Morphology, repulsion, and ordering of red blood cells in viscoelastic flows under confinement.

Red blood cells (RBC), the primary carriers of oxygen in the body, play a crucial role across several biomedical applications, while also being an essential model system of a deformable object in the microfluidics and soft matter fields. However, RBC behavior in viscoelastic liquids, which holds promise in enhancing microfluidic diagnostic applications, remains poorly studied. We here show that using viscoelastic polymer solutions as a suspending carrier causes changes in the clustering and shape of flowing RBC in microfluidic flows when compared to a standard Newtonian suspending liquid. Additionally, when the local RBC concentration increases to a point where hydrodynamic interactions take place, we observe the formation of equally-spaced RBC structures, resembling the viscoelasticity-driven ordered particles observed previously in the literature, thus providing the first experimental evidence of viscoelasticity-driven cell ordering. The observed RBC ordering, unaffected by polymer molecular architecture, persists as long as the surrounding medium exhibits shear-thinning, viscoelastic properties. Complementary numerical simulations reveal that viscoelasticity-induced repulsion between RBCs leads to equidistant structures, with shear-thinning modulating this effect. Our results open the way for the development of new biomedical technologies based on the use of viscoelastic liquids while also clarifying fundamental aspects related to multibody hydrodynamic interactions in viscoelastic microfluidic flows.

Bacteria hinder large-scale transport and enhance small-scale mixing in time-periodic flows.

Understanding mixing and transport of passive scalars in active fluids is important to many natural (e.g., algal blooms) and industrial (e.g., biofuel, vaccine production) processes. Here, we study the mixing of a passive scalar (dye) in dilute suspensions of swimming Escherichia coli in experiments using a two-dimensional (2D) time-periodic flow and in a simple simulation. Results show that the presence of bacteria hinders large-scale transport and reduces overall mixing rate. Stretching fields, calculated from experimentally measured velocity fields, show that bacterial activity attenuates fluid stretching and lowers flow chaoticity. Simulations suggest that this attenuation may be attributed to a transient accumulation of bacteria along regions of high stretching. Spatial power spectra and correlation functions of dye-concentration fields show that the transport of scalar variance across scales is also hindered by bacterial activity, resulting in an increase in average size and lifetime of structures. On the other hand, at small scales, activity seems to enhance local mixing. One piece of evidence is that the probability distribution of the spatial concentration gradients is nearly symmetric with a vanishing skewness. Overall, our results show that the coupling between activity and flow can lead to nontrivial effects on mixing and transport.

Exploring the relationship between softness and excess entropy in glass-forming systems.

We explore the relationship between a machine-learned structural quantity (softness) and excess entropy in simulations of supercooled liquids. Excess entropy is known to scale well the dynamical properties of liquids, but this quasi-universal scaling is known to breakdown in supercooled and glassy regimes. Using numerical simulations, we test whether a local form of the excess entropy can lead to predictions similar to those made by softness, such as the strong correlation with particles' tendency to rearrange. In addition, we explore leveraging softness to compute excess entropy in the traditional fashion over softness groupings. Our results show that the excess entropy computed over softness-binned groupings is correlated with activation barriers to rearrangement.

Formation of stable aggregates by fluid-assembled solid bridges.

When a colloidal suspension is dried, capillary pressure may overwhelm repulsive electrostatic forces, assembling aggregates that are out of thermal equilibrium. This poorly understood process confers cohesive strength to many geological and industrial materials. Here we observe evaporation-driven aggregation of natural and synthesized particulates, probe their stability under rewetting, and measure bonding strength using an atomic force microscope. Cohesion arises at a common length scale (∼5 µm), where interparticle attractive forces exceed particle weight. In polydisperse mixtures, smaller particles condense within shrinking capillary bridges to build stabilizing "solid bridges" among larger grains. This dynamic repeats across scales, forming remarkably strong, hierarchical clusters, whose cohesion derives from grain size rather than mineralogy. These results may help toward understanding the strength and erodibility of natural soils, and other polydisperse particulates that experience transient hydrodynamic forces.

Scaling of relaxation and excess entropy in plastically deformed amorphous solids.

When stressed sufficiently, solid materials yield and deform plastically via reorganization of microscopic constituents. Indeed, it is possible to alter the microstructure of materials by judicious application of stress, an empirical process utilized in practice to enhance the mechanical properties of metals. Understanding the interdependence of plastic flow and microscopic structure in these nonequilibrium states, however, remains a major challenge. Here, we experimentally investigate this relationship, between the relaxation dynamics and microscopic structure of disordered colloidal solids during plastic deformation. We apply oscillatory shear to solid colloidal monolayers and study their particle trajectories as a function of shear rate in the plastic regime. Under these circumstances, the strain rate, the relaxation rate associated with plastic flow, and the sample microscopic structure oscillate together, but with different phases. Interestingly, the experiments reveal that the relaxation rate associated with plastic flow at time t is correlated with the strain rate and sample microscopic structure measured at earlier and later times, respectively. The relaxation rate, in this nonstationary condition, exhibits power-law, shear-thinning behavior and scales exponentially with sample excess entropy. Thus, measurement of sample static structure (excess entropy) provides insight about both strain rate and constituent rearrangement dynamics in the sample at earlier times.

Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter-Particle Crosslinking.

Granular hydrogels are an exciting class of microporous and injectable biomaterials that are being explored for many biomedical applications, including regenerative medicine, 3D printing, and drug delivery. Granular hydrogels often possess low mechanical moduli and lack structural integrity due to weak physical interactions between microgels. This has been addressed through covalent inter-particle crosslinking; however, covalent crosslinking often occurs through temporal enzymatic methods or photoinitiated reactions, which may limit injectability and material processing. To address this, a hyaluronic acid (HA) granular hydrogel is developed with dynamic covalent (hydrazone) inter-particle crosslinks. Extrusion fragmentation is used to fabricate microgels from photocrosslinkable norbornene-modified HA, additionally modified with either aldehyde or hydrazide groups. Aldehyde and hydrazide-containing microgels are mixed and jammed to form adhesive granular hydrogels. These granular hydrogels possess enhanced mechanical integrity and shape stability over controls due to the covalent inter-particle bonds, while maintaining injectability due to the dynamic hydrazone bonds. The adhesive granular hydrogels are applied to 3D printing, which allows the printing of structures that are stable without any further post-processing. Additionally, the authors demonstrate that adhesive granular hydrogels allow for cell invasion in vitro. Overall, this work demonstrates the use of dynamic covalent inter-particle crosslinking to enhance injectable granular hydrogels.

A perfusion phantom for ASL MRI based on impinging jets.

PURPOSE: We present a novel perfusion phantom for validation of arterial spin labeled (ASL) perfusion MRI methods and protocols. METHODS: Impinging jets, driven by a peristaltic pump, were used to achieve perfusion-like mixing of magnetically labeled inflowing fluid within a perfusion compartment. The phantom was validated by varying pump rates and obtaining ASL-MRI data at multiple postlabeling delays using a pseudo-continuous ASL sequence with a 3D stack-of-spirals readout. An additional data set was acquired using a pseudo-continuous ASL sequence with a 2D EPI readout. Phantom sensitivity to pseudo-continuous ASL labeling efficiency was also tested. RESULTS: Fluid dynamics simulations predicted that maximum mixing would occur near the central axis of the perfusion compartment. Experimentally observed signal changes within this region were reproducible and well fit by the standard Buxton general kinetic model. Simulations and experimental data showed no label outflow from the perfusion chamber and calculated perfusion rates, averaged over the entire phantom volume, agreed with the expected volumetric flow rates provided by the flow pump. Phantom sensitivity to pseudo-continuous ASL labeling parameters was also demonstrated. CONCLUSION: Perfusion-like signal can be simulated using impinging jets to create a well-mixed compartment. Observed perfusion and transit time values were reproducible and within the physiological range for brain perfusion. This phantom design has a broad range of potential applications in both basic and clinical research involving ASL MRI.

Bacterial activity hinders particle sedimentation.

Sedimentation in active fluids has come into focus due to the ubiquity of swimming micro-organisms in natural and industrial processes. Here, we investigate sedimentation dynamics of passive particles in a fluid as a function of bacteria E. coli concentration. Results show that the presence of swimming bacteria significantly reduces the speed of the sedimentation front even in the dilute regime, in which the sedimentation speed is expected to be independent of particle concentration. Furthermore, bacteria increase the dispersion of the passive particles, which determines the width of the sedimentation front. For short times, particle sedimentation speed has a linear dependence on bacterial concentration. Mean square displacement data shows, however, that bacterial activity decays over long experimental (sedimentation) times. An advection-diffusion equation coupled to bacteria population dynamics seems to capture concentration profiles relatively well. A single parameter, the ratio of single particle speed to the bacteria flow speed can be used to predict front sedimentation speed.

Active Reversible Swimming of Magnetically Assembled "Microscallops" in Non-Newtonian Fluids.

Miniaturized devices capable of active swimming at low Reynolds numbers are of fundamental importance and possess potential biomedical utility. The design of colloidal microswimmers requires not only miniaturizing reconfigurable structures but also understanding their interactions with media at low Reynolds numbers. We investigate the dynamics of "microscallops" made of asymmetric magnetic cubes, which are assembled and actuated using magnetic fields. One approach to achieving directional propulsion is to break the symmetry of the viscous forces by coupling the reciprocal motions of such microswimmers with the nonlinear rheology inherent in non-Newtonian fluids. When placed in shear-thinning fluids, the local viscosity gradient resulting from nonuniform shear stresses exerted by time-asymmetric strokes of the microscallops generates propulsive thrust through an effect we term "self-viscophoresis". Surprisingly, we found that the direction of propulsion changes with the size and structure of these assemblies. We analyze the origins of their directional propulsion and explain the variable propulsion direction in terms of multiple counterbalancing domains of shear dissipation around the microscale structures. The principles governing the locomotion of these microswimmers may be extended to other reconfigurable microbots assembled from colloidal-scale units.

Quantification of plasticity via particle dynamics above and below yield in a 2D jammed suspension.

The yield transition of amorphous materials is characterized by a swift increase of energy dissipation. The connection between particle dynamics, dissipation, and overall material rheology, however, has still not been elucidated. Here, we take a new approach relating trajectories to yielding, using a custom built interfacial stress rheometer, which allows for measurement of shear moduli (G',G'') of a dense athermal suspension's microstructure while simultaneously tracking particle trajectories undergoing cyclic shear. We find an increase in total area traced by particle trajectories as the system is stressed well below to well above yield. Trajectories may be placed into three categories: reversibly elastic paths; reversibly plastic paths, associated with smooth limit cycles; and irreversibly plastic paths, in which particles do not return to their original position. We find that above yield, reversibly plastic trajectories are predominantly found near to the shearing surface, whereas reversibly elastic paths are more prominent near the stationary wall. This spatial transition between particles acting as liquids to those acting as solids is characteristic of a 'melting front', which is observed to shift closer to the wall with increasing strain. We introduce a non-dimensional measure of plastic dissipation based on particle trajectories that scales linearly with strain amplitude both above and below yield, and that is unity at the rheological yield point. Surprisingly, this relation collapses for three systems of varying degrees of disorder.

Three-dimensional structures and symmetry breaking in viscoelastic cross-channel flow.

Using holographic particle tracking, we report the three-dimensional flow structure organizing the viscoelastic instability in cross-channel flow. Beyond a critical Wi, the advective core flow undergoes an out-of-plane instability marked by the emergence of tertiary flow, resembling that of the toroidal vortices in Taylor-Couette geometry. The out-of-plane flow component distorts the separatrix between the impinging inflow streams, triggering symmetry breaking normal to the extension plane. As extensional rate increases, progressively higher order modes of the separatrix are observed, akin to Euler buckling of a rigid column. The disturbances propagate upstream via stress fluctuations despite viscous dissipation. These complex flow structures may be generic to elastic turbulence in mixed flows.

Flow Resistance and Structures in Viscoelastic Channel Flows at Low Re.

The flow of viscoelastic fluids in channels and pipes remains poorly understood, particularly at low Reynolds numbers. Here, we investigate the flow of polymeric solutions in straight channels using pressure measurements and particle tracking. The flow friction factor f_{η} versus flow rate exhibits two regimes: a transitional regime marked by rapid increase in drag, and a turbulentlike regime characterized by a sudden decrease in drag and a weak dependence on flow rate. Lagrangian trajectories show finite transverse modulations not seen in Newtonian fluids. These curvature perturbations far downstream can generate sufficient hoop stresses to sustain the flow instabilities in the parallel shear flow.

Dynamics and thermodynamics of air-driven active spinners.

We report on the collective behavior of active particles in which energy is continuously supplied to rotational degrees of freedom. The active spinners are 3D-printed disks, 1 cm in diameter, that have an embedded fan-like structure, such that a sub-levitating up-flow of air forces them to spin. Single spinners exhibit Brownian motion with a narrow Gaussian velocity distribution function, P(v), for translational motion. We study the evolution of P(v) as the packing fraction and the average single particle spin speeds are varied. The interparticle hydrodynamic interaction is negligible, and the dynamics is dominated by hyperelastic collisions and dissipative forces. As expected for nonequilibrium systems, P(v) for a collection of many spinners deviates from Gaussian behavior. However, unlike translationally active systems, phase separation is not observed, and the system remains spatially homogeneous. We then search for a near-equilibrium counterpart for our active spinners by measuring the equation of state. Interestingly, it agrees well with a hard-sphere model, despite the dissipative nature of the single particle dynamics.

Shear-induced reversibility of 2D colloidal suspensions in the presence of minimal thermal noise.

The effects of minimal thermal noise on particle rearrangements in cyclically sheared colloidal suspensions are experimentally investigated using particle tracking methods. Our experimental model system consists of polystyrene microspheres adsorbed at an oil-water interface, in which the particles exhibit small but non-negligible Brownian motion. Experiments are performed on bidisperse (1.0 and 1.2 µm in diameter) systems, which form area fractions of 0.20 and 0.32 at the interface. We first characterize the thermal (Brownian) noise using particle diffusivities at quiescent states, and show that under our experimental flow conditions both systems (0.20 and 0.32 area fraction) behave as athermal, in the sense that the particle diffusion time scale is larger than the flow time scale. We then characterize particle rearrangements as a function of strain amplitude, and show that small but finite levels of thermal noise affect the reversibility dynamics, even in effectively athermal systems. Our data indicate that as thermal noise is slightly increased in a cyclically sheared athermal system, the fraction of reversible rearrangements is reduced, the reversible cycles become unstable, and the rearrangement hysteresis is significantly hindered.

Particle diffusion in active fluids is non-monotonic in size.

We experimentally investigate the effect of particle size on the motion of passive polystyrene spheres in suspensions of Escherichia coli. Using particles covering a range of sizes from 0.6 to 39 microns, we probe particle dynamics at both short and long time scales. In all cases, the particles exhibit super-diffusive ballistic behavior at short times before eventually transitioning to diffusive behavior. Surprisingly, we find a regime in which larger particles can diffuse faster than smaller particles: the particle long-time effective diffusivity exhibits a peak in particle size, which is a deviation from classical thermal diffusion. We also find that the active contribution to particle diffusion is controlled by a dimensionless parameter, the Péclet number. A minimal model qualitatively explains the existence of the effective diffusivity peak and its dependence on bacterial concentration. Our results have broad implications on characterizing active fluids using concepts drawn from classical thermodynamics.

Role of disorder in finite-amplitude shear of a 2D jammed material.

A material's response to small but finite deformations can reveal the roots of its response to much larger deformations. Here, we identify commonalities in the responses of 2D soft jammed solids with different amounts of disorder. We cyclically shear the materials while tracking their constituent particles, in experiments that feature a stable population of repeated structural relaxations. Using bidisperse particle sizes creates a more amorphous material, while monodisperse sizes yield a more polycrystalline one. We find that the materials' responses are very similar, both at the macroscopic, mechanical level and in the microscopic motions of individual particles. However, both locally and in bulk, crystalline arrangements of particles are stiffer (greater elastic modulus) and less likely to rearrange. Our work supports the idea of a common description for the responses of a wide array of materials.

Mechanical and microscopic properties of the reversible plastic regime in a 2D jammed material.

At the microscopic level, plastic flow of a jammed, disordered material consists of a series of particle rearrangements that cannot be reversed by subsequent deformation. An infinitesimal deformation of the same material has no rearrangements. Yet between these limits, there may be a self-organized plastic regime with rearrangements, but with no net change upon reversing a deformation. We measure the oscillatory response of a jammed interfacial material, and directly observe rearrangements that couple to bulk stress and dissipate energy, but do not always give rise to global irreversibility.

Dendritic tree extraction from noisy maximum intensity projection images in C. elegans.

BACKGROUND: Maximum Intensity Projections (MIP) of neuronal dendritic trees obtained from confocal microscopy are frequently used to study the relationship between tree morphology and mechanosensory function in the model organism C. elegans. Extracting dendritic trees from noisy images remains however a strenuous process that has traditionally relied on manual approaches. Here, we focus on automated and reliable 2D segmentations of dendritic trees following a statistical learning framework. METHODS: Our dendritic tree extraction (DTE) method uses small amounts of labelled training data on MIPs to learn noise models of texture-based features from the responses of tree structures and image background. Our strategy lies in evaluating statistical models of noise that account for both the variability generated from the imaging process and from the aggregation of information in the MIP images. These noisy models are then used within a probabilistic, or Bayesian framework to provide a coarse 2D dendritic tree segmentation. Finally, some post-processing is applied to refine the segmentations and provide skeletonized trees using a morphological thinning process. RESULTS: Following a Leave-One-Out Cross Validation (LOOCV) method for an MIP databse with available "ground truth" images, we demonstrate that our approach provides significant improvements in tree-structure segmentations over traditional intensity-based methods. Improvements for MIPs under various imaging conditions are both qualitative and quantitative, as measured from Receiver Operator Characteristic (ROC) curves and the yield and error rates in the final segmentations. In a final step, we demonstrate our DTE approach on previously unseen MIP samples including the extraction of skeletonized structures, and compare our method to a state-of-the art dendritic tree tracing software. CONCLUSIONS: Overall, our DTE method allows for robust dendritic tree segmentations in noisy MIPs, outperforming traditional intensity-based methods. Such approach provides a useable segmentation framework, ultimately delivering a speed-up for dendritic tree identification on the user end and a reliable first step towards further morphological characterizations of tree arborization.

Effect of fluid elasticity on the emergence of oscillations in an active elastic filament.

Many microorganisms propel themselves through complex media by deforming their flagella. The beat is thought to emerge from interactions between forces of the surrounding fluid, the passive elastic response from deformations of the flagellum and active forces from internal molecular motors. The beat varies in response to changes in the fluid rheology, including elasticity, but there are limited data on how systematic changes in elasticity alter the beat. This work analyses a related problem with fixed-strength driving force: the emergence of beating of an elastic planar filament driven by a follower force at the tip of a viscoelastic fluid. This analysis examines how the onset of oscillations depends on the strength of the force and viscoelastic parameters. Compared to a Newtonian fluid, it takes more force to induce the instability in viscoelastic fluids, and the frequency of the oscillation is higher. The linear analysis predicts that the frequency increases with the fluid relaxation time. Using numerical simulations, the model predictions are compared with experimental data on frequency changes in the bi-flagellated alga Chlamydomonas reinhardtii. The model shows the same trends in response to changes in both fluid viscosity and Deborah number and thus provides a possible mechanistic understanding of the experimental observations.

To biofilm or not to biofilm.

A new model helps to predict under which conditions a species of bacteria will switch to a static lifestyle.