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.

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.

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 screening applications. However, 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 bioreactors. The requirements are: i) damping the shear layer instability that develops inside the injector arising from the co-annular flow configuration of liquid phases having contrasting viscoelastic properties; ii) controlling the capillary instability of the compound jet by superposing a harmonic perturbation onto the shell flow; iii) avoiding coalescence of drops during jet fragmentation as well as during drop flight towards the gelling bath; iv) ensuring 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 multicellular 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 modeling have been used to analyze Histatin 5, 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 small angle X-ray scattering (SAXS), at both high and low salt concentrations. The aim was to achieve a molecular understanding and a physico-chemical insight of the obtained SAXS results and to gain information of the conformational changes of Histatin 5 due to altering salt content, charge distribution, and net charge. From a modeling perspective, the accuracy of the electrostatic interactions are of special interest. The used coarse-grained model was 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 all atomistic details, a great correspondence is obtained with the experimental results. Proteins 2016; 84:777-791.

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 μm). 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 time-dependent 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 m−1), 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.

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.

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 AB_{2}, 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.

Determining the phenotype and genotype of single cells is central to understand microbial evolution. DNA sequencing technologies allow the detection of mutants at high resolution, but similar approaches for phenotypic analyses are still lacking. We show that a drop-based millifluidic system enables the detection of heritable phenotypic changes in evolving bacterial populations. At time intervals, cells were sampled and individually compartmentalized in 100 nL drops. Growth through 15 generations was monitored using a fluorescent protein reporter. Amplification of heritable changes–via growth–over multiple generations yields phenotypically distinct clusters reflecting variation relevant for evolution. To demonstrate the utility of this approach, we follow the evolution of Escherichia coli populations during 30 days of starvation. Phenotypic diversity was observed to rapidly increase upon starvation with the emergence of heritable phenotypes. Mutations corresponding to each phenotypic class were identified by DNA sequencing. This scalable lineage-tracking technology opens the door to large-scale phenotyping methods with special utility for microbiology and microbial population biology.

We present the MilliDrop Analyzer (MDA), a droplet-based millifluidic system for digital antimicrobial susceptibility testing (D-AST), which enables us to determine minimum inhibitory concentrations (MICs) precisely and accurately. The MilliDrop technology was validated by using resazurin for fluorescence readout, for comparison with standard methodology, and for conducting reproducibility studies. In this first assessment, the susceptibility of a reference Gram-negative strain Escherichia coli ATCC 25922 to gentamicin, chloramphenicol, and nalidixic acid were tested by the MDA, VITEK®2, and broth microdilution as a reference standard. We measured the susceptibility of clinically relevant Gram-positive strains of Staphylococcus aureus to vancomycin, including vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and vancomycin-susceptible S. aureus (VSSA) strains. The MDA provided results which were much more accurate than those of VITEK®2 and standard broth microdilution. The enhanced accuracy enabled us to reliably discriminate between VSSA and hVISA strains.

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.

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 dramatically changes 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.

We present the principle of a fast magnetic field enhanced colloidal agglutination assay, which is based on the acceleration of the recognition rate between ligands and receptors induced by magnetic forces.1 By applying a homogeneous magnetic field of 20 mT for only 7 s, we detect CRP (C-reactive protein) in human serum at a concentration as low as 1 pM for a total cycle time of about 1 min in a prototype analyzer. Such a short measurement time does not impair the performances of the assay when compared to longer experiments. The concentration range dynamic is shown to cover 3 orders of magnitude. An analytical model of agglutination is also successfully fitting our data obtained with a short magnetic pulse.

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.

Large-Scale Lineage Analysis Refines the Relationship between Birth Order and Cell Fate
The anchor cell (AC) is a unique cell in the proximal region of the developing gonad that serves as the signaling nexus for uterine and vulval patterning and in connecting the uterus and the vulva [12, 13]; its correct specification is therefore critical for maximizing reproductive success. Initially, four cells in the developing somatic primordium have the potential to be the AC (Figure 1A). As described further below, the conserved transcription factor HLH-2 is required to endow these cells with AC potential. The “β cells” soon lose AC potential and always become ventral uterine precursor cells (VUs); the two α cells maintain AC potential and interact via LIN-12/Notch to resolve which will become the AC and which will become another VU