109 research outputs found
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. Because of the vast number of ultrasound- and microbubble-related parameters that can be altered and the variability in different models, the translation from basic research to (pre)clinical studies has been hindered. This review aims at connecting the knowledge gained from fundamental microbubble studies to the therapeutic efficacy seen in in vitro and in vivo studies, with an emphasis on a better understanding of the response of a microbubble upon exposure to ultrasound and its interaction with cells and tissues. More specifically, we address the acoustic settings and microbubble-related parameters (i.e., bubble size and physicochemistry of the bubble shell) that play a key role in microbubble cell interactions and in the associated therapeutic outcome. Additionally, new techniques that may provide additional control over the treatment, such as monodisperse microbubble formulations, tunable ultrasound scanners, and cavitation detection techniques, are discussed. An in-depth understanding of the aspects presented in this work could eventually lead the way to more efficient and tailored microbubble-assisted ultrasound therapy in the future
Time-resolved velocity and pressure field quantification in a flow-focusing device for ultrafast microbubble production
Flow-focusing devices have gained great interest in the past decade, due to
their capability to produce monodisperse microbubbles for diagnostic and
therapeutic medical ultrasound applications. However, up-scaling production to
industrial scale requires a paradigm shift from single chip operation to highly
parallelized systems. Parallelization gives rise to fluidic interactions
between nozzles that, in turn, may lead to a decreased monodispersity. Here, we
study the velocity and pressure field fluctuations in a single flow-focusing
nozzle during bubble production. We experimentally quantify the velocity field
inside the nozzle at 100 ns time resolution, and a numerical model provides
insight into both the oscillatory velocity and pressure fields. Our results
demonstrate that, at the length scale of the flow focusing channel, the
velocity oscillations propagate at fluid dynamical time scale (order of
microseconds) whereas the dominant pressure oscillations are linked to the
bubble pinch-off and propagate at a much faster time scale (order of
nanoseconds).Comment: 30 pages, 7 figure
Rayleigh-Taylor instability by segregation in an evaporating multi-component microdroplet
The evaporation of multi-component droplets is relevant to various
applications but challenging to study due to the complex physicochemical
dynamics. Recently, Li (2018) reported evaporation-triggered segregation in
1,2-hexanediol-water binary droplets. In this present work, we added 0.5 wt%
silicone oil into the 1,2-hexanediol-water binary solution. This minute
silicone oil concentration dramatically modifies the evaporation process as it
triggers an early extraction of the 1,2-hexanediol from the mixture.
Surprisingly, we observe that the segregation of 1,2-hexanediol forms plumes,
rising up from the rim of the sessile droplet towards the apex during the
droplet evaporation. By orientating the droplet upside down, i.e., by studying
a pendant droplet, the absence of the plumes indicates that the flow structure
is induced by buoyancy, which drives a Rayleigh-Taylor instability (i.e.,
driven by density differences & gravitational acceleration). From micro-PIV
measurement, we further prove that the segregation of the non-volatile
component (1,2-hexanediol) hinders the evaporation near the contact line, which
leads to a suppression of the Marangoni flow in this region. Hence, on long
time scales, gravitational effects play the dominant role in the flow
structure, rather than Marangoni flows. We compare the measurement of the
evaporation rate with the diffusion model of Popov (2005), coupled with
Raoult's law and the activity coefficient. This comparison indeed confirms that
the silicone-oil-triggered segregation of the non-volatile 1,2-hexanediol
significantly delays the evaporation. With an extended diffusion model, in
which the influence of the segregation has been implemented, the evaporation
can be well described
Monodisperse versus polydisperse ultrasound contrast agents: nonlinear response, sensitivity, and deep tissue imaging potential
Monodisperse microbubble ultrasound contrast agents have been proposed to
further increase the signal-to-noise-ratio of contrast enhanced ultrasound
imaging. Here, the sensitivity of a polydisperse preclinical agent was compared
experimentally to that of its size- and acoustically-sorted derivatives by
using narrowband pressure- and frequency-dependent scattering and attenuation
measurements. The sorted monodisperse agents showed up to a two orders of
magnitude increase in sensitivity, i.e. in the average scattering cross-section
per bubble. Moreover, we demonstrate here, for the first time, that the highly
nonlinear response of acoustically sorted microbubbles can be exploited to
confine scattering and attenuation to the focal region of ultrasound fields
used in clinical imaging. This property is a result of minimal prefocal
scattering and attenuation and can be used to minimize shadowing effects in
deep tissue imaging. Moreover, it potentially allows for more localized therapy
using microbubbles through the spatial control of resonant microbubble
oscillations
Wetting of two-component drops: Marangoni contraction versus autophobing
The wetting properties of multi-component 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
alkane diols and water. These diols behave surfactant-like in water. However,
the contact angles of such mixtures on solid substrates are surprisingly large.
We experimentally reveal that the contact angle is determined by two separate
mechanisms of completely different nature, namely Marangoni contraction
(hydrodynamic) and autophobing (molecular). It turns out that the length of the
alkyl tail of the alkane diol determines which mechanism is dominant,
highlighting the intricate coupling between molecular physics and the
macroscopic wetting of complex fluids
- …