions) on the surface of the YSZ are driven by the thermal kinetic energy of the micro-jets formed by the collapse of micro-bubbles, and they permeate to occupy more oxygen vacancies in the crystal lattice. Atomic force microscopy and nano-indentation tests show that the micro-protrusions on the surface of the YSZ preferentially undergo phase transformation, and their hardness decreases. This promotes abrasives to preferentially remove rough spots on the surface and achieve more efficient polishing. We believe this work adds valuable insights regarding low-temperature degradation and ultra-precise machining of YSZ ceramic materials.

Coronary artery cavitation as a trigger for atherosclerotic plaque progression: a numerical and computational fluid dynamic demonstration

Abstract Background Coronary cavitation is supposed to be generated by both concentric and eccentric coronary artery stenosis creating microbubbles which exploded when the fluid pressure was lower than the vapor pressure at a local thermodynamic state. Aims To assess, using computational fluid dynamic analysis (CFD), the potential role of cavitation in inducing coronary artery endothelial damage and promote atherosclerotic plaque progression. Methods We retrospectively reviewed the procedural records of consecutive patients evaluated between 1st January 2013 and 1st January 2014 with an isolated hemodynamically significant Left Main (LM) disease. Each bifurcation was reconstructed on the patient-specific geometries derived from the CCTA applying patient-specific hemodynamic features. Vapour has been modelled as discrete vapour bubbles and its trajectory determined using a Lagrangian frame of reference. Cavitation started with micro-cavitation nuclei which subsequently grow into bubbles undergoing different physical processes determined in a stochastic Monte-Carlo approximation. Results Among the 12 patients analysed [8 males, mean age 68.2±12.8 years old], the mean LM stenosis was 72.3±3.6%. In all subjects, LM stenoses induced cavitation which propagates downstream the vessel. The higher concentration of vapour region was detected before the carina (within 0.8 to 1.3 cm from the stenosis). The mean bubbles radius observed before the carina was 4.2±1.4 μm; their impact with the endothelial surface generated a mean peak pressure of 3.9±0.5 MPa determining a local shockwave (Figure 1). Conclusion The collapse of micro-bubbles alongside the endothelium generated micro-shockwaves determining repeated dynamic load measurable as an instantaneous pressure-peaks able to induce endothelial injury or dysfunction. Funding Acknowledgement Type of funding sources: None. Figure 1. (A) The simulation illustrates the vapour fraction iso-surfaces and the scattered bubble plots as predicted by the Langrangian model. Notably, most cavitation bubbles that form at the inlet of left main bifurcation do not collapse immediately but they are transported towards the vessel determining several interactions with the endothelium. (B) Graphical representation of the bubble radius modification and related pressure transmitted to the endothelium if the bubble collapse happened near to this last one. The magnification in boxes (B1-B4) evidences the dynamic modification of bubbles. The re-entry jet causing the collapse is evidenced with a red arrow.

Photoechogenic Inflatable Nanohybrids for Upconversion-Mediated Sonotheranostics.

Hybrid nanostructures are promising for ultrasound-triggered drug delivery and treatment, called sonotheranostics. Structures based on plasmonic nanoparticles for photothermal-induced microbubble inflation for ultrasound imaging exist. However, they have limited therapeutic applications because of short microbubble lifetimes and limited contrast. Photochemistry-based sonotheranostics is an attractive alternative, but building near-infrared (NIR)-responsive echogenic nanostructures for deep tissue applications is challenging because photolysis requires high-energy (UV-visible) photons. Here, we report a photochemistry-based echogenic nanoparticle for in situ NIR-controlled ultrasound imaging and ultrasound-mediated drug delivery. Our nanoparticle has an upconversion nanoparticle core and an organic shell carrying gas generator molecules and drugs. The core converts low-energy NIR photons into ultraviolet emission for photolysis of the gas generator. Carbon dioxide gases generated in the tumor-penetrated nanoparticle inflate into microbubbles for sonotheranostics. Using different NIR laser power allows dual-modal upconversion luminescence planar imaging and cross-sectional ultrasonography. Low-frequency (10 MHz) ultrasound stimulated microbubble collapse, releasing drugs deep inside the tumor through cavitation-induced transport. We believe that the photoechogenic inflatable hierarchical nanostructure approach introduced here can have broad applications for image-guided multimodal theranostics.

Quantitative evaluation of the mortality rate of HeLa cells induced by microbubble vibration and collapse under pulsed ultrasound irradiation

Drug delivery systems (DDS) using ultrasound and microbubbles have been proposed to enhance drug efficacy and reduce undesirable side effects. While several researchers have reported the vibrational characteristics of lipid-coated microbubbles under ultrasound irradiation and the effects on cell damage, it is necessary to quantitatively evaluate the effects to establish the safety criteria of ultrasound DDS. In this paper, the effects of the microbubble behavior on adhesive HeLa cells under ultrasound irradiation were evaluated. Microbubbles coated with a phospholipid shell were fabricated and two size distributions of bubbles were prepared. The HeLa cells were exposed to pulsed ultrasound at 1 MHz with microbubbles in a water tank, and the cell mortality rate was measured quantitatively under fluorescent observation. The collapse of the microbubbles with a resonance size of approximately 2 μm enhanced the cell mortality rate. Greater sound pressure amplitude produced a higher collapsing rate of the microbubble and cell mortality rate, implying the destruction of microbubbles with resonance size generated a shock wave or microjet, inducing cell damage. While the cell mortality rate decreased exponentially with the increase in distance between cells and microbubbles, a smaller distance induced a higher cell mortality rate: 84% of the HeLa cells died within 2.5 μm of microbubbles produced by a pulsed ultrasound with 1.0 MPa at 1 MHz.

Different Aspects of Using Ultrasound to Combat Microorganisms

AbstractGrowing resistance of microorganisms to antibiotics due to their widespread use has led to multiple bacterial infections posing a serious threat to health and human life. Low‐frequency ultrasound is one of physical methods for inactivation of pathogenic microbial cells. Application of ultrasound is safe, demonstrates good tissue penetration without significant attenuation of energy, and does not induce microbial resistance. Bactericidal effect of ultrasound is based on acoustic cavitation—the growth and collapse of microbubbles in a liquid medium, resulting in shock waves, shear forces, and microjets which cause irreversible damage and inactivation of microorganisms. The present review combines and analyzes literature data on in vitro and in vivo studies and summarizes works demonstrating the ability of ultrasound, alone or in combination with other methods, to combat pathogenic microorganisms. The results of various studies presented in this review show that low‐frequency ultrasound has a noticeable antimicrobial effect on planktonic cells of microorganisms and biofilms. Ultrasound synergistically enhances the effectiveness of other antibacterial agents and activates molecules called sonosensitizers, resulting in the formation of compounds toxic to microbial cells. Ultrasound can also promote local release of antimicrobial drugs from liposomes, as well as from medical implants.