Microbubble Diameter Research Articles

Separation of Pollutants from Oil-Containing Restaurant Wastewater by Novel Microbubble Air Flotation and Traditional Dissolved Air Flotation

Novel microbubble air flotation (MAF) and traditional dissolved air flotation (DAF) systems were compared based on the separation ability of pollutants from oil-containing restaurant wastewater, which was used to verify the strengths of MAF system. The results showed that, when the operational parameters were a PAC dosage of 20 mg/L, reaction time of 15 min, operational pressure of 0.35 MPa, and reflux ratio of 25%, the removal efficiencies of oil, CODcr, and turbidity in MAF were 10.3%, 22.6%, and 15.0% higher than that in DAF, respectively. The maximum removal efficiencies of oil and turbidity in the MAF system were 98.0% and 97.5%. In addition, the minimum microbubble diameter in the MAF system was 20 µm under the operational pressure of 0.9 MPa, which could be successively and steadily produced. The maximum oil removal efficiency was achieved in the MAF system when the microbubbles and oil-droplets were similar sizes. Therefore, the application of the MAF technology could alleviate the pressure of downstream treatment of oil-containing wastewater.

Zeta potential of air bubbles conditioned with typical froth flotation reagents

The effect of chemical flotation reagents on the zeta potential (ζ) of particles is well known, but their effect on bubbles is practically unknown. This study characterizes the ζ of air bubbles conditioned with typical froth flotation reagents and presents a novel experimental setup and method for estimating the electrophoretic velocity. It was observed that collectors strongly affect ζ in the following order from more to less anionic: xanthate, dithiophosphinate, deionized water, mercaptobenzothiazole and dodecylamine. By contrast, frothers affect ζ only slightly. In this study, it was also observed that pH affects the microbubble diameter and that under acidic or basic conditions, the bubble diameter decreases.

Thermal Activation of Superheated Lipid-Coated Perfluorocarbon Drops

This study explored the thermal conditions necessary for the vaporization of superheated perfluorocarbon nanodrops. Droplets C3F8 and C4F10 coated with a homologous series of saturated diacylphosphatidylcholines were formed by condensation of 4 μm diameter microbubbles. These drops were stable at room temperature and atmospheric pressure, but they vaporized back into microbubbles at higher temperatures. The vaporization transition was measured as a function of temperature by laser light extinction. We found that C3F8 and C4F10 drops experienced 90% vaporization at 40 and 75 °C, respectively, near the theoretical superheat limits (80-90% of the critical temperature). We therefore conclude that the metastabilty of these phase-change agents arises not from the droplet Laplace pressure altering the boiling point, as previously reported, but from the metastability of the pure superheated fluid to homogeneous nucleation. The rate of C4F10 drop vaporization was quantified at temperatures ranging from 55 to 75 °C, and an apparent activation energy barrier was calculated from an Arrhenius plot. Interestingly, the activation energy increased linearly with acyl chain length from C14 to C20, indicating that lipid interchain cohesion plays an important role in suppressing the vaporization rate. The vaporized drops (microbubbles) were found to be unstable to dissolution at high temperatures, particularly for C14 and C16. However, proper choice of the fluorocarbon and lipid species provided a nanoemulsion that could undergo at least ten reversible condensation/vaporization cycles. The vaporization properties presented in this study may facilitate the engineering of tunable phase-shift particles for diagnostic imaging, targeted drug delivery, tissue ablation, and other applications.

Membrane blebbing as a recovery manoeuvre in site-specific sonoporation mediated by targeted microbubbles.

Site-specific perforation of the plasma membrane can be achieved through ultrasound-triggered cavitation of a single microbubble positioned adjacent to the cell. However, for this perforation approach (sonoporation), the recovery manoeuvres invoked by the cell are unknown. Here, we report new findings on how membrane blebbing can be a recovery manoeuvre that may take place in sonoporation episodes whose pores are of micrometres in diameter. Each sonoporation site was created using a protocol involving single-shot ultrasound exposure (frequency: 1 MHz; pulse length: 30 cycles; peak negative pressure: 0.45 MPa) which triggered inertial cavitation of a single targeted microbubble (diameter: 1-5 µm). Over this process, live confocal microscopy was conducted in situ to monitor membrane dynamics, model drug uptake kinetics and cytoplasmic calcium ion (Ca(2+)) distribution. Results show that blebbing would occur at a recovering sonoporation site after its resealing, and it may emerge elsewhere along the membrane periphery. The bleb size was correlated with the pre-exposure microbubble diameter, and 99% of blebbing cases at sonoporation sites were inflicted by microbubbles larger than 1.5 µm diameter (analysed over 124 sonoporation episodes). Blebs were not observed at irreversible sonoporation sites or when sonoporation site repair was inhibited via extracellular Ca(2+) chelation. Functionally, the bleb volume was found to serve as a buffer compartment to accommodate the cytoplasmic Ca(2+) excess brought about by Ca(2+) influx during sonoporation. These findings suggest that membrane blebbing would help sonoporated cells restore homeostasis.

An in vitro study of subharmonic emissions from monodisperse lipid-coated microbubbles

Subharmonic imaging is an ultrasound imaging method which utilizes the subharmonic response of a contrast agent to ultrasound excitation. It is possible to achieve high agent-to-tissue contrast because tissues do not emit subharmonic signals. In this project, we investigated the relationship between subharmonic emissions from monodisperse lipid-coated microbubbles and acoustic pressure. First, the resonance frequency for monodisperse microbubble suspension was determined from attenuation spectra measured using a through-transmission technique. Next, the microbubbles were excited at the resonance and at twice the resonance frequency. A transducer positioned orthogonal to the excitation transducer was used to detect acoustic emissions from the microbubbles at half the excitation frequency. It was found that the pressure required for subharmonic emissions was lower when monodisperse microbubbles were excited at twice the resonance frequency. For example, 6.5μm diameter microbubbles with a resonance frequency of 1.4 MHz had a pressure threshold for subharmonic emissions of approximately 30 kPa at 2.8 MHz excitation while those excited at 1.4 MHz could not be forced into subharmonic oscillations for the pressure range we used in this study (i.e., below 150 kPa). Implications of these results on the use of monodisperse lipid-coated microbubbles for subharmonic imaging will be discussed.

In Vivo Transfection and Detection of Gene Expression of Stem Cells Preloaded with DNA-carrying Microbubbles.

To determine whether (a) stem cells loaded with DNA-carrying microbubbles (MBs) can be transfected in vivo, (b) the cells remain alive to express the gene, and (c) gene expression is sufficiently robust to be detected in vivo. The study was approved by the Institutional Animal Care and Use Committee. Cationic MBs were prepared, characterized, and loaded with pLuciferase green fluorescent protein (GFP) plasmid. Loading was confirmed with SYBR Gold staining (Life Technologies, Carlsbad, Calif). C17.2 cells were loaded with the DNA-carrying MBs. Two hundred thousand cells suspended in 20 μL phosphate-buffered saline were mixed with 200 μL Matrigel (BD Biosciences, San Jose, Calif) and injected in both flanks of eight nude mice. One of the Matrigel (BD Biosciences) injections contained 50 000 cells pretransfected in vitro by using lipofectamine as a positive control. Nine flanks were exposed to 2.25-MHz ultrasonic pulses at 50% duty cycle for 1 minute at 1 W/cm(2) (n = 3) or 2 W/cm(2) (n = 6), and six flanks served as the negative control. Two days later, bioluminescent images were acquired in each mouse every 3 minutes for 1 hour after the intraperitoneal injection of d-luciferin (Perkin Elmer, Waltham, Mass). Differences between groups were assessed by using the nonparametric Kruskal-Wallis test with Wilcoxon rank sum tests for follow-up comparisons. Mice were then killed, plugs were explanted, and alternate sections were stained with hematoxylin-eosin or stained for GFP expression. Mean DNA-loaded MB diameter ± standard deviation was 2.87 μm ± 1.69 with the DNA associated with the MB shell. C17.2 cells were associated with 2-4 MBs each, and more than 90% were viable. Peak background subtracted bioluminescent signal was fourfold higher when cells were exposed to 2 W/cm(2) pulses as compared with 1 W/cm(2) pulses (P = .02) and negative controls (P = .002). Histologic examination showed cells within the Matrigel (BD Biosciences) with robust GFP expression only after 2 W/cm(2) ultrasound exposure and lipofectamine transfection. Stem cells loaded with DNA-carrying MBs can be transfected in vivo with ultrasonic pulses and remain alive to demonstrate robust gene expression.

Effects of bubble size on air-scoured backwashing efficiency in a biofilter

The effect of bubble size on air-scoured backwashing efficiency in a biofilter was investigated using experiments and simple mathematical models based on collapse-pulsing theory. Four types of backwashing experiments were conducted: water alone, water and large bubbles (diameter = about 1 cm), water and small bubbles (diameter = about 0.2 cm), and water containing dissolved air. The third type, water and small bubbles, was found to be the most efficient. Modeling results confirmed the experimental results, indicating that even when the same volume of air was used, smaller bubbles generate higher shear stress on the surface of the medium, resulting in more efficient removal of biomass. In the case of dissolved air, however, micro-bubbles (diameter = 10–100 μm) are too small and rise too slowly to produce a strong-enough collapse-pulsing effect. This produces less shear stress and ultimately results in poor backwashing efficiency.

In vivo imaging of microfluidic-produced microbubbles.

Microfluidics-based production of stable microbubbles for ultrasound contrast enhancement or drug/gene delivery allows for precise control over microbubble diameter but at the cost of a low production rate. In situ microfluidic production of microbubbles directly in the vasculature may eliminate the necessity for high microbubble production rates, long stability, or small diameters. Towards this goal, we investigated whether microfluidic-produced microbubbles directly administered into a mouse tail vein could provide sufficient ultrasound contrast. Microbubbles composed of nitrogen gas and stabilized with 3 % bovine serum albumin and 10 % dextrose were injected for 10 seconds into wild type C57BL/6 mice, via a tail-vein catheter. Short-axis images of the right and left ventricle were acquired at 12.5 MHz and image intensity over time was analyzed. Microbubbles were produced on the order of 10(5) microbubbles/s and were observed in both the right and left ventricles. The median rise time, duration, and decay time within the right ventricle were 2.9, 21.3, and 14.3 s, respectively. All mice survived the procedure with no observable respiratory or heart rate distress despite microbubble diameters as large as 19 μm.

Effectiveness of localized ultrasound-targeted microbubble destruction with doxorubicin liposomes in H22 mouse hepatocellular carcinoma model

Objective: In order to increase local drug concentration and reduce systemic side effects of liver cancer chemotherapy, it is desirable to develop novel non-invasive technologies for drug targeting, such as ultrasound-targeted microbubble destruction (UTMD).Methods: H22 hepatocellular carcinoma (HCC) xenograft transplantation model was generated in UTMD study. BALB/c mice were randomly divided into six groups: doxorubicin HCl liposomal injection (DOX), DOX + US, UTMD, DOX + UTMD, H22 liver tumor control (CH control) and blank control group. The therapeutic schedule started on day 4 after tumor inoculation.Results: Average survival time of the animal model was approximately 18 d. The UTMD therapy parameters were optimized in the H22 mouse model to be: microbubble (MB) diameter, 2.30 ± 0.25 μm; MB density, 4.0 × 109 bubbles/ml; treatment dose, 0.2 ml per 20 g mouse body weight; sonication frequency, 1.3 MHz; and sonication power, 2.06 W/cm2. Mice treated with DOX + UTMD had the smallest tumor volume and weight (p < 0.001), and the highest tumor inhibition rate (p < 0.01), intratumoral DOX concentration (p < 0.001) and survival rate among all tumor-burden groups (p < 0.001). Cell viability in different treatment groups was also assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Conclusion: An improved antitumor effect was observed with the combination therapy of DOX and UTMD, as compared with treatment with DOX, DOX + US or UTMD, which implicates a novel approach for HCC treatment.

Cleaning polymer ink from a glass substrate using microbubbles generated by a hydrogen bubble method

To find strategies for improved cleaning with microbubbles (MBs), we used an MB cleaning and microscopic observation system to investigate (a) radius distributions of MBs generated by a hydrogen bubble method, (b) the behavior of MBs adsorbed on a polymer black ink (contact angle to water=60°), and (c) the performance of the MBs in removing the ink from a substrate. The radius distribution of MBs was not affected by changing the cathode diameter or the applied voltage between the anode and cathode. The number of MBs increased when we used thicker cathodes and applied higher voltages. MBs adsorbed onto the ink surface increased in radius during the cleaning process. The rates of increase in adsorbed MB diameters on the ink surface were lesser than those for MBs that were not adsorbed, because of ink movement on the adsorbed MB surfaces. We determined the response of ink weight loss from the substrate due to changes in height from the cathode, applied voltage, and cathode diameter. The ink weight loss increased with decreased height between the ink and cathode and increased applied voltage and cathode diameter. These results suggest that increases in weight loss were strongly influenced by the number of MBs (10–100μm in diameter). MBs adsorbed onto the substrate removed trace amounts of ink from the substrate; after removal of the ink, adsorption of other MBs was induced. The diameter distribution of MBs had a lesser effect on weight loss than the number of MBs generated. Important processes for cleaning the ink are as follows: (1) adsorption of MB onto the surface of the ink, (2) increasing diameter of the adsorbed MB, and (3) removal of the adsorbed MB from the ink surface. We also would like to suggest that the cleaning efficiency for hydrophobic ink could be improved by increasing the number of adsorbed MBs, and MBs must be generated closest to the surface of the ink.

Microbubbles: from cancer detection to theranostics

Microbubbles have proven to be useful as diagnostic agents for ultrasound[1,2]. However, they have the potential for a far wider range of uses, both in unmodified form (thus minimising regulatory barriers) and in new forms[3]. These future uses may be divided into diagnostic and therapeutic categories. Routine diagnostic uses of microbubbles relevant to oncology are mainly in the liver, where they have been endorsed by NICE for the characterisation of focal liver lesions[4]. The key attribute here is the fact that malignancies do not have the functioning sinusoidal system that accounts for the late retention of microbubbles in the normal liver and in solid focal lesions - in this application, microbubbles are as effective as CT with contrast but less costly. Many similar oncological uses exploit microbubbles' exquisite ability to define both the macro- and microvasculature of tissue. Examples include characterising BI-RADS 3 and 4a breast masses, distinguishing pancreatic adenocarcinoma (hypoperfused) from focal pancreatitis (well perfused) and distinguishing complex-appearing real cysts from cystic carcinomas. A potentially important extension is to develop targeted microbubbles that attach preferentially to cell surface molecules of interest[5]. Since conventional microbubbles of micron diameter cannot escape from the blood pool, the initial target is the blood vasculature. Ligands to VEGF1 can be attached to microbubbles; numerous preclinical studies have shown these to be effective ways to image malignant neovascularisation and the first human trial in prostate cancer has been completed[6]. A difficulty has been the relatively poor binding power of the targeted microbubbles, especially in the non-immunogenic form suitable for human use. The same strategies that are used for molecular imaging in nuclear medicine and MR can be deployed: improve the specific binding or wait for clearance of the unbound agent from the blood stream. Another approach makes use of the fast time resolution of ultrasound and tries to recognise which microbubbles are fixed and which are moving, thus enabling the bound population to be selectively imaged. Efforts have also been made to detect differences in the echoes from free versus bound microbubbles. An important advance in allowing access to tissue beyond the endothelium is the development of nanodroplets, made by cooling and pressurising microbubbles - at around 200nm in diameter, they are able to cross the endothelium, especially where its is leaky[7]. Sonication with acceptable ultrasound intensity can then be used to reform the original microbubbles, with their ligands intact. This opens the way to imaging tissues beyond the endothelium. The simplest approach to therapy employing microbubbles is to make use of their mechanical vibrations[8] and this has been used to accelerate thrombus breakdown to promote revascularisation of the middle cerebral artery[9]. An interesting approach uses low ultrasound frequencies and intensities along with microbubbles to ‘massage’ the endothelium or other surfaces (remote palpation), relying on the effect of acoustic radiation force impulses (ARFI) to move microbubbles along the ultrasound beam[10]. This allows temporary opening of tight endothelial junctions, for example to open the blood-brain barrier and improve the penetration of co-administered i.v. drugs. Co-administration obviates some of the regulatory barriers to modified microbubbles and has been used to augment chemotherapy of pancreatic cancer with gemcitabine[11]. Further such trials are anticipated. Microbubbles might also be used to augment high intensity focussed ultrasound (HIFU) which would speed up the method, thus removing one of the main barriers to its wider use. The most direct approach to treatment with microbubbles is to tag them with active drugs such as chemotherapeutic agents; breaking these microbubbles with high MI pulses releases the agent so that high concentrations can be achieved locally. This has been shown in small animals to minimise the cardiotoxicity of adriamycin in breast cancer[12]. This therapeutic avenue could be combined with the nanodroplets method and with remote palpation to access tumours. Thus, the diagnostic and therapeutic possibilities for microbubbles are extensive; clinically useful approaches in oncology can be anticipated in the not too distant future.

Van der Waals force-induced loading of proangiogenic nanoparticles on microbubbles for enhanced neovascularization.

Nanoparticles emerged as carriers of promising diagnostic and therapeutic molecules due to their unique size, injectability, and potential to sustainably release molecular cargos. However, with local injection of particles into target tissue, the significant particle loss caused by external biomechanical forces is a great challenge yet to be resolved to date. We hypothesized that nanoparticles associated with tissue-adherent microbubbles in the form of core-shell particles due to van der Waals attractive forces would stably remain on an implanted site and significantly increase therapeutic efficacy of drug cargos. To examine this hypothesis, we used 100 nm diameter nanoparticles made of poly(lactide-co-glycolic acid) (PLGA) as a model nanoparticle and 50 μm diameter microbubbles made of poly(2-hydroxyethyl aspartamide) (PHEA) grafted with octadecyl chains, PHEA-g-C18, as a model microbubble. Simple mixing of PLGA nanoparticles and PHEA-g-C18 microbubbles resulted in the core-shell particles. Following implantation, the PHEA-g-C18 microbubbles acted as glue to minimize the displacement of PLGA nanoparticles, because of the association between the octadecyl chains on PHEA-g-C18 and the epithelium of the tissue. As a consequence, the core-shell particles prepared with Angiopoietin-1 (Ang1)-encapsulated PLGA nanoparticles significantly promoted vascularization in the implanted tissue. Overall, the results of this study provide a simple but advanced strategy for improving therapeutic efficacy of drug-carrying nanoparticles without altering their surface chemistry and potential.

Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents

Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml−1. The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic.

Temporal stability evaluation of fluorescein-nanoparticles loaded on albumin-coated microbubbles

Purpose: This study aims to evaluate the temporal stability of newly designed FITC-nanoparticles (NPs) loaded on albumin-coated microbubbles (MBs) to be used for future drug delivery purposes. Materials and Methods: MBs (3.6 108 MB/mL) were obtained by sonicating 5% bovine serum albumin and 15% dextrose solution. NPs (5 mg/mL) were produced from fluorescein (FITC)-PLA polymers and functionalized using EDC/NHS. NP-loaded MBs resulted from the covalent linking between functionalized NPs and MBs via carbodiimide technique. Three parameters were quantitatively monitored over a 4-week duration at 8 time points: MB diameter was determined using a circle detection routine based on the Hough transform, MB number density was evaluated using a hemocytometer, and NP-loading yield was assessed based on the loaded-MB fluorescence uptake. Based on the hypotheses, analyses of variance or Kruskal Wallis test were run to evaluate the stability of these physical parameters over the time of the experiment. Results: Statistical analysis exhibited no significant differences in NP-loaded MB mean sizes, number densities, and loading yields over time (p > 0.05). Conclusion: Newly designed NP-loaded MBs are stable over at least a 4-week duration and can be used without extra precaution concerning their temporal stability. [This work was supported by NIH R37EB002641.]

Microbubble-inducing characteristics depending on various nozzle and pressure in dissolved air flotation process

The Dissolved Air Flotation (DAF) process has been widely used for removing suspended solids with low density in water. Size and distribution curve of microbubbles were evaluated at various pressure and nozzle condition. The change in nozzle size affects significantly on the microbubble rather than that in pressure. Also, at a fixed pressure, the treatment efficiency increased with the decrease in nozzle size or the increase in pressure. Finally, the change in pressure and nozzle size can be controlled microbubble diameter and improved treatment efficiency without the additional investment.

Theoretical Analysis of CO&lt;sub&gt;2&lt;/sub&gt; Bubble Formation in Anode Flow Field of μDMFC

A mathematical model was established and validated to predict the microbubble diameter when it departing from the carbon paper and moving into the channel of μDMFC. Single bubble behaviors were studied using the model, which took the gas velocity, liquid cross-flow velocity, micro porous diameter and other parameters into account. Results indicate that the microbubble departure diameter decreases with the increasing liquid velocity, and increases with the increasing micro porous diameter and increasing gas velocity.

Formation of protein and protein-gold nanoparticle stabilized microbubbles by pressurized gyration.

A one-pot single-step novel process has been developed to form microbubbles up to 250 μm in diameter using a pressurized rotating device. The microbubble diameter is shown to be a function of rotational speed and working pressure of the processing system, and a modified Rayleigh-Plesset equation has been derived to explain the bubble-forming mechanism. A parametric plot is constructed to identify a rotating speed and working pressure regime, which allows for continuous bubbling. Bare protein (lysozyme) microbubbles generated in this way exhibit a morphological change, resulting in microcapsules over a period of time. Microbubbles prepared with gold nanoparticles at the bubble surface showed greater stability over a time period and retained the same morphology. The functionalization of microbubbles with gold nanoparticles also rendered optical tunability and has promising applications in imaging, biosensing, and diagnostics.

Manipulating nanoscale features on the surface of dye-loaded microbubbles to increase their ultrasound-modulated fluorescence output.

The nanoscale surface features of lipid-coated microbubbles can dramatically affect how the lipids interact with one another as the microbubble diameter expands and contracts under the influence of ultrasound. During microbubble manufacturing, the different lipid shell species naturally partition forming concentrated lipid islands. In this study the dynamics of how these nanoscale islands accommodate the expansion of the microbubbles are monitored by measuring the fluorescence intensity changes that occur as self-quenching lipophilic dye molecules embedded in the lipid layer change their distance from one another. It was found that when the dye molecules were concentrated in islands, less than 5% of the microbubbles displayed measurable fluorescence intensity modulation indicating the islands were not able to expand sufficiently for the dye molecules to separate from one another. When the microbubbles were heated and cooled rapidly through the lipid transition temperature the islands were melted creating an even distribution of dye about the surface. This resulted in over 50% of the microbubbles displaying the fluorescence-modulated signal indicating that the dye molecules could now separate sufficiently to change their self-quenching efficiency. The separation of the surface lipids in these different formations has significant implications for microbubble development as ultrasound and optical contrast agents.

Drug delivery through the opened blood-brain barrier in mice and non-human primates

Over five million U.S. men and women suffer from neurodegenerative diseases. Although great progress has been made in recent years toward understanding of these diseases, few effective treatments and no cures are currently available. This is mainly due to the impermeability of the blood-brain barrier (BBB) that allows only 5% of more than 7000 small-molecule drugs available to treat only a tiny fraction of these diseases. Safe and localized opening of the BBB has been proven to present a significant challenge. Focused ultrasound (FUS), in conjunction with microbubbles, remains the sole technique that can induce localized BBB opening noninvasively and regionally. In the past, our group has focused on cavitation monitoring during BBB opening in both mice and non-human primates, assessment of safety and drug efficacy using behavioral testing, delivery of molecules of variant size through the opened BBB, investigation on the role of the microbubble diameter and use of nanodroplets. We will briefly highlight these past findings as well as introduce newer accomplishments such as its role in enhancement of drugs for neuroprotection and neuroregeneration in the treatment of Parkinson's, the use of alternative routes of systemic administration for larger drug dosage, dependence of the BBB opening size on the acoustic pressure, real-time monitoring of the microbubble perfusion of the brain, cavitation prediction of the timeline of BBB opening, and targeted delivery using adeno-associated viruses.

Acoustic investigation of pressure-dependent resonance and shell elasticity of lipid-coated monodisperse microbubbles

In this study, frequency-dependent attenuation was measured acoustically for monodisperse lipid-coated microbubble suspensions as a function of excitation pressure and radius. The resonance frequency was identified from the attenuation spectra and had an inverse relationship with mean microbubble diameter and excitation pressure. A reduction in the estimated shell elasticity constant from 0.50 N/m to 0.29 N/m was observed as the excitation pressure was increased from 25 kPa to 100 kPa, respectively, which suggests a nonlinear relationship exists between lipid shell stiffness and applied strain. These findings support the viewpoint that lipid shells coating microbubbles exist as heterogeneous mixtures that undergo dynamic and rapid variations in mechanical properties under applied strains.