Ring-shaped colloidal patterns on saline water films.

Hypothesis: Electrostatically stabilised colloidal particles destabilise when brought into contact with cations causing the particles to aggregate in clusters. When a drop with stabilised colloidal partices is deposited on a liquid film containing cations the delicate balance between the fluid-mechanical and physicochemical properties of the system governs the spreading dynamics and formation of colloidal particle clusters.

Experiments: High-speed imaging and digital holographic microscopy were used to characterise the spreading process.

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

Objective: Ultrasound-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.

Methods: In this work, the response of microbubbles with a coating consisting of poly(2-ethyl-butyl cyanoacrylate) (PEBCA) nanoparticles and denatured casein was characterized.

Dependence of sonoporation efficiency on microbubble size: An in vitro monodisperse microbubble study.

Sonoporation is the process where intracellular drug delivery is facilitated by ultrasound-driven microbubble oscillations. Several mechanisms have been proposed to relate microbubble dynamics to sonoporation including shear and normal stress. The present work aims to gain insight into the role of microbubble size on sonoporation and thereby into the relevant mechanism(s) of sonoporation.

Buckling of lipidic ultrasound contrast agents under quasi-static load.

Collapse of lipidic ultrasound contrast agents under high-frequency compressive load has been historically interpreted by the vanishing of surface tension. By contrast, buckling of elastic shells is known to occur when costly compressible stress is released through bending. Through quasi-static compression experiments on lipidic shells, we analyse the buckling events in the framework of classical elastic buckling theory and deduce the mechanical characteristics of these shells.

Time-resolved absolute radius estimation of vibrating contrast microbubbles using an acoustical camera.

Ultrasound (US) contrast agents consist of microbubbles ranging from 1 to 10 μm in size. The acoustical response of individual microbubbles can be studied with high-frame-rate optics or an "acoustical camera" (AC). The AC measures the relative microbubble oscillation while the optical camera measures the absolute oscillation.

Resonance behavior of a compliant piezo-driven inkjet channel with an entrained microbubble.

Microbubbles entrained in a piezo-driven drop-on-demand printhead disturb the acoustics of the microfluidic ink channel and, thereby, the jetting behavior. Here, the resonance behavior of an ink channel as a function of the microbubble size and number of bubbles is studied through theoretical modeling and experiments. The system is modeled as a set of two coupled harmonic oscillators: one corresponds to the compliant ink channel and the other corresponds to the microbubble.

Multi-timescale Microscopy Methods for the Characterization of Fluorescently-labeled Microbubbles for Ultrasound-Triggered Drug Release.

Microbubble contrast agents hold great promise for drug delivery applications with ultrasound. Encapsulating drugs in nanoparticles reduces systemic toxicity and increases circulation time of the drugs. In a novel approach to microbubble-assisted drug delivery, nanoparticles are incorporated in or on microbubble shells, enabling local and triggered release of the nanoparticle payload with ultrasound.

Feedback-controlled microbubble generator producing one million monodisperse bubbles per second.

Monodisperse lipid-coated microbubbles are a promising route to unlock the full potential of ultrasound contrast agents for medical diagnosis and therapy. Here, we present a stand-alone lab-on-a-chip instrument that allows microbubbles to be formed with high monodispersity at high production rates. Key to maintaining a long-term stable, controlled, and safe operation of the microfluidic device with full control over the output size distribution is an optical transmission-based measurement technique that provides real-time information on the production rate and bubble size.

Wetting of Two-Component Drops: Marangoni Contraction Versus Autophobing.

The wetting properties of multicomponent liquids are crucial to numerous industrial applications. The mechanisms that determine the contact angles for such liquids remain poorly understood, with many intricacies arising due to complex physical phenomena, for example, due to the presence of surfactants. Here, we consider two-component drops that consist of mixtures of vicinal alkanediols and water.

High-Frequency Acoustic Droplet Vaporization is Initiated by Resonance.

Vaporization of low-boiling point droplets has numerous applications in combustion, process engineering, and in recent years, in clinical medicine. However, the physical mechanisms governing the phase conversion are only partly explained. Here, we show that an acoustic resonance can arise from the large speed of sound mismatch between a perfluorocarbon microdroplet and its surroundings.

Monodisperse versus Polydisperse Ultrasound Contrast Agents: In Vivo Sensitivity and safety in Rat and Pig.

Recent advances in the field of monodisperse microbubble synthesis by flow focusing allow for the production of foam-free, highly concentrated and monodisperse lipid-coated microbubble suspensions. It has been found that in vitro, such monodisperse ultrasound contrast agents (UCAs) improve the sensitivity of contrast-enhanced ultrasound imaging. Here, we present the first in vivo study in the left ventricle of rat and pig with this new monodisperse bubble agent.

Evaporating droplets on oil-wetted surfaces: Suppression of the coffee-stain effect.

The evaporation of suspension droplets is the underlying mechanism in many surface-coating and surface-patterning applications. However, the uniformity of the final deposit suffers from the coffee-stain effect caused by contact line pinning. Here, we show that control over particle deposition can be achieved through droplet evaporation on oil-wetted hydrophilic surfaces.

Ultrasound Contrast Agent Modeling: A Review.

Ultrasound is extensively used in medical imaging, being safe and inexpensive and operating in real time. Its scope of applications has been widely broadened by the use of ultrasound contrast agents (UCAs) in the form of microscopic bubbles coated by a biocompatible shell. Their increased use has motivated a large amount of research to understand and characterize their physical properties as well as their interaction with the ultrasound field and their surrounding environment.

Microbubble Agents: New Directions.

Microbubble ultrasound contrast agents have now been in use for several decades and their safety and efficacy in a wide range of diagnostic applications have been well established. Recent progress in imaging technology is facilitating exciting developments in techniques such as molecular, 3-D and super resolution imaging and new agents are now being developed to meet their specific requirements. In parallel, there have been significant advances in the therapeutic applications of microbubbles, with recent clinical trials demonstrating drug delivery across the blood-brain barrier and into solid tumours.

Three Decades of Ultrasound Contrast Agents: A Review of the Past, Present and Future Improvements.

Initial reports from the 1960s describing the observations of ultrasound contrast enhancement by tiny gaseous bubbles during echocardiographic examinations prompted the development of the first ultrasound contrast agent in the 1980s. Current commercial contrast agents for echography, such as Definity, Optison, Sonazoid and SonoVue, have proven to be successful in a variety of on- and off-label clinical indications. Whereas contrast-specific technology has seen dramatic progress after the introduction of the first approved agents in the 1990s, successful clinical translation of new developments has been limited during the same period, while understanding of microbubble physical, chemical and biologic behavior has improved substantially.

Evaporation of Dilute Sodium Dodecyl Sulfate Droplets on a Hydrophobic Substrate.

Evaporation of surfactant-laden sessile droplets is omnipresent in nature and industrial applications such as inkjet printing. Soluble surfactants start to form micelles in an aqueous solution for surfactant concentrations exceeding the critical micelle concentration (CMC). Here, the evaporation of aqueous sodium dodecyl sulfate (SDS) sessile droplets on hydrophobic surfaces was experimentally investigated for SDS concentrations ranging from 0.

The Role of Ultrasound-Driven Microbubble Dynamics in Drug Delivery: From Microbubble Fundamentals to Clinical Translation.

In the last couple of decades, ultrasound-driven microbubbles have proven excellent candidates for local drug delivery applications. Besides being useful drug carriers, microbubbles have demonstrated the ability to enhance cell and tissue permeability and, as a consequence, drug uptake herein. Notwithstanding the large amount of evidence for their therapeutic efficacy, open issues remain.

Improved coalescence stability of monodisperse phospholipid-coated microbubbles formed by flow-focusing at elevated temperatures.

Monodisperse phospholipid-coated ultrasound contrast agent (UCA) microbubbles can be directly synthesized in a lab-on-a-chip flow-focusing device. However, high total lipid concentrations are required to minimize on-chip bubble coalescence. Here, we characterize the coalescence probability and the long-term size stability of microbubbles formed using DPPC and DSPC based lipid mixtures as a function of temperature.

High-precision acoustic measurements of the nonlinear dilatational elasticity of phospholipid coated monodisperse microbubbles.

The acoustic response of phospholipid-coated microbubble ultrasound contrast agents (UCA) is dramatically affected by their stabilizing shell. The interfacial shell elasticity increases the resonance frequency, the shell viscosity increases damping, and the nonlinear shell viscoelasticity increases the generation of harmonic echoes that are routinely used in contrast-enhanced ultrasound imaging. To date, the surface area-dependent interfacial properties of the phospholipid coating have never been measured due to the extremely short time scales of the MHz frequencies at which the microscopic bubbles are driven.

Monodisperse Versus Polydisperse Ultrasound Contrast Agents: Non-Linear Response, Sensitivity, and Deep Tissue Imaging Potential.

It has been proposed that monodisperse microbubble ultrasound contrast agents further increase the signal-to-noise ratio of contrast-enhanced ultrasound imaging. Here, the sensitivity of a polydisperse pre-clinical agent was compared experimentally with that of its size- and acoustically sorted derivatives by using narrowband pressure- and frequency-dependent scattering and attenuation measurements. The sorted monodisperse agents had up to a two-orders-of-magnitude increase in sensitivity, that is, in the average scattering cross section per bubble.

Universal Equations for the Coalescence Probability and Long-Term Size Stability of Phospholipid-Coated Monodisperse Microbubbles Formed by Flow Focusing.

Resonantly driven monodisperse phospholipid-coated microbubbles are expected to substantially increase the sensitivity and efficiency in contrast-enhanced ultrasound imaging and therapy. They can be produced in a microfluidic flow-focusing device, but questions remain as to the role of the device geometry, the liquid and gas flow, and the phospholipid formulation on bubble stability. Here, we develop a model based on simple continuum mechanics equations that reveals the scaling of the coalescence probability with the key physical parameters.

Optical verification and in-vitro characterization of two commercially available acoustic bubble counters for cardiopulmonary bypass systems.

Introduction: Gaseous microemboli (GME) introduced during cardiac surgery are considered as a potential source of morbidity, which has driven the development of the first bubble counters. Two new generation bubble counters, introduced in the early 2000s, claim correct sizing and counting of GME. This in-vitro study aims to validate the accuracy of two bubble counters using monodisperse bubbles in a highly controlled setting at low GME concentrations.

Uniform scattering and attenuation of acoustically sorted ultrasound contrast agents: Modeling and experiments.

The sensitivity and efficiency in contrast-enhanced ultrasound imaging and therapy can potentially be increased by the use of resonant monodisperse bubbles. However, bubbles of the same size may respond differently to ultrasound due to differences in their phospholipid shell. In an acoustic bubble sorting chip, resonant bubbles can be separated from the polydisperse agent.

Stability of Monodisperse Phospholipid-Coated Microbubbles Formed by Flow-Focusing at High Production Rates.

Monodisperse microbubble ultrasound contrast agents may dramatically increase the sensitivity and efficiency in ultrasound imaging and therapy. They can be produced directly in a microfluidic flow-focusing device, but questions remain as to the interfacial chemistry, such as the formation and development of the phospholipid monolayer coating over time. Here, we demonstrate the synthesis of monodisperse bubbles with radii of 2-10 μm at production rates ranging from 10(4) to 10(6) bubbles/s.

Bubble sorting in pinched microchannels for ultrasound contrast agent enrichment.

Ultrasound contrast agent (UCA) suspensions contain encapsulated microbubbles with a wide size distribution, with radii between 1 and 10 μm. Medical transducers generally operate at a narrow frequency bandwidth, severely limiting the fraction of bubbles that resonates to the driving ultrasound. Thus, the sensitivity of contrast enhanced ultrasound imaging, molecular imaging with targeted bubbles, and drug delivery with microbubbles can be improved by narrowing down the size distribution of the bubble suspension.