Attenuation Spectroscopy Research Articles

Volume Phase Transition of Thermoresponsive Microgels Scrutinized by Dynamic Light Scattering and Turbidity: Correlations Depend on Microgel Homogeneity.

Thermoresponsive microgels experience a volume phase transition triggered by temperature changes, a phenomenon often analyzed using dynamic light scattering to observe overall size alterations via the diffusion coefficient. However, local structural changes are typically assessed using more intricate and expensive techniques like small-angle neutron or X-ray scattering. In our research, we investigate the volume phase transition of poly-N-isopropylacrylamide (PNIPAM)-based microgels by employing a combination of temperature-dependent dynamic light scattering and simpler, faster, and more efficient attenuation measurements. We utilize attenuation at a fixed wavelength as a direct measure of dispersion turbidity, linking the absolute changes in hydrodynamic radius to the absolute changes in turbidity. This approach allows us to compare "classical" PNIPAM microgels from precipitation polymerization, charged copolymer microgels from precipitation copolymerization, and core-shell microgels from seeded precipitation polymerization. Our study includes a systematic analysis and comparison of 30 different microgels. By directly comparing data from dynamic light scattering and attenuation spectroscopy, we gain insights into structural heterogeneity and deviations from the established fuzzy sphere morphology. Furthermore, we demonstrate how turbidity data can be converted to swelling curves.

Effect of temperature on the acoustic response and stability of size-isolated protein-shelled ultrasound contrast agents and SonoVue.

Limited work has been reported on the acoustic and physical characterization of protein-shelled UCAs. This study characterized bovine serum albumin (BSA)-shelled microbubbles filled with perfluorobutane gas, along with SonoVue, a clinically approved contrast agent. Broadband attenuation spectroscopy was performed at room (23 ± 0.5 °C) and physiological (37 ± 0.5 °C) temperatures over the period of 20 min for these agents. Three size distributions of BSA-shelled microbubbles, with mean sizes of 1.86 μm (BSA1), 3.54 μm (BSA2), and 4.24 μm (BSA3) used. Viscous and elastic coefficients for the microbubble shell were assessed by fitting de Jong model to the measured attenuation spectra. Stable cavitation thresholds (SCT) and inertial cavitation thresholds (ICT) were assessed at room and physiological temperatures. At 37 °C, a shift in resonance frequency was observed, and the attenuation coefficient was increased relative to the measurement at room temperature. At physiological temperature, SCT and ICT were lower than the room temperature measurement. The ICT was observed to be higher than SCT at both temperatures. These results enhance our understanding of temperature-dependent properties of protein-shelled UCAs. These findings study may guide the rational design of protein-shelled microbubbles and help choose suitable acoustic parameters for applications in imaging and therapy.

Characterizing Viscoelastic Polyvinyl Alcohol Phantoms for Ultrasound Elastography.

Ultrasound phantoms mimic the acoustic and mechanical properties of native tissues. Polyvinyl alcohol (PVA) phantoms are used extensively as models for validating ultrasound elastography approaches. However, the viscous properties of PVA phantoms have not been investigated adequately. Glycerol is a viscous liquid that has been reported to increase the speed of sound of phantoms. This study aims to assess the acoustic and viscoelastic properties of PVA phantoms and PVA mixed with glycerol at varying concentrations. The phantoms were fabricated with 10% w/v PVA in water with varying concentrations of glycerol (10%, 15% and 20% v/v) and 2% w/v silicon carbide particles as acoustic scatterers. The phantoms were subjected to either one, two, or three 24-h freeze-thaw cycles. The longitudinal sound speeds of all PVA phantoms were measured, and ranged from 1529 to 1660 m/s. Attenuation spectroscopy was performed in the range of 5 to 20 MHz. The measured attenuation followed a power-law relationship with frequency, wherein the power-law fit constants and exponents ranged from 0.02 to 0.1 dB/cm/MHzn and from 1.6 to 1.9, respectively. These results were in agreement with previous reports for soft tissues. Viscoelasticity of PVA phantoms was assessed using rheometry. The estimated values of shear modulus and viscosity using the Kelvin-Voigt and Kelvin-Voigt fractional derivative models were within the range of previously-reported tissue-mimicking phantoms and soft tissues. The number of freeze-thaw cycles were shown to alter the viscosity of PVA phantoms, even in the absence of glycerol. Scanning electron microscopy images of PVA phantoms without glycerol showed a porous hydrogel network, in contrast to those of PVA-glycerol phantoms with non-porous structure. Phantoms fabricated in this study possess tunable acoustic and viscoelastic properties within the range reported for healthy and diseased soft tissues. This study demonstrates that PVA phantoms can be manufactured with glycerol for applications in ultrasound elastography.

Combining Ultrasound and Capillary-Embedded T-Junction Microfluidic Devices to Scale Up the Production of Narrow-Sized Microbubbles through Acoustic Fragmentation.

Microbubbles are tiny gas-filled bubbles that have a variety of applications in ultrasound imaging and therapeutic drug delivery. Microbubbles can be synthesized using a number of techniques including sonication, amalgamation, and saline shaking. These approaches can produce highly concentrated microbubble suspensions but offer minimal control over the size and polydispersity of the microbubbles. One of the simplest and effective methods for producing monodisperse microbubbles is capillary-embedded T-junction microfluidic devices, which offer great control over the microbubble size. However, lower production rates (∼200 bubbles/s) and large microbubble sizes (∼300 μm) limit the applicability of such devices for biomedical applications. To overcome the limitations of these technologies, we demonstrate in this work an alternative approach to combine a capillary-embedded T-junction device with ultrasound to enhance the generation of narrow-sized microbubbles in aqueous suspensions. Two T-junction microfluidic devices were connected in parallel and combined with an ultrasonic horn to produce lipid-coated SF6 core microbubbles in the size range of 1-8 μm. The rate of microbubble production was found to increase from 180 microbubbles/s in the absence of ultrasound to (6.5 ± 1.2) × 106 bubble/s in the presence of ultrasound (100% ultrasound amplitude). When stored in a closed environment, the microbubbles were observed to be stable for up to 30 days, with the concentration of the microbubble suspension decreasing from ∼2.81 × 109/mL to ∼2.3 × 106/mL and the size changing from 1.73 ± 0.2 to 1.45 ± 0.3 μm at the end of 30 days. The acoustic response of these microbubbles was examined using broadband attenuation spectroscopy, and flow phantom imaging was performed to determine the ability of these microbubble suspensions to enhance the contrast relative to the surrounding tissue. Overall, this approach of coupling ultrasound with microfluidic parallelization enabled the continuous production of stable microbubbles at high production rates and low polydispersity using simple T-junction devices.

Process Analytical Technology for the Production of Parenteral Lipid Emulsions According to Good Manufacturing Practices

The good manufacturing practices (GMP) and process analytical technology (PAT) initiatives of the US Food and Drug Administration, in conjunction with International Council for Harmonisation (ICH) quality guidelines Q8, Q9, and Q10, ensure that manufacturing processes for parenteral formulations meet the requirements of increasingly strict regulations. This involves the selection of suitable process analytics for process integration and aseptic processing. In this article, we discuss the PAT requirements for the GMP-compliant manufacturing of parenteral lipid emulsions, which can be used for clinical nutrition or for the delivery of lipophilic active ingredients. There are risks associated with the manufacturing processes, including the potential for unstable emulsions and the formation of large droplets that can induce embolisms in the patient. Parenteral emulsions are currently monitored offline using a statistical approach. Inline analytics, supplemented by measurements of zeta potential, could minimize the above risks. Laser scanning technology, ultrasound attenuation spectroscopy, and photo-optical sensors combined with image analysis may prove to be useful PAT methods. In the future, these technologies could lead to better process understanding and control, thus improving production efficiency.

Carbon nanotubes added to Portland cement pastes containing nano-silica

This study assesses the effect of size, as well as binary and ternary mixtures of three different carbon nanotubes added to Portland cement pastes containing nano-silica. Carbon nanotubes were characterized in terms of size and morphology by transmission electron microscopy, particle size distribution by laser granulometry and electroacoustic attenuation spectroscopy and specific surface area by gas adsorption. The combination of more than one characterization technique helps to identify the finer or coarser carbon nanotube suspensions. The use of low amount of carbon nanotubes and nano-silica does not affect the rheological properties of cementitious matrices. The compressive strength decreases, but flexural strength improves for the finer carbon nanotube. The microstructural analysis showed the adherence of carbon nanotubes on the surface of matrix’s particles, and the nucleation of hydration products on the surface of carbon nanotubes.

Ultrasound Study of Magnetic and Non-Magnetic Nanoparticle Agglomeration in High Viscous Media.

Ultrasound attenuation spectroscopy has found wide application in the study of colloidal dispersions such as emulsions or suspensions. The main advantage of this technique is that it can be applied to relatively high concentration systems without sample preparation. In particular, the use of Epstein-Carhart-Allegra-Hawley’s (ECAH) ultrasound scattering theory, along with experimental data of ultrasound velocity or attenuation, provide the method of estimation for the particle or droplet size from nanometers to millimeters. In this study, suspensions of magnetite and silica nanoparticles in high viscous media (i.e., castor oil) were characterized by ultrasound spectroscopy. Both theoretical and experimental results showed a significant difference in ultrasound attenuation coefficients between the suspensions of magnetite and silica nanoparticles. The fitting of theoretical model to experimental ultrasound spectra was used to determine the real size of objects suspended in a high viscous medium that differed from the size distributions provided by electron microscopy imaging. The ultrasound spectroscopy technique demonstrated a greater tendency of magnetic particles toward agglomeration when compared with silica particles whose sizes were obtained from the combination of experimental and theoretical ultrasonic data and were more consistent with the electron microscopy images.

Extraction, detection, and imaging of the macular carotenoids.

The term "macular carotenoids" refers to the lutein, zeaxanthin, and meso-zeaxanthin that are highly concentrated at the center of the human retina. Intraretinal levels of these carotenoids are inversely associated with the risk of age-related macular degeneration (AMD), and oral supplementation with these carotenoids can significantly reduce AMD risk. To make macular carotenoid analysis more accessible, we systematically review the current methods for extraction, detection, and imaging of macular carotenoids in both basic and clinical research. We first introduce carotenoid extraction methods from the retina, retinal pigment epithelium (RPE)/choroid, serum, and liver of the human and animal models, such as mice and Japanese quails, as well as from algae, bacteria, and chicken egg yolks and cultured cells. We then review macular carotenoid detection by spectroscopy and HPLC, while particularly introducing carotenoid separation via cyano columns, chiral columns, and C30 columns. In the end, we summarize the common methods used to image carotenoids in living human eyes: resonance Raman spectroscopy, autofluorescence attenuation spectroscopy, and reflection spectroscopy, and we then review the utility of confocal resonance Raman microscopy to image the macular carotenoids in tissue sections of human and mouse retinas.

Characterization of particle size distribution in slurries using ultrasonic attenuation spectroscopy: Addressing challenges of unknown physical properties

Ultrasonic attenuation spectroscopy (UAS) has many advantages in online in-process characterization of particle size distribution (PSD) in slurries. It can be applied to systems with relatively high solid concentration and wide particle size range from nanometres to millimetres sized particles. The model used by a UAS instrument to estimate the PSD from an attenuation spectrum requires some physical properties of both the liquid and solid phases to be known. For instance, the most popular UAS model, the Epstein–Carhart and Allegra–Hawley (ECAH) model, requires fourteen physical properties. Therefore, applications where all or some of the required physical properties are unknown or difficult to measure, such as crystallization, pose a major challenge to its use. In this work, a procedure for estimating the unknown physical properties is proposed. This is done by iteratively learning the unknown physical properties to minimise the difference between the measured attenuation spectra and that predicted by the ECAH model. One of the main challenges of this procedure is the presence of multiple local minima but these can be eliminated by a combination of a global optimisation algorithm, the use of multiple particle size distributions and solid concentrations. The procedure was validated using Silica and Titania standard reference materials, and applied to the estimation of the relevant physical properties of saturated aqueous solution of SrCl2.6H2O and Sr(OH)2.8H2O. The properties thus obtained was used for acoustic monitoring of the real-time evolution of PSD during the batch cooling crystallization of SrCl2.6H2O in water.

Acoustic characterization and stability assessment of size-isolatedprotein-shelled microbubbles

The side size distribution of ultrasound contrast agents has a strong effect on their performance in therapy and imaging. In this work, attenuation spectroscopy was performed to characterize the acoustic response and stability of three size-isolated populations of protein-shelled microbubbles with mean diameters ranging from 1.66 to 3.77 μm.

Cavitation Emissions Nucleated by Definity Infused through an EkoSonic Catheter in a Flow Phantom

The EkoSonic endovascular system has been cleared by the U.S. Food and Drug Administration for the controlled and selective infusion of physician specified fluids, including thrombolytics, into the peripheral vasculature and the pulmonary arteries. The objective of this study was to explore whether this catheter technology could sustain cavitation nucleated by infused Definity, to support subsequent studies of ultrasound-mediated drug delivery to diseased arteries. The concentration and attenuation spectroscopy of Definity were assayed before and after infusion at 0.3, 2.0 and 4.0 mL/min through the EkoSonic catheter. PCI was used to map and quantify stable and inertial cavitation as a function of Definity concentration in a flow phantom mimicking the porcine femoral artery. The 2.0 mL/min infusion rate yielded the highest surviving Definity concentration and acoustic attenuation. Cavitation was sustained throughout each 15 ms ultrasound pulse, as well as throughout the 3 min infusion. These results demonstrate a potential pathway to use cavitation nucleation to promote drug delivery with the EkoSonic endovascular system.

Non-negative differential evolution for particle sizing from ultrasonic attenuation spectroscopy

Ultrasonic attenuation spectroscopy (UAS) is a potentially characterising technique for nano-meter size materials. It is the inversion of the ultrasonic attenuation spectrum to particle size distribution (PSD) by using an optimisation technique. Because the particle size is non-negative number, the inversion has to be optimised in the non-negative real number domain. However, many optimisation techniques have traditionally added the non-negative constrain into a cost function as a result the function becoming complex. In this article, the modification of the differential evolution (DE) technique has been proposed to narrow the searching solution domain bounded in the non-negative real number domain. An absolute function has been added to a mutant vector of the DE technique to guarantee the solution is non-negative real number. This technique is called DE-Nonneg technique. The technique has been demonstrated by characterising size of silica suspension. The optimisation results show that the PSD predictions are comparatively to simulated annealing (SA) technique. Moreover, the performance of DE-Nonneg could be improved via adjusting the parameters (expanding factor, cross over, number of parameters and mutation type) following the guideline addressed here. In addition, it is also possible to predict the PSD without using the structural PSD model. With this advantage, DE-Nonneg could possibly be applied for other non-negative optimisation problems.

Study of Dispersions of Carbon Nanotubes Modified by the Method of Rapid Expansion of Supercritical Suspensions.

The effectiveness of carbon nanotubes (CNT) deagglomeration by rapid expansion of supercritical suspensions (RESS) in nitrogen and carbon dioxide fluids was studied in this work. Two different mechanisms of deagglomeration were proposed for these two fluids at various temperature and pressure conditions. Ultrasound attenuation spectroscopy was applied as an express method of determining median diameter and aspect ratio of CNTs. At least twofold reduction of the diameter was shown for CNT bundles processed by RESS technique. Aspect ratio of processed CNTs, calculated from acoustic attenuation spectra, increased to 340. These results were in a good agreement with atomic force microscopy data.

Thermodynamic and Kinetic Pathways to Agitated and Spontaneous Emulsification.

Emulsification of an oil (dodecane and diesel fuel) in salinized water was studied under turbulent and agitation-free conditions in the presence of a mixture of an ionic and a nonionic surfactant. The properties of the air-water and the oil-water interfaces were investigated using the methods of du-Nouy ring, drop resonance vibrometry, and Langmuir film balance that allowed pinpointing the relevance of certain interfacial properties in emulsification. Estimation of the droplet size and its distribution from the nanometer-to-micrometer range was carried out with optical microscopy, acoustic attenuation spectroscopy, and continuous hydrodynamic flow fractionation. These measurements provided the platform for the comparison of the emulsion droplet size with those predicted from the fluctuation of the dynamic stress in the turbulent water via a capillary hydrodynamic model. While such a comparison was reasonably meaningful for micron size emulsion droplets, production of nanometer size droplets was beyond such a rudimentary expectation. We thus carried out systematic investigations into other factors that contribute to emulsification under both agitated and agitation-free conditions. An important finding of these studies is that the infusion of air bubbles that profoundly enhance the hydrodynamic fluctuation produces mainly submicroscopic emulsion droplets, while a fluctuation inhibiting water-soluble polymer has the opposite effect. Furthermore, while a hydrophilic polymer dissolved in water enhances the ripening of the droplets with time, hydrophobic polymer in oil thwarts aging, plausibly by osmotic backpressure and interfacial stiffening, which, upon compression, acts against surface tension, thereby decreasing the chemical potential of the trapped oil molecules inside the droplet. These effects are similarly observed in spontaneous emulsifications, that is, when a layer of oil containing the additives is deposited upon the surface of the aqueous phase in the absence of any external work input.

Acoustic attenuation spectroscopy and helium ion microscopy study of rehydration of dairy powder

Complete hydration is essential for the production of structured dairy products from powders. It is essential that the ingredients used hydrate completely. Determination of an end point of rehydration is non-trivial, but ultrasound-based methodologies have demonstrated potential in this area and are well suited to measuring bulk samples in situ. Here, acoustic attenuation spectroscopy (AAS) is used to monitor rehydration of skim milk powder, and recombined systems of micellar casein isolate with lactose and whey protein isolate. Dynamic light scattering, zeta-potential measurements and AAS as a function of pH characterise each component around its isoelectric point to assess its functionality. Scanning helium ion microscopy was used to image the dry powders, without any conductive coating, producing resolution equivalent to scanning electron microscopy, but with much larger focal lengths and fewer imaging artefacts. Imaging the powders provides information on particle size and morphology which can affect dissolution behaviour. Reconstituted skim milk powder and recombined samples were monitored showing there are changes occurring over several hours. Attenuation coefficients are shown to predict the end point of hydration. Model fitting is used to extract volume fractions and average particle sizes of large and small particle populations in recombined samples over time. AAS is demonstrated to be capable of tracking the dynamics in rehydrating dispersions over time. Physical parameters such as the volume fraction and particle size of the dispersed phase can be determined.

In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke

The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized using an inverted microscope. The perfusate consisted of either (1) plasma alone, (2) rt-PA, (3) OFP t-ELIP, (4) rt-PA and US, (5) OFP t-ELIP and US, (6) Definity and US, or (7) rt-PA, Definity, and US (n = 16 clots per group). An intermittent US insonation scheme was employed (220 kHz frequency, and 0.44 MPa peak-to-peak pressures) for 30 min. Microscopic imaging revealed that OFP t-ELIP included a variety of structures such as liposomes (with and without gas) and lipid-shelled microbubbles. OFP t-ELIP preserved up to 76% of rt-PA activity in the presence of PAI-1, whereas only 24% activity was preserved for unencapsulated rt-PA. The use of US with rt-PA and Definity enhanced lytic efficacy (p < 0.05) relative to rt-PA alone. US combined with OFP t-ELIP enhanced lysis over OFP t-ELIP alone (p < 0.01). These results demonstrate that ultrasound combined with Definity or OFP t-ELIP can enhance the lytic activity relative to rt-PA or OFP t-ELIP alone, respectively.

Characterization and Imaging of Lipid-Shelled Microbubbles for Ultrasound-Triggered Release of Xenon.

Xenon (Xe) is a bioactive gas capable of reducing and stabilizing neurologic injury in stroke. The goal of this work was to develop lipid-shelled microbubbles for xenon loading and ultrasound-triggered release. Microbubbles loaded with either xenon (Xe-MB) or xenon and octafluoropropane (Xe-OFP-MB) (9:1 v/v) were synthesized by high-shear mixing. The size distribution and the frequency-dependent attenuation coefficient of Xe-MB and Xe-OFP-MB were measured using a Coulter counter and a broadband acoustic attenuation spectroscopy system, respectively. The Xe dose was evaluated using gas chromatography/mass spectrometry. The total Xe doses in Xe-MB and Xe-OFP-MB were 113.1 ± 13.5 and 145.6 ± 25.5μl per mg of lipid, respectively. Co-encapsulation of OFP increased the total xenon dose, attenuation coefficient, microbubble stability (in an undersaturated solution), and shelf life of the agent. Triggered release of gas payload was demonstrated with 6-MHz duplex Doppler and 220-kHz pulsed ultrasound. These results constitute the first step toward the use of lipid-shelled microbubbles for applications such as neuroprotection in stroke.

Lipid-shelled microbubbles for ultrasound-triggered release of bioactive gases to treat stroke and cardiovascular disease

Ischemia-reperfusion-induced neurological injury is a primary cause of stroke disability. Xenon (Xe), a bioactive gas, has potential as an effective and nontoxic neuroprotectant for the treatment of ischemic stroke. Nitric oxide (NO) is a potent bioactive gas capable of inducing vasodilatory, anti-inflammatory, neuroprotectant and bactericidal effects. The goal of this work was to develop lipid-shelled microbubbles for site-specific release of Xe or NO upon pulsed ultrasound exposure. Gas-loaded microbubbles were synthesized by high-shear mixing of a lipid dispersion in a vial that contained, Xe or NO, and octafluoropropane (OFP) in combination. Attenuation spectroscopy measurements demonstrate the feasibility of 6-MHz pulsed Doppler ultrasound-triggered release of Xe or NO from microbubbles. The addition of OFP in the lipid-shelled microbubbles increased the number density, size, and stability of the microbubbles, particularly in undersaturated saline. Gas chromatography mass spectrometry was employed to measure Xe dose (127 ± 29 μl Xe/mg lipid). The payload of NO in the microbubbles (97 ± 12 μl NO/mg lipid) was assessed using an amperometric sensor. Intravenous administration of microbubbles carrying a neuroprotective or a vasodilatory gas in combination with ultrasound exposure has potential as a novel noninvasive strategy for local therapeutic delivery to modulate the effects or duration of cerebral ischemia.

High-speed, inline measurement of protein activity and inactivation processes by supercontinuum attenuation spectroscopy.

Some proteins such as catalase and glutamate dehydrogenase (GDH) are very sensitive to external factors such as irradiation or heat, which may cause inactivation. Since proteins are used in a wide field of applications, the entire activity has to be ensured during the whole process. By default, activity is measured by invasive and offline activity assays. To avoid the need for a time-consuming offline analysis, we developed an optical high-speed measurement technique, which may form the basis for the non-invasive inline control of enzyme processes e.g. in the textile or food industry. The technique is based on attenuation spectroscopy using a supercontinuum laser source in combination with multivariate data analysis, in particular partial least squares regression (PLSR). For verification of the approach, samples treated by various stresses were analyzed in parallel by activity assays and our new method. Applying this technique, we were able to determine the activity in the turbid catalase samples after heat treatment, addition of guanidine-HCl or irradiation with UV light by applying partial least squares regression. Furthermore, we demonstrate that the combination of broadband attenuation spectroscopy and PLSR enables us to determine also the activity of GDH in clear solutions after heat treatment.

Lipid-shelled microbubbles for ultrasound-triggered release of xenon

Xenon is a cellular protectant shown to stabilize or reduce neurologic injury in stroke. The goal of this work was to develop lipid-shelled microbubbles for ultrasound-triggered xenon release. Microbubbles loaded with either xenon alone (Xe-MB) or xenon and octafluoropropane (Xe-OFP-MB) were synthesized by high-shear mixing lipids with either 100% xenon, or 90% (v/v) xenon and 10% (v/v) octafluoropropane. The size distribution and the attenuation coefficient of Xe-MB and Xe-OFP-MB were measured using a Coulter counter and a broadband attenuation spectroscopy system, respectively. Gas chromatography/mass spectrometry (GC/MS) was performed to assess the dose and stability of encapsulated xenon. The feasibility of xenon release using 5-MHz pulsed Doppler ultrasound and 220-kHz pulsed ultrasound was tested by ultrasound attenuation spectroscopy. Co-encapsulation of OFP increased the number density, attenuation coefficient, and temporal stability of microbubbles. The GC/MS measurements revealed that 143 ± 20 μL/mg and 131 ± 33 μL/mg of xenon was loaded in Xe-MB and Xe-OFP-MB, respectively. Xe-MB and Xe-OFP-MB retained 54 ± 11% and 66 ± 1% of the xenon payload within 15 min of activation, respectively. Attenuation measurements confirmed ultrasound-triggered xenon release. These results suggest that lipid-shelled microbubbles with OFP could serve as ultrasound-triggered xenon delivery agents to attenuate cellular breakdown.