Accumulation Of Microbubbles Research Articles

Scaling-Free Cathodes: Enabling Electrochemical Extraction of High-Purity Nano-CaCO3 and -Mg(OH)2 in Seawater.

For electrochemical application in seawater or brine, continuous scaling on cathodes will form insulation layers, making it nearly impossible to run an electrochemical reaction continuously. Herein, we report our discovery that a cathode consisting of conical nanobundle arrays with hydrophobic surfaces exhibits a unique scaling-free function. The hydrophobic surfaces will be covered with microbubbles created by electrolytic water splitting, which limits scale crystals from standing only on nanotips of conical nanobundles, and the bursting of large bubbles formed by the accumulation of microbubbles will cause a violent disturbance, removing scale crystals automatically from nanotips. Benefiting from the scaling-free properties of the cathode, high-purity nano-CaCO3 (98.9%) and nano-Mg(OH)2 (99.5%) were extracted from seawater. This novel scaling-free cathode is expected to eliminate the inherent limitations of electrochemical technology and open up a new route to seawater mining.

AHNAK-modified microbubbles for the intracranial delivery of triptolide: In-vitro and in-vivo investigations

Autophagic dysfunction related cascade events might induce the accumulation of α-synuclein (αSyn) in Parkinson’s disease (PD). Triptolide (T10) has been reported as a potential autophagy inducer but limited by hepatotoxicity, low solubility and rapid metabolism. In this study, a novel AHNAK-targeted microbubbles integrated with T10 (T10-AHNAK-MBs) was developed to alleviate motor deficit in rAAV2/5-wild type and A53T mutant αSyn transfected PD mouse model. AHNAK facilitated the accumulation of microbubbles (MBs) near the cerebral vessel wall. Furthermore, bubble cavitation caused by focused-ultrasound (FUS) exposure could simultaneously induce drug release and blood-brain-barrier opening in the area of interest. The results of western blotting, thioflavin S staining, immunofluorescence, ELISA and behavior test demonstrated that T10-AHNAK-MBs with FUS exposure (T10-AHNAK-MBs-FUS) could significantly delivery more T10 into substantia nigra, promote clearance of various forms of αSyn, reduce tyrosine hydroxylase positive neuron loss, restore dopamine secretion, and eventually alleviate motor deficits, along with largely reduced adverse effects. The analyses of autophagic markers suggested that autophagy lysosome pathway (ALP) might dominate the T10-induced αSyn degeneration, including the oligomers and pre-formed fibrils. Thus, T10-AHNAK-MBs-FUS constitutes a promising strategy against the motor deficits in PD by promoting clearance of pathogenic αSyn aggregates via inducing ALP.

Contrast enhanced magneto-motive ultrasound in lymph nodes - modelling and pre-clinical imaging using magnetic microbubbles.

Despite advances in MRI, the detection and characterisation of lymph nodes in rectal cancer remains complex, especially when assessing the response to neo-adjuvant treatment. An alternative approach is functional imaging, previously shown to aid characterization of cancer tissues. We report proof-of-concept of the novel technique Contrast-Enhanced Magneto-Motive Ultrasound (CE-MMUS) to recover information relating to local perfusion and lymphatic drainage, and interrogate tissue mechanical properties through magnetically induced tissue deformations. The feasibility of the proposed application was explored using a combination of pre-clinical ultrasound imaging and finite element analysis. First, contrast enhanced ultrasound imaging on one wild type mouse recorded lymphatic drainage of magnetic microbubbles after bolus injection. Second, preliminary CE-MMUS data were acquired as a proof of concept. Third, the magneto-mechanical interactions of a magnetic microbubble with an elastic solid were simulated using finite element software. Accumulation of magnetic microbubbles in the inguinal lymph node was verified using contrast enhanced ultrasound, with peak enhancement occurring 3.7 s post-injection. Preliminary CE-MMUS indicates the presence of magnetic contrast agent in the lymph node. The finite element analysis explores how the magnetic force is transferred to motion of the solid, which depends on elasticity and bubble radius, indicating an inverse relation with displacement. Combining magnetic microbubbles with MMUS could harness the advantages of both techniques, to provide perfusion information, robust lymph node delineation and characterisation based on mechanical properties. Clinical Relevance- Robust detection and characterisation of lymph nodes could be aided by visualising lymphatic drainage of magnetic microbubbles using contrast enhanced ultrasound imaging and magneto-motion, which is dependent on tissue mechanical properties.

Modelling of magnetic microbubbles to evaluate contrast enhanced magnetomotive ultrasound in lymph nodes - a pre-clinical study.

Despite advances in MRI the detection and characterisation of lymph nodes in rectal cancer remains complex, especially when assessing the response to neoadjuvant treatment. An alternative approach is functional imaging, previously shown to aid characterisation of cancer tissues. We report proof of concept of the novel technique Contrast-Enhanced Magneto-Motive Ultrasound (CE-MMUS) to recover information relating to local perfusion and lymphatic drainage, and interrogate tissue mechanical properties through magnetically induced deformations. The feasibility of the proposed application was explored using a combination of experimental animal and phantom ultrasound imaging, along with finite element analysis. First, contrast-enhanced ultrasound imaging on one wild type mouse recorded lymphatic drainage of magnetic microbubbles after bolus injection. Second, tissue phantoms were imaged using MMUS to illustrate the force- and elasticity dependence of the magnetomotion. Third, the magnetomechanical interactions of a magnetic microbubble with an elastic solid were simulated using finite element software. Accumulation of magnetic microbubbles in the inguinal lymph node was verified using contrast enhanced ultrasound, with peak enhancement occurring 3.7 s post-injection. The magnetic microbubble gave rise to displacements depending on force, elasticity, and bubble radius, indicating an inverse relation between displacement and the latter two. Combining magnetic microbubbles with MMUS could harness the advantages of both techniques, to provide perfusion information, robust lymph node delineation and characterisation based on mechanical properties. (a) Lymphatic drainage of magnetic microbubbles visualised using contrast-enhanced ultrasound imaging and (b) magnetomechanical interactions between such bubbles and surrounding tissue could both contribute to (c) robust detection and characterisation of lymph nodes.

Microfluidic Device for the Determination of Water Chlorination Levels Combining a Fluorescent meso-Enamine Boron Dipyrromethene Probe and a Microhydrocyclone for Gas Bubble Separation.

Chlorination procedures are commonly applied in swimming pool water and wastewater treatment, yet also in food, pharmaceutical, and paper production. The amount of chlorine in water needs to be strictly controlled to ensure efficient killing of pathogens but avoid the induction of negative health effects. Miniaturized microfluidic fluorescence sensors are an appealing approach here when aiming at online or at-site measurements. Two meso-enamine-substituted boron dipyrromethene (BODIPY) dyes were found to exhibit favorable indication properties, their reaction with hypochlorite leading to strong fluorescence enhancement. Real-time assays became possible after integration of these fluorescent probes with designed two-dimensional (2D) and three-dimensional (3D) microfluidic chips, incorporating a passive sinusoidal mixer and a microhydrocyclone, respectively. A comparison of the two microfluidic systems, including their abilities to prevent accumulation or circulation of microbubbles produced by the chemical indication reaction, showed excellent fluidic behavior for the microhydrocyclone-based device. After coupling to a miniaturized optical reader for fluorescence detection, the 2D microfluidic system showed a promising detection range of 0.04-0.5 mg L-1 while still being prone to bubble-induced fluctuations and suffering from considerably low signal gain. The microhydrocyclone-based system was distinctly more robust against gas bubbles, showed a higher signal gain, and allowed us to halve the limit of detection to 0.02 mg L-1. The use of the 3D system to quantify the chlorine content of swimming pool water samples for sensitive and quantitative chlorine monitoring was demonstrated.

Acoustic radiation force induced accumulation and dynamics of microbubbles on compliant surfaces

Ultrasound stimulated microbubbles have been shown to be capable of breaking up blood clots through micro-scale interactions occurring near the clot surface. However, only a small fraction of bubbles circulating in the bloodstream will be in close proximity to such boundaries, where they must be to elicit therapeutic effects. Here, the accumulation and subsequent behavior of microbubbles displaced from an overlying flow channel to a boundary under radiation forces were examined. Experimental data were acquired using a novel high speed microscopy configuration and simulations were conducted to provide insight into the accumulation process. There was broad agreement between experiments and simulations, both indicating that the size distribution and number of bubbles arriving at the boundary depended on channel flow rate, applied pressure, and bubble concentration. For example, higher flow rates and lower pressures favored the accumulation of larger bubbles relative to the native agent distribution. Moreover, bubble dynamics were dependent on the surface type, exhibiting rapid translation along agarose gel surfaces whereas on fibrin surfaces, they accumulated in localized regions inducing repetitive strain cycles. The results indicate that the process of bringing bubbles from within a vessel to a boundary is complex and should be an important consideration in the development of therapeutic applications such as sonothrombolysis.

To the issue of the mechanism of cell migration

The paper presents the experimental and theoretical aspects of studying the migration of cancer cells through narrow microchannels when interacting with a chemical substance — an attractant. Chemical agents were injected directly from the respective separate reservoir via hydrostatic head. The presence of migration channels of different sizes allowed us to analyze the migration abilities inherent in the cells. Experimental studies on the migration of cancer cell lines were carried out using a microfluidic binary migration cell. It consists of two chambers 50 μm deep, connected by a series of narrow microchannels 10 μm high. The chambers are connected to the tanks from which cancer cells and activating media come. The model features smooth transitions from all tanks to microchannels to prevent accumulation of microbubbles and cells, the presence of a restrictive barrier between a chemoattractant container and a nutrient medium to reduce the effect of capillary forces, sealing the supply channels and cells with cells using a glass plate glued on top. In a series of experiments, the ability of epithelial-like cells of the metastatic prostate cancer DU145 to migrate in the migration microfluidic system developed by us was revealed. The nature of migration depends on the width of the channel and the location of the cells at the time of adding the chemical agent. In wider channels, cells adhere more slowly and are able to perform rolling movements. In narrower channels, the cells are spread over the glass. The mathematical model of concentration-capillary movement, which is a system of equations of the dynamics of an incompressible viscous fluid, written separately for the cell contents and for its environment, is considered as the basis for a theoretical study of cell migration.

Ultrasound contrast plane wave imaging

Monitoring the accumulation of microbubbles within tissue vasculature with ultrasound allows both molecular and perfusion imaging. Unfortunately, conventional imaging with focused pulses can destroy a large fraction of the microbubbles it is trying to follow. Using coherent synthetic summation, ultrafast plane wave imaging could attain similar image quality, while reducing the peak acoustic pressure and bubble disruption. In these experiments, microbubbles were flowed in a wall-less vessel phantom. Images were obtained on a programmable clinical scanner with a set of line-per-line focused pulses for conventional contrast imaging and with compounded plane wave transmission adapted for nonlinear imaging. Imaging was performed between 14 and 650 kPa peak negative pressure at 7.5 MHz. The disruption of the microbubbles was evaluated by comparing the microbubble intensity before and after acquisition of a set of 100 images at various pressures. The acoustic intensity required to disrupt 50% of the microbubbles was 24 times higher with plane-wave imaging compared with conventional focused pulses. Although both imaging approaches yield similar resolution, at the same disruption level, plane-wave imaging showed better contrast. In particular, at similar disruption ratio (50% after 100 images), contrast-pulse sequencing (CPS) performed with plane waves displayed an improvement of 11 dB compared with conventional nonlinear imaging. In each resolution cell of the image, plane-wave imaging spread the spatial peak acoustic intensity over more pulses, reducing the peak pressure and, hence, preserving the microbubbles. This method could contribute to molecular imaging by allowing the continuous monitoring of the accumulation of microbubbles with improved contrast.

Drug-loaded nano/microbubbles for combining ultrasonography and targeted chemotherapy

A new class of multifunctional nanoparticles that combine properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated drug delivery has been developed. At room temperature, the developed systems comprise perfluorocarbon nanodroplets stabilized by the walls made of biodegradable block copolymers. Upon heating to physiological temperatures, the nanodroplets convert into nano/microbubbles. The phase state of the systems and bubble size may be controlled by the copolymer/perfluorocarbon volume ratio. Upon intravenous injections, a long-lasting, strong and selective ultrasound contrast is observed in the tumor volume indicating nanobubble extravasation through the defective tumor microvasculature, suggesting their coalescence into larger, highly echogenic microbubbles in the tumor tissue. Under the action of tumor-directed ultrasound, microbubbles cavitate and collapse resulting in a release of the encapsulated drug and dramatically enhanced intracellular drug uptake by the tumor cells. This effect is tumor-selective; no accumulation of echogenic microbubbles is observed in other organs. Effective chemotherapy of the MDA MB231 breast cancer tumors has been achieved using this technique.

Investigation of Microbubble Boundary Layer Using Particle Tracking Velocimetry

Particle tracking velocimetry has been used to measure the velocity fields of both continuous phase and dispersed microbubble phase, in a turbulent boundary layer, of a channel flow. Hydrogen and oxygen microbubbles were generated by electrolysis. The average size of the microbubbles was 15μm in radius. Drag reductions up to 40% were obtained, when the accumulation of microbubbles took place in a critical zone within the buffer layer. It is confirmed that a combination of concentration and distribution of microbubbles in the boundary layer can achieve high drag reduction values. Microbubble distribution across the boundary layer and their influence on the profile of the components of the liquid mean velocity vector are presented. The spanwise component of the mean vorticity field was inferred from the measured velocity fields. A decrease in the magnitude of the vorticity is found, leading to an increase of the viscous sublayer thickness. This behavior is similar to the observation of drag reduction by polymer and surfactant injection into liquid flows. The results obtained indicate that drag reduction by microbubble injection is not a simple consequence of density effects, but is an active and dynamic interaction between the turbulence structure in the buffer zone and the distribution of the microbubbles.

Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: in vitro verification

Recent research has shown that targeted ultrasound contrast microbubbles achieve specific adhesion to regions of intravascular pathology, but not in areas of high flow. It has been suggested that acoustic radiation can be used to force free-stream microbubbles toward the target, but this has not been verified for actual targeted contrast agents. We present evidence that acoustic radiation indeed increases the specific targeted accumulation of microbubbles. Lipid microbubbles bearing an antibody as a targeting ligand were infused through a microcapillary flow chamber coated with P-selectin as the target protein. A 2.0 MHz ultrasonic pulse was applied perpendicular to the flow direction. Microbubble accumulation was observed on the flow chamber surface opposite the transducer. An acoustic pressure of 122 kPa enhanced microbubble adhesion up to 60-fold in a microbubble concentration range of 0.25 x 10(6) to 75 x 106) ml(-1). Acoustic pressure mediated the greatest adhesion enhancement at concentrations within the clinical dosing range. Acoustic pressure enhanced targeting nearly 80-fold at a wall shear rate of 1244 s(-1), suggesting that this mechanism is appropriate for achieving targeted microbubble delivery in high-flow vessels. Microbubble adhesion increased with the square of acoustic pressure between 25 and 122 kPa, and decreased substantially at higher pressures.

Phagocytosis of microbubbles by Kupffer cells and delayed parenchymal imaging of the liver

In vitro study: Microbubbles that could be phagocytosed by Kupffer cells were Levovist, Optison, and Sonazoid. Microbubbles that could be phagocytosed were recognized and attached to the cell surface initially and then trapped by the tentacle. Microbubbles that were pinocytosed from the cell membrane moved towards the nucleus. SonoVue and Imavist were not trapped and phagocytosed by Kupffer cells. Destruction and disappearance of microbubbles were observed microscopically during exposure of pulsed ultrasound. Microbubbles inside the Kupffer cells were diminished in size and disappeared under exposure of ultrasound pulses. The shell remains after disappearance of bubble gas. Time intensity curves of Levovist: The time intensity curves from the aorta and portal vein indicate a sharp rise of concentration and gradual decrease. The intensity of the parenchyma reaches at the maximum 6 minutes after injection. The curve indicates a plateau, continues for 20 minutes, and decreases gradually up to 60 minutes. Clinical study: Hepatocellular carcinoma (HCC) often shows an accumulation of microbubbles in delayed parenchymal phase. The degree and figure of accumulation are dependent on the tumor size and the histological characters. Well-differentiated HCCs indicate a partial defect or homogeneously decreased accumulation. Moderately or poorly differentiated HCCs indicate a complete defect. However, when the size is more than 2 cm, a delayed image shows a so-called mosaic pattern. Delayed parenchymal imaging brings quantitative and functional information in diffuse liver diseases. The peak intensity is decreased, and the declining slope is steeper in cirrhosis and acute hepatitis than normal liver.

A Cyclic Cavitation Process

A type of acoustic cavitation has been studied that occurs at the face of a vibrator with a small diameter. A gas bubble grows to near-resonant size by accumulation of microbubbles. The process then reverses and the parent bubble rapidly throws off a cloud of microbubbles. This phase is accompanied by severe surface distortion of the main bubble, with emission of strong harmonics and a good deal of white noise. Under suitable conditions, a cyclic process is set up at a very regular repetition rate that depends on the acoustic pressure and the physical properties of the liquid. Acoustic streaming has an important rôle in maintaining the cycle. High-speed movies have been taken, and these, along with measurements of the acoustic emission, show clearly the progress of the cycle. A technique is discussed for using this process to generate bubbles of defined size.

Periodic Small-Scale Cavitation Process

A type of acoustic cavitation has been studied which occurs at the face of a vibrator with a small diameter. A gas bubble grows to near-resonant size by accumulation of microbubbles. The process then reverses and the parent bubble rapidly throws off a cloud of microbubbles. This phase is accompanied by severe surface distortion of the main bubble, with emission of strong harmonics and a good deal of white noise. Under suitable conditions, a cyclic process is set up at a very regular repetition rate that depends on the acoustic pressure and the liquid properties. Acoustic streaming has an important rôle in maintaining the cycle. High-speed movies have been taken, and these, along with measurements of the acoustic emission, show clearly the progress of the cycle. Techniques are discussed for using this process to generate bubbles of defined size. [Work supported by grants from the National Institutes of Health and from the Air Force Office of Scientific Research.]