Publications

Oil and water can only be mixed by dispersing droplets of one fluid in the other. When two droplets approach one another, the thin film that separates them invariably becomes unstable, causing the droplets to coalesce. The only known way to avoid this instability is through addition of a third component, typically a surfactant, which stabilizes the thin film at its equilibrium thickness. We report the observation that a thin fluid film of oil separating two water droplets can lead to an adhesive interaction between the droplets. Moreover, this interaction prevents their coalescence over timescales of several weeks, without the use of any surfactant or solvent

https://www.science.org/stoken/author-tokens/ST-1810/full

Rheology of concentrated protein solutions is crucial for the understanding of macromolecular crowding dynamics as well as the formulation of protein therapeutics. The cost and scarcity of most protein samples prevents wide-scale rheological studies as conventional viscosity measurement methods require large sample volume. There is a growing need for a precise and robust viscosity measurement tool that minimizes consumption and simplifies the handling of highly concentrated protein solutions. This objective is achieved by combining microfluidics and microrheology: we developed a specific microsystem to study the viscosity of aqueous solutions at high concentrations. The PDMS chip allows in situ production, storing and monitoring of water-in-oil nanoliter droplets. We perform precise viscosity measurements inside individual droplets by particle-tracking microrheology of fluorescent probes. Pervaporation of water through a PDMS membrane induces aqueous droplet shrinking, concentrating the sample up to 150 times, thus allowing viscosity measurements along an extended concentration range in just one experiment. The methodology is precisely validated by studying the viscosity of sucrose solutions. Two model proteins are also studied with sample consumption reduced to as little as 1 μL of diluted solution, showcasing the viability of our approach for the study of biopharmaceuticals.

https://pubs.rsc.org/en/content/articlelanding/2023/lc/d3lc00073g

Aluminium salts such as aluminium chlorohydrate (ACH) are the active ingredients of antiperspirant products. Their mechanism of action involves a temporary and superfcial plugging of eccrine sweat pores at the skin surface. We developed a microfuidic system that allows the real time observation of the interactions between sweat and ACH in conditions mimicking physiological sweat fow and pore dimensions. Using artifcial sweat containing bovine serum albumin as a model protein, we performed experiments under fowing conditions to demonstrate that pore clogging results from the aggregation of proteins by aluminium polycations at specifc location in the sweat pore. Combining microfuidic experiments, confocal microscopy and numerical models helps to better understand the physical chemistry and mechanisms involved in pore plugging. The results show that plugging starts from the walls of sweat pores before expanding into the centre of the channel. The simulations aid in explaining the infuence of ACH concentration as well as the impact of fow conditions on the localization of the plug. Altogether, these results outline the potential of both microfuidic confocal observations and numerical simulations at the single sweat pore level to understand why aluminium polycations are so efcient for sweat channel plugging.

Completing a Swiss-cheese theorem of Lieb and Lebowitz (LL), we prove that any population of spheres with power-law radius distribution can completely fill 3D Euclidean space if the exponent is such that 2.8 ≤ d_f < 3. This sufficient condition extends considerably the known part of the ensemble of space-filling populations of polydisperse spheres. The self-similar spatial arrangement of the polydisperse spheres related to the theorem is discussed using a numerical example with d_f = 2.875. By calculating the small-angle scattering structure factor of the resulting packing, we found it to present several crystalline peaks indicating some regularity. This is significantly different from the featureless structure factor of an Apollonian packing which represents total disorder. We thereby argue that the LL algorithm for filling space with spheres is fundamentally different from Apollonian constructions.

The removal of ultrathin amorphous polymer films in contact with an aqueous gelled solution containing small amounts of good solvent is addressed by means of specular and off-specular neutron reflectometry. The distribution of heavy water and benzyl alcohol is revealed inside Laropal A81, often employed as a protective varnish layer for Culture Heritage in the restoration of easel paintings. The swelling kinetics, interface roughness, and film morphologies were recorded as a function of temperature and increasing benzyl alcohol concentration in the dispersion of Pemulen TR-2, a hydrophobically modified acrylic acid copolymer. The addition of small amounts of good solvent results in the appearance of water-filled cavities inside the varnish, which grow with time. It is shown that while increasing the solvent concentration greatly enhances the hole growth kinetics, an increase in temperature above the glass transition temperature does not have such a big effect on the kinetics.

We have discovered the existence of extremely polydisperse High Internal-Phase-Ratio Emulsions (HIPEs) in which the internal-phase droplets, present at 95% volume fraction, remain spherical and organize themselves in the available space according to Apollonian packing rules. Such Apollonian emulsions are obtained from dispersing oil dropwise in water in the presence of very little surfactant, and allowing them to evolve at rest for at least a week. The packing structure of the droplets was confirmed through size distribution measurements that evolved spontaneously towards power laws with the known Apollonian exponents, as well as comparison of the structure factors of aged HIPEs measured by Small-Angle X-ray Scattering with that of a numerically simulated Random Apollonian Packing. Thanks to the perfect sphericity of the droplets, Apollonian emulsions were found to display Newtonian flow even at such extremely high volume fraction. We argue that these fascinating space-filling assemblies of spherical droplets are a result of coalescence and fragmentation processes obeying simple geometrical rules of conserving total volume and sphericity, and minimizing the elastic energy associated with interactions of neighbouring droplets.

We characterize the motility of athermal swimming droplets within the framework of a persistent random walk. Just like active colloids, their trajectories can be modeled with a constant velocity $V$ and a slow angular diffusion, but the random changes in direction are not thermally driven. Instead, $V$ is determined by the interfacial tension gradient along the droplet surface, while reorientation of the surfactant gradient leads to changes in direction with a persistence time $\tau$. We show that the origin of locomotion is the difference in the critical micellar concentration in the front and the back of the droplet, $\Delta \mathrm{CMC}$. Tuning this parameter by salt controls $V$ from 3 to 15 diameters $d/s$. Surfactant concentration has little effect on speed, but leads to a dramatic decrease in $\tau$ over 4 orders of magnitude. The corresponding range of the persistence length $â„“=V\tau$ extends beyond the realm of synthetic or living swimmers, in which $V$ is limited by fuel consumption and $\tau$ is set by thermal fluctuations or biological activity, respectively. Our tunable swimmers are ideal candidates for the study of the departure from equilibrium to high levels of activity. We show that their collective behavior exhibits the formation of active clusters of a well-defined size.

Measuring the structure factor, S(q), of a dispersion of particles by small-angle X-ray scattering provides a unique method to investigate the spatial arrangement of colloidal particles. However, it is impossible to find the exact location of the particles from S(q) because some information is inherently lacking in the measured signal. The two standard ways to analyse an experimental S(q) are then to compare it either with structure factors computed from simulated systems or with analytical ones calculated from approximated systems. However, such approaches may prove inadequate for dispersions of variously polydisperse particles. While Vrij, Bloom and Stell established a mean-field approach that could yield fairly accurate approximations for experimental S(q), this solution has remained underused because of its mathematical complexity. In the present work, the complete Percus–Yevick solution for general polydisperse hard-sphere systems is derived in a concise form that is straightforward to use. The form of the solution has been simplified enough to provide experimentalists with ready solutions of several commonly encountered particle-radius distributions in real systems (Schulz, truncated normal and inverse Gaussian). The approach is also illustrated with a case study of the exponential radius distribution. Finally, the application of the proposed solution to the power-law radius distribution is discussed in detail by comparing the calculations with experimentally measured S(q) for an Apollonian packing of spherical droplets recently reported in high-internal-phase-ratio emulsions.

We have discovered the existence of polydisperse high internal-phase-ratio emulsions (HIPE) in which the internal-phase droplets, present at 95% volume fraction, remain spherical and organise themselves according to Apollonian packing rules. These polydisperse HIPEs are formed by emulsifying oil dropwise in a surfactant-poor aqueous continuous phase. After stirring has ceased, their droplet size distributions begin to evolve spontaneously and continuously through coalescence towards well-defined power laws with the Apollonian exponent. Small-angle X-ray Scattering performed on aged HIPEs demonstrate that the droplet packing structure agrees with that of a numerically simulated random Apollonian packing. We argue that when such concentrated emulsions are allowed to evolve, the coalescing droplets must obey volume and sphericity conservation. This leads to a mechanism that differs from typical coalescence in dilute emulsions.

The removal of ultrathin amorphous polymer films in contact with nonsolvent/solvent binary mixtures is addressed by means of neutron reflectometry and atomic force microscopy. The high resolution of neutron scattering makes it possible to resolve the distribution profiles of heavy water and benzyl alcohol inside Laropal (R) A81, often employed as a protective varnish layer for Culture Heritage in restoration of easel paintings. The swelling kinetics and distribution profiles were recorded as a function of time and increasing benzyl alcohol concentration in water. The varnish film swells by penetration of the good solvent. At higher concentrations water-filled cavities appear inside the varnish and grow with time. Contrary to homogeneous dissolution dewetting is observed at late stages of exposure to the liquid which leads to the Breakup of the film. The high resolution measurements are compared to bulk behaviour characterized by the ternary phase diagram and the Flory-Huggins interaction parameters are calculated and used to predict the swelling and solvent partition in the films. Distinct differences of the thin film to bulk behaviour are found. The expectations made previously for the behaviour of solvent/non-solvent mixtures on the removal of thin layers in the restoration of easel paintings should be revised in view of surface interactions.

Monte Carlo simulations, fully constrained by experimental parameters, are found to agree well with a measured phase diagram of aqueous dispersions of nanoparticles with a moderate size polydispersity over a broad range of salt concentrations, c(s), and volume fractions, phi. Upon increasing phi, the colloids freeze first into coexisting compact solids then into a body centered cubic phase (bcc) before they melt into a glass forming liquid. The surprising stability of the bcc solid at high phi and c(s) is explained by the interaction (charge) polydispersity and vibrational entropy.

The flow of two immiscible liquids or fluids in bounded systems where confinement geometry varies can lead to drop or bubble formation. This phenomenon has been reported in the context of oil recovery and named snap-off, or exploited for making emulsions, and then foams, by using microfluidic systems, namely, microchannel emulsification or step emulsification. We report a comprehensive experimental investigation of such an emulsification process occurring at the end of a glass rectangular tube filled with oil and immersed in a water bath. This allows us to clearly visualize the breakup event of the dispersed phase liquid finger at the capillary's end. Below a critical flow rate, the drop size varies slowly with the flow rate and it is linked to the pinching time of the dispersed phase. A semiempirical law that gives the resulting drop size as a function of fluid and geometrical properties is proposed. However, this feature is altered for an aspect ratio of the rectangular tube below 2.5 where the forming drop hinders the counterflow of the continuous phase leading to larger drops. Then, above a critical flow rate, or capillary number that weakly depends on the viscosity ratio of the two liquids, the neck adopts a quasistatic shape well accounted for by a model based on a Hele-Shaw flow. In that case, drop formation is driven by gravity and a transition from a dripping regime to a jetting regime is observed at higher flow rates. Monodisperse foam can also be formed by injecting air. While the overall dynamics of bubble formation shares similarities with an incompressible fluid, the bubble size and the critical capillary number do not follow the same scaling laws.

Convective dispersion of solutes is inherent to flow in channels because of the nonuniformity of the velocity profile. When diffusion is negligible, for large particles for example, the trajectory of particles can be solely described by a kinematic approach. Here, we investigate such a phenomenon for micrometer-size beads flowing in a circular pipe. We show that the presence of large bubbles, namely in the case of a segmented flow, either prevents the convective dispersion or leads to the accumulation of particles at the rear of the bubble moving in front. The destabilization of the initially homogeneous suspension occurs when liquid inertia comes into play. Indeed, for moderate Reynolds number of the particles, particles move away from the wall, thus exploring different flow lines that finally impact the axial dispersion features. Moreover, since the bubbles impose an axial boundary condition of the mean velocity, a net flux of particles directed along the flow direction is built up above a critical particle Reynolds number. This work is motivated by the understanding of the flow behavior of biological samples, and especially in the context of cell encapsulation.

The osmotic pressure of polyelectrolyte solutions as a function of concentration has been calculated by Monte Carlo simulations of a spherical cell model and by molecular dynamics simulations with periodic boundary conditions. The results for the coarse-grained polyelectrolyte model are in good agreement with experimental results for sodium polyacrylate and the cell model is validated by the bulk simulations. The cell model offers an alternative perspective on osmotic pressure and also forms a direct link to even simpler models in the form of the Poisson-Boltzmann approximation applied to cylindrical and spherical geometries. As a result, the non-monotonic behaviour of the osmotic coefficient seen in simulated salt-free solutions is shown not to rely on a transition between a dilute and semi-dilute regime, as is often suggested when the polyion is modelled as a linear flexible chain. The non-monotonic behaviour is better described as the combination of a finite-size effect and a double-layer effect. Parameters that represent the linear nature of the polyion, including an alternative to monomer concentration, make it possible to display a generalised behaviour of equivalent chains, at least at low concentrations. At high concentrations, local interactions become significant and the exact details of the model become important. The effects of added salt are also discussed and one conclusion is that the empirical additivity rule, treating the contributions from the polyelectrolyte and any salt separately, is a reasonable approximation, which justifies the study of salt-free solutions.

Some bacteria can act as catalysts to oxidize (or reduce) organic or inorganic matter with the potential of generating electrical current. Despite their high value for sustainable energy, organic compound production and bioremediation, a tool to probe the natural biodiversity and to select most efficient microbes is still lacking. Compartmentalized cell culture is an ideal strategy for achieving such a goal but the appropriate compartment allowing cell growth and electron exchange must be tailored. Here, we develop a conductive composite hydrogel made of a double network of alginate and carbon nanotubes. Homogeneous mixing of carbon nanotubes within the polyelectrolyte is obtained by a surfactant assisted dispersion followed by a desorption step for triggering electrical conductivity. Dripping the mixture in a gelling bath through simple extrusion or a double one allows the formation of either plain hydrogel beads or liquid core hydrogel capsules. The process is shown to be compatible with the bacterial culture (Geobacter sulfurreducens). Bacteria can indeed colonize the outer wall of plain beads or the inner wall of the conductive capsules’ shell that function as an anode from which electrons produced by the cells are collected.

We report on the impact of surface hydrophobization on the structure of aqueous silica dispersions and how this structure resists drying stress. Hydrophilic silica particles were hydrophobized directly in water using a range of organosilane precursors, with a precise control of the grafting density. The resulting nanostructure was precisely analyzed by a combination of small-angle X-ray scattering (SAXS) and cryo-microscopy (cryo-TEM). Then, the dispersion was progressively concentrated by drying, and the evolution of the nanostructures as a function of the grafting density was followed by SAXS. At the fundamental level, because the hydrophobic character of the silica surfaces could be varied continuously through a precise control of the grafting density, we were able to observe how the hydrophobic interactions change particles interactions and aggregates structures. Practically, this opened a new route to tailor the final structure, the residual porosity, and the damp-proof properties of the fully dried silica. For example, regardless of the nature of the hydrophobic precursor, a grafting density of 1 grafter per nm² optimized the interparticle interactions in solution in view to maximize the residual porosity in the dried material (0.9 cm³/g) and reduced the water uptake to less than 4% in weight compared to the typical value of 13% for hydrophilic particles (at T = 25 °C and relative humidity = 80%).

DOI: 10.1021/acs.langmuir.6b04505

Aluminium salts are widely used to control sweating for personal hygiene purposes. Their mechanism of
action as antiperspirants was previously thought to be a superficial plugging of eccrine sweat pores by
the aluminium hydroxide gel. Here we present a microfluidic T junction device that mimics sweat ducts,
and is designed for the real time study of interactions between sweat and ACH (Aluminium Chloro
Hydrate) under conditions that lead to plug formation. We used this device to image and measure the
diffusion of aluminium polycationic species in sweat counter flow. We report the results of small angle
X-ray scattering experiments performed to determine the structure and composition of the plug, using
BSA (Bovine Serum Albumin) as a model of sweat proteins. Our results show that pore occlusion occurs
as a result of the aggregation of sweat proteins by aluminium polycations. Mapping of the device shows
that this aggregation is initiated in the T junction at the location where the flow of aluminium
polycations joins the flow of BSA. The mechanism involves two stages: (1) a nucleation stage in which
aggregates of protein and polycations bind to the wall of the sweat duct and form a tenuous
membrane, which extends across the junction; (2) a growth stage in which this membrane collects
proteins that are carried by hydrodynamic flow in the sweat channel and polycations that diffuse into
this channel. These results could open up perspectives to find new antiperspirant agents with an
improved efficacy.

DOI: 10.1039/c6sm02510b

We report on a measurement of forces between particles adsorbed at a water–oil interface in the presence of an oil-soluble polymer. The cationic polymer interacts electrostatically with the negatively charged particles, thereby modulating the particle contact angle and the magnitude of capillary attraction between the particles. However, polymer adsorption to the interface also generates an increase in the apparent interfacial viscosity over several orders of magnitude in a time span of a few hours. We have designed an experiment in which repeated motion trajectories are measured on pairs of particles. The experiment gives an independent quantification of the interfacial drag coefficient (10–7–10–4 Ns/m) and of the interparticle capillary forces (0.1–10 pN). We observed that the attractive capillary force depends on the amount of polymer in the oil phase and on the particle pair. However, the attraction appears to be independent of the surface rheology, with changes over a wide range of apparent viscosity values due to aging. Given the direction (attraction), the range (∼μm), and the distance dependence (∼1/S5) of the observed interparticle force, we interpret the force as being caused by quadrupolar deformations of the fluid–fluid interface induced by particle surface roughness. The results suggest that capillary forces are equilibrated in the early stages of interface aging and thereafter do not change anymore, even though strong changes in surface rheology still occur. The described experimental approach is powerful for studying dissipative as well as conservative forces of micro- and nanoparticles at fluid–fluid interfaces for systems out of equilibrium.

DOI: 10.1021/acs.langmuir.6b03910

Liquid core capsules having a hydrogel membrane are becoming a versatile tool for three- dimensional culture of micro-organisms and mammalian cells. Making sub-millimeter capsules at a high rate, via the breakup of a compound jet in air, opens the way to high throughput screen- ing applications. However, a control of the capsule size monodispersity, especially required for quantitative bioassays, was still lacking. Here, we report how the understanding of the underlying hydrodynamic instabilities that occur during the process can lead to calibrated core-shell biore- actors. This implies: i) to damp the shear layer instability that develops inside the injector arising from the co-annular flow configuration of liquid phases having contrasted viscoelastic properties; ii) to control the capillary instability of the compound jet by superposing a harmonic perturbation to the shell flow; iii) to avoid coalescence of drop during jet fragmentation as well as during drop flight towards the gelling bath, and iv) to ensure a proper engulfment of the compound drops into the gelling bath for building a closed hydrogel shell. We end up with the creation of numerous identical compartments in which cells are able to form mutlicellular aggregates, namely spheroids. In addition, we implement an intermediate composite hydrogel layer, composed of alginate and collagen, allowing cell adhesion and thus the formation of epithelia or monolayers of cells.
 

We obtained osmotic pressure data of lysozyme solutions, describing their physical states over a wide
concentration range, using osmotic stress for pressures between 0.05 bar and about 40 bar and volume
fractions between 0.01 and 0.61. The osmotic pressure vs. volume fraction data consist of a dilute, gas-phase
regime, a transition regime with a high-compressibility plateau, and a concentrated regime where the system is
nearly incompressible. The first two regimes are shifted towards a higher protein volume fraction upon
decreasing the strength or the range of electrostatic interactions. We describe this shift and the overall shape of
the experimental data in these two regimes through a model accounting for a steric repulsion, a short-range
van der Waals attraction and a screened electrostatic repulsion. The transition is caused by crystallization, as
shown by small-angle X-ray scattering. We verified that our data points correspond to thermodynamic equilibria,
and thus that they consist of the reference experimental counterpart of a thermodynamic equation of state.

Monte Carlo simulations and coarse-grained modelling have been used to analyze
Histatin 5, which is an unstructured short cationic salivary peptide known to have anticandidical
properties. The calculated scattering functions have been compared with
intensity curves and the distance distribution function P(r) obtained from SAXS, at
both high and low salt concentrations. The aim is to achieve a molecular understanding
and a physico-chemical insight of the obtained SAXS results and to gain information of
conformational changes of Histatin 5 due to altering salt content, charge distribution,
and net charge. From a modelling perspective, the accuracy of the electrostatic interaction
is of special interest. The used coarse-grained model is based on the primitive
model in which charged hard spheres differing in charge and in size represent the ionic
particles, and the solvent only enters the model through its relative permittivity. The
Hamiltonian of the model comprises three different contributions: (i) excluded volumes,
(ii) electrostatic, and (iii) van der Waals interactions. Even though the model can be
considered as gross omitting atomistic details, a great correspondence is obtained with
experimental results.

DOI 10.1002/prot.25025

Liquid jets ultimately break up into droplets through an instability driven by surface tension. For highly viscous liquids, drops are connected by cylindrical liquid filaments whose radii linearly decrease with time, thus forming drops on a string structure. For a jet composed of two aqueous phases made in air by coaxial extrusion, we observe that, for moderate Weber and capillary numbers, drops slow down with different velocities, leading to drop coalescence. The origin of the traffic collision is linked to the spatial feature of the capillary instability where capillary and viscous forces acting on the drops evolve along the jet and ultimately amplify small velocity fluctuations. The emergence of such fluctuations is related to the unstable nature of the annular coflow of liquids having contrasting viscoelastic properties. From a practical point of view, flow and actuation conditions can be adjusted to inhibit drop collision and thus drop coalescence. These findings allow then the fabrication of monodisperse submillimeter core-shell objects based on the fragmentation of compound jets made of polymer solutions that find applications for three-dimensional cell culture.
 

The fabrication of alginate hydrogel microparticles with embedded liposomes and magnetic nanoparticles for radiofrequency controlled release of encapsulated chemical cargo was considered. An extractive gelation process was implemented in a microfluidic device, which enabled the production of uniform composite microparticles of dimensions comparable to those of blood cells (between 5 and 10 mm). The critical parameters that control the extractive gelation process were systematically explored and feasible values that provide microgel particles of a defined size and morphology were identified. First, the initial water-in-oil droplet is formed in a flow-focusing junction whose size is controlled by the flow-rate of the oil phase. Then, the train of droplets is sandwiched between two streams of oil containing calcium ions. In that way, a flux of water molecules from the droplets towards the continuous phase as well as a transport of calcium ions towards the disperse phase are initiated. The final microparticle properties were thus found to be sensitive to three elementary sub-processes: (i) the initial droplet size; (ii) the extraction of water into the oil phase, which was controlled by the volume of the oil phase and its initial moisture content; and (iii) the kinetics of ionic cross-linking of the alginate matrix, which was controlled by the varying calcium concentration. The size and morphology of the final composite microgels were fully characterized.
 

We describe an interfacial rheometry technique based on pairs of micrometer-sized magnetic particles
at a fluid–fluid interface. The particles are repeatedly attracted and repelled by well-controlled magnetic
dipole–dipole forces, so-called interfacial rheometry by intra-pair magnetophoresis (IPM). From the
forces (pN), displacements (µm) and velocities (µm s-1) of the particles we are able to quantify the
interfacial drag coefficient of particles within a few seconds and over very long timescales. The use of
local dipole–dipole forces makes the system insensitive to fluid flow and suited for simultaneously
recording many particles in parallel over a long period of time. We apply IPM to study the timedependent
adsorption of an oil-soluble amino-modified silicone polymer at a water–oil interface using
carboxylated magnetic particles. At low polymer concentration the carboxylated particles remain on the
water side of the water–oil interface, while at high polymer concentrations the particles transit into the
oil phase. Both conditions show a drag coefficient that does not depend on time. However, at intermediate
polymer concentrations data show an increase of the interfacial drag coefficient as a function
of time, with an increase over more than three orders of magnitude (10^-7 to 10^-4 N s m1), pointing to
a strong polymer-polymer interaction at the interface. The time-dependence of the interfacial drag
appears to be highly sensitive to the polymer concentration and to the ionic strength of the aqueous
phase. We foresee that IPM will be a very convenient technique to study fluid–fluid interfaces for a
broad range of materials systems.

DOI: 10.1039/c5sm02917a

A modified version of the Gibbs-ensemble Monte-Carlo method reveals how polydisperse charged colloidal particles can build complex colloidal crystals. It provides general rules that are applicable to this fractionated crystallization that stems from size segregation. It explains the spontaneous formation of complex crystals with very large unit-cells in suspensions of nanoparticles with a broad size distribution.

DOI: 10.1039/C5FD00145E

We report small-angle x-ray scattering experiments on aqueous dispersions of colloidal silica with a broad monomodal size distribution (polydispersity, 14%; size, 8 nm). Over a range of volume fractions, the silica particles segregate to build first one, then two distinct sets of colloidal crystals. These dispersions thus demonstrate fractional crystallization and multiple-phase (bcc, Laves AB2, liquid) coexistence. Their remarkable ability to build complex crystal structures from a polydisperse population originates from the intermediate-range nature of interparticle forces, and it suggests routes for designing self-assembling colloidal crystals from the bottom up.

http://dx.doi.org/10.1103/PhysRevLett.116.208001

Physics (viewpoint), at http://physics.aps.org/articles/v9/57

Ce travail de thèse est principalement axé sur la création d’un nouveau réacteur biocompatible permettant l’encapsulation et l’étude de bactéries électroactives. Ce compartiment de taille millimétrique, réalisé par coextrusion, est une capsule à cœur liquide possédant une membrane d’hydrogel conducteur. La synthèse de ce bioréacteur a nécessité la formulation d’un hydrogel composite alginate/nanotubes de carbone en deux étapes. Une première étape rapide crée la matrice d’hydrogel par diffusion d’ions divalents dans un mélange Alginate/nanotubes de carbone. Une seconde étape, plus lente, permet la dialyse du tensioactif stabilisant les nanotubes et la création d’un réseau conducteur au sein de l’hydrogel pour des pourcentages massiques de charges supérieurs à 0,5 %. Ce matériau composite présente alors une conductivité macroscopique d’environ 0,1 S.m^-1. Une étude du matériau par voie électrochimique permet entre autres de suivre cinétiquement la connexion des nanotubes de carbone. Des bactéries peuvent adhérer à la surface de cet hydrogel composite. Nous démontrons qu’il est alors possible de mesurer l’électroactivité d’un biofilm bactérien développé sur la paroi interne d’une capsule conductrice. Ce nouveau compartiment biocompatible ouvre la voie vers le développement d’un outil de criblage pour la sélection de bactéries électroactives mais offre également des perspectives innovantes pour la fabrication de piles bactériennes.

We investigate, through osmotic pressure measurements, the validity of the single-parameter equation of state (EOS) for solutions of polyethylene glycols in water, by Cohen et al.^1,2 We show that it is physically meaningful and that a reasonable good correspondence between the osmotic pressures for PEG35 in large range of concentrations is obtained. We also take the chain length dependence into account in our analysis, as suggested by Cohen et al. By recalculating the experimental pressures in the paper by Jönsson et al.³ applying the new calibration curve, which is based on the experimental results obtained in this study and the EOS obtained by Cohen et al., there is almost a perfect correspondence between the simulations and the experiments. These results have implications for correctly probing macromolecular interactions in wide range of systems when applying the osmotic stress method.

doi:10.1016/j.polymer.2015.10.056

The dissolution and swelling properties of montmorillonite at different pH have been studied, using small angle X-ray scattering (SAXS), imaging and osmotic stress methods combined with Monte Carlo simulations. The acidity of montmorillonite dispersions has been varied as well as the counterions to the net negatively charged platelets. At low pH, Na montmorillonite dissolves and among other species Al3+is released, hydrated, polymerized and then it replaces the counterions in the clay. This dramaticallychanges the microstructure of Na montmorillonite, which instead of having fully exfoliated platelets, turns into a structure of aggregated platelets, so-called tactoids. Montmorillonite dispersion still has a significant extra-lamellar swelling among the tactoids due to the presence of very small nanoplatelets.

Reinforcing precipitated silica systems have a complex hierarchical structure consisting of a branched
network made of connected clusters composed of small silica beads welded together into larger dense
aggregates. Here, we study the evolution of such structural features during a filtration process. The
typical behaviour is that the cakes formed at constant pressure do not reorganize at local scale during
a filtration experiment. Accordingly, the creep resistance of a precipitated silica network is high.
Overall, there is a percolation threshold, which appears when the branches are pushed into each other.
Once this percolation path is reached, the cake withstands compression over more than a decade of
applied pressure. Beyond, it seemed useful to make predictions of the filtration properties knowing the
typical length scales – small silica beads, dense aggregates, and consolidation behaviour of the cake.
A simple approach introducing the concept of an effective medium approximation into Darcy’s law
was tested. This approach treats the network as a pseudo-continuum of porous medium built at two main
length scales: the size of dense aggregates and a length scale representing the typical distance between
the aggregates. The quality of the fit of experimental filtration rates by this simple model indicates that a
description based on a continuous network made of two material phases is accurate.

http://dx.doi.org/10.1016/j.seppur.2015.10.005

Montmorillonite is a key ingredient in a number of technical applications. However, little is known regarding the microstructure and the forces between silicate platelets. The size of montmorillonite platelets from different natural sources can vary significantly. This has an influence on their swelling behavior in water as well as in salt solutions, particularly when tactoid formation occurs, that is when divalent counterions are present in the system. A tactoid consists of a limited number of platelets aggregated in a parallel arrangement with a constant separation. The tactoid size increases with platelet size and with very small nanoplatelets, ∼30 nm, no tactoids are observed irrespectively of the platelet origin and concentration of divalent ions. The formation and dissociation of tactoids seem to be reversible processes. A large proportion of small nanoplatelets in a mixed-size system affects the tactoid formation, reduces the aggregation number and increases the extra-lamellar swelling in the system.

DOI: 10.1039/C5NR04615G

The local functionalities of biocompatible objects can be characterized under conditions similar to their operating ones by scanning electrochemical microscopy (SECM). In the case of alginate beads entrapping carbon nanotubes (CNTs), SECM allows evidencing the local conductivity, the organization, and the communication between CNTs. It shows that the CNTs network is active enough to allow long range charge evacuation, enabling the use of alginate/CNT beads as soft 3D electrodes. Direct connection or local interrogation by microelectrodes allows visualizing their communication as a network and eventually studying them individually at the nanoscale.

Two coarsening mechanisms of emulsions are well established: droplet coalescence (fusion of two droplets) and Ostwald ripening (molecular exchange through the continuous phase). Here a third mechanism is identified, contact ripening, which operates through molecular exchange upon droplets collisions. A contrast manipulated small-angle neutron scattering experiment was performed to isolate contact ripening from coalescence and Ostwald ripening. A kinetic study was conducted, using dynamic light scattering and monodisperse nanoemulsions, to obtain the exchange key parameters. Decreasing the concentration or adding ionic repulsions between droplets hinders contact ripening by decreasing the collision frequency. Using long surfactant chains and well-hydrated heads inhibits contact ripening by hindering fluctuations in the film. Contact ripening can be controlled by these parameters, which is essential for both emulsion formulation and delivery of hydrophobic ingredients.

DOI: 10.1002/anie.201407858

Cette thèse, menée en collaboration avec Michelin dans le cadre de la fabrication de matériaux composites, porte sur la stabilité colloïdale du latex de caoutchouc naturel (NR). Ce latex est une dispersion colloïdale polydisperse d’un polymère naturel dans un sérum aqueux. Les particules sont stabilisées par une couche complexe de phospholipides et de protéines. Cette dispersion peut être coagulée de façon irréversible par voie physique (sous cisaillement) ou par voie physico-chimique (ajout de cations divalents ou de particules hydrophobes). Dans ce travail, nous avons étudié la coagulation du latex par les cations divalents. Pour cela nous avons utilisé des outils physico-chimiques : diagrammes de stabilité en présence de divers cations, suivi cinétique de l’agrégation des particules et mesures rhéologiques. Ensuite, nous avons sondé la surface de particules de NR, par électrophorèse, en présence de tensioactifs et aussi selon la taille des particules. Pour expliquer la coagulation, nous suggérons que l’augmentation de la force ionique écrante les interactions répulsives et que les cations forment des ponts ioniques entre les particules. Ces ponts les maintiennent au contact et l’irréversibilité du phénomène est assurée par l’adhésion entre les chaines de polymères proches de la surface. L’adsorption des tensioactifs modifie la surface des particules et la coagulation du latex. Une légère différence de charge de surface a été observée entre les particules de NR selon leur taille. Enfin, un phénomène de coagulation similaire a été obtenu avec un latex synthétique, ce qui ouvre la voie à l’exploitation industrielle de ce phénomène de coagulation.
 

The actin cytoskeleton has the unique capability of producing pushing forces at the leading edge of motile cells without the implication of molecular motors. This phenomenon has been ex- tensively studied theoretically, and molecular models, including the widely known Brownian ratchet, have been proposed. However, supporting experimental work is lacking, due in part to hardly accessible molecular length scales. We designed an experiment to directly probe the mechanism of force generation in a setup where a population of actin filaments grows against a load applied by magnetic microparticles. The filaments, arranged in stiff bundles by fascin, are constrained to point toward the applied load. In this protrusion-like geometry, we are able to directly measure the velocity of filament elongation and its dependence on force. Using numerical simulations, we provide evidence that our experimental data are consistent with a Brownian ratchet-based model. We further demonstrate the existence of a force regime far below stalling where the mechanical power transduced by the ratcheting filaments to the load is maximal. The actin machinery in migrating cells may tune the number of filaments at the leading edge to work in this force regime.

Capsules having a thin alginate hydrogel membrane and an aqueous core can be obtained by a process that involves a co-extrusion step in air followed by a sol–gel transition of the shell after immersion into a gelling bath. The possibility to encapsulate cells that further grow in these biocompatible compartments, and thus offer a versatile tool for cell culture, led us to investigate the physicochemical properties of the capsules. A cut-off pore size of the semi-permeable membrane is extrapolated from the release of polymers out of the capsule. When polymers cannot diffuse through the membrane, the osmotic pressure mismatch between the core and the surrounding medium triggers an inflation of the capsule. The swelling may reach a steady state that allows the determination of the elastic features of the hydrogel shell. On the other hand, the capsule membrane may rupture and then contract. From this stress-relaxation process, a critical deformation of the hydrogel shell above which plasticity occurs can be deduced. Finally, thanks to the physical nature of the hydrogel, the core content can be released by dissolving the membrane with the help of small electrolytes. The shell life is shown to vary inversely with the ionic strength of the solution.

Les colloïdes sont utilisés dans de nombreuses applications médicales tels les agents de contraste en IRM ou l'immuno-agglutination magnétique dans le diagnostic. Pour en améliorer leurs performances, l'interaction entre les particules et les milieux biologiques – en particulier les protéines – a été étudiée depuis plus de 150 ans ; mais ce phénomène n'est toujours pas correctement décrit.
La première partie de cette thèse est dédiée à une des applications des colloïdes : la détection de protéines cible. Basée sur l’orientation d’agrégats magnétiques anisotropes, une nouvelle méthode a été mise au point, permettant de mesurer un signal d'agrégation uniquement proportionnel à la quantité de protéines à doser, la limite de détection est donc abaissée. Cette technique a été validée sur un système réel : la protéine C-réactive.
La seconde partie de cette thèse est consacrée à l’adsorption des protéines sur les colloïdes. Le premier objectif a été la mise au point d'un protocole de mesure capable de fournir des données fiables ; l'adsorption a ainsi pu être caractérisée sur un système modèle, l'albumine de sérum bovin sur la silice. Les mesures obtenues ont ainsi permis de lever certains paradoxes et de proposer un nouveau modèle d’adsorption.
Enfin, ces  connaissances ont permis de comprendre comment des protéines, en s’adsorbant sur deux particules, agrègent les colloïdes. En quantité suffisante, elles peuvent également les protéger de l’agrégation, ouvrant la voie à une nouvelle méthode de stabilisation des particules.

Lipid nanocapsules (LNCs) and lipid nanoemulsions (LNEs) are biomimetic synthetic nanocarriers. Their in vitro and in vivo performance was evaluated as a function of their size (25, 50 and 100 nm) and the surface PEG chain length. Analysis methods included complement activation test, particle uptake in macrophage and HEK293(beta 3) cells and biodistribution studies with tumor-grafted mice by fluorescence imaging. A particular attention was paid to keep the concentration of each nanocarrier and to the amount of fluorescent dye in comparable conditions between the in vitro and in vivo studies. Under these conditions, no significant differences were found among the three tested particle sizes and the two nanocarrier types. Longer PEG chains on the LNE surface provided better stealth properties, whereas PEG modification on the LNC formulations inhibited the production of stable nanocarriers. Passive accumulation of LNCs and LNEs in different tumor types depended on the degree of tumor vascularization.

Synopsis Dermo-pharmacy and cosmetic industries have utilized nanotechnologies for two decades. Initially proposed as vector systems for encapsulation of actives, they gained interest in increasing cutaneous bioavailability. Here, we assay the benefits of self-assembled nanoemulsions bearing ligands for targeting specific skin cells. Nanoemulsions, small droplets ranging typically from 20nm to 150nm, possess key properties for further use in cosmetics: long-term stability, optical transparency, extended range of textures and versatility. We investigated this nanoemulsion system and show ability to encapsulate a range of cosmetic actives with various physicochemical properties. Furthermore, this nanoemulsion presents a low cytotoxicity and is capable of directly targeting skin cells through simple addition of specific ligand in a one-step production protocol. This is of interest for increasing bioavailability of actives encapsulated into nanoemulsion droplets which may have penetrated the skin barrier to specific skin cell. Taken together, these chemical and in vitro observations suggest follow-up with in vivo models. Resume L'utilisation des nanotechnologies en cosmetique et en dermo-pharmacie a commencee il y a vingt ans. Initialement simples vecteurs pour l'encapsulation d'actifs, de nombreux systemes nanoparticulaires ont ete developpes afin d'ameliorer la biodisponibilte cutanee des actifs. Dans notre etude nous proposons un systeme de nanoemulsion pour le ciblage specifique de certaines cellules cutanees, dont les gouttelettes presentent des ligands auto-assembles en surface. Les nanoemulsions, dont la taille des gouttelettes varie entre 20 et 150nm, offrent de nombreux avantages dans leur utilisation en cosmetique: une stabilite prolongee, une transparence optique, une texture modifiable et une polyvalence d'emploi. Nous avons effectivement demontre la possibilite d'utiliser ces nanoemulsions afin d'encapsuler des actifs ayant des proprietes physicochimiques differentes, sans affecter la stabilite du systeme. De plus, ces nanoemulsions presentent une cytotoxicite minime et sont capables de cibler specifiquement certaines cellules cutanees par simple ajout de ligands specifiques lors de leur production en une etape. Ces nanoemulsions offrent un interet majeur dans l'amelioration de la biodisponibilite des actifs encapsules en concentrant les gouttelettes ayant traversees la barriere cutanee sur les cellules cibles. Les caracteristiques physico-chimiques ainsi que les observations in vitro realisees dans cette etude encouragent a tester ces nanoemulsions sur modele in vivo.

Deciphering the multifactorial determinants of tumor progression requires standardized high-throughput preparation of 3D in vitro cellular assays. We present a simple microfluidic method based on the encapsulation and growth of cells inside permeable, elastic, hollow microspheres. We show that this approach enables mass production of size-controlled multicellular spheroids. Due to their geometry and elasticity, these microcapsules can uniquely serve as quantitative mechanical sensors to measure the pressure exerted by the expanding spheroid. By monitoring the growth of individual encapsulated spheroids after confluence, we dissect the dynamics of pressure buildup toward a steady-state value, consistent with the concept of homeostatic pressure. In turn, these confining conditions are observed to increase the cellular density and affect the cellular organization of the spheroid. Postconfluent spheroids exhibit a necrotic core cemented by a blend of extracellular material and surrounded by a rim of proliferating hypermotile cells. By performing invasion assays in a collagen matrix, we report that peripheral cells readily escape preconfined spheroids and cell–cell cohesivity is maintained for freely growing spheroids, suggesting that mechanical cues from the surrounding microenvironment may trigger cell invasion from a growing tumor. Overall, our technology offers a unique avenue to produce in vitro cell-based assays useful for developing new anticancer therapies and to investigate the interplay between mechanics and growth in tumor evolution.

Ce travail de thèse concerne l'étude des propriétés physico-chimiques de capsules millimétriques à cœur liquide possédant une membrane fine d'hydrogel d'alginate.
Nous avons dans un premier temps caractérisé le transport de molécules à travers la coque d'hydrogel et estimé le rayon de coupure de cette membrane semi-perméable. De plus, il est possible de limiter la fuite de petits solutés hydrophiles en ajoutant une couche hydrophobe entre le cœur aqueux et la membrane d'alginate. Nous démontrons alors que le temps caractéristique de fuite est déterminé par la géométrie du système (épaisseur de la couche hydrophobe et rayon de la capsule) ainsi que la solubilité et le coefficient de diffusion du soluté dans la phase huileuse.
D'autre part, le gonflement d'une capsule soumise à une différence de pression osmotique nous a permis d'identifier les régimes viscoélastique et viscoplastique de la membrane sous étirement. Nous en déduisons un module élastique de l'hydrogel, qui diminue au-delà du seuil de plasticité. A contrario, lors de la compression de capsules, l'hydrogel est concentré par expulsion irréversible de l'eau, ce qui entraîne une rigidification de sa structure.
Enfin, nous nous sommes intéressés à l'écoulement d'une suspension concentrée de capsules à coeur huileux dans l'eau. Il existe une friction entre les capsules qu'il est possible de contrôler par ajout de tensioactif. Nous avons donc étudié son rôle dans l'écoulement de capsules dans une constriction de type sablier. Ainsi, nous démontrons que le flux est constant et qu'il ne dépend pas de la friction, mais qu'il est fixé par la taille de l'étranglement. En effet, l'écoulement est uniquement déterminé par l'hydrodynamique en phase fluide dans le col du sablier.

Dry skin concerns many individuals, conferring discomfort and even impacting the lives of those severely affected. However, in most cases it can be adequately managed with current moisturizing products.¹

Glycerol is one humectant commonly employed due to its high hygroscopic and hyperosmotic properties. It is used in cosmetics as a moisturizer and in pharmaceutical formulations as an active compound.² Being naturally present in the skin, glycerol was quickly identified for its role in skin hydration, similar to natural moisturizing factors (NMF). A byproduct of triglyceride lipolysis, it is transported from the dermis through keratinocytes by a transmembrane water/glycerol transporting protein, aquaporin 3.^{3, 4}

Glycerol also protects skin against irritant dermatitis and accelerates the recovery of irritated skin.^{5, 6} One in vivo study by Flurh et al.⁷ assumes that the stimulus for barrier repair occurs through water flux due to the hygroscopic properties of glycerol. Likewise, most studies about skin barrier recovery are performed with relatively high concentrations of glycerol, e.g., from 5% to 50%, often dispersed in an emulsion.

The question arises as to whether glycerol acts solely through its hygroscopic properties or implies more specific mechanisms. Indeed, diglycerol and triglycerol, with higher humectant activity, have demonstrated low improvements in skin dryness, compared with glycerol.⁸ Also, one in vivo attempt has been made to characterize the effects of low glycerol doses, e.g. from 1% up to 10%, on water transport through the skin after acute chemical irritation by sodium lauryl sulfate (SLS).⁹ The present article therefore summarizes and clarifies the benefit of glycerol on irritated skin.

Lipid nanoparticles, based on nanoemulsion templates, are interesting candidates for contrast agent and active ingredient transport and delivery due to their small size, biodegradable nature and high versatility. An optimized nanosystem for drug delivery should present an important encapsulation ratio, as well as controlled release kinetics. In this context, the influence of the lipid nanoparticle core composition on the encapsulation and release behavior of the Nile Red fluorophore, used as a model molecule of intermediate lipophilicity, is explored. For that purpose, the lipid nanoparticle physical state, the encapsulated molecule localization, and the encapsulation/release behavior are studied. Careful characterization of lipid nanoparticles is performed by DSC and 1H NMR analysis.Nile Red localization is evaluated by complementary fluorescence spectroscopy and 1H NMR techniques. The encapsulation of Nile Red is governed and limited by its solubility in the lipids. A double localization of the fluorophore at the membrane and in the particle core is observed, resulting in a two-phase release kinetics: a quick burst release, followed by a slow prolonged release. Adding wax to the formulation increases the lipid nanoparticle internal viscosity while favoring Nile Red localization in the core, which results in slower release kinetics.

The incorporation of mineral particles into a polymer matrix leads to extra properties of the polymeric material that are linked to the homogeneity of the mixture. A fine homogeneity can be obtained by using a latex route where the two components are first dispersed in water and then dried. Here, we show a novel way to make an elastomeric composite material via a bulk destabilization of a binary colloidal dispersion. The mixture is composed of a natural rubber latex, which is naturally stabilized, and carbon black particles that are dispersed in water with the help of surfactants. We observe either a transition towards a weak gel, which is a reversible state, or a transition towards an irreversible elastic solid. These structural transitions are mainly controlled by the surfactant concentration that tunes the interaction between natural rubber and carbon black particles, the latter bridging polymer droplets together. We also show that the weak gel can become an irreversible elastic solid under a high shear. This shearinduced heteroaggregation phenomenon exhibits the features of a thermally activated process.

Les colloïdes superparamagnétiques sont utilisés dans de nombreuses études pour appliquer une force sur des cellules ou des molécules d’ADN. Dans une première partie, nous explorons le processus physique par lequel ces objets acquièrent une aimantation leur permettant d’exercer des forces. Nous montrons comment la présence de quelques gros grains ferromagnétiques dans les colloïdes leur permet de s’orienter dans un champ externe. La robustesse de ce modèle est démontrée par sa généralisation à plusieurs tailles de colloïdes et sa cohérence avec les propriétés du ferrofluide ayant servi à les fabriquer. Dans une seconde partie, la réaction de filaments d’actine à la pression exercée par des colloïdes superparamagnétiques est étudiée. Nous sondons ainsi le mécanisme par lequel la polymérisation d’actine peut générer les forces à l’origine du phénomène de motilité cellulaire. La maîtrise de l’organisation des filaments autorise à étudier deux situations idéales. Dans l’une les filaments sont très fluctuants, et nous montrons que leur longueur est indépendante de la force appliquée. Ceci n’est plus vrai dans la deuxième situation, où les filaments rigides poussent face à la charge. Nous mesurons ainsi pour la première fois l’eet d’une force sur la vitesse de polymérisation de l’actine. Un modèle numérique de type Brownian ratchet sans partage de la charge permet de décrire la force générée.

Lipid nanoparticles (LNP) have been designed based on low cost and human-use approved excipients, and manufactured by an easy, robust, and up-scalable process. Fluid colloidal dispersions or gel viscous formulations of highly stable nanoparticles (more than 12 month stability is achieved for some formulations) can be obtained. Their physicochemical properties are studied by Dynamic Light Scattering, Differential Scanning Calorimetry, and NMR. The results picture nanoparticles with a non-crystalline core, which viscosity can be finely tuned by the lipid composition and the temperature. A design of experiments has been used to investigate the limits of the system colloidal stability. The impact of core and surfactant weight fractions have been explored both experimentally and using the design of experiments. The versatility of this physicochemical system could open the way to a wide range of future pharmaceutical applications.

Liquid pearls designate liquid core capsules having a thin elastic shell.

Practical and theoretical considerations that apply when aiming to formulate by ultrasonication very small nanoemulsions (particle diameter up to 150 nm) with very high stability are presented and discussed. The droplet size evolution during sonication can be described by a monoexponential function of the sonication time, the characteristic time scale depending essentially on the applied power. A unique master curve is obtained when plotting the mean diameter size evolution as a function of sonication energy. We then show that Ostwald ripening remains the main destabilization mechanism whereas coalescence can be easily prevented due to the nanometric size of droplets. The incorporation of “trapped species” within the droplet interior is able to counteract Ostwald ripening, and this concept can be extended to the membrane compartment. We finally clarify that nanoemulsions are not thermodynamically stable systems, even in the case where their composition lies very close to the demixing line of a thermodynamically stable microemulsion domain. However, as exemplified in the present work, nanoemulsion systems can present very long-term kinetic stability.

Les tests de diagnostic ont pour but de détecter et de quantifier un ou plusieurs analytes en milieu complexe. Depuis les années 80, leur évolution s'est concentrée sur la détection de très faibles quantités d'analytes. Actuellement, cette ligne directrice subsiste mais en parallèle les développements se portent sur de nouveaux objectifs comme la mise au point de tests simples, rapides, transportables et sensibles afin de répondre au mieux aux attentes des nouveaux marchés : le point of care et les pays émergents. Au cours de ce travail, nous nous sommes confrontés à ces nouvelles problématiques. Nous avons choisi d'améliorer la sensibilité du test d'agglutination magnétique précédemment développé au laboratoire en raison de sa simplicité (test homogène) et de sa rapidité (manipulation de billes magnétiques). Nous avons montré que deux paramètres conditionnaient le seuil de détection de ce test à savoir le bruit (variabilité du signal sans antigène) et le signal émis par les billes. Le premier facteur dépend principalement du nombre de billes et le deuxième nous a amené à travailler avec de grandes billes nécessitant une nouvelle méthode de détection, la cytométrie en flux. Le gain en sensibilité n'a pas été clairement démontré en raison de la très faible réactivité des billes utilisées (500 fois moins réactives que les billes "habituelles"). Une chose est sûre, de grandes billes améliorent le signal, la cinétique et la thermodynamique au détriment d'une plus faible mobilité des objets sous champ. Sous couvert d'une bonne réactivité, nous nous sommes aperçus que la première étape de notre test d'agglutination devenait thermodynamiquement et cinétiquement limitante aux faibles concentrations en analyte. Dans le cadre du projet européen DetectHIV, nous avons essayé d'une part de franchir ces barrières à travers un système microfluidique et d'autre part de mettre au point un test complètement intégré. De nouvelles technologies ont vu le jour à l'EPFL (plug magnétique) et à DTU (cytométrie sur puce). Le système développé par l'EPFL est thermodynamiquement favorable, valide l'idée de préconcentration mais nécessiterait un nouveau dimensionnement fluidique pour réellement supplanter les tests en volume. L'intégration, quant à elle, a permis d'acquérir un certain savoir faire dans le domaine de la microfluidique, d'identifier les verrous technologiques et de développer un nouveau mode de circulation des fluides. Pour conclure, ce travail a permis de cerner l'évolution possible des tests d'agglutination magnétique. La sensibilité du test originel c'est-à-dire en volume couplé à une détection turbidimétrique est fixée par le bruit de l'appareil de mesure. Ce paramètre étant peu optimisable, seule une augmentation de la taille des billes permettrait d'augmenter significativement la sensibilité du test (un facteur 10 en théorie). Au delà, une détection individuelle des objets via la cytométrie est nécessaire. D'une part, elle permet de travailler avec de gros objets afin d'amplifier grandement le signal et d'autre part, elle permet de s'affranchir du bruit de l'appareil de mesure. Le bruit mesuré est uniquement dû à la comptabilisation des populations, bruit inhérent au test de diagnostic. Avec cette configuration, un gain de sensibilité passe par une diminution du non-spécifique (relatif au comptage des populations) et par une augmentation de la réactivité des "grosses" billes. En dessous de la dizaine de femtomoles, la formation de complexe n'est plus assurée et devient longue, un changement de format fluidique est alors nécessaire. Le nouveau format fluidique testé, la microfluidique, s'avère très prometteur à condition d'intégrer une méthode de détection (cytométrique ou autre) et d'augmenter les débits.

L'invention décrit un procédé pour isoler un ou plusieurs éléments génétiques codant pour un produit de gène ayant une activité désirée, comprenant les étapes suivantes: (a) compartimenter les éléments génétiques dans des microcapsules, et (b) trier les éléments génétiques qui expriment le produit du gène ayant l‘activité désirée, où au moins une étape est sous contrôle microfluidique. L'invention permet l'évolution in vitro des acides nucléiques et des protéines par mutagenèse répétée et des applications itératives de la méthode de l'invention.

Gratiam enim amicos si simulatione dixisse tum quos quos se tum ut habuisset dumtaxat fit se plerumque posset Coluntur ut.

Lipid nanoparticles (LNP) coated by a poly(oxyethylene) polymer have been manufactured from low cost and human use-approved materials, by an easy, robust, and up-scalable process. The incorporation in the formulation of maleimide-grafted surfactants allows the functionalization of the lipid cargos by targeting ligands such as the cRGD peptide binding to avb3 integrin, a well-known angiogenesis biomarker. LNP are able to encapsulate efficiently lipophilic molecules such as a fluorescent dye, allowing their in vivo track- ing using fluorescence imaging. In vitro study on HEK293(b3) cells over-expressing the avb3 integrins demonstrates the functionalization, specific targeting, and internalization of cRGD-functionalized LNP in comparison with LNP-cRAD or LNP-OH used as negative controls. Following their intravenous injection in Nude mice, LNP-cRGD can accumulate actively in slow-growing HEK293(b3) cancer xenografts, leading to tumor over skin fluorescence ratio of 1.53 ± 0.07 (n = 3) 24 h after injection. In another fast-growing tumor model (TS/A-pc), tumor over skin fluorescence ratio is improved (2.60 ± 0.48, n = 3), but specificity between the different LNP functionalizations is no more observed. The different results obtained for the two tumor models are discussed in terms of active cRGD targeting and/or passive nanoparticle accumu- lation due to the Enhanced Permeability and Retention effect.

Lipid nanocapsules (LNCs) were modified by adsorbing sequentially dextran sulfate (DS) and chitosan (CS) on their surface by the layer-by-layer (LBL) approach. Tangential flow filtration (TFF) was used in intermediate purifications of the LNC dispersion during the LBL process. The surface modification was based on electrostatic interactions between the coating polyelectrolytes (PEs) and the LNCs. Therefore, a cationic surfactant, lipochitosan (LC), was synthesised by coupling stearic anhydride on chitosan, and the surface of LNCs was first modified by this LC by the post-insertion technique. The PEs could be successfully adsorbed on the LNC surface as verified by alternating zeta potential and increase in size. To present a therapeutic application, fondaparinux sodium (FP), a heparin-like synthetic pentasaccharide, was introduced on the LNC surface instead of DS.

We report an experimental investigation on the formation of liquid-core capsules having a thin hydrogel elastic membrane, named ‘liquid pearls’. These fish-egg-like structures are initially made of a millimetric liquid drop, aqueous or not, coated with an aqueous liquid film containing sodium alginate that gels once the double drop enters a calcium chloride bath. The creation of such pearls with a micrometer-thick membrane requires the suppression of mixing until gelling takes place. Here, we show that superimposing a two-dimensional surfactant precipitation at the interface confers a transient rigidity that can damp the shear-induced instability at impact. Based on this, pearls containing almost any type of liquid can be created. This opens the possibility to use such structures as a new tool for screening microorganism survival and growth in various three-dimensional environments.

Fluorescence is a very promising radioactive-free technique for functional imaging in small animals and, in the future, in humans. However, most commercial near-infrared dyes display poor optical properties, such as low fluorescence quantum yields and short fluorescence lifetimes. In this paper, we explore whether the encapsulation of infrared cyanine dyes within the core of lipid nanoparticles (LNPs) could improve their optical properties. Lipophilic dialkylcarbocyanines DiD and DiR are loaded very efficiently in 30-35-nm-diam lipid droplets stabilized in water by surfactants. No significant fluorescence autoquenching is observed up to 53 dyes per particle. Encapsulated in LNP, which are stable for more than one year at room temperature in HBS buffer (HEPES 0.02 M, EDTA 0.01 M, pH 5.5), DiD and DiR display far improved fluorescence quantum yields Phi (respectively, 0.38 and 0.25) and longer fluorescence lifetimes tau (respectively, 1.8 and 1.1 ns) in comparison to their hydrophilic counterparts Cy5 (Phi = 0.28, tau = 1.0 ns) and Cy7 (Phi = 0.13, tau = 0.57 ns). Moreover, dye-loaded LNPs are able to accumulate passively in various subcutaneous tumors in mice, thanks to the enhanced permeability and retention effect. These new fluorescent nanoparticles therefore appear as very promising labels for in vivo fluorescence imaging.

Biotechnological applications of emulsions, such as micro-reactors or drug carriers, demand accurate characterization techniques, able to measure the size and biochemical content of the droplets at the individual level. Since no available characterization technique completely fulfills these needs, we extended the use of flow cytometry, which was originally developed for cell studies, to the straightforward and quantitative characterization of micron-sized emulsions. Our method determines the size of soybean oil droplets from flow cytometric measurements of forward scattering and side scattering intensities combined with the theoretical scattered intensities exactly derived from Mie theory and numerically integrated with respect to the optical setup of the instrument. We evaluate the accuracy of our method by comparing the size distribution obtained for a monodisperse emulsion sample to the corresponding distribution measured with a commercial instrument. Applied to emulsion droplets functionalized with fluorescent streptavidin, our method allows for monitoring of the rate of grafted molecules on interfaces with a precision never obtained before.

Chirality is an important element of biology, chemistry and physics. Once symmetry is broken and a handedness is established, biochemical pathways are set. In DNA, the double helix arises from the existence of two competing length scales, one set by the distance between monomers in the sugar backbone, and the other set by the stacking of the base pairs1. Here we use a colloidal system to explore a simple forcing route to chiral structures. To do so we have designed magnetic colloids that, depending on both their shape and induced magnetization, self-assemble with controlled helicity. We model the two length scales with asymmetric colloidal dumbbells linked by a magnetic belt at their waist. In the presence of a magnetic field the belts assemble into a chain and the steric constraints imposed by the asymmetric spheres force the chain to coil. We show that if the size ratio between the spheres is large enough, a single helicity is adopted, right or left. The realization of chiral colloidal clusters opens up a new link between colloidal science and chemistry. These colloidal clusters may also find use as mesopolymers, as optical and light-activated structures2, and as models for enantiomeric separation.

Plusieurs mécanismes biologiques utilisent la polymérisation des filaments d’actine comme moteur mécanique. L’énergie chimique libérée à l’addition d’un monomère dans le filament est convertie en travail mécanique et une force est générée. Les filaments ainsi formés s’organisent grâce à des protéines liant l’actine et forment des structures qui diffèrent par leurs propriétés mécaniques et élastiques mais aussi de leurs fonctions dans les différents processus biologiques. Notre système expérimental permet d’étudier le lien entre les propriétés mécaniques et les mécanismes à l’origine de la production de la force. La polymérisation des filaments est directement initiée sur la surface de particules magnétiques. En présence d’un champ magnétique, ces dernières s’organisent en chaîne par des interactions dipôle-dipôle, et une force magnétique compressive est induite sur les filaments qui polymérisent. La polymérisation écartent les particules au cours du temps et en fonction de la force appliquée, la vitesse d’écartement des particules est ralentie. En suivant l’évolution de la distance entre particules, nous détaillons la relation force-vitesse et les propriétés mécaniques des filaments.

La nanomédecine représente le champ d’application des nanotechnologies, et plus
particulièrement des nanoparticules, à la médecine. Ce nouveau domaine est très prometteur
notamment en ce qui concerne la détection et le traitement de pathologies d’origine
infectieuse, génétique ou cancéreuse. Nous avons développé de nouvelles nanoparticules
biocompatibles et évalué leur potentiel en tant que nanocargos d’agents thérapeutiques ou
diagnostiques grâce à l’imagerie de fluorescence in vivo. Ces particules sont des nanoémulsions
de type huile dans eau, de quelques dizaines de nanomètres de diamètre, stabilisées
par une couche de surfactants composée de phospholipides et d’agents de furtivité.
L’encapsulation dans le coeur des nanoparticules de fluorophores organiques absorbant et
émettant dans les longueurs d’onde compatibles avec les dispositifs d’imagerie de
fluorescence permet de suivre leur biodistribution après injection dans des souris Nude. Ces
nano-émulsions furtives et fluorescentes peuvent également être fonctionnalisées sur leur
surface par des ligands de ciblage actifs tels que le peptide cRGD. De telles nano-émulsions
fonctionnalisées montrent in vitro une adhésion spécifique avec les cellules exprimant
l’intégrine αvβ3, un biomarqueur de l’angiogénèse. L’accumulation, passive et/ou active
médiée par les cRGD, des particules au sein de différents modèles de tumeurs sous-cutanées
implantés chez la souris Nude, est observée par imagerie de fluorescence non invasive.

Le travail de recherche exposé dans cette thèse, montre dans la premier partie la mise en oeuvre de la méthode d'émulsification pour la préparation de petits agrégats de forme anisotrope monodisperse et de forme géométrique bien définie et on a montré que la maîtrise des paramètres de la formulation permet la sélection et la production d'un maximum d'agrégats de formes données (dimère, trimère, tétramère). On a montré la faisabilité et la possibilité d'assembler tête-tête les différents types d'agrégats de façon organisée et directionnelle, grâce à la fonctionnalisation des têtes des agrégats, avec des fonctions réactives utilisant la force d'adhésion spécifique (couple biotine/streptavidine). En deuxième partie, on a fait intervenir des forces magnétiques pour forcer et accélérer le processus d'assemblage par rapport à des forces spécifiques qui sont basées sur les effets de diffusion ; on a montré la formation de chaînes colloïdales de structure variable avec la mise en évidence des effets de relaxation sur les chaînes, rotation et torsion, qui dépendent de l'intensité de champ appliqué et de la morphologie des particules (Janus avec une partie magnétique, doublets avec un anneau). Enfin, nous avons conçu des doublets asymétriques avec des anneaux magnétiques qui engendrent la formation de chaînes chirales sous forme d'hélice. Et on a mis en évidence l'analogie entre les colloïdes et les macromolécules sur le plan structural par un simple auto-assemblage.

Le domaine de l’évolution dirigée regroupe des approches technologiques s’inspirant, en laboratoire et à l’échelle moléculaire, de l’évolution Darwinienne. Grâce à des algorithmes moléculaires stochastiques, on peut ainsi améliorer des protéines existantes ou même créer de nouvelles protéines. Dans une première partie, les différentes façons de générer de la diversité génétique sont introduites, ainsi que notre contribution au développement d’une technologie de mutagenèse dirigée très haut débit (MM). En particulier, deux variants deMMsont présentés :MMC, une méthode utilisant de très larges banques d’oligonucléotides synthétisés en parallèle sur des puces à ADN et MMS, une méthode de recombinaison in vitro circulaire simple et efficace. Dans une deuxième partie, après avoir rappellé les différentes modalités de tri des protéines améliorées, on présente notre contribution au domaine naissant et prometteur du criblage haut-débit en émulsion d’activité catalytique . On décrit les premières étapes de la validation d’une méthode de criblage bidimensionnel d’une émulsion inverse cristallisable. Appliquée à l’évolution moléculaire, cette nouvelle technologie pourrait permettre d’augmenter de plusieurs ordres de grandeur le débit des meilleures techniques actuelles par cytométrie de flux. Sont également évoquées, dans une troisième partie, d’autres applications de cette technique de criblage à plat d’émulsions cristallisées dans le domaine du diagnostic et pour l’analyse du cycle cellulaire

We describe a six-step method for making colloidal clusters of 2, 3, or 4 silica particles with a radius of 1.2 um. This method, originally described by Manoharan et al. (Manoharan, V. N.; Elsesser, M. T.; Pine, D. J. Science 2003, 301, 483), is based on the encapsulation of silica spheres in emulsion droplets. The originality of our work lies in the preparation of monodisperse emulsions, which allows us to obtain some high yields of small aggregates over a wide range of conditions. Using optical microscopy and disk centrifugation, we show that the relative fractions of 2, 3, and 4 particle aggregates are controlled by the emulsification conditions, particularly the concentration of silica in the dispersed phase. Our best yields are obtained using low to moderate shear rates, a highly viscous continuous phase, and intermediate amounts of silica. The sedimentation of the colloidal solution into a gradient of concentration leads to aqueous suspensions of identical clusters. Since the overall process can easily be scaled up, large quantities of identical clusters may be prepared, which should allow the thermodynamic properties of these new colloidal objects to be measured for the first time. These nonspherical particles could serve as building blocks for more complex assemblies, such as colloidal crystals which could find applications as photonic materials.

Ce manuscrit présente une étude des cinétiques de réactions ligand-récepteur sur des surfaces en regard, fondée sur l'utilisation de particules magnétiques colloïdales. Notre démarche repose sur la mesure de cinétiques de formation de doublets indépendants de particules, déclenchée par l'application d'un champ magnétique. Ces mesures sont directement reliées aux constantes cinétiques du couple ligand-récepteur à la surface des particules magnétiques. En considérant le couple streptavidine-biotine, nous avons validé notre approche et mis en évidence une source de variabilité des constantes d'association en surface : le degré de confinement des réactifs sur les surfaces. Pour les configurations les plus rapides, nous avons appréhendé la constante d'association comme limitée par des processus de diffusion, associés à la dynamique des particules colloïdales. Pour les configurations les plus lentes, où les réactifs sont les plus confinés en surface, le ralentissement observé est attribué à une diminution de l'efficacité des rencontres entre réactifs. Nous avons également étudié la cinétique d'association entre cadhérines, molécules directement impliquées dans l'adhésion cellulaire. Nous avons mis en évidence l'influence des conditions de contact sur l'état d'adhésion entre cadhérines. Pour les deux états d'adhésion « profonds » observés, nous avons mesuré une constante cinétique d'association plus lente que celle de l'interaction streptavidine-biotine.

Nous avons exploré la capacité des émulsions à adhérer de manière spécifique à des surfaces modèles solides et notamment la relation entre la composition des gouttes à leur interface et la formation d'un angle de contact macroscopique. Nous avons développé une méthode de fonctionnalisation covalente in-situ de l'interface liquide de gouttes d'émulsion H/E par de la biotine puis par de la streptavidine. La distribution de taille et la densité de streptavidine à la surface des gouttes sont caractérisées à l'aide d'une technique originale utilisant un cytomètre à flux. Nous avons montré que l'angle de contact et l'énergie d'adhésion croissent linéairement en fonction de la densité de biotine sur la lamelle et nous avons observé une répartition spatiale différente (disque, couronne) de la streptavidine dans la zone de contact suivant la densité totale en PEG, suggérant une transition de phase à 2D.

Ce manuscrit présente l'étude de la stabilité et des propriétés d'encapsulation et de relargage des émulsions doubles cristallisables. Notre démarche a été de remplacer l'huile liquide classiquement utilisée pour les émulsions doubles par une huile solide à température ambiante. Une barrière répulsive stérique assure la stabilité de ces objets au repos. Sous écoulement, les objets s'agrègent : l'énergie fournie par le cisaillement réduit la barrière répulsive alors comparable à kT et facilement franchissable. Ceci se traduit par une dépendance exponentielle du temps caractéristique d'agrégation avec le taux de cisaillement. Sous régime iso-osmotique, la nature solide de la membrane ralentit les cinétiques de libération par diffusion des espèces initialement encapsulées. Sous régime hypo-osmotique, le matériau solide libère rapidement l'espèce encapsulée. Les processus mis en jeu et les différents paramètres permettant de contrôler les cinétiques de libération ont été identifiés.

La présente invention concerne un procédé de synthèse de composés comprenant les étapes consistant: (a) à répartir au moins deux ensembles de composés primaires dans des microcapsules de façon qu'une certaine proportion de ces microcapsules contienne au moins deux composés; et (b) à former des composés secondaires dans les microcapsules au moyen de réactions chimiques réalisées entre des composés primaires de différents ensembles, l'étape (a) et/ou (b) étant mise(s) en oeuvre sous contrôle microfluidique, de préférence sous contrôle microfluidique électronique. Cette invention permet également d'identifier des composés qui se lient à un composant cible d'un système biochimique ou qui modulent l'activité de la cible et qui sont co-répartis dans des microcapsules.

L'invention concerne une méthode d'identification de composés qui se lient à un composé cible d'un système biochimique ou modulent l'activité de la cible. Ladite méthode consiste à a) compartimenter les composés dans des microcapsules avec la cible, de telle manière que seul un sous-ensemble du répertoire est représenté dans plusieurs copies dans une des microcapsules, et b) identifier le composé qui se lie ou module l'activité de la cible, au moins une étape étant réalisée sous régulation microfluidique. Ladite invention a aussi pour objet le criblage de répertoires importants de molécules qui peuvent servir de fils au développement de médicaments.

We demonstrate here the wet chemical synthesis of cobalt doped γ-Fe₂O₃ nanoparticles and the subsequent effect on magnetic properties with the variation in dopant concentration. It is observed that cobalt can be homogeneously doped into the γ-Fe₂O₃ lattice up to 5 mol% without any appreciable change in the particle size (~6 nm). Further increase in cobalt concentration (10 mol% here) resulted in an increase in particle size (~9 nm) due to possible adsorption of a cobalt layer on the surface of γ-Fe₂O₃ nanoparticles rather than complete doping in the iron oxide lattice. The ac susceptibility measurements revealed an increase in blocking temperature (T_B) with percentage variation in cobalt doping (2–10%), indicating substitution of Fe³⁺ ions by Co²⁺ ions in the γ-Fe₂O₃ lattice. The dc magnetization measurements showed an increase in saturation magnetization only up to 5%, beyond which it significantly diminished. The reduction in saturation magnetization is attributed to the contribution from surface anisotropy in cobalt coated γ-Fe₂O₃ nanoparticles.

We perform oil coating of hydrophobic solid surfaces via aqueous media, from emulsions, and under the presence of a shear flow. The principle of such coating is based on the use of a system at the limit of aggregation to give rise to adhesion, with asymmetrical interfaces (oil droplet/water and solid surface/water) in order to favor the oil/surface adhesion in comparison to the oil/oil adhesion. This way, droplets stick to the solid substrate, whereas they are stable and homogeneously dispersed in the bulk. We have realized coatings from two systems of emulsions made of a mixture of hydroxy-terminated silicone oil and classical silicone oil and a mixture of sunflower oil and mineral oil. The kinetics of the coating is described by a Langmuir model where the adhesion between the oil particle and the surface is modeled as a first-order reaction. The resulting coatings are formed of oil droplets uniformly covering the solid surface. The coating density can vary with the nature of the experimental systems.

In this letter, we investigate the mechanism of formation of a recently discovered new type of colloid, irreversible flexible chains of magnetic particles. The chain formation mechanism is based on magnetically induced bridging by adsorbed polymers, andweinvestigate here the associated phase diagrams, considering both thermodynamic and kinetic aspects. This phase diagram is the consequence of a balance between entropic repulsion between polymer layers at the particles surfaces, depletion forces pushing the particles together, and a short-range attractive force developing when polymers can bridge two particles. We end up with a very simple protocol allowing the formation of long, extremely regular chains, which can find numerous applications in chemistry and biology. The perspectives for the development of a new field of “macrocolloidal chemistry” are discussed.

Silica particles are dispersed in the continuous phase of bitumen-in-water emulsions. The mixture remains dispersed in quiescent storage conditions. However, rapid destabilization occurs once a shear is applied. Observations under the microscope reveal that the bitumen droplets form a colloidal gel and coalesce upon application of a shear. We follow the kinetic evolution of the emulsions viscosity at constant shear rate remains initially constant and exhibits a dramatic increase after a finite time, t. We study the influence of various parameters on the evolution of t: bitumen droplet size and volume fraction, silica diameter and concentration, shear rate, etc.

Oils containing both fluorescent semiconductor and magnetic oxide nanoparticles are used to produce oil in water emulsions. This technique produces oil droplets with homogeneous fluorescence and high magnetic nanoparticle concentrations. The optical properties of the oil droplets are studied as a function of the droplet sizes for various concentrations of fluorescent and magnetic nanoparticles. For all concentrations tested, we find a linear variation of the droplet fluorescent intensity as a function of the droplet volume. For a given size and a given quantum dot (QD) concentration, the droplet fluorescence intensity drops sharply as a function of the magnetic nanoparticle concentration.Weshow that this decrease is due mainly to the strong absorption cross section of the magnetic nanoparticles and to a lesser extent to the dynamicandstatic quenching of theQDfluorescence.Therole of the iron oxide nanoparticle localization in the droplet (surface versus volume) is also discussed.

Ce mémoire contient deux parties consacrées à deux applications des chaînes de particules magnétiques.
Le premier chapitre décrit la conception d'un capteur de forces intercolloïdales. Nous présentons différentes expériences permettant de caractériser les particules utilisées. Nous décrivons ensuite la réalisation du montage expérimental et le traitement des données. Enfin, nous comparons cette technique aux autres techniques.
Le second chapitre décrit la conception et la réalisation de nageurs à l'échelle microscopique. Nous fabriquons des filaments magnétiques flexibles en alignant des particules sous l'effet d'un champ magnétique. Les particules adjacentes sont reliées par des agents pontants. Nous avons étudié le comportement de ces filaments sous champ. Sous l'effet d'un champ magnétique oscillant, le filament se déforme : une onde se propage alors le long du filament, ce qui engendre une force propulsive, dont nous démontrons l'effet sur un nageur spermatomorphe. Enfin, nous vérifions des prédictions théoriques antérieures.

L'invention concerne une composition comprenant une phase lipidique monodisperse dispersée dans une phase aqueuse continue, dans laquelle la phase lipidique comprend au moins un lipide cristallisable, au moins un principe actif et au moins un composé portant deux chaînes d'acides gras et une chaîne polyéthylène glycol.Elle concerne également le procédé de préparation de telles compositions via une émulsion simples H/E ou doubles E/H/E monodisperses.

L'invention concerne un procédé de préparation de microsphères biodégradables monodisperses comprenant les étapes de :a) préparation d'une émulsion comportant au moins une phase polymérique et au moins une phase aqueuse, le rapport des viscosités entre la phase polymérique dispersée et la phase aqueuse continue étant comprise entre 0,1 et 10 ;b) soumission de l'émulsion obtenue à un cisaillement laminaire contrôlé ;c) élimination du solvant de la phase polymérique ; etd) isolement des microsphères ainsi obtenues.Elle concerne aussi les utilisations des microsphères ainsi préparées.

La présente invention a pour objet principal un assemblage de particules colloïdales sous la forme d'une ou plusieurs chaînes caractérisé en ce que lesdites chaînes sont organisées de manière irréversible et sont porteuses d'au moins un site de reconnaissance pour une espèce, ledit site étant différent des sites impliqués dans l'organisation linéaire desdites particules.Elle vise également un procédé de préparation d'un tel assemblage et l'utilisation de cet assemblage, notamment à des fins de détection et/ou de dosage d'au moins une espèce dans un fluide.L'invention concerne également un élément de surface fonctionnalisé à l'aide d'un assemblage de chaînes colloïdales et un réseau d'hybridation comportant un tel élément de surface.

Ce manuscrit présente l'étude de latex magnétiques auto-organisés.
Dans un premier temps, l'obtention de filaments magnétiques, composées d'assemblages linéaires et permanents de particules magnétiques, est présentée. Ces objets nouveaux introduisent une méthode originale pour sonder la flexibilité à l'échelle moléculaire. Sous champ, ils adoptent une configuration métastable: ils se plient en forme d'épingle à cheveux. A partir de la mesure macroscopique de leur rayon de courbure, corrélée à la mesure par diffusion de la lumière de la longueur du lien, la rigidité de flexion de ce dernier peut être déduite. La modélisation de ce phénomène est aussi décrite.
Enfin, l'organisation de ces filaments, dans des microcanaux, constitue une nouvelle matrice de séparation que l'on a cherché à appliquer, ici, au tri cellulaire.
L'obtention d'un réseau de pas contrôlé, l'accrochage des filaments à la paroi,leur décoration par des anticorps spécifiques sont détaillés. Enfin la possibilité de procéder à une chromatographie des cellules est introduite.
Ces nouveaux objets ouvrent un champ d'applications dans le domaine des laboratoires sur puce.

La présente invention a pour objet une méthode de détection et/ou de quantification d'au moins un analyte dans un milieu liquide, caractérisée en ce qu'elle met en oeuvre des particules colloïdales magnétiques fonctionnalisées en surface par au moins un ligand spécifique d'un analyte à détecter etlou doser et en ce qu'elle comprend : - la mise en contact desdites particules avec ledit milieu à analyser, - l'application d'un champ magnétique audit milieu, à une intensité suffisante pour provoquer la structuration desdites particules magnétiques sous forme de chaînes, - le maintien de ce champ magnétique une durée suffisante pour permettre le couplage ou l'association de l'analyte considéré avec au moins deux ligands spécifiques présents respectivement sur deux particules voisines d'une chaîne, - l'annulation du champ magnétique, et- la détermination de la présence et/ou l'absence dudit analyte et, le cas échéant, de sa concentration via la présence etlou l'absence des dites chaînes permanente (s) de particules magnétiques.

La présente invention a pour objet une émulsion multiple alimentaire composée d'une émulsion primaire inverse dispersée au sein d'une phase continue aqueuse, caractérisée en ce que ladite émulsion est stabilisée à l'aide d'un système tensioactif lipophile naturel présent au sein de l'émulsion primaire. La présente invention a également pour objet un procédé de préparation de ladite émulsion et ses applications dans le domaine alimentaire.

La présente invention se rapporte à un procédé pour libérer de manière contrôlée un principe actif contenu dans une émulsion multiple de type eau dans huile dans eau caractérisé en ce que: ladite émulsion multiple comprend une émulsion inverse Ei avec une phase aqueuse A1 qui contient au moins un principe actif hydrophile, ladite émulsion Ei étant dispersée sous forme de gouttelettes d'émulsion directe Ed, dans une phase continue aqueuse A2, avec les deux émulsions Ed et Ei stabilisées par au moins un agent de surface, présent au niveau de leurs phases continues respectives et en ce que ladite émulsion multiple est mise en présence d'une quantité suffisante d'un agent, de manière à la transformer en une émulsion directe et à induire la libération du principe actif, contenu dans la phase aqueuse A1 de l'émulsion Ei, dans la phase aqueuse A2.

Nanosphères composites présentant un diamètre compris entre environ 50 et 1000 nm plus ou moins 5%, de préférence entre environ 100 et 500 nm plus ou moins 5% et avantageusement entre 100 et 200 nm plus ou moins 5%, et comprenant :- un coeur essentiellement liquide constitué d'une phase organique et de nanoparticules inorganiques distribuées à l'intérieur de la phase organique, et- une enveloppe constituée au moins d'un polymère hydrophile qui est issu de la polymérisation d'au moins un monomère hydrosoluble, en particulier un N-alkylacrylamide ou un N-N-dialkylacrylamide; conjugués dérivés desdites nanosphères; leur procédé de préparation et leurs utilisations.

Particules composites comprenant un polymère hydrophobe et des nanoparticules inorganiques, lesdites particules présentant un diamètre de l'ordre d'environ 50 à 1000 nm, de préférence d'environ 100 à 500 nm et avantageusement d'environ 100 à 250 nm et comprenant le polymère hydrophobe qui constitue une matrice polymère et les nanoparticules inorganiques stabilisées et distribuées de manière relativement homogène à l'intérieur de ladite matrice ; conjugués dérivés desdites particules composites ; leur procédé de préparation et leurs utilisations.

La présente invention concerne une émulsion double stable, polydisperse, fractionnable, de type eau dans l'huile dans eau constituée de 50 à 95 % en poids, par rapport au poids total de l'émulsion double, de gouttelettes d'une émulsion inverse Ei monodisperse dispersées dans une phase aqueuse continue; la phase aqueuse continue comprenant un agent épaississant polysaccharidique à raison de 1 à 10 % en poids par rapport au poids total de la phase aqueuse continue; un copolymère séquencé hydrosoluble d'oxyde d'éthylène et d'oxyde de propylène à titre de tensioactif; et un agent d'équilibrage de la pression osmotique; l'émulsion Ei présentant une viscosité inférieure ou égale à la viscosité de la phase aqueuse continue et étant constituée de 50 à 95 % en poids, par rapport au poids total de Ei, de gouttelettes d'une phase aqueuse interne dispersées dans une phase huileuse; la phase aqueuse interne comprenant au moins une substance active hydrophile; la phase huileuse comprenant du polyricinoléate de polyglycérol à titre de tensioactif. L'invention a en outre pour objet l'émulsion double, monodisperse, correspondante, de même formulation et son procédé de préparation au départ de l'émulsion double polydisperse revendiquée.

La présente invention a pour objet des granulés redispersables dans l'eau comprenant: au moins une matière active sous forme de liquide hydrophobe, au moins un tensio-actif non ionique choisi parmi les dérivés polyoxyalkylénés, au moins un composé hydrosoluble choisi parmi les polyélectrolytes appartenant à la famille des polyacides faibles. L'invention a de même pour objet un procédé de préparation de tels granulés consistant à mettre en oeuvre les étapes suivantes: on prépare une émulsion dans l'eau d'au moins une matière active, d'au moins un tensio-actif non ionique, d'au moins un composé hydrosoluble, on sèche l'émulsion ainsi obtenue.

Méthode de séparation de particules ou de molécules dans laquelle on introduit ces particules ou molécules dans un milieu de séparation et on leur applique au sein dudit milieu au moins une force motrice, caractérisée en ce que le milieu de séparation est un ferrofluide, c'est-à-dire une suspension colloïdale de particules magnétiques et en ce qu'on applique à ce ferrofluide un champ magnétique qui y crée au moins une alternance d'une zone riche et d'une zone pauvre en particules magnétiques, une partie au moins de la région du ferrofluide dans laquelle est créée cette alternance étant traversée par les particules ou molécules à séparer lors de leur migration.

L'invention concerne un procédé de préparation d'une émulsion
secondaire constituée de gouttelettes d'une phase A, dispersées dans une
phase B, A n'étant pas miscible dans B, au départ d'une émulsion primaire
polydisperse de formulation identique et constitué de gouttelettes de ladite
phase A dispersées dans ladite phase B, les gouttelettes de l'émulsion
secondaire présentant un diamètre dans tous les cas inférieur au diamètre des
gouttelettes de l'émulsion primaire, caractérisé en ce que l'émulsion primaire
de
départ est viscoélastique et en ce qu'on soumet ladite émulsion primaire de
départ à un cisaillement contrôlé de telle sorte qu'un même cisaillement
maximal
soit appliqué à l'ensemble de l'émulsion. Ce procédé permet d'obtenir des
émulsions monodispersés et à faible teneur en tensioactif, utilisables dans de
nombreux domaines incluant, entre autre les domaines pharmaceutiques ou
cosmétiques, le domaine des détergents et le domaine phytosanitaire.

Procédé de préparation de dispersions aqueuses de particules de polymère magnétisable de distribution resserrée à partir de dispersions aqueuses de distribution étalée caractérisé en ce que : a) on ajuste la quantité d'eau de la dispersion aqueuse de distribution étalée de manière à ce que la teneur pondérale en particules de polymère magnétisable soit comprise entre environ 1 et 40 % de ladite dispersion ; b) on augmente la concentration en agent tensio-actif de la dispersion obtenue à l'étape a) jusqu'à obtenir deux phases, une phase dite liquide et une phase dite solide ; c) on sépare les deux phases ; d) on recommence éventuellement les étapes a), b) et c) sur la phase solide autant de fois qu'il est nécessaire ; e) on récupère la dispersion aqueuse de distribution resserrée.