Effect of pH on the viscoelastic properties of pig gastric mucus.

Mucus is a biomaterial with peculiar, gel-like viscoelastic properties, and bearing different functionalities, depending on the different mucosae it covers. It is clear that these functionalities have to stay effective throughout the in vivo broad range of physiological pH values at which the mucus is exposed. We sought here to determine the effect of pH on the rheological properties of ex vivo mucus. We demonstrate that viscoelastic properties of gastric mucus are quite "stable" to pH changes, in marked contrast with the pH sensitivity of purified mucin gels. We also find that the rheological features of porcine gastric mucus are reversible when the system is first alkalized up to solubilization (pH > 8.5) and then re-acidified to its initial pH value.

Numerical design of a T-shaped microfluidic device for deformability-based separation of elastic capsules and soft beads.

We propose a square cross-section microfluidic channel with an orthogonal side branch (asymmetric T-shaped bifurcation) for the separation of elastic capsules and soft beads suspended in a Newtonian liquid on the basis of their mechanical properties. The design is performed through three-dimensional direct numerical simulations. When suspended objects start near the inflow channel centerline and the carrier fluid is equally partitioned between the two outflow branches, particle separation can be achieved based on their deformability, with the stiffer ones going "straight" and the softer ones being deviated to the "side" branch. The effects of the geometrical and physical parameters of the system on the phenomenon are investigated. Since cell deformability can be significantly modified by pathology, we give a proof of concept on the possibility of separating diseased cells from healthy ones, thus leading to illness diagnosis.

Reply to "Comment on 'Locomotion of a microorganism in weakly viscoelastic liquids' ".

In the present reply we show that the comments casting doubts on the results of our recent paper [M. De Corato et al., Phys. Rev. E 92, 053008 (2015)PLEEE81539-375510.1103/PhysRevE.92.053008] are based on a misinterpretation of the second-order fluid constitutive equation. Nevertheless, we show that, by considering alternative constitutive equations for the viscoelastic stress, we recover, to first-order in the Deborah number, the same results already obtained by De Corato et al. [Phys. Rev. E 92, 053008 (2015)PLEEE81539-375510.1103/PhysRevE.92.053008], thus dissipating any possible doubt about their validity.

Locomotion of a microorganism in weakly viscoelastic liquids.

In the present work we study the motion of microorganisms swimming by an axisymmetric distribution of surface tangential velocity in a weakly viscoelastic fluid. The second-order fluid constitutive equation is used to model the suspending fluid, while the well-known "squirmer model" [M. J. Lighthill, Comm. Pure Appl. Math. 5, 109 (1952); J. R. Blake, J. Fluid Mech. 46, 199 (1971)] is employed to describe the organism propulsion mechanism. A regular perturbation expansion up to first order in the Deborah number is performed, and the generalized reciprocity theorem from Stokes flow theory is then used, to derive analytical formulas for the squirmer velocity. Results show that "neutral" squirmers are unaffected by viscoelasticity, whereas "pullers" and "pushers" are slowed down and hastened, respectively. The power dissipated by the swimming microorganism and the "swimming efficiency" are also analytically quantified.

Hydrodynamics and Brownian motions of a spheroid near a rigid wall.

In this work, we study in detail the hydrodynamics and the Brownian motions of a spheroidal particle suspended in a Newtonian fluid near a flat rigid wall. We employ 3D Finite Element Method (FEM) simulations to compute how the mobility tensor of the spheroid varies with both the particle-wall separation distance and the particle orientation. We then study the Brownian motion of the spheroid by means of a discretized Langevin equation. We specifically focus on the additional drift terms arising from the position and orientational dependence of the mobility matrix. In this respect, we also propose a numerically convenient approximation of the orientational divergence of the mobility matrix that is required in the solution of the Langevin equation. Our results illustrate that both hydrodynamics and Brownian motions of a spheroidal particle near a confining wall display novel features from those of a sphere in the same type of confinement.

Dynamics of prolate spheroidal elastic particles in confined shear flow.

We investigate through numerical simulations the dynamics of a neo-Hookean elastic prolate spheroid suspended in a Newtonian fluid under shear flow. Both initial orientations of the particle within and outside the shear plane and both unbounded and confined flow geometries are considered. In unbounded flow, when the particle starts on the shear plane, two stable regimes of motion are found, i.e., trembling, where the particle shape periodically elongates and compresses in the shear plane and the angle between its major semiaxis and the flow direction oscillates around a positive mean value, and tumbling, where the particle shape periodically changes and its major axis performs complete revolutions around the vorticity axis. When the particle is initially oriented out of the shear plane, more complex dynamics arise. Geometric confinement of the particle between the moving walls also influences its deformation and regime of motion. In addition, when the particle is initially located in an asymmetric position with respect to the moving walls, particle lateral migration is detected. The effects on the particle dynamics of the geometric and physical parameters that rule the system are investigated.

Optimizing design and fabrication of microfluidic devices for cell cultures: An effective approach to control cell microenvironment in three dimensions.

The effects of gradients of bioactive molecules on the cell microenvironment are crucial in several biological processes, such as chemotaxis, angiogenesis, and tumor progression. The elucidation of the basic mechanisms regulating cell responses to gradients requires a tight control of the spatio-temporal features of such gradients. Microfluidics integrating 3D gels are useful tools to fulfill this requirement. However, even tiny flaws in the design or in the fabrication process may severely impair microenvironmental control, thus leading to inconsistent results. Here, we report a sequence of actions aimed at the design and fabrication of a reliable and robust microfluidic device integrated with collagen gel for cell culturing in 3D, subjected to a predetermined gradient of biomolecular signals. In particular, we developed a simple and effective solution to the frequently occurring technical problems of gas bubble formation and 3D matrix collapsing or detaching from the walls. The device here proposed, in Polydimethylsiloxane, was designed to improve the stability of the cell-laden hydrogel, where bubble deprived conditioning media flow laterally to the gel. We report the correct procedure to fill the device with the cell populated gel avoiding the entrapment of gas bubbles, yet maintaining cell viability. Numerical simulations and experiments with fluorescent probes demonstrated the establishment and stability of a concentration gradient across the gel. Finally, chemotaxis experiments of human Mesenchymal Stem Cells under the effects of Bone Morphogenetic Protein-2 gradients were performed in order to demonstrate the efficacy of the system in controlling cell microenvironment. The proposed procedure is sufficiently versatile and simple to be used also for different device geometries or experimental setups.

Bistability and metabistability scenario in the dynamics of an ellipsoidal particle in a sheared viscoelastic fluid.

The motion of an ellipsoidal particle in a viscoelastic liquid subjected to an unconfined shear flow is addressed by numerical simulations. A complex dynamics is found with different transients and long-time regimes depending on the Deborah number De (De is the product of the viscoelastic liquid intrinsic time times the applied shear rate). Spiraling orbits toward a log-rolling motion around the vorticity are observed for low Deborah numbers, whereas the particle aligns with its major axis near to the flow direction at high Deborah numbers. The transition from vorticity to flow alignment is characterized by a periodic regime with small amplitude oscillations around orientations progressively shifting from vorticity to flow direction by increasing De. A range of Deborah numbers is detected such that the periodic solution coexists with the flow alignment regime (bistability). A further range of De is found where flow alignment is attained differently for particles starting far from or next to the shear plane: in the latter case, very long transients are found; hence an effective bistability (metabistability) is predicted to occur in a large time lapse before reaching the fully aligned state. Finally, the computed Deborah number values for flow alignment favorably compare with available experimental data.

On the choice of the optimal periodic operation for a continuous fermentation process.

In this contribution we investigate the impact of the forcing waveform on the productivity of a continuous bioreactor governed by an unstructured, nonlinear kinetic model. The (periodic) forcing is applied on the substrate concentration in the feed. To this end, some alternative waveforms commonly encountered in practice are evaluated and their performance is compared. An analytical/numerical approach is used. The preliminary analytical step is based on the π-criterion that gives useful information for small amplitudes. The extension to larger amplitudes, when significant improvements are expected, is then performed through a continuation-optimization procedure. It is found that the choice of the specific waveform has an impact on the performance of the process and there is no unique best forcing for any process condition, but its choice depends on the operating parameters and the forcing amplitude and frequency values. Further, the influence of the waveform functions on the wash-out conditions are extensively examined. The analysis shows that all the waveforms examined in this work may lead to significant enlargement of the nontrivial regime with respect to a steady state operation. In particular, square-wave forcing leads in practice to the extinction of the wash-out conditions for any feed substrate concentration and for a well defined choice of the forcing parameters.

Bifurcational and dynamical analysis of a continuous biofilm reactor.

A dynamical model of a continuous biofilm reactor is presented. The reactor consists of a three-phase internal loop airlift operated continuously with respect to the liquid and gaseous phases, and batchwise with respect to the immobilized cells. The model has been applied to the conversion of phenol by means of immobilized cells of Pseudomonas sp. OX1 whose metabolic activity was previously characterized (Viggiani, A., Olivieri, G., Siani, L., Di Donato, A., Marzocchella, A., Salatino, P., Barbieri, P., Galli, E., 2006. An airlift biofilm reactor for the biodegradation of phenol by Pseudomonas stutzeri OX1. Journal of Biotechnology 123, 464-477). The model embodies the key processes relevant to the reactor performance, with a particular emphasis on the role of biofilm detachment promoted by the fluidized state. Results indicate that a finite loading of free cells establishes even under operating conditions that would promote wash out of the suspended biophase. The co-operative/competitive effects of free cells and immobilized biofilm result in rich bifurcational patterns of the steady state solutions of the governing equations, which have been investigated in the phase plane of the process parameters. Direct simulation under selected operating conditions confirms the importance of the dynamical equilibrium establishing between the immobilized and the suspended biophase and highlights the effect of the initial value of the biofilm loading on the dynamical pattern.

Stress tensor of a dilute suspension of spheres in a viscoelastic liquid.

The stress tensor for a dilute suspension of buoyancy-free, inertialess, non-Brownian, rigid spheres immersed in a viscoelastic liquid is determined via a perturbative expansion. The perturbation parameter is the Deborah number De, giving the ratio between the characteristic time of the liquid and the characteristic time of the imposed flow. The stress is also calculated from numerical simulations of continuity and momentum equations for the single sphere problem. Excellent agreement is found between the two predictions. Good agreement is found also with respect to experimental data found in the literature.

Short-term ursodeoxycholic acid treatment improves gallbladder bile turnover in gallstone patients: a randomized trial.

UNLABELLED: Ursodeoxycholic acid (UDCA) prevents in vitro gallbladder (GB) muscle damage caused by acute cholecystitis and reduces risk of biliary pain and complications in gallstone (GS) patients. These effects could be partially explained by the improved GB bile turnover. OBJECTIVES: To assess the effect of short-term UDCA treatment on GB motility and bile turnover. METHODS: Ultrasonographic (US) assessment of GB volumes was performed in 16 GS patients, in the postprandial phase, for 90 min with a time sampling of 1 min, before and after 30 days of UDCA (10 mg kg(-1) die(-1)) or placebo, randomly assigned. US data were analysed with statistical tools and with computer fluido-dynamic (CFD) software Fluent(TM) to simulate GB bile flow. RESULTS: After therapy, fasting volume (FV) increased from 21.6 +/- 9 to 28.2 +/- 12 mL (p < 0.001) while the ejection fraction (EF) remained unchanged (44.5 +/- 17% vs 45.1 +/- 20%; p: ns). Volumes before and after treatment were poorly correlated (0.02 < r < 0.35), unlike those in placebo patients (r > 0.6). The average GB volume was increased in 7 out of 10 patients following UDCA (range 7-67%). CFD analysis supports the finding of improved bile flow after treatment. CONCLUSIONS: Unlike results of conventional US parameters of GB motility, CFD analysis shows that UDCA improves GB bile turnover in GS patients.

Prediction and observation of sustained oscillations in a sheared liquid crystalline polymer.

Experimental observations of sustained oscillations of both shear stress and first normal stress differences are reported in flowing liquid crystalline polymers in a limited range of shear rates. The results can be described by considering the response of a rigid-rod model. Depending on the initial conditions, the frequency spectrum of the stress signal contains either one or two characteristic frequencies. This can be explained by the occurrence of either pure "wagging" or the coexistence of wagging and "log-rolling" behavior of the director.

Prediction of chaotic dynamics in sheared liquid crystalline polymers.

A rheological model for rodlike polymers in the nematic liquid-crystalline phase is analyzed to characterize irregular dynamical response under pure shear flows. The model is studied with a continuation approach, and a period doubling scenario is detected. Time series generated via simulation are studied with nonlinear analysis tools to prove the existence of chaotic regimes.