Modeling Colloidal Particle Aggregation Using Cluster Aggregation with Multiple Particle Interactions.

In this study, we investigate the aggregation dynamics of colloidal silica by generating simulated structures and comparing them to experimental data gathered through scanning transmission electron microscopy (STEM). More specifically, diffusion-limited cluster aggregation and reaction-limited cluster aggregation models with different functions for the probability of particles sticking upon contact were used. Aside from using a constant sticking probability, the sticking probability was allowed to depend on the masses of the colliding clusters and on the number of particles close to the collision between clusters. The different models of the sticking probability were evaluated based on the goodness-of-fit of spatial summary statistics. Furthermore, the models were compared to the experimental data by calculating the structures' fractal dimension and mass transport properties from simulations of flow and diffusion. The sticking probability, depending on the interaction with multiple particles close to the collision site, led to structures most similar to the STEM data.

A Highly Accurate Pixel-Based FRAP Model Based on Spectral-Domain Numerical Methods.

We introduce a new, to our knowledge, numerical model based on spectral methods for analysis of fluorescence recovery after photobleaching data. The model covers pure diffusion and diffusion and binding (reaction-diffusion) with immobile binding sites, as well as arbitrary bleach region shapes. Fitting of the model is supported using both conventional recovery-curve-based estimation and pixel-based estimation, in which all individual pixels in the data are utilized. The model explicitly accounts for multiple bleach frames, diffusion (and binding) during bleaching, and bleaching during imaging. To our knowledge, no other fluorescence recovery after photobleaching framework incorporates all these model features and estimation methods. We thoroughly validate the model by comparison to stochastic simulations of particle dynamics and find it to be highly accurate. We perform simulation studies to compare recovery-curve-based estimation and pixel-based estimation in realistic settings and show that pixel-based estimation is the better method for parameter estimation as well as for distinguishing pure diffusion from diffusion and binding. We show that accounting for multiple bleach frames is important and that the effect of neglecting this is qualitatively different for the two estimation methods. We perform a simple experimental validation showing that pixel-based estimation provides better agreement with literature values than recovery-curve-based estimation and that accounting for multiple bleach frames improves the result. Further, the software developed in this work is freely available online.

An overview of the transport of liquid molecules through structured polymer films, barriers and composites - Experiments correlated to structure-based simulations.

Films engineered to control the transport of liquids are widely used through society. Examples include barriers in packaging, wound care products, and controlled release coatings in pharmaceutics. When observed at the macroscopic scale such films commonly appear homogeneous, however, a closer look reveals a complex nano- and microstructure that together with the chemical properties of the different domains control the transport properties. In this review we compare and discuss macroscopic transport properties, measured using the straightforward, yet highly powerful technique "modified Ussing chambers", also denoted side-by-side diffusion cells, for a wide range of structured polymer films and composites. We also discuss and compare the macroscopic observations and conclusions on materials properties with that of lattice Boltzmann simulations of transport properties based on underlying material structure and chemistry. The survey of the field: (i) highlights the use and power of modified Ussing Chambers for determining liquid transport properties of polymer films, (ii) demonstrates the predictability in both directions between macroscopic observations of transport using modified Ussing chambers and structure-based simulations, and (iii) provides experimental and theoretical insights regarding the transport-determining properties of structured polymer films and composites.

Dynamics of capillary transport in semi-solid channels.

Capillary action has been described by Lucas and Washburn and extensively studied experimentally in hard materials, but few studies have examined capillary action in soft materials such as hydrogels. In tissue engineering, cells or dispersions must be often distributed within a hydrogel via microporous paths. Capillary action is one way to disperse such substances. Here, we examine the dynamics of capillary action in a model system of straight capillaries in two hydrogels. The channels had a circular cross-section in the micrometer size range (180-630 µm). The distance travelled over time was recorded and compared with the predictions of Lucas and Washburn. Besides water, we used a sucrose solution and a hydroxyethyl cellulose solution, both with viscosities slightly higher than that of water. The results showed that the distance travelled is proportional to the square root of time, , and that larger capillaries and lower viscosities result, as expected, in faster speeds. However, the absolute experimental values display large discrepancies from the predictions. We demonstrate that several possible reasons for these discrepancies can be ruled out and we describe a novel hypothesis for the cause of the retarded meniscus movement.

Computational high-throughput screening of fluid permeability in heterogeneous fiber materials.

We explore computational high-throughput screening as a design strategy for heterogeneous, isotropic fiber materials. Fluid permeability, a key property in the design of soft porous materials, is systematically studied using a multi-scale lattice Boltzmann framework. After characterizing microscopic permeability as a function of solid volume fraction in the microstructure, we perform high-throughput computational screening of in excess of 35 000 macrostructures consisting of a continuous bulk interrupted by spherical/elliptical domains with either lower or higher microscopic permeability (hence with two distinct microscopic solid volume fractions and therefore two distinct microscopic permeabilities) to assess which parameters determine macroscopic permeability for a fixed average solid volume fraction. We conclude that the fractions of bulk and domains and the distribution of solid volume fraction between them are the primary determinants of macroscopic permeability, and that a substantial increase in permeability compared to the corresponding homogenous material is attainable.

Interplay between flow and diffusion in capillary alginate hydrogels.

Alginate gels with naturally occurring macroscopic capillaries have been used as a model system to study the interplay between laminar flow and diffusion of nanometer-sized solutes in real time. Calcium alginate gels that contain homogeneously distributed parallel-aligned capillary structures were formed by external addition of crosslinking ions to an alginate sol. The effects of different flow rates (0, 1, 10, 50 and 100 µl min(-1)) and three different probes (fluorescein, 10 kDa and 500 kDa fluorescein isothiocyanate-dextran) on the diffusion rates of the solutes across the capillary wall and in the bulk gel in between the capillaries were investigated using confocal laser scanning microscopy. The flow in the capillaries was produced using a syringe pump that was connected to the capillaries via a tube. Transmission electron microscopy revealed an open aggregated structure close to the capillary wall, followed by an aligned network layer and the isotropic network of the bulk gel. The most pronounced effect was observed for the 1 nm-diameter fluorescein probe, for which an increase in flow rate increased the mobility of the probe in the gel. Fluorescence recovery after photobleaching confirmed increased mobility close to the channel, with increasing flow rate. Mobility maps derived using raster image correlation spectroscopy showed that the layer with the lowest mobility corresponded to the anisotropic layer of ordered network chains. The combination of microscopy techniques used in the present study elucidates the flow and diffusion behaviors visually, qualitatively and quantitatively, and represents a promising tool for future studies of mass transport in non-equilibrium systems.

Investigation of the Effect of the Tortuous Pore Structure on Water Diffusion through a Polymer Film Using Lattice Boltzmann Simulations.

Understanding how the pore structure influences the mass transport through a porous material is important in several applications, not the least in the design of polymer film coatings intended to control drug release. In this study, a polymer film made of ethyl cellulose and hydroxypropyl cellulose was investigated. The 3D structure of the films was first experimentally characterized using confocal laser scanning microscopy data and then mathematically reconstructed for the whole film thickness. Lattice Boltzmann simulations were performed to compute the effective diffusion coefficient of water in the film and the results were compared to experimental data. The local porosities and pore sizes were also analyzed to determine how the properties of the internal film structure affect the water effective diffusion coefficient. The results show that the top part of the film has lower porosity, lower pore size, and lower connectivity, which results in a much lower effective diffusion coefficient in this part, largely determining the diffusion rate through the entire film. Furthermore, the local effective diffusion coefficients were not proportional to the local film porosity, indicating that the results cannot be explained by a single tortuosity factor. In summary, the proposed methodology of combining microscopy data, mass transport simulations, and pore space analysis can give valuable insights on how the film structure affects the mass transport through the film.

Probe diffusion in phase-separated bicontinuous biopolymer gels.

Probe diffusion was determined in phase separated bicontinuous gels prepared by acid-induced gelation of the whey protein isolate-gellan gum system. The topological characterization of the phase-separated gel systems is achieved by confocal microscopy and the diffusion measurements are performed using pulsed field gradient (PFG) NMR and fluorescence recovery after photo-bleaching (FRAP). These two techniques gave complementary information about the mass transport at different time- and length scales, PFG NMR provided global diffusion rates in the gel systems, while FRAP enabled the measurements of diffusion in different phases of the phase-separated gels. The results revealed that the phase-separated gel with the largest characteristic wavelength had the fastest diffusion coefficient, while the gel with smaller microstructures had a slower probe diffusion rate. By using the diffusion data obtained by FRAP and the structural data from confocal microscopy, modelling through the lattice-Boltzmann framework was carried out to simulate the global diffusion and verify the validity of the experimental measurements. With this approach it was found that discrepancies between the two experimental techniques can be rationalized in terms of probe distribution between the different phases of the system. The combination of different techniques allowed the determination of diffusion in a phase-separated biopolymer gel and gave a clearer picture of this complex system. We also illustrate the difficulties that can arise if precautions are not taken to understand the system-probe interactions.

Fluid volume kinetics of dilutional hyponatremia; a shock syndrome revisited.

OBJECTIVE: To evaluate whether the pathophysiology of shock syndromes can be better understood by comparing central hemodynamics with kinetic data on fluid and electrolyte shifts. METHODS: We studied the dilutional hyponatremic shock that developed in response to overhydration with electrolyte-free irrigating fluid - the so-called 'transurethral resection syndrome' - by comparing cardiac output, arterial pressures, and volume kinetic parameters in 17 pigs that were administered 150 ml/kg of either 1.5% glycine or 5% mannitol by intravenous infusion over 90 minutes. RESULTS: Natriuresis appeared to be the key factor promoting hypovolemic hypotension 15-20 minutes after fluid administration ended. Excessive sodium excretion, due to osmotic diuresis caused by the irrigant solutes, was associated with high estimates of the elimination rate constant (k10) and low or negative estimates of the rate constant describing re-distribution of fluid to the plasma after translocation to the interstitium (k21). These characteristics indicated a high urinary flow rate and the development of peripheral edema at the expense of plasma volume and were correlated with reductions in cardiac output. The same general effects of natriuresis were observed for both irrigating solutions, although the volume of infused 1.5% glycine had a higher tendency to enter the intracellular fluid space. CONCLUSION: Comparisons between hemodynamics and fluid turnover showed a likely sequence of events that led to hypovolemia despite intravenous administration of large amounts of fluid.

Fluid volume kinetics of dilutional hyponatremia; a shock syndrome revisited

OBJECTIVE: To evaluate whether the pathophysiology of shock syndromes can be better understood by comparing central hemodynamics with kinetic data on fluid and electrolyte shifts. METHODS: We studied the dilutional hyponatremic shock that developed in response to overhydration with electrolyte-free irrigating fluid - the so-called ‘transurethral resection syndrome' - by comparing cardiac output, arterial pressures, and volume kinetic parameters in 17 pigs that were administered 150 ml/kg of either 1.5% glycine or 5% mannitol by intravenous infusion over 90 minutes. RESULTS: Natriuresis appeared to be the key factor promoting hypovolemic hypotension 15-20 minutes after fluid administration ended. Excessive sodium excretion, due to osmotic diuresis caused by the irrigant solutes, was associated with high estimates of the elimination rate constant (k10) and low or negative estimates of the rate constant describing re-distribution of fluid to the plasma after translocation to the interstitium (k21). These characteristics indicated a high urinary flow rate and the development of peripheral edema at the expense of plasma volume and were correlated with reductions in cardiac output. The same general effects of natriuresis were observed for both irrigating solutions, although the volume of infused 1.5% glycine had a higher tendency to enter the intracellular fluid space. CONCLUSION: Comparisons between hemodynamics and fluid turnover showed a likely sequence of events that led to hypovolemia despite intravenous administration of large amounts of fluid. .

Interactions between the volume effects of hydroxyethyl starch 130/0.4 and Ringer´s acetate.

INTRODUCTION: The turnover of Ringer´s solutions is greatly dependent on the physiological situation, such as the presence of dehydration or anaesthesia. The present study evaluates whether the kinetics is affected by previous infusion of colloid fluid. METHODS: Ten male volunteers with a mean age of 22 years underwent three infusion experiments, on separate days and in random order. The experiments included 10 mL/kg of 6% hydroxyethyl starch 130/0.4 (Voluven™), 20 mL/kg of Ringer's acetate, and a combination of both, where Ringer´s was administered 75 minutes after the starch infusion ended. The kinetics of the volume expansion was analysed by non-linear least- squares regression, based on urinary excretion and serial measurement of blood haemoglobin concentration for up to 420 minutes. RESULTS: The mean volume of distribution of the starch was 3.12 L which agreed well with the plasma volume (3.14 L) estimated by anthropometry. The volume expansion following the infusion of starch showed monoexponential elimination kinetics with a half-life of two hours. Two interaction effects were found when Ringer´s acetate was infused after the starch. First, there was a higher tendency for Ringer´s acetate to distribute to a peripheral compartment at the expense of the plasma volume expansion. The translocated amount of Ringer´s was 70% higher when HES had been infused earlier. Second, the elimination half-life of Ringer´s acetate was five times longer when administered after the starch (88 versus 497 minutes, P<0.02). CONCLUSIONS: Starch promoted peripheral accumulation of the later infused Ringer´s acetate solution and markedly prolonged the elimination half-life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01195025.

µPIV methodology using model systems for flow studies in heterogeneous biopolymer gel microstructures.

A methodology for studying flow in heterogeneous soft microstructures has been developed. The methodology includes: (1) model fractal or random heterogeneous microstructures fabricated in PDMS and characterised using CLSM; (2) µPIV measurements; (3) Lattice-Boltzmann simulations of flow. It has been found that the flow behaviour in these model materials is highly dependent on pore size as well as on the connectivity and occurrence of dead ends. The experimental flow results show good agreement with predictions from the Lattice-Boltzmann modelling. These simulations were performed in geometries constructed from 3D CLSM images of the actual PDMS structures. Given these results, mass transport behaviour may be predicted for even more complex structures, like gels or composite material in, e.g., food or biomaterials. This is a step in the direction towards predictive science with regards to tailoring soft biomaterials for specific mass transport properties.

TScratch: a novel and simple software tool for automated analysis of monolayer wound healing assays.

Cell migration plays a major role in development, physiology, and disease, and is frequently evaluated in vitro by the monolayer wound healing assay. The assay analysis, however, is a time-consuming task that is often performed manually. In order to accelerate this analysis, we have developed TScratch, a new, freely available image analysis technique and associated software tool that uses the fast discrete curvelet transform to automate the measurement of the area occupied by cells in the images. This tool helps to significantly reduce the time needed for analysis and enables objective and reproducible quantification of assays. The software also offers a graphical user interface which allows easy inspection of analysis results and, if desired, manual modification of analysis parameters. The automated analysis was validated by comparing its results with manual-analysis results for a range of different cell lines. The comparisons demonstrate a close agreement for the vast majority of images that were examined and indicate that the present computational tool can reproduce statistically significant results in experiments with well-known cell migration inhibitors and enhancers.

Edge detection in microscopy images using curvelets.

BACKGROUND: Despite significant progress in imaging technologies, the efficient detection of edges and elongated features in images of intracellular and multicellular structures acquired using light or electron microscopy is a challenging and time consuming task in many laboratories. RESULTS: We present a novel method, based on the discrete curvelet transform, to extract a directional field from the image that indicates the location and direction of the edges. This directional field is then processed using the non-maximal suppression and thresholding steps of the Canny algorithm to trace along the edges and mark them. Optionally, the edges may then be extended along the directions given by the curvelets to provide a more connected edge map. We compare our scheme to the Canny edge detector and an edge detector based on Gabor filters, and show that our scheme performs better in detecting larger, elongated structures possibly composed of several step or ridge edges. CONCLUSION: The proposed curvelet based edge detection is a novel and competitive approach for imaging problems. We expect that the methodology and the accompanying software will facilitate and improve edge detection in images available using light or electron microscopy.