A viscosity measurement technique for ultra-low sample volumes.

We describe a unique method to measure the viscosity of liquids based on the fluid mechanics of thin films. A drop of sample is spread over a substrate by contacting a blade with the drop and moving the blade across the substrate. The thickness of the film is determined by the capillary number, which measures the competition between the viscous force that smears the liquid over the glass slide and the surface tension that resists the deformation of the interface. We show that the length of the smear for a fixed sample volume is also set by capillary number and can be used as a reliable measure of fluid viscosity. The technique is especially suitable for viscosity measurements of biological fluids where viscosities are low and sample sizes are small. The technique can detect small changes in blood viscosity enabling it to be used as a non-specific, screening tool for diseases and therapeutic interventions.

Critical cracking thickness of drying polymer films.

Polymer coatings are used for a number of applications such as for decorative purposes, to protect surfaces and as functional parts of devices. The mechanical integrity of the coatings is critical to their function and hence it is important that the coatings do not fail during their lifetime. Here, we present a simple model to determine conditions under which drying films of polymer solutions can crack. The model accounts for the properties of the polymer film and substrate and predicts the tensile stress developed in the drying film. As the tensile stress increases and exceeds a critical value, the film relaxes by nucleating a crack. The model predicts a critical thickness below which the film does not crack. The predicted critical cracking thickness is compared with experiments performed on drying films of silicone resin on six different substrates with the value of Young's modulus spanning over six decades. The predicted trend matches the measurements.

Universality in the buckling behavior of drying suspension drops.

Fast evaporation of particle-suspension drops results in complex morphologies of the final dried granules. Understanding the morphological transformations is important to industrial processes such as spray drying where droplets of particulate suspensions are dried at a fast rate to produce granules of thermally sensitive materials. The transformation of an initial spherical shell to complex morphologies of the final dried granule has been attributed to the buckling of particle-packed shells. Here, we demonstrate a universal scaling law for buckling that depends on the particle size, hardness, particle packing and size of drying drop. The critical transition for buckling is set by a dimensionless number that measures the competition between the compressive stress generated by capillary forces and the elastic strength of the packing. The same dimensionless number is also responsible for cracking of drying colloidal films, suggesting a universality in the mechanical behaviour of particle packings saturated with a solvent. These results should enable design of hierarchically structured, buckle-free granules with varying porosity, surface composition and internal structure.

Experimental Evaluation of the Impact of Rapid Environmental Changes on Stress Distribution in Tablet Coatings.

Drying-induced cracks in tablet coatings are undesirable as they not only affect tablet's appearance, but they may also interfere with its function. While it is well known that tensile stresses in the coating are responsible for coating failures, few have measured the stress in tablet coatings, especially when exposed to rapid environmental changes. In this study, two commercial tablet coatings based on Hydroxy Propyl Methyl Cellulose (HPMC) and Poly Vinyl Alcohol (PVA) are exposed to rapid variations in temperature and humidity to observe the variation in residual stress. Reducing temperature at a fixed humidity or reducing humidity at fixed temperature, both lead to high residual stresses. When both the humidity and temperature were reduced together, the residual stresses were very high causing delamination in the PVA-based film and cracking in the HPMC-based film. The changes in residual stress are almost instantaneous for the HPMC-based film while it is slower for the PVA-based film. The results highlight the importance of environmental conditions on the residual stress in the film and the resulting coating failure.

Impact of Rapid Environmental Changes on Stress Distribution in Tablet Coatings: Simulations.

Immediate-release film coatings, also known as "non-functional" film coating, are applied to core tablets to improve product appearance and swallowability, impart taste-masking properties, improve handling and stability of the dosage form, and reduce exposure to active drug substance for caregivers. The coatings have no measurable impact on bio-performance of the drug product but they protect tablets from negative effects of environment such as humidity, oxidation, and light. The mechanical stability and integrity of tablet coatings are therefore important to maintain drug product quality attributes such as appearance and stability. Therefore, environmental conditions under which these coatings may crack are important to understand so as to prevent their occurrence. In this work, we present a novel computational framework to assess the mechanical integrity of tablet coatings exposed to rapid variations in environmental conditions. We perform detailed stress and strain analysis of tablet coatings on tablet surfaces with debossed regions and identify conditions for cracking. Coatings with both elastic and viscoelastic properties are considered. Rapid changes in environmental temperature and humidity can cause differential expansion/contraction of coating and tablet core resulting in stresses that are higher than those experienced during the drying process in a coater. Debossed regions on the tablet surface with sharp surface curvatures act as stress concentrators that nucleate cracks. Small changes in the design of the debossed regions lead to modest reductions in the peak stress. Stress calculations show that coatings that are well bonded to tablet surface can crack only under very extreme conditions.

A low-cost flow cell for flow cytometry.

Flow cytometry is an essential analytical technique used in biomedical diagnostics to measure properties of cells, micro-organisms, and particles. Laser light is scattered from particles focused in a flow cell and collected by light sensors, where the intensity of the scattered light is a function of the scattering angle, the refractive index of the particle and surrounding medium, the wavelength of light, and the size and the shape of the particle. One of the critical parts of the cytometer is the flow cell where the particle stream is constrained into a tight region within 10-30 µm using hydrodynamic focusing. The conventional flow cells use thick quartz flow cells, which are expensive and therefore not suitable for instruments targeted for resource-constrained settings. We demonstrate a compact, economical, bio-compatible flow cell assembly design that incorporates inexpensive and easily available capillaries attached to sturdy polymer fixtures in a simple manner that performs the focusing of a sample stream of particles. The flow cell has been tested by studying the relation between sample core diameter, and sample and sheath flow rates. Small-angle scattering (forward scatter) and wide-angle scattering (side scatter) have been captured for the enumeration and characterization of particles. We show excellent agreement between the size distribution obtained via direct imaging and that obtained from light scattering. The flow cell was also used to successfully size white blood cells in human blood samples.

Moving cracks in drying colloidal films.

Drying colloidal films are encountered in many applications ranging from paints and coatings to ceramic and semiconductor processing. In many cases, shrinkage stresses are generated during drying, which can fracture the film. While much of the previous experimental and theoretical work has focused on cracking in static cracks, there are very few studies on the dynamics of cracks in colloidal coatings. Here, we derive an analytical solution for the stress, displacement, and pressure fields near the crack tip for a steadily moving crack. We consider first the two extreme cases, namely, the undrained limit where the crack motion is much faster than the Darcy flow rate and the opposite extreme of very slow crack propagation, the drained limit. Next, we consider the general case where the timescale for crack-tip motion is comparable to that for the interstitial flow. The results incorporate the micro-structural details of the system including the particle volume fraction and nature of packing, and the mechanical properties of the particles such as shear modulus and Poisson's ratio. While the predicted results are in line with those for brittle materials, the predicted crack speeds are at least an order of magnitude higher than those observed in experiments. We conclude with the possible reasons for the discrepancy.

Osmotic tablet coatings: Drying stress, mechanical properties and microstructure.

The coatings in osmotic tablets play a critical role in controlling the release of active pharmaceutical ingredient. Coatings are formed by spraying dilute polymer solution onto the tablet surface. During drying, the films develop shrinkage stress, which can cause cracking. The coatings are also subject to large tensile stress generated by osmotic pressure during the dissolution process, which may rupture the coating. Despite the role of tensile stress in causing fracture in osmotic tablet coatings, a rigorous quantification of the drying stress, mechanical properties and microstructure is missing. The present work fills this gap via detailed measurement of drying stress, Young's modulus and fracture properties of osmotic tablet coatings of cellulose acetate mixed with two different plasticisers, namely polyethylene glycol and hydroxypropyl cellulose. The measurements were complemented with imaging of the surface and the cross-section of films using scanning electron microscopy so as to relate the drying stress and mechanical properties to the microstructure of the films. The phase separation during the drying process increases the pore size, while simultaneously decreasing the modulus and the peak drying stress of the drying films. The results suggest that films with strong adhesion to the tablet surface will not rupture but if the films delaminate, the drying stress are sufficiently large to cause rupture. The detailed study presented here provides guidelines to the formulator for designing rupture-free osmotic coatings.

Solventborne Polymer Coatings: Drying, Film Formation, Stress Evolution, and Failure.

Polymer coatings find use in a wide range of industrial applications, from conventional paints and coatings in building and construction to the pharmaceutical industry, organic solar cell production, and lithium battery technology. Despite their importance, there are gaps in our understanding of the drying process, the stress development during drying, and their influence on the final mechanical properties of the dried film. This perspective focuses on the fundamental aspects of the drying and film formation process, highlights the gaps, and suggests directions for future work.

Modeling the drying of polymer coatings.

We investigate the drying phenomenon in polymer coatings by developing a model that accounts for the polymer-lean phase (liquid) and the polymer-rich phase (solid), while predicting the stress in the coating. The governing equations are developed for the two phases separately. In the dilute polymer region, the effect of polymer diffusion on its concentration distribution is considered. The polymer-rich phase is modeled as a porous structure, with entangled polymer chains whose diffusive motion is arrested. We employ Biot's theory to model the porous skin and to determine the stress in the coating. The governing equations are solved by employing a finite difference scheme. The effects of polymer diffusion and the skin's permeability on the coating stress are studied. We find good agreement between the predictions of the polymer concentration profile and that obtained from measurements.

Ligand sensing enhances bacterial flagellar motor output via stator recruitment.

It is well known that flagellated bacteria, such as Escherichia coli, sense chemicals in their environment by a chemoreceptor and relay the signals via a well-characterized signaling pathway to the flagellar motor. It is widely accepted that the signals change the rotation bias of the motor without influencing the motor speed. Here, we present results to the contrary and show that the bacteria is also capable of modulating motor speed on merely sensing a ligand. Step changes in concentration of non-metabolizable ligand cause temporary recruitment of stator units leading to a momentary increase in motor speeds. For metabolizable ligand, the combined effect of sensing and metabolism leads to higher motor speeds for longer durations. Experiments performed with mutant strains delineate the role of metabolism and sensing in the modulation of motor speed and show how speed changes along with changes in bias can significantly enhance response to changes in its environment.

Cracking in drying films of polymer solutions.

Thin films of polymer coatings have important industrial applications ranging from paints and coatings to pharmaceuticals. In many applications, the coatings are obtained by applying thin films of dilute polymer solutions, wherein the solvent evaporates to leave behind a thin polymer film. In some cases, the thin films may crack due to shrinkage stresses developed during drying. While a number of studies have focused on the stress development, the phenomenon of cracking in polymer films is not fully investigated. In the present work, thin films of a silicone polymer solution were cast on substrates of varying Young's moduli and investigated for cracking as a function of film thickness and substrate modulus. Micro-Raman spectroscopy measurements show that thin films dry uniformly while thick films form a skin at the top surface leading to slow drying rates. Transverse stresses were measured using the cantilever technique and related to the extent of cracking in the film. We investigated the influence of substrate rigidity on the cracking behavior and found that decreasing the stiffness of the substrate increases the extent of cracking.

Micro-mechanical theory of shear yield stress for strongly flocculated colloidal gel.

Shear yield stress is an important parameter in the processing of colloidal suspensions as it characterizes the solid-to-fluid transition. Although shear rheology of colloidal gel is of widespread academic and industrial interest, first principles theory that connects the microscopic properties to the macroscopic mechanical response in a self-consistent manner is lacking. In this work, we derive a constitutive relation to predict the yield stress for a strongly attractive gel undergoing quasi-static shear deformation as a function of volume fraction, inter-particle potential, contact scale properties and the micro-structure of a strongly-aggregated colloidal gel. The model also predicts the strain at which the colloidal gel network will yield under shear load. To test the model, discrete element simulation is performed using a non-central potential with friction while accounting for the rolling resistance, which is important in real colloidal gel systems. The theoretical predictions are not only in good agreement with the simulation results, but also with previous experiments.

Capillary-Induced Motion of Particles Bridging Interfaces of a Free-Standing Thin Liquid Film.

We demonstrate a new form of capillary force experienced by neutrally buoyant spherical particles adsorbed simultaneously at both interfaces of a thin liquid film of spatially varying thickness. The force is proportional to the slope of the interface and the difference between the local contact angle and the equilibrium value, and exists even when the two bounding interfaces have zero curvature. We derive the expression for the force, which when balanced against the hydrodynamic drag gives the trajectory of the particle. The measured trajectories for spherical particles of varying diameters in thin films compare well with predictions.

Buckling of a drying colloidal drop.

It is well known that drying drops of colloidal dispersions undergo complex morphological transitions involving buckling of a particle-packed outer shell during drying. Although capillary stresses generated during drying have been identified as the cause for buckling, the exact conditions for buckling and its relation to the particle size, rigidity, and nature of packing have not been understood. Here, we derive explicit expressions for the critical capillary pressure for buckling of droplets based on the mechanical properties of the particle network formed during drying and the conditions under which buckling can be avoided. We anticipate our results to form the basis for design of formulations for the pharmaceutical, food and ceramics industry.

Dynamics of Radially Expanding Liquid Sheets.

The process of atomization often involves ejecting thin liquid sheets at high speeds from a nozzle that causes the sheet to flap violently and break up into fine droplets. The flapping of the liquid sheet has long been attributed to the sheet's interaction with the surrounding gas phase. Here, we present experimental evidence to the contrary and show that the flapping is caused by the thinning of the liquid sheet as it spreads out from the nozzle exit. The measured growth rates of the waves agree remarkably well with the predictions of a recent theory that accounts for the sheet's thinning but ignores aerodynamic interactions. We anticipate these results to not only lead to more accurate predictions of the final drop-size distribution but also enable more efficient designs of atomizers.

Free-standing monolayer films of ordered colloidal particles.

We report a novel method for the fabrication of large area, free standing monolayer films of close-packed colloidal particles. The method involves creating a free-standing, wet film of colloidal dispersion containing mono-dispersed hard particles (such as polystyrene or silica) mixed with smaller and softer polymer particles. During drying, hard particles present in the free standing film arrange in a hexagonal close-packed structure in a monolayer while the softer particles fill the interstices, and deform and coalesce to produce a continuous matrix around the hard particles. The deformation of the soft particles dissipates the stress generated during drying thereby preventing rupture of the monolayer film. The method is facile and very general, applicable to a large variety of colloidal particles. The monolayer films exhibit strong iridescence indicating potential application in photonic devices.

Universality in consolidation of colloidal gels.

Consolidation of colloidal dispersions under external load is a complex process involving inter-particle interactions, thermal forces and hydrodynamics. Despite its importance in diverse industrial applications, past studies involving experiments, scaling approaches and simulations are yet to provide a comprehensive understanding of how the microstructure determines the mechanical response in three dimensional colloidal gels. Here, we develop a model that accounts for the microstructural details and predicts the mechanical response under slow, uniaxial compression of a strongly aggregated three dimensional colloidal gel. The particle network assumes a fractal structure that is independent of the strength of inter-particle interactions. While the yield strain changes negligibly during the entire process, the yield stress increases by several orders of magnitude. The predicted yield stress and strain are in close agreement with those observed in simulations and experiments with diverse colloidal systems, suggesting a universality in the consolidation process.

Escherichia coli modulates its motor speed on sensing an attractant.

It is well known that Escherichia coli achieves chemotaxis by modulating the bias of the flagellar motor. Recent experiments have shown that the bacteria vary their swimming speeds as well in presence of attractants. However, this increase in the swimming speed in response to the attractants has not been correlated with the increase in the flagellar motor speed. Using flickering dark-field microscopy, we measure the head-rotation speed of a large population of cells to correlate it with the flagellar motor speed. Experiments performed with wild-type and trg-deletion mutant strains suggest that the cells are capable of modulating the flagellar motor speed via mere sensing of a ligand. The motor speed can be further correlated with the swimming speed of the cells and was found to be linear. These results suggest the existence of a hitherto unknown intra-cellular pathway that modulates the flagellar motor speed in response to sensing of chemicals, thereby making chemotaxis more efficient than previously known.

Dynamics of cracking in drying colloidal sheets.

Colloidal dispersions are known to display a fascinating network of cracks on drying. We probe the fracture mechanics of free-standing films of aqueous polymer-particle dispersions. Thin films of the dispersion are cast between a pair of plain steel wires and allowed to dry under ambient conditions. The strain induced on the particle network during drying is relieved by cracking. The stress which causes the films to crack has been calculated by measuring the deflection of the wires. The critical cracking stress varied inversely to the two-thirds' power of the film thickness. We also measure the velocity of the tip of a moving crack. The motion of a crack has been modeled as a competition between the release of the elastic energy stored in the particle network, the increase in surface energy as a result of the growth of a crack, the rate of viscous dissipation of the interstitial fluid and the kinetic energy associated with a moving crack. There is fair agreement between the measured crack velocities and predictions.