Microbubble Size Research Articles

Experimental investigation on the effect of concentration on the resonance frequency of lipid coated ultrasonically excited microbubbles

This study presents an experimental investigation of the influence of MB concentration on the resonance frequency of lipid-coated microbubbles (MBs). Expanding on theoretical models and numerical simulations from previous research, this work experimentally investigates the effect of MB size on the rate of resonance frequency increase with concentration, a phenomenon observed across MBs with two different lipid compositions: propylene glycol (PG) and propylene glycol and glycerol (PGG). Employing a custom-designed ultrasound attenuation measurement setup, we measured the frequency-dependent attenuation of MBs, isolating MBs based on size to generate distinct monodisperse sub-populations for analysis. The resonance frequency of MBs was determined by identifying the attenuation peak in the broadband attenuation ultrasound attenuation measurements. Our experimental findings confirm that larger MBs (≈2.1μm) demonstrate a more significant shift in resonance frequency (≈ 5 MHz, ≈ 40%) as a function of MB concentration. In contrast, smaller MBs (≈1.3μm) show a minor shift in the resonant frequency (≈ 1.8MHz, ≈ 8%), underlining the importance of size in determining acoustic behavior compared to changes in the lipid shell properties. Additionally, we observed that resonance frequency increase with concentration reaching a saturation point at higher concentrations. This plateau occurs at higher concentrations for larger MBs (≈2.1μm), while smaller MBs (≈1.6μm and ≈1.3μm) reach this saturation point at lower concentrations. Furthermore, the study highlights the small effect of bubble-bubble interactions on the resonance frequency of MB populations, particularly at lower MB concentrations and for smaller MBs. This insight is important for applications utilizing MB clusters, such as contrast-enhanced ultrasound imaging and MB-mediated therapies. While both size and lipid shell composition influence resonance frequency, MB size has a more significant effect. In conclusion, our findings affirm the need to consider both MB size and concentration when utilizing MBs for clinical and industrial ultrasonic applications.

Ultrasound-triggered drug release and cytotoxicity of microbubbles with diverse drug attributes

Ultrasound (US)-triggered cavitation of drug-loaded microbubbles (MBs) represents a promising approach for targeted drug delivery, with substantial benefits attainable through precise control over drug release dosage and form. This study investigates Camptothecin-loaded MBs (CPT-MBs) and Doxorubicin-loaded MBs (DOX-MBs), focusing on how properties such as hydrophilicity, hydrophobicity, and charged functional groups affect their interaction with the lipid surfaces of MBs, thereby influencing the fundamental characteristics and acoustic properties of the drug-loaded MBs. In comparison to DOX-MBs, CPT-MBs showed larger MB size (2.2 ± 0.3 and 1.4 ± 0.1 μm, respectively), a 2-fold increase in drug loading, and an 18 % reduction in leakage after 2 h at 37℃. Under 1 MHz US with a 100 ms pulse repetition interval (PRI), 1000 cycles, 5-minute duration, and 550 kPa acoustic pressure, CPT-MBs undergo inertial cavitation, while DOX-MBs undergo stable cavitation. Drug particles released from these MBs under US-induced cavitation were analyzed using dynamic light scattering, NanoSight, cryo-electron microscopy, and density gradient ultracentrifugation. Results showed that CPT-MBs mainly release free CPT, while DOX-MBs release multilayered DOX-lipid aggregates. The cytotoxicity to C6 cells induced by US-triggered cavitation of these two types of MBs also differed. DOX-lipid aggregates delayed initial uptake, leading to less pronounced short-term (2 h) effects compared to the rapid release of free CPT from CPT-MBs. These findings underscore the need to optimize drug delivery strategies by fine-tuning MB composition and US parameters to control drug release kinetics and achieve the best tumoricidal outcomes.

Graphene-Loaded Aphron Microbubbles for Enhanced Drilling Fluid Performance and Carbon Capture and Storage.

Maintaining the stability of microbubbles is essential for enhancing the longevity of aphronic water-based drilling fluid usage in drilling depleted reservoirs and other under-pressured zones. Here, we introduce the integration of partially reduced graphene oxide (PrGO) nanosheets into the shell of aphron microbubbles (AMBS) to enhance the stability and size distribution, particularly for drilling fluid applications and carbon geological storage. The amphiphilic characteristic of PrGO nanosheets, due to meticulous control of the reduction process of graphene oxide, facilitates their spontaneous adsorption at interfaces, thereby reducing the interfacial energy as a two-dimensional surfactant. The loading of PrGO nanosheets in the polymeric shell of AMBs enhances mechanical strength, stability, and resistance to gas diffusion, prolonging the half-life of the microbubbles to over 120%. According to the results, a more uniform size distribution and reduction of microbubble size up to 60% have been achieved at a concentration of 0.30 wt % PrGO. Rheological studies using various models indicate the optimal PrGO concentration for improved stability in aphronic fluids. Filtration tests indicate the loaded PrGO can reduce filtration loss by up to 45% at 0.50 wt % by forming a cohesive and compressible cake, improving filtration control. Changes in the Fourier-transform infrared spectra and contact angle measurements suggest increased surface hydrophobicity with higher graphene concentrations in aphronic fluid cakes. Moreover, the study elucidates that the stability of microbubbles is influenced by the type of core gas, with N2 gas yielding the highest stability and CO2 the lowest. Ultimately, these results highlight the beneficial effect of incorporation of PrGO nanosheets in aphron microbubbles to boost the drilling fluid performance and efficiency, which will pave the way toward ultralightweight fluids that can even be used as carrier and injection fluids in carbon capture and leak-free geological storage technologies.

Effect of Microbubble Size, Composition, and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening.

Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubbles (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model. Using MRI-guided MB + FUS, we targeted the striatum and assessed extravasation of an MRI contrast agent to assess BBBO and RNaseq to assess SIR. Our results revealed distinct effects of these parameters on BBBO and SIR. Specifically, at a matched microbubble volume dose (MVD), MB size did not affect the extent of BBBO, but smaller (1 μm diameter) MBs exhibited a lower classification of SIR than larger (3 or 5 μm diameter) MBs. Lipid-shelled microbubbles exhibited greater BBBO and a more pronounced SIR compared to albumin-shelled microbubbles, likely owing to the latter's poor in vivo stability. As expected, increasing the number of sonication points resulted in greater BBBO and SIR. Furthermore, correlation analysis revealed strong associations between passive cavitation detection measurements of harmonic and inertial MB echoes, BBBO, and the expression of SIR gene sets. Our findings highlight the critical role of MB and FUS parameters in modulating BBBO and subsequent SIR in the brain. These insights inform the development of targeted drug delivery strategies and the mitigation of adverse inflammatory reactions in neurological disorders.

Sonopermeation With Size-sorted Microbubbles Synergistically Increases Survival and Enhances Tumor Apoptosis With L-DOX by Increasing Vascular Permeability and Perfusion in Neuroblastoma Xenografts

ObjectiveDespite aggressive therapy, approximately 50% of patients with neuroblastoma (NB) fail to respond, and survivors endure lifelong toxicities. Sonopermeation increases drug uptake via cell bilayer disruption through focused ultrasound and microbubbles (MBs)—gas-filled, sound sensitive lipid spheres. MB response to a given ultrasound pulse (cavitation) varies according to MB size. We asked whether size-sorted MBs (SSMB) 4 to 5 µm in diameter will more consistently and predictably enhance doxorubicin uptake, compared with polydisperse MBs (PMB, 0.5–10 µm in diameter), thereby increasing drug delivery to NB xenografts. MethodsHuman NB cells were implanted into the left kidney of nude mice and grown for 5 to 6 wk. Mice received sonopermeation alongside either PMB or SSMB at low (0.6 MPa) or high (2 MPa) negative pressures. Some mice also received different chemotherapy agents (doxorubicin, etoposide or cyclophosphamide). Circulating tumor cells were assessed by flow cytometry 1 h after treatment. Survival was assessed for up to 21 d, a subset of mice was euthanized 24 h after treatment for histological assessment of apoptosis, vascular lumen size and tight junctions. ResultsTumors treated with SSMB and high pressure showed synergy with liposomal doxorubicin (L-DOX) owing to increased vascular lumen and disruption of tight junctions, resulting in drug uptake, apoptosis, lack of tumor growth and increased survival. We found no difference in the numbers of circulating tumor cells. ConclusionSonopermeation with SSMB at 2 MPa synergizes with L-DOX delivery, increasing apoptosis, perfusion and vascular permeability, suggesting that SSMB sonopermeation at high pressure is promising for NB-targeted treatment, especially in combination with L-DOX.

Control of photothermal liquid jets through microbubble Regulation: Fundamental mechanisms and Developing Strategies

Plasmon-induced photoacoustic streaming, considered as a potential application for micro-pumps in microfluidics, currently encounters ongoing debates concerning its fundamental mechanisms. In this study, we investigate the crucial role played by microbubbles in generation of jets in an ethanol aqueous solution. The power density threshold for bubble generation and its dependency on jet initiation are confirmed and the microbubble behavior is well regulated by manipulating the laser and liquid properties. Through simulations coupling fluidic and thermal fields, the significant role of Marangoni effect is validated in jet formation. Specifically, the temperature gradient of microbubbles is determined to be a pivotal factor in the generation of collimated jets. Additionally, factors influencing jetting, such as microbubble size and temperature gradients are studied, and noticeably, a stabilized jet lasting over 4 h is achieved based upon.

Application of microbubble air flotation to harvest Microcystis sp. from agriculture wastewater: The regulation and mechanisms.

The harvesting of microalgae is the main bottleneck of its large-scale biomass production, and seeking an efficient, green, and low-cost microalgae harvesting technology is one of the urgent problems to be solved. Microbubble air flotation has been proven to be an effective measure, but the mechanisms of microbubbles-algal cell attachment are still unclear. In this study, microbubble air flotation was used as a harvesting method for Microcystis cultured in agricultural wastewater. The process mechanism of microbubble air flotation harvesting microalgae in wastewater was fully revealed from three aspects (the design of bubble formation, the adhesion law, and the recovery rate of microalgae under different working conditions). The results show that the length of the release pipe is the main factor affecting the proportion of microbubbles with a particle size of less than 50 μm. In the process of adhesion, when the particle size of microbubbles is 0.6-1.7 times the size of Microcystis, the adhesion efficiency of microbubbles to Microcystis is the highest. Under the conditions of pressure 0.45 MPa, gas-liquid ratio 5%, and release pipe length 100 cm, the harvesting performance of Microcystis was the best. Microbubble air flotation has better harvesting performance (63.5%, collection rate) of Microcystis with higher density. By understanding the mechanism of microbubble flotation, the technical parameters of microbubble flotation for harvesting energy microalgae are optimized to provide support for the development of efficient and low-cost devices and equipment for collecting microalgae.

Experimental measurement of the size distribution of microbubbles prepared by reciprocating syringe technique

Microbubbles have captured the attention of scholars due to their exceptional physical and chemical properties that exhibit practical applications. Transcranial Doppler ultrasound is a diagnostic tool used in clinical medicine to identify patent foramen ovale (PFO) heart disease caused by incomplete fusion of primary and secondary septum after birth, using microbubbles. The volume of gas and size of the bubbles determine the consequences of air entering the bloodstream. Therefore, it is imperative to investigate stable and efficient microbubble generation technology. The team designed and developed a new type of bubble generator and performed basic research on the flow and mixing rules in the gas-liquid two-phase system in the syringe. The shadow imaging method was used to explore the influence of the equipment operation parameters on the experimental system's microbubble flow process. After analyzing multiple sets of experimental data, it was found that the diameter of bubbles decreases as the frequency increases. After ten times of high-frequency reciprocating movement of the equipment, the microbubble size distribution is mainly between 10–100 μm, the mean diameter is between 23–26 μm, and the relative standard deviation is less than 4.5 %. Compared to manual methods, the device exhibits good accuracy and repeatability.

Numerical simulation study on opening blood–brain barrier by ultrasonic cavitation

Experimental studies have shown that ultrasonic cavitation can reversibly open the blood–brain barrier (BBB) to assist drug delivery. Nevertheless, the majority of the present study focused on experimental aspects of BBB opening. In this study, we developed a three-bubble-liquid-solid model to investigate the dynamic behavior of multiple bubbles within the blood vessels, and elucidate the physical mechanism of drug molecules through endothelial cells under ultrasonic cavitation excitation. The results showed that the large bubbles have a significant inhibitory effect on the movement of small bubbles, and the vibration morphology of intravascular microbubbles was affected by the acoustic parameters, microbubble size, and the distance between the microbubbles. The ultrasonic cavitation can significantly enhance the unidirectional flux of drug molecules, and the unidirectional flux growth rate of the wall can reach more than 5 %. Microjets and shock waves emitted from microbubbles generate different stress distribution patterns on the vascular wall, which in turn affects the pore size of the vessel wall and the permeability of drug molecules. The vibration morphology of microbubbles is related to the concentration, arrangement and scale of microbubbles, and the drug permeation impact can be enhanced by optimizing bubble size and acoustic parameters. The results offer an extensive depiction of the factors influencing the blood–brain barrier opening through ultrasonic cavitation, and the model may provide a potential technique to actively regulate the penetration capacity of drugs through endothelial layer of the neurovascular system by regulating BBB opening.

The role of microbubble dose in combined microflotation of fine particles

Flotation of small particles is one of the global challenges facing the mineral raw materials processing industry. Large amounts of non-ferrous and rare metals are lost in the flotation tailings in the form of mineral particles below 15 µm in size as a result of the low effectiveness of their capture by coarse bubbles generated in conventional flotation machines. The method of combined microflotation, developed in recent years, uses conventional coarse bubbles (CB) and microbubbles (MB) produced in the stand-alone generator of air-in-water microdispersion, which serves as the flotation carriers. Depending on the MB dose, the effect of their application may be positive or negative. The theoretical analysis of various mechanisms of particle transfer onto the surface of coarse bubbles and further into the froth layer allowed to obtain the formula for the optimal MB dose f=d<sub>d</sub>/2d<sub>p</sub>r<sub>p</sub>, where d<sub>d</sub> is MB size; d<sub>p</sub> and r<sub>p</sub> respectively are the size and the density of particles. Experiments performed on the copper ore flotation tailings at the Atalaya Mining (Spain) and Chaarat Kapan (Armenia) concentrators showed that, besides the optimal MB dose in the range of 1-3 ml/g, there is another optimal MB dose in the range of 10-20 ml/g, where the copper recovery increases by several percent compared to the reference test (f = 0). The deep minimum in copper recovery is observed in the area between the optimal MB doses, which is by several percent lower than the value in the reference test.

Bubble Characteristics Required for the Complete Removal of Alumina Inclusions from Steel Melts

Gas bubbling can be an effective means to float out alumina inclusions from liquid steel in a ladle. However, large spherical cap bubbles are formed when using porous plugs, as the liquid steel is nonwetting to the porous refractory. These bubbles rise rapidly through the liquid steel, forming a fast‐moving bubble plume, restricting contact times. Sized microbubbles, by contrast, have now been generated in liquid metals by shearing methods, involving linear crossflows to an entering flow of gas, or alternatively by rotational shearing. Combined with these convective shearing forces, local kinetic energy of turbulence can also play an important part in determining final microbubble size distributions. As microbubbles have much smaller rise velocities and present a far greater inclusion capture surface area than those of a single large bubble of the same gross volume, this will allow us to remove sub‐50 μm inclusions from liquid steel. It is expected that this goal will require a redesign of current ladle shrouds.

High-Speed Optical Characterization of Protein-and-Nanoparticle–Stabilized Microbubbles for Ultrasound-Triggered Drug Release

BackgroundUltrasound-triggered bubble-mediated local drug delivery has shown potential to increase therapeutic efficacy and reduce systemic side effects, by loading drugs into the microbubble shell and triggering delivery of the payload on demand using ultrasound. Understanding the behavior of the microbubbles in response to ultrasound is crucial for efficient and controlled release. MethodsIn this work, we characterize the response of microbubbles with a coating consisting of poly(2-ethyl-butyl cyanoacrylate) (PEBCA) nanoparticles and denatured casein. High-speed recordings are taken of single microbubbles, both in bright-field and fluorescence. ResultsThe nanoparticle-loaded microbubbles show resonance behavior, but with a large variation in response, demonstrating a substantial inter-bubble variation in mechanical shell properties. The probability of shell rupture and the probability of nanoparticle release were found to strongly depend on the microbubble size, and the most effective size was inversely proportional to the driving frequency. Both the rupture and release probabilities increased with increasing driving pressure amplitude. Rupture of the microbubble shell occurred after fewer cycles of ultrasound as the driving pressure amplitude or driving frequency was increased. ConclusionsThe results highlight the importance of careful selection of the driving frequency, driving pressure amplitude, and duration of the ultrasound to achieve the most efficient ultrasound-triggered shell rupture and nanoparticle release of protein-and-nanoparticle-stabilized microbubbles.

Eulerian–Lagrangian multiscale numerical analysis of multimodal partial shedding dynamics

The objective of this paper is to investigate the multimodal partial shedding dynamics from a multiscale perspective of cloud cavitating flows under two distinct cavity shedding mechanisms, namely the re-entrant jet mechanism and the shock wave propagation mechanism. A two-way Eulerian–Lagrangian coupling algorithm is applied to capture the multiscale vapor topologies from microbubble to large-scale cavities. The large-scale cavity evolution is solved through large eddy simulations (LES) with the volume of fraction (VOF) method in Eulerian frame. The sub-grid microbubbles are tracked in Lagrangian frame based on the discrete bubble model (DBM) method. The predictions agree well with experimental observation of the periodical cavity evolution and microbubble dynamics under both the re-entrant jet mechanism and shock wave mechanism around a NACA66 hydrofoil. The numerical simulation provides detailed analysis of the cavitating turbulent flow on the microbubble behavior with emphasis on the spatial-temporal distribution characteristics of microbubbles. The results show that the number and mean size of microbubbles in the cavitation region increase gradually with the growth of attached sheet cavity, development of re-entrant jet and collapse of largescale cavity for both cavitation patterns. Meanwhile, microbubbles are mainly distributed on the largescale interfaces where have high value of vorticity and turbulent kinetic energy under the effect of re-entrant jet and vortex structures. And the probability density functions (PDFs) of microbubble exhibit gamma distributions with a dominant peak at approximately 50 μm for both shedding mechanisms. However, the shock wave formation and propagation process only occurs in the final stage of cavitating flow under shock wave mechanism causing the condensation of vapor and the decrease of the number and mean size of microbubbles. Moreover, the microbubbles are uniformly distributed along the streamwise and vertical directions behind shock wave front.

Effect of microbubbles on immersion freezing of grape tomato

Microbubbles (MBs) were incorporated into calcium chloride solution as a novel freezing medium for immersion freezing of grape tomato. The effects of MB size (39, 43, 48 μm mean diameter), entrapped gas (air, N2, CO2) and freezing temperature (−10, −15, −20 °C) on the freezing behavior and quality attributes of tomato were investigated. MBs increased the nucleation temperature from −7.4 to −3.5 °C and reduced the onset time of nucleation from 5.8 to 2.9 min at freezing temperature of −20 °C, which facilitated the formation of small ice crystals within tomato. MB-assisted freezing reduced the drip loss by 13.7–17.0% and improved the firmness of tomato, particularly when MB size and freezing temperature decreased. Freezing tomato with air-MBs did not compromise its nutritional quality, using N2- and CO2-MBs even increased its lycopene content, by 31% and 23%, respectively. The results proved the preservation effect of MBs on fruit during immersion freezing. This study can benefit the fruit and vegetable industry by providing an efficient freezing technology for producing frozen products with high sensory and nutritional quality.

Understanding the effects of microbubble concentration on localization accuracy in super-resolution ultrasound imaging.

Super-resolution ultrasound (SRUS) through localising and tracking of microbubbles (MBs) can achieve sub-wavelength resolution for imaging microvascular structure and flow dynamics in deep tissuein vivo. The technique assumes that signals from individual MBs can be isolated and localised accurately, but this assumption starts to break down when the MB concentration increases and the signals from neighbouring MBs start to interfere. The aim of this study is to gain understanding of the effect of MB-MB distance on ultrasound images and their localisation. Ultrasound images of two MBs approaching each other were synthesised by simulating both ultrasound field propagation and nonlinear MB dynamics. Besides the distance between MBs, a range of other influencing factors including MB size, ultrasound frequency, transmit pulse sequence, pulse amplitude and localisation methods were studied. The results show that as two MBs approach each other, the interference fringes can lead to significant and oscillating localisation errors, which are affected by both the MB and imaging parameters. When modelling a clinical linear array probe operating at 6 MHz, localisation errors between 20 and 30μm (∼1/10 wavelength) can be generated when MBs are ∼500μm (2 wavelengths or ∼1.7 times the point spread function (PSF)) away from each other. When modelling a cardiac probe operating at 1.5 MHz, the localisation errors were as high as 200μm (∼1/5 wavelength) even when the MBs were more than 10 wavelengths apart (2.9 times the PSF). For both frequencies, at smaller separation distances, the two MBs were misinterpreted as one MB located in between the two true positions. Cross-correlation or Gaussian fitting methods were found to generate slightly smaller localisation errors than centroiding. In conclusion, caution should be taken when generating and interpreting SRUS images obtained using high agent concentration with MBs separated by less than 1.7 to 3 times the PSF, as significant localisation errors can be generated due to interference between neighbouring MBs.

Optimizing fouling mitigation in membrane distillation by controlled microbubble size and concentration

Fouling control strategies play a crucial role in membrane distillation (MD) process, primarily due to the significant limitation of fouling during the scaling-up process. The utilization of microbubbles (MBs) aeration has exhibited promising potential in mitigating membrane fouling when treating high salinity wastewater. Aeration can introduce gas-liquid two-phase flow on the membrane surface, thereby increasing the membrane surface shear force. The mechanism of aeration technology for controlling fouling includes the following points: introduction of gas-liquid two-phase flow; physical substitution of concentration polarization layer; pressure pulses caused by bubbles flowing through the membrane surface and increasement of the cross flow velocity. This research aims to optimizing the effect of air MBs with different concentrations and sizes introduced in the feed side on membrane fouling control, we creatively used the method of releasing pressure gradiently to achieve size regulation of MBs within a certain range for the first time, firstly regulated the generation of MBs by manipulating gas flow rate and release pressure. Under the optimal condition of 40 mL/min and 0.6 MPa, it will yield concentration of 1.58 × 104/mL and D50 Sauter size of 64.69 μm MBs with pure water permeance flux of 12.32 kg/(m2·h). It was observed that higher gas flow rates primarily increased MBs concentration, while lower pressures predominantly reduced MBs size through the method of inline imaging. Experimental results indicated that introduction of MBs can slightly improve the temperature polarization coefficient and mass transfer coefficient under different operating modes. Consequently, further investigations focused on the influence of MBs characteristics on different fouling control. All conditions reach 99 % rejection for inorganic salt and HA. This study provided empirical evidence that higher concentration and larger size of MBs intensify the gas-liquid two-phase flow disruption and exhibit a better shear effect on scaling phenomena, which yield advantageous outcomes in terms of augmenting permeance flux and water vapor production, with permeance flux increased from 40.12 % to 55.42 % for inorganic fouling and increased from 68.35 % to 80.15 % for inorganic and HA fouling. These results were confirmed via membrane surface using scanning electron microscopy and energy dispersive spectroscopy. In summary, this research aided in identifying appropriate operating conditions for mitigating inorganic and composite scaling by implementing air-infused MBs in direct contact membrane distillation (DCMD), which provides scientific and technical guidance for controlling fouling in MD in practical applications.

Effect of Poly(ethylene glycol) Configuration on Microbubble Pharmacokinetics.

Microbubbles (MBs) hold substantial promise for medical imaging and therapy; nonetheless, knowledge gaps persist between composition, structure, and in vivo performance, especially with respect to pharmacokinetics. Of particular interest is the role of the poly(ethylene glycol) (PEG) layer, which is thought to shield the MB against opsonization and rapid clearance but is also known to cause an antibody response upon multiple injections. The goal of this study was, therefore, to elucidate the role of the PEG layer in circulation persistence of MBs in the naïve animal (prior to an adaptive immune response). Here, we directly observe the number and size of individual MBs obtained from blood samples, unifying size and concentration into the microbubble volume dose (MVD) parameter. This approach enables direct evaluation of the pharmacokinetics of intact MBs, comprising both the lipid shell and gaseous core, rather than separately assessing the lipid or gas components. We examined the in vivo circulation persistence of 3 μm diameter phospholipid-coated MBs with three different mPEG2000 content: 2 mol % (mushroom), 5 mol % (intermediate), and 10 mol % (brush). MB size and concentration in the blood were evaluated by a hemocytometer analysis over 30 min following intravenous injections of 20 and 40 μL/kg MVD in Sprague-Dawley rats. Interestingly, pharmacokinetic analysis demonstrated that increasing PEG concentration on the MB surface resulted in faster clearance. This was evidenced by a 1.6-fold reduction in half-life and area under the curve (AUC) (p < 0.05) in the central compartment. Conversely, the AUC in the peripheral compartment increased with PEG density, suggesting enhanced MB trapping by the mononuclear phagocyte system. This was supported by an in vitro assay, which showed a significant rise in complement C3a activation with a higher PEG content. In conclusion, a minimal PEG concentration on the MB shell (mushroom configuration) was found to prolong circulation and mitigate immunogenicity.

Microbubble oscillation on localized heat source affected by dissolved gases in water

Recently, we demonstrated that the local heating of degassed water can generate water vapor microbubbles and induce a rapid flow around the bubble. Although flow generation involves the self-excited oscillation of bubbles at a local heating point, the conditions under which the bubbles oscillate are not fully understood. In this study, the dependence of microbubble size and oscillation frequency on the concentration of non-condensable gases in water was investigated. A continuous-wave laser beam was focused on a β-FeSi2 thin film, and water was locally heated using the photothermal conversion properties of the film. The results showed that the lower the concentration of non-condensable gases dissolved in water, the smaller the bubble size and the higher the oscillation frequency. Furthermore, it was found that the bubbles oscillate when the amount of non-condensable gas absorbed by the bubbles, i.e., the bubble size, falls below a specific level. This study can provide a new understanding of the bubble oscillation mechanism and lead to the development of fluid control technology using bubbles.

Monodisperse microbubble-mediated drug delivery: Influence of microbubbles size on drug delivery outcome

As the microbubble's resonance frequency is size-dependent, polydisperse microbubbles induce varying drug delivery outcomes at one ultrasound frequency. This study aimed to investigate drug delivery outcome of monodisperse MBs (mMBs) with radii ranging from 1.5–2.9 μm insonified at 2 MHz. Phospholipid-coated mMBs were generated using the Horizon microfluidic flow-focusing device. In vitro experiments were conducted on single microbubble-endothelial cells (n = 68) using confocal microscopy and 10 Mfps ultra-high-speed imaging. At 220 kPa PNP for 10 cycles, the 1.5 μm mMBs exhibited the highest PI uptake in 81.3% of cases, followed by 77.3% for 2.2 μm, 36.8% for 2.7 μm and 13.3% for 2.9 μm mMBs. Conversely, the 1.5 μm mMBs had the second lowest excursion amplitude (R;max-R;0) of 0.8 ± 0.3 μm as this was 1.2 ± 0.3 μm for 2.2 μm mMBs, 1.0 ± 0.3 μm for 2.7 μm mMBs, and 0.7 ± 0.2 μm for 2.9 μm mMBs. Additionally, for the 1.5, 2.2, and 2.7 μm mMBs, PI uptake and tunnel formation occurred more often (1.6, 1.8, and 1.3 times, respectively) than PI uptake and a resealing membrane pore. During insonification, mMB pinch-off occurred more frequently in tunnel formation (70.8%) than resealing pore formation (53.3%). This research revealed the impact of mMBs size on drug delivery outcome.

Numerical investigation of the effect of bubble properties on the linear resonance frequency shift due to inter-bubble interactions in ultrasonically excited lipid coated microbubbles

Ultrasonically excited microbubbles (MBs) have numerous applications in various fields, such as drug delivery, and imaging. Ultrasonically excited MBs are known to be nonlinear oscillators that generate secondary acoustic emissions in the media when excited by a primary ultrasound wave. The propagation of acoustic waves in the liquid is limited to the speed of sound, resulting in each MB receiving the primary and secondary waves at different times depending on their distance from the ultrasound source and the distance between MBs. These delays are referred to as primary and secondary delays, respectively. A previous study demonstrated that the inclusion of secondary delays in a model describing the interactions between MBs exposed to ultrasound results in an increase in the linear resonance frequency of MBs as they approach each other. This work investigates the impact of various MB properties on the change in linear resonance frequency resulting from changes in inter-bubble distances. The effects of shell properties, including the initial surface tension, surface dilatational viscosity of the shell monolayer, elastic compression modulus of the shell, and the initial radius of the MBs, are examined. MB size is a significant factor influencing the rate of linear resonance frequency increase with increasing concentration. Moreover, it is found that the shell properties of MBs play a negligible role in the rate of change in linear resonance frequency of MBs as the inter-bubble distances change.The findings of this study have implications for various applications of MBs in the biomedical field. By understanding the impact of inter-bubble distances and shell properties on the linear resonance frequency of MBs, the utilization of MBs in applications reliant on their resonant behavior can be optimized.