Philippe Marmottant

Controlled vesicle deformation and lysis by single oscillating bubbles.

The ability of collapsing (cavitating) bubbles to focus and concentrate energy, forces and stresses is at the root of phenomena such as cavitation damage, sonochemistry or sonoluminescence. In a biomedical context, ultrasound-driven microbubbles have been used to enhance contrast in ultrasonic images. The observation of bubble-enhanced sonoporation—acoustically induced rupture of membranes—has also opened up intriguing possibilities for the therapeutic application of sonoporation as an alternative to cell-wall permeation techniques such as electroporation and particle guns. However, these pioneering experiments have not been able to pinpoint the mechanism by which the violently collapsing bubble opens pores or larger holes in membranes. Here we present an experiment in which gentle (linear) bubble oscillations are sufficient to achieve rupture of lipid membranes. In this regime, the bubble dynamics and the ensuing sonoporation can be accurately controlled. The use of microbubbles as focusing agents makes acoustics on the micrometre scale (microacoustics) a viable tool, with possible applications in cell manipulation and cell-wall permeation as well as in microfluidic devices.

A model for large amplitude oscillations of coated bubbles accounting for buckling and rupture

We present a model applicable to ultrasound contrast agent bubbles that takes into account the physical properties of a lipid monolayer coating on a gas microbubble. Three parameters describe the properties of the shell: a buckling radius, the compressibility of the shell, and a break-up shell tension. The model presents an original non-linear behavior at large amplitude oscillations, termed compression-only, induced by the buckling of the lipid monolayer. This prediction is validated by experimental recordings with the high-speed camera Brandaris 128, operated at several millions of frames per second. The effect of aging, or the resultant of repeated acoustic pressure pulses on bubbles, is predicted by the model. It corrects a flaw in the shell elasticity term previously used in the dynamical equation for coated bubbles. The break-up is modeled by a critical shell tension above which gas is directly exposed to water.

The role of fluctuations and stress on the effective viscosity of cell aggregates

Cell aggregates are a tool for in vitro studies of morphogenesis, cancer invasion, and tissue engineering. They respond to mechanical forces as a complex rather than simple liquid. To change an aggregates shape, cells have to overcome energy barriers. If cell shape fluctuations are active enough, the aggregate spontaneously relaxes stresses (“fluctuation-induced flow”). If not, changing the aggregates shape requires a sufficiently large applied stress (“stress-induced flow”). To capture this distinction, we develop a mechanical model of aggregates based on their cellular structure. At stress lower than a characteristic stress τ*, the aggregate as a whole flows with an apparent viscosity η*, and at higher stress it is a shear-thinning fluid. An increasing cell–cell tension results in a higher η* (and thus a slower stress relaxation time tc). Our constitutive equation fits experiments of aggregate shape relaxation after compression or decompression in which irreversibility can be measured; we find tc of the order of 5 h for F9 cell lines. Predictions also match numerical simulations of cell geometry and fluctuations. We discuss the deviations from liquid behavior, the possible overestimation of surface tension in parallel-plate compression measurements, and the role of measurement duration.

Microfluidics with ultrasound-driven bubbles

Microstreaming from oscillating bubbles is known to induce vigorous vortex flow. Here we show how to harness the power of bubble streaming in an experiment to achieve directed transport flow of high velocity, allowing design and manufacture of microfluidic MEMS devices. By combining oscillating bubbles with solid protrusions positioned on a patterned substrate, solid beads and lipid vesicles are guided in desired directions without microchannels. Simultaneously, the flow exerts controlled localized forces capable of opening and reclosing lipid membranes.

Ultra-fast underwater suction traps

Carnivorous aquatic Utricularia species catch small prey animals using millimetre-sized underwater suction traps, which have fascinated scientists since Darwins early work on carnivorous plants. Suction takes place after mechanical triggering and is owing to a release of stored elastic energy in the trap body accompanied by a very fast opening and closing of a trapdoor, which otherwise closes the trap entrance watertight. The exceptional trapping speed—far above human visual perception—impeded profound investigations until now. Using high-speed video imaging and special microscopy techniques, we obtained fully time-resolved recordings of the door movement. We found that this unique trapping mechanism conducts suction in less than a millisecond and therefore ranks among the fastest plant movements known. Fluid acceleration reaches very high values, leaving little chance for prey animals to escape. We discovered that the door deformation is morphologically predetermined, and actually performs a buckling/unbuckling process, including a complete trapdoor curvature inversion. This process, which we predict using dynamical simulations and simple theoretical models, is highly reproducible: the traps are autonomously repetitive as they fire spontaneously after 5–20 h and reset actively to their ready-to-catch condition.

Fragmentation of stretched liquid ligaments

The dynamics and fragmentation of stretched liquid ligaments is investigated. The ligaments are produced by the withdrawal of a tube initially dipping at a free surface. Time resolved high speed motion experiments reveal two different elongation behaviors, depending on the nondimensional number t, ratio of the extension rate to the capillary contraction rate 1/t, with t the capillary time based on the tube diameter. For slow extensions (small t) the liquid bridge linking the tube to the reservoir contracts above a critical elevation, eventually following a self-similar contraction before break-up. For fast extensions (large t) the bridge takes the form of a cylindrical ligament, stabilized by the stretching motion. Whatever the elongation rate is, the ligament detaches from the surface at a time of order t after the beginning of the extension. If only one small droplet is produced with a slowly stretched bridge, a set of droplets with distributed sizes is obtained from the break-up of the ligament submitted to a fast extension. We discover that an aggregative process comes into play between the blobs constitutive of the ligament as it fragments. The outcoming Gamma distribution describes well the observed broad drop size distributions

Fast acoustic tweezers for the two-dimensional manipulation of individual particles in microfluidic channels

This paper presents a microfluidic device that implements standing surface acoustic waves in order to handle single cells, droplets, and generally particles. The particles are moved in a very controlled manner by the two-dimensional drifting of a standing wave array, using a slight frequency modulation of two ultrasound emitters around their resonance. These acoustic tweezers allow any type of motion at velocities up to few ×10 mm/s, while the device transparency is adapted for optical studies. The possibility of automation provides a critical step in the development of lab-on-a-chip cell sorters and it should find applications in biology, chemistry, and engineering domains.

Buckling resistance of solid shell bubbles under ultrasound

Thin solid shell contrast agents bubbles are expected to undergo different volume oscillating behaviors when the acoustic power is increased: small oscillations when the shell remains spherical, and large oscillations when the shell buckles. Contrary to bubbles covered with thin lipidic monolayers that buckle as soon as compressed: the solid shell bubbles resist compression, making the buckling transition abrupt. Numerical simulations that explicitly incorporate a shell bending modulus give the critical buckling pressure and post-buckling shape, and show the appearance of a finite number of wrinkles. These findings are incorporated in a model based on the concept of effective surface tension. This model compares favorably to experiments when adjusting two main parameters: the buckling tension and the rupture shell tension. The buckling tension provides a direct estimation of the acoustic pressure threshold at which buckling occurs.

Manipulation of confined bubbles in a thin microchannel: Drag and acoustic Bjerknes forces

Bubbles confined between the parallel walls of microchannels experience an increased drag compared to freestanding bubbles. We measure and model the additional friction from the walls, which allows the calibration of the drag force as a function of velocity. We then develop a setup to apply locally acoustic waves and demonstrate the use of acoustic forces to induce the motion of bubbles. Because of the bubble pulsation, the acoustic forces—called Bjerknes forces—are much higher than for rigid particles. We evaluate these forces from the measurement of bubble drift velocity and obtain large values of several hundreds of nanonewtons. Two applications have been developed to explore the potential of these forces: asymmetric bubble breakup to produce very well controlled bidisperse populations and intelligent switching at a bifurcation.

Birth and growth of cavitation bubbles within water under tension confined in a simple synthetic tree.

Water under tension, as can be found in several systems including tree vessels, is metastable. Cavitation can spontaneously occur, nucleating a bubble. We investigate the dynamics of spontaneous or triggered cavitation inside water filled microcavities of a hydrogel. Results show that a stable bubble is created in only a microsecond time scale, after transient oscillations. Then, a diffusion driven expansion leads to filling of the cavity. Analysis reveals that the nucleation of a bubble releases a tension of several tens of MPa, and a simple model captures the different time scales of the expansion process.