Spatial Concentration Profile Research Articles

Abstracts from The International Society for Aerosols in Medicine 23rd ISAM Congress Boise, Idaho May 22–26, 2021

Abstracts from The International Society for Aerosols in Medicine 23rd ISAM Congress Boise, Idaho May 22–26, 2021

Measurement and verification of concentration-dependent diffusion coefficient: Ray tracing imagery of diffusion process**Project supported by the National Natural Science Foundation of China (Grant No. 11804296), the Joint Key Project of Yunnan Province, China (Grant Nos. 2018FY001-020 and 2018ZI002), and the Fund from the Educational Department of Yunnan Province, China (Grant No. 2016CYH05).

Ray tracing method is used to study the propagation of collimated beams in a liquid–core cylindrical lens (LCL), which has dual functions of diffusion cell and image formation. The diffusion images on the focal plane of the used LCL are simulated by establishing and solving both linear and nonlinear ray equations, the calculated results indicate that the complex imaging results of LCL in inhomogeneous media can be treated by the law of ray propagation in homogeneous media under the condition of small refractive index gradient of diffusion solution. Guided by the calculation conditions, the diffusion process of triethylene glycol aqueous solution is experimentally studied at room temperature by using the LCL in this paper. The spatial and temporal concentration profile Ce(z, t) of diffusion solution is obtained by analyzing diffusion image appearing on the focal plane of the LCL; Then, the concentration-dependent diffusion coefficient is assumed to be a polynomial D(C) = D0 × (1 + α1C + α2C2 + α3C3 + ⋅). The finite difference method is used to solve the Fick diffusion equation for calculating numerically the concentration profiles Cn(z, t). The D(C)of triethylene glycol aqueous solution is obtained by comparing the Cn(z, t) with Ce(z,t). Finally, the obtained polynomial D(C) is used to calculate the refractive index profiles nn(z,t)s of diffusion solution in the used LCL. Based on the ray propagation law in inhomogeneous media and the calculated n(z,t), the ray tracing method is used again to simulate the dynamic images of the whole experimental diffusion process to varify the correctness of the calculated D(C). The method presented in this work opens up a new way for both measuring and verifying the concentration-dependent liquid diffusion coefficients.

CFD simulations to study the effect of ventilation rate on 220Rn concentration distribution in a test house

Measurement and interpretation of the distribution patterns of indoor 220Rn concentration is important for inhalation dosimetry in occupational and residential areas. The shorter half-life of radioactive 220Rn gas greatly affects its patterns resulting in non-homogeneity in the spatial concentration profile. In addition, the distribution profile also changes with variations in the ambient atmospheric parameters (ventilation rate, humidity etc.). The Computational fluid dynamics (CFD) technique has gained a lot of attention in recent times for the prediction and visualization of the distribution pattern of indoor 222Rn/220Rn concentration. This study aims to apply the CFD technique for studying the effect of variations in the ventilation rate on the distribution pattern of the 220Rn concentration in a thoron test house. Experimentally measured 220Rn flux from the surfaces of the experimental test house is used as input for the CFD simulations. Ventilation rate is varied from 0.1 h−1 to 9.0 h−1 and the simulated results of velocity and 220Rn concentration profile for the entire test domain are interpreted. It is observed that the increase of ventilation rate leads to the flow induced turbulence enhancing the mixing of 220Rn in indoor air. Results of this study demonstrate the inter-play of radionuclide half-life and turbulent mixing induced transportation. Inferences are discussed in order to improve the dosimetric deductions for indoor conditions.

Modeling of hydraulic fracturing and designing of online pumping schedules to achieve uniform proppant concentration in conventional oil reservoirs

We present a novel control framework for the closed-loop operation of a hydraulic fracturing process. Initially, we focus on the development of a first-principle model of a hydraulic fracturing process. Second, a novel numerical scheme is developed to efficiently solve the coupled partial differential equations defined over a time-dependent spatial domain. Third, a reduced-order model is constructed, which is used to design a Kalman filter to accurately estimate unmeasurable states. Lastly, model predictive control theory is applied for the design of a feedback control system to achieve uniform proppant concentration across the fracture at the end of pumping by explicitly taking into account the desired fracture geometry, total amount of proppant injected, actuator limitations, and safety considerations. We demonstrate that the proposed control scheme is able to generate a spatial concentration profile which is uniform and close to the target concentration compared to that of the benchmark, Nolte's pumping schedule.

3D electrochemical and ion current imaging using scanning electrochemical-scanning ion conductance microscopy.

Local cell-membrane permeability and ionic strength are important factors for maintaining the functions of cells. Here, we measured the spatial electrochemical and ion concentration profile near the sample surface with nanoscale resolution using scanning electrochemical microscopy (SECM) combined with scanning ion-conductance microscopy (SICM). The ion current feedback system is an effective way to control probe-sample distance without contact and monitor the kinetic effect of mediator regeneration and the chemical concentration profile. For demonstrating 3D electrochemical and ion concentration mapping, we evaluated the reaction rate of electrochemical mediator regeneration on an unbiased conductor and visualized inhomogeneous permeability and the ion concentration 3D profile on a single fixed adipocyte cell surface.

Concentration Sensing by the Moving Nucleus in Cell Fate Determination: A Computational Analysis.

During development of the vertebrate neuroepithelium, the nucleus in neural progenitor cells (NPCs) moves from the apex toward the base and returns to the apex (called interkinetic nuclear migration) at which point the cell divides. The fate of the resulting daughter cells is thought to depend on the sampling by the moving nucleus of a spatial concentration profile of the cytoplasmic Notch intracellular domain (NICD). However, the nucleus executes complex stochastic motions including random waiting and back and forth motions, which can expose the nucleus to randomly varying levels of cytoplasmic NICD. How nuclear position can determine daughter cell fate despite the stochastic nature of nuclear migration is not clear. Here we derived a mathematical model for reaction, diffusion, and nuclear accumulation of NICD in NPCs during interkinetic nuclear migration (INM). Using experimentally measured trajectory-dependent probabilities of nuclear turning, nuclear waiting times and average nuclear speeds in NPCs in the developing zebrafish retina, we performed stochastic simulations to compute the nuclear trajectory-dependent probabilities of NPC differentiation. Comparison with experimentally measured nuclear NICD concentrations and trajectory-dependent probabilities of differentiation allowed estimation of the NICD cytoplasmic gradient. Spatially polarized production of NICD, rapid NICD cytoplasmic consumption and the time-averaging effect of nuclear import/export kinetics are sufficient to explain the experimentally observed differentiation probabilities. Our computational studies lend quantitative support to the feasibility of the nuclear concentration-sensing mechanism for NPC fate determination in zebrafish retina.

Simulation of rail yard emissions transport to the near-source environment

Rail yards are important nodes in the freight transportation network. However, they are also a focus of public health concern when located in highly populated areas. Field characterization of near-rail yard air quality is challenging due to spatially- and temporally-variable emissions. Numerical models can provide valuable insight into factors affecting emission dispersion and resulting near-field air pollution. This study utilizes computational fluid dynamics (CFD) modeling to investigate near-field air pollution surrounding a generic, moderate-sized intermodal rail yard with emissions of a neutrally buoyant gaseous pollutant. Rail yard and surrounding neighborhood structures were added in succession to a base case to study the influence of surface roughness on the generic pollutant's spatial concentration profile. A spatially weighted emissions scenario revealed highly variable pollutant levels in downwind neighborhoods, strongly affected by wind direction. Rail yard topography resulted in a modest increase in near-field pollution levels. Densely located two-story homes surrounding the rail yard reduced downwind concentrations by 16% and 15% at 25 m and 100 m downwind of the rail yard boundary, respectively. A 6 m boundary wall surrounding the rail yard, with four open sections enabling traffic flow, reduced downwind pollution levels by 25% and 12% at 25 m and 100 m downwind, respectively. While average pollution levels were lower with the addition of neighborhoods and a surrounding boundary wall, high spatial variability in pollution levels resulted in some near-field areas experiencing increased pollution that are offset by reductions in other areas.

The Spatial Distribution of Nitric Oxide‐evoked cGMP Can Produce Biphasic Effects on Na+/H+ Exchanger‐1 Activity in the Rat Ventricular Myocyte

We investigated the effects of nitric oxide (NO)‐signalling on Na+/H+ Exchanger (NHE1), the principal H+‐extruding protein in ventricular cardiac myocytes.H+‐extrusion by NHE1 was activated by ammonium pre‐pulse (HEPES‐buffered Tyrode) and measured by pH‐sensitive fluorescence (cSNARF1).NHE1 was inhibited by high [NO] (20nM; released from NOC‐12), but activated by low [NO] (2nM; NOC‐12 plus NO‐scavenger CPTIO). These biphasic effects were blocked by the guanylate cyclase (GC) inhibitor ODQ, implicating the NO‐GC‐cGMP pathway. The stimulatory effect of low [NO] was mimicked by the phosphodiesterase (PDE)‐resistant cGMP analogue, 8pCPTcGMP. In contrast, the inhibitory effect of high [NO] may be attributed to a cGMP‐evoked rise in cAMP (NHE1 inhibitor) involving PDE3 (high cGMP inhibits cAMP degradation by PDE3). Indeed, the inhibitory effect of high [NO] was mimicked by the PDE3 inhibitor cilostamide. To explore the spatial aspects of NO signalling, dual microperfusion was used to restrict [NO] to the proximal region of the cell (confirmed with DAR4 fluorescence). High [NO] applied locally to one end of the cell stimulated NHE1 distally, beyond the compartmentalized [NO] zone, in an ODQ‐sensitive manner, arguing against direct S‐nitros(yl)ation. Results suggest that cGMP is a mobile messenger, reaching low concentrations distally, sufficient to stimulate NHE1 but below the threshold for evoking a local rise in cAMP.The net effect of NO on NHE1 activity is set by the balance between activation by cGMP and inhibition via cGMP‐cAMP coupling. This balance depends on the spatial concentration profile of cGMP evoked by NO. NO can modulate intracellular pH with an unprecedented degree of plasticity.Funded by BHF

Methodology for Optical Imaging of NAPL 3D Distribution in Transparent Porous Media

Three-dimensional mapping of non-aqueous phase liquid (NAPL) distribution within saturated porous media is an important issue in bench-scale geo-environmental studies. In this paper, a methodology for optical imaging of 3D multiphase liquid distribution is presented. The natural aquifer is simulated using a transparent soil surrogate that represents the macroscopic behavior of natural sand. To achieve transparency transparent fused quartz grains were saturated with a matched refractive index mineral oil solution that represents the natural aquifer and injected with a green-dyed sucrose solution to simulate dense NAPL contamination. The spatial volume was first estimated and then reconstructed using orthogonal images acquired at the model boundaries at various stages of contamination and remediation. Color space analysis was employed to segment the NAPL zone and transform pixel information into integrated concentration values using a previously published calibration model. The chromatic components CR and a of YCBCR and Lab, respectively, were combined to render the spatial concentration profile. A novel iterative reconstruction algorithm named 3D carving was used to resolve three 2D projections into a 3D model. The results show that the proposed methodology provides better efficacy for NAPL zone reconstruction in comparison with conventional image analysis routines. The technology presented in this paper is a sustainable, fast, accurate, non-intrusive, and inexpensive method for spatial mapping of contamination zones using bench-scale transparent soil models.

Visualization of subcutaneous insulin injections by x-ray computed tomography

We report how the three-dimensional structure of subcutaneous injections of soluble insulin can be visualized by x-ray computed tomography using an iodine based contrast agent. The injections investigated are performed ex vivo in porcine adipose tissue. Full tomography scans carried out at a laboratory x-ray source with a total acquisition time of about 1 min yield CT-images with an effective pixel size of 109 × 109 μm2. The depots are segmented using a modified Chan–Vese algorithm and we are able to observe differences in the shape of the injection depot and the position of the depot in the skin among equally performed injections. To overcome the beam hardening artefacts, which affect the quantitative prediction of the volume injected, we additionally present results concerning the visualization of two injections using synchrotron radiation. The spatial concentration distribution of iodine is calculated to show the dilution of the insulin drug inside the depot. Characterisation of the shape of the depot and the spatial concentration profile of the injected fluid is important knowledge when improving the clinical formulation of an insulin drug, the performance of injection devices and when predicting the effect of the drug through biomedical simulations.

Special Issue on Toxics and Pathogens in the Environment

Special Issue on Toxics and Pathogens in the Environment

WE‐G‐220‐02: Ultrasound Symposium: Computational Modeling of High‐Intensity Focused Ultrasound Mediated Drug Delivery

Purpose: Low‐Temperature Sensitive Liposomes (LTSL) are drug delivery vehicles with that release the drug upon heating above ∼40 °C. The combination of LTSL with local heat generated by focused ultrasound may thus allow non‐invasively targeted drug delivery. The complex interplay between heat based cancer treatments like thermal ablation and chemotherapy requires computational models to identify the relationship between heat exposure and pharmacokinetics in order to optimize drug delivery. Methods: We developed mathematical models combining a model of tissue heating with a drug delivery model. Deposited HIFU energy (i.e. SAR) was calculated from phantom experiments, and used as input data for the model. Microvascular perfusion was modeled according to Pennesˈ Bioheat Equation, and was varied with temperature. A spatio‐temporal multi‐compartment pharmacokinetic model was created to describe the release of doxorubicin (DOX) from LTSL into the tumor plasma, subsequent transport into the interstitium, and finally uptake by the cells. Tissue was heated for varying times to target temperatures between 42 °C and 60 °C at the ultrasound focal spot, and spatio‐temporal drug concentration profiles were calculated. Results: At target temperatures in the hyperthermic range, maximum drug concentrations of ∼ 9 ug/g were observed in the central heating area, with very localized drug deposition. At ablative temperatures similar maximum drug concentrations were observed, with a ring‐like spatial concentration profile due to progressive shut‐down of perfusion at temperatures above 45 °C. Concentration increased approximately linearly with time during the examined time periods.Conclusion: HIFU mediated targeted drug delivery via LTSL locally keeps plasma concentration of bioavailable drug high during hyperthermic temperature exposure, allowing for localized cellular uptake at heated locations. Heating induced temperature changes in perfusion considerably affect drug delivery, particularly if cessation of perfusion is induced. Multi‐ physics mathematical models may allow for optimization of heat‐mediated targeted drug delivery from LTSL, as well as for treatment planning.Educational objectives:1. Learn basic components of a drug delivery model2. Learn how computational models allow optimization of drug delivery3. Learn importance of treatment planning in targeted drug delivery

Concentration Profiles and Spatial Moments for Reactive Transport through Porous Media

AbstractWe use an advection-dispersion-reaction equation, which accounts for both physical and chemical nonequilibrium, to study the effect of heterogeneity of the porous media on a spatial concentration profile. Distance-dependent and time-dependent dispersivity is used to account for the heterogeneity. A sensitivity analysis has been performed to illustrate the effect of various factors on breakthrough curves for reactive transport through homogeneous porous media. An exponential function for the dispersion coefficient is used to simulate experimental data for spatial moments of nonreactive and reactive chemicals. An implicit finite-difference method has been used for the numerical solution of the governing equations. The distance-dependent dispersion coefficient resulted in higher peak value of concentration than the equivalent time-dependent dispersion coefficient. With an increase in time, the spatial concentration profile is steeper for the distance-dependent dispersion coefficient. Experimental dat...

Heterogeneous studies in pulping of wood: Modelling mass transfer of dissolved lignin

A kinetic model is proposed for the mass transfer of dissolved lignin from the interior of the chip to the bulk liquor, during the kraft pulping of Eucalyptus globulus wood. The model is based on extensive experimental data which include the dissolved lignin concentration both inside and outside the chips, along pulping time. The lignin concentration in the entrapped liquor was shown to be much higher than the one in the free liquor, and reached a maximum value during the cook. The model follows a lumped parameter estimation approach, where the spatial concentration profile of lignin inside the chip is represented by its average. This strategy enables estimating the effective diffusion coefficient that characterizes the internal resistance to mass transfer. This coefficient was expressed by an Arrhenius-type equation with an activation energy for diffusion of 29 kJ mol −1, multiplied by the cooking yield raised to an exponent whose estimated value was 5. This high value corresponds to an increasing resistance to lignin diffusion along pulping time. The resistance to mass transfer in the film surrounding the wood chips was found to have a contribution of 20–30% to the overall mass transfer resistance at the beginning of the cook, which is significant and should not be neglected. The model proved to enable a good fitting of the experimental data on the dissolved lignin concentration in the free liquor.

Direct Observation of Flow-Concentration Coupling in a Shear-Banding Fluid

We present the first direct evidence of flow-concentration coupling in a shear-banding fluid using the first measurements of scanning narrow-aperture flow ultrasmall-angle neutron scattering. Transmission measurements in the flow-gradient shear plane determine the spatial concentration profile of the material. Shear banding in a model fluid composed of wormlike micelles near an equilibrium isotropic-nematic transition is shown to be concomitant with shear-induced demixing, providing new insight into the nonequilibrium phase behavior of the fluid. The new experimental approach and analysis apply generally to any fluid, and will enable more rigorous testing of theories for shear-banding and shear-induced phase separation.

Time and spatial concentration profile inside a membrane by means of a memory formalism

In this note, the profile concentration of diffusing particles inside a membrane has been calculated on the basis of the Fick diffusion equation modified by introducing a memory formalism. In highly heterogeneous systems, such as biological membranes, the intrinsic structural complexity of the medium restricts the applicability of continuum diffusion models and suggests that diffusion parameters could depend at a certain time or position on what happens at preceding times (diffusion with memory). Here, we deal with two particular cases, the diffusion of glucose across an erythrocyte membrane, when the concentration at both sides of the membrane are assigned, and the permeation transport of small molecular weight solute through an artificial hydrogel polymeric membrane. However, the present procedure can be easily extended to more general conditions. The knowledge of the concentration profile within a membranous structure, which is usually not easily experimentally accessible, completes the description of the rather complex phenomenon of the transport across a highly structured confined medium and can also lead to an improvement in controlled drug-delivery systems.

Universal Ratios of Characteristic Lengths in Semidilute Polymer Solutions

We use experimental and simulation data from the literature to infer five characteristic lengths, denoted $\xi_s$, $\xi_f$, $\xi_\Pi$, $\xi_\phi$, and $\xi_D$ of a semidilute polymer solution. The first two of these are defined in terms of scattering from the solution, the third is defined in terms of osmotic pressure, the fourth by the spatial monomer concentration profile, and the last by co-operative diffusion. In a given solution the ratios of any of these five lengths are expected to be universal constants. Knowing these constants thus allows one to use one measured property of a solution as a means of inferring others. We calculate these ratios and estimate their uncertainties for solutions in theta as well as good-solvent conditions. The analysis is strengthened by use of scattering properties of isolated polymers inferred from computer simulations.

A Computational Study into Thermally Induced Phase Separation in Polymer Solutions under a Temperature Gradient

The influence of spatial temperature on the morphological development in polymer solutions undergoing thermally induced phase separation was studied using mathematical modeling and computer simulation. The one-dimensional mathermatical model describing this phenomenon incorporates the nonlinear Cahn-Hilliard theory for spinodal decomposition (SD), the Flory-Huggins theory for polymer solution thermodynamics, and the slow-mode theory and Rouse-law for polymer diffusion. The resulting governing equation and auxiliary conditions were solved using the Galerkin finite element method. The temporal evolution of the spatial concentration profile from the computer simulation illustrates that an anisotropic morphology (see Figure) results when a temperature gradient is maintained along the polymer solution sample. The final anisotorpic morphology depends on the overali phase separation time. If phase separation is terminated at very early stages, smaller (larger droplets are formed in the lower (higher) temperature regions due to be deep (shallow) quench effect. On the other hand, if phase separation is allowed to proceed for a long period of time. then larger droplets are formed in the low-temperature regions, whereas smaller droplets are developed at higher temperatures. This is due to the fact that the low-temperature regions have entered the late stage of SD. while the high temperture regions are still in the early stage of SD.The presence of a temperature gradient during thermally induced phase separation introduced spatial variations in the change of chemical potential, which is the driving force for phase separation. These numerical results provide a better understanding or the control and optimization during the fabrication of anisotropic polymeric materials using the thermally induced phase separation technique.

A Novel Voltammetric Probe with Individually Addressable Gel-Integrated Microsensor Arrays for Real-Time High Spatial Resolution Concentration Profile Measurements

In this article, the development of a novel voltammetric system for real-time, high spatial resolution trace element concentration profile measurements at the sediment-water interface, or other interfaces, is reported. The heart of this system is a novel gel-integrated Hg-plated Ir-based 64 individually addressable microsensor arrays. The gel membrane minimizes fouling problems and insures high stability of the Hg semidrops. Measurements were performed simultaneously over the 64 lines using a powerful multiplexing system and a single potentiostat. The voltammetric probe and sensor have been described in detail. This voltammetric system has been characterized by running both cyclic voltammetry (CV) in hexacyanoferrate(III) solution using the gel-integrated Ir-based microsensor and square-wave anodic stripping voltammetry (SWASV) in Pb(II) and Cd(II) solution using the gel-integrated Hg-plated Ir-based microsensor. The results showed that reproducible and reliable simultaneous measurements can be obtained over the 64 individually addressable lines even with fast dynamic techniques such as SWASV. Moreover, theoretical and experimental data were in good agreement. Profiling capability has also been demonstrated.

A Novel Voltammetric Probe with Individually Addressable Gel-Integrated Microsensor Arrays for Real-Time High Spatial Resolution Concentration Profile Measurements

A Novel Voltammetric Probe with Individually Addressable Gel-Integrated Microsensor Arrays for Real-Time High Spatial Resolution Concentration Profile Measurements