Propagation of extended fractures by local nucleation and rapid transverse expansion of crack-front distortion.

Fractures are ubiquitous and can lead to the catastrophic material failure of materials. Although fracturing in a two-dimensional plane is well understood, all fractures are extended in and propagate through three-dimensional space. Moreover, their behaviour is complex. Here we show that the forward propagation of a fracture front occurs through an initial rupture, nucleated at some localized position, followed by a very rapid transverse expansion at velocities as high as the Rayleigh-wave speed. We study fracturing in a circular geometry that achieves an uninterrupted extended fracture front and use a fluid to control the loading conditions that determine the amplitude of the forward jump. We find that this amplitude correlates with the transverse velocity. Dynamic rupture simulations capture the observations for only a high transverse velocity. These results highlight the importance of transverse dynamics in the forward propagation of an extended fracture.

Controlled Continuous Evolution of Enzymatic Activity Screened at Ultrahigh Throughput Using Drop-Based Microfluidics.

Enzymes are highly specific catalysts delivering improved drugs and greener industrial processes. Naturally occurring enzymes must typically be optimized which is often accomplished through directed evolution; however, this is still a labor- and capital-intensive process, due in part to multiple molecular biology steps including DNA extraction, in vitro library generation, transformation, and limited screening throughput. We present an effective and broadly applicable continuous evolution platform that enables controlled exploration of fitness landscape to evolve enzymes at ultrahigh throughput based on direct measurement of enzymatic activity. This drop-based microfluidics platform cycles cells between growth and mutagenesis followed by screening with minimal human intervention, relying on the nCas9 chimera with mutagenesis polymerase to produce in vivo gene diversification using sgRNAs tiled along the gene. We evolve alditol oxidase to change its substrate specificity towards glycerol, turning a waste product into a valuable feedstock. We identify a variant with a 10.5-fold catalytic efficiency.

Dynamic Speckle Holography.

We introduce dynamic speckle holography, a new technique that combines imaging and scattering to measure three-dimensional maps of displacements as small as ten nanometers over several centimeters, greatly extending the capabilities of traditional imaging systems. We attain this sensitivity by imaging speckle patterns of light collected at three scattering angles and measuring the decay in the temporal correlation due to local motion. We use dynamic speckle holography to measure the strain field of a colloidal gel undergoing fracture and establish the surprising role of internal tension in driving the fracture.

Cemental tear: An overlooked finding associated with rapid periodontal destruction. A case series.

Cemental tear is defined as cementum fragment completely or partially detached from the root surface, and it has been associated with localized rapid periodontal breakdown. Although history of trauma and/or attrition may be risk factors, the etiopathology of cemental tear remains unknown. This case series aims to discuss the clinical, radiographic and histopathologic features of cemental tears to aid clinicians in making differential diagnosis. Three teeth from three patients presenting a periradicular lesion underwent an exploratory surgery to determine the cause and provide treatment. Soft and hard tissue biopsies were obtained from each lesion and forwarded for histopathologic evaluation. Two patients received a guided tissue regeneration (GTR) procedure, which allowed the tooth to be retained. One patient received an extraction with simultaneous guided bone regeneration (GBR) due to a hopeless prognosis of the tooth. The results after histopathologic evaluation yielded a final diagnosis of cemental tear for all three patients. Cemental tears may be overlooked, and therefore, they should be included in the differential diagnosis of periapical periodontitis, endodontic-periodontal lesion and vertical root fracture (VRF).

The vortex-driven dynamics of droplets within droplets.

Understanding the fluid-structure interaction is crucial for an optimal design and manufacturing of soft mesoscale materials. Multi-core emulsions are a class of soft fluids assembled from cluster configurations of deformable oil-water double droplets (cores), often employed as building-blocks for the realisation of devices of interest in bio-technology, such as drug-delivery, tissue engineering and regenerative medicine. Here, we study the physics of multi-core emulsions flowing in microfluidic channels and report numerical evidence of a surprisingly rich variety of driven non-equilibrium states (NES), whose formation is caused by a dipolar fluid vortex triggered by the sheared structure of the flow carrier within the microchannel. The observed dynamic regimes range from long-lived NES at low core-area fraction, characterised by a planetary-like motion of the internal drops, to short-lived ones at high core-area fraction, in which a pre-chaotic motion results from multi-body collisions of inner drops, as combined with self-consistent hydrodynamic interactions. The onset of pre-chaotic behavior is marked by transitions of the cores from one vortex to another, a process that we interpret as manifestations of the system to maximize its entropy by filling voids, as they arise dynamically within the capsule.

Self-Limited Accumulation of Colloids in Porous Media.

We present local direct imaging of the progressive adsorption of colloidal particles inside a 3D model porous medium. By varying the interparticle electrostatic interactions, we observe a large range of particle deposition regimes, from a single layer of particles at the surface of the medium to multiple layers and eventually clogging of the system. We derive the complete deposition dynamics and show that colloid accumulation is a self-limited mechanism towards a deposited fraction associated with a balance between the particle interactions and the imposed flow rate. These trends are explained and predicted using a simple probability model considering the particle adsorption energy and the variation of the drag energy with evolving porosity. This constitutes a direct validation of speculated particle transport mechanisms, and a further understanding of accumulation mechanisms.

Traveling surface acoustic wave (TSAW) microfluidic fluorescence activated cell sorter (µFACS).

We report a microfluidic fluorescence activated cell-sorting (µFACS) device that employs traveling surface acoustic waves (TSAW) to sort cells at rates comparable to conventional jet-in-air FACS machines, with high purity and viability. The device combines inertial flow focusing and sheath flow to align and evenly space cells, improving the sorting accuracy and screening rate. We sort with an interdigital transducer (IDT) whose tapered geometry allows precise positioning of the TSAW for optimal cell sorting. We sort three different cell lines at several kHz, at cell velocities exceeding one meter per second, while maintaining both sorting purity and cell viability at around 90% simultaneously.

Determining the lipid specificity of insoluble protein transmembrane domains.

While the specificity of protein-lipid interactions is a key feature in the function of biological membranes, studying the specifics of these interactions is challenging because most membrane proteins are insoluble in water due to the hydrophobic nature of their transmembrane domains (TMDs). Here, we introduce a method that overcomes this solubility limitation and identifies the affinity profile of protein TMDs to specific lipid formulations. Using 5 human TMDs as a sample group, our results demonstrate that TMDs are highly selective and that these specific lipid-TMD interactions can involve either a single lipid, or the combination of multiple lipid species.

Enhanced surface acoustic wave cell sorting by 3D microfluidic-chip design.

We demonstrate an acoustic wave driven microfluidic cell sorter that combines advantages of multilayer device fabrication with planar surface acoustic wave excitation. We harness the strong vertical component of the refracted acoustic wave to enhance cell actuation by using an asymmetric flow field to increase cell deflection. Precise control of the 3-dimensional flow is realized by topographical structures implemented on the top of the microchannel. We experimentally quantify the effect of the structure dimensions and acoustic parameter. The design attains cell sorting rates and purities approaching those of state of the art fluorescence-activated cell sorters with all the advantages of microfluidic cell sorting.

Reply to the 'Comment on "Robust scalable high throughput production of monodisperse drops"' by M. Nakajima, Lab Chip, 2017, 17, DOI: 10.1039/C7LC00181A.

This reply to the comment by Nakajima on our article that appeared in Lab on a Chip (E. Amstad, M. Chemama, M. Eggersdorfer, L. R. Arriaga, M. Brenner and D. A. Weitz, Lab Chip, 2016, 16, 4163-4172) highlights the differences between the microchannel step emulsification devices developed by the Nakajima group and the millipede device reported by us in Lab on a Chip.

Efficient extraction of oil from droplet microfluidic emulsions.

Droplet microfluidic techniques can perform large numbers of single molecule and cell reactions but often require controlled, periodic flow to merge, split, and sort droplets. Here, we describe a simple method to convert aperiodic flows into periodic ones. Using an oil extraction module, we efficiently remove oil from emulsions to readjust the droplet volume fraction, velocity, and packing, producing periodic flows. The extractor acts as a universal adaptor to connect microfluidic modules that do not operate under identical flow conditions, such as droplet generators, incubators, and merger devices.

Tandem emulsification for high-throughput production of double emulsions.

Core-shell double emulsions produced using microfluidic methods with controlled structural parameters exhibit great potential in a wide range of applications, but the low production rate of microfluidic methods hinders the exploitation of the capabilities of microfluidics to produce double emulsions with well-defined features. A major obstacle towards the scaled-up production of core-shell double emulsions is the difficulty of achieving robust spatially controlled wettability in integrated microfluidic devices. Here, we use tandem emulsification, a two-step process with microfluidic devices, to scale up the production. With this method, single emulsions are generated in a first device and are re-injected directly into a second device to form uniform double emulsions. We demonstrate the application of tandem emulsification for scalable core-shell emulsion production with both integrated flow focusing and millipede devices and obtain emulsions of which over 90% are single-core monodisperse double emulsion drops. With both mechanisms, the shell thickness can be controlled, so that shells as thin as 3 µm are obtained for emulsions 50 µm in radius.

Triple Junction at the Triple Point Resolved on the Individual Particle Level.

At the triple point of a repulsive screened Coulomb system, a fcc crystal, a bcc crystal, and a fluid phase coexist. At their intersection, these three phases form a liquid groove, the triple junction. Using confocal microscopy, we resolve the triple junction on a single-particle level in a model system of charged PMMA colloids in a nonpolar solvent. The groove is found to be extremely deep and the incommensurate solid-solid interface to be very broad. Thermal fluctuations hence appear to dominate the solid-solid interface. This indicates a very low interfacial energy. The fcc-bcc interfacial energy is quantitatively determined based on Young's equation and, indeed, it is only about 1.3 times higher than the fcc-fluid interfacial energy close to the triple point.

Dynamic sound scattering: Field fluctuation spectroscopy with singly scattered ultrasound in the near and far fields.

Dynamic sound scattering (DSS) is a powerful acoustic technique for investigating the motion of particles or other inclusions inside an evolving medium. In DSS, this dynamic information is obtained by measuring the field autocorrelation function of the temporal fluctuations of singly scattered acoustic waves. The technique was initially introduced 15 years ago, but its technical aspects were not adequately discussed then. This paper addresses the need for a more complete account of the method by describing in detail two different implementations of this sound scattering technique, one of which is specifically adapted to a common experimental situation in ultrasonics. The technique is illustrated by the application of DSS to measure the mean square velocity fluctuations of particles in fluidized suspensions, as well as the dynamic velocity correlation length. By explaining the experimental and analytical methods involved in realizing the DSS technique in practice, the use of DSS will be facilitated for future studies of particulate suspension dynamics and particle properties over a wide range of particle sizes and concentrations, from millimeters down to nanometers, where the use of optical techniques is often limited by the opacity of the medium.

Water retention against drying with soft-particle suspensions in porous media.

Polymers suspended in granular packings have a significant impact on water retention, which is important for soil irrigation and the curing of building materials. Whereas the drying rate remains constant during a long period for pure water due to capillary flow providing liquid water to the evaporating surface, we show that it is not the case for a suspension made of soft polymeric particles called microgels: The drying rate decreases immediately and significantly. By measuring the spatial water saturation and concentration of suspended particles with magnetic resonance imaging, we can explain these original trends and model the process. In low-viscosity fluids, the accumulation of particles at the free surface induces a recession of the air-liquid interface. A simple model, assuming particle transport and accumulation below the sample free surface, is able to reproduce our observations without any fitting parameters. The high viscosity of the microgel suspension inhibits flow towards the free surface and a drying front appears. We show that water vapor diffusion over a defined and increasing length sets the drying rate. These results and model allow for better controlling the drying and water retention in granular porous materials.

Robust scalable high throughput production of monodisperse drops.

Monodisperse drops with diameters between 20 µm and 200 µm can be used to produce particles or capsules for many applications such as for cosmetics, food, and biotechnology. Drops composed of low viscosity fluids can be conveniently made using microfluidic devices. However, the throughput of microfluidic devices is limited and scale-up, achieved by increasing the number of devices run in parallel, can compromise the narrow drop-size distribution. In this paper, we present a microfluidic device, the millipede device, which forms drops through a static instability such that the fluid volume that is pinched off is the same every time a drop forms. As a result, the drops are highly monodisperse because their size is solely determined by the device geometry. This makes the operation of the device very robust. Therefore, the device can be scaled to a large number of nozzles operating simultaneously on the same chip; we demonstrate the operation of more than 500 nozzles on a single chip that produces up to 150 mL h-1 of highly monodisperse drops.

Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.

Transporter-mediated drug-drug interactions (DDIs) are a major cause of drug toxicities. Using published genome-wide association studies (GWAS) of the human metabolome, we identified 20 metabolites associated with genetic variants in organic anion transporter, OATP1B1 (P < 5 × 10-8 ). Of these, 12 metabolites were significantly higher in plasma samples from volunteers dosed with the OATP1B1 inhibitor, cyclosporine (CSA) vs. placebo (q-value < 0.2). Conjugated bile acids and fatty acid dicarboxylates were among the metabolites discovered using both GWAS and CSA administration. In vitro studies confirmed tetradecanedioate (TDA) and hexadecanedioate (HDA) were novel substrates of OATP1B1 as well as OAT1 and OAT3. This study highlights the use of multiple datasets for the discovery of endogenous metabolites that represent potential in vivo biomarkers for transporter-mediated DDIs. Future studies are needed to determine whether these metabolites can serve as qualified biomarkers for organic anion transporters. Quantitative relationships between metabolite levels and modulation of transporters should be established.

Scalable single-step microfluidic production of single-core double emulsions with ultra-thin shells.

We report a versatile and robust device for the continuous production of double emulsion drops with very thin shell thicknesses, of about 5% of the radius: for emulsions 50 µm in radius the shells can be as thin as a few micrometers. Importantly, the viscosity of the oil shell can be varied from that of water up to 70 times that of water without compromising device operation. Furthermore, this device can be easily scaled-up as it is made through soft lithography; this may enable the production of industrial quantities of double emulsion drops with ultra-thin shells, which may serve as templates to form capsules with homogeneous shell thicknesses, useful beyond scientific applications.

Local shear transformations in deformed and quiescent hard-sphere colloidal glasses.

We perform a series of deformation experiments on a monodisperse, hard-sphere colloidal glass while simultaneously following the three-dimensional trajectories of roughly 50,000 individual particles with a confocal microscope. In each experiment, we deform the glass in pure shear at a constant strain rate [(1-5)×10(-5) s(-1)] to maximum macroscopic strains (5%-10%) and then reverse the deformation at the same rate to return to zero macroscopic strain. We also measure three-dimensional particle trajectories in an identically prepared quiescent glass in which the macroscopic strain is always zero. We find that shear transformation zones exist and are active in both sheared and quiescent colloidal glasses, revealed by a distinctive fourfold signature in spatial autocorrelations of the local shear strain. With increasing shear, the population of local shear transformations develops more quickly than in a quiescent glass and many of these transformations are irreversible. When the macroscopic strain is reversed, we observe partial elastic recovery, followed by plastic deformation of the opposite sign, required to compensate for the irreversibly transformed regions. The average diameter of the shear transformation zones in both strained and quiescent glasses is slightly more than two particle diameters.

Spatial propagation of protein polymerization.

We consider the spatial dependence of filamentous protein self-assembly. Through studying the cases where the spreading of aggregated material is dominated either by diffusion or by growth, we derive analytical results for the spatial evolution of filamentous protein aggregation, which we validate against Monte Carlo simulations. Moreover, we compare the predictions of our theory with experimental measurements of two systems for which we identify the propagation as either growth or diffusion controlled. Our results connect the macroscopic observables that characterize the spatial propagation of protein self-assembly with the underlying microscopic processes and provide physical limits on spatial propagation and prionlike behavior associated with protein aggregation.