Impact of a polysidpersed fuel distribution on the ignition characteristic.

Determining the thermal profile of ignition is important because the desired ignition behavior varies with the objective. For example, extended ignition prolongs the time that the engine runs; however, fast ignition offers a higher power gain. The pollution caused by undesirable chemical reactions, as determined by the ignition profile, is another important aspect. Based on a previously developed method, we examined the impact of different theoretical particle size distributions (PSDs) on the thermal ignition profile. We compared different PSDs of polydispersed fuel spray with normal distributions with various means, each corresponding to the same fuel volume.  Our results revealed a significant dependence of thermal ignition on the PSD. Systems that comprised only low-radius droplets did not reach ignition, whereas systems with only high-radius droplets required a long time to establish ignition. Moreover, the change in the mean droplet radius unexpectedly resulted in a double hump in the maximum temperature of the combustion process.

DECODE: Contamination-Free Digital CRISPR Platform for Point-of-Care Detection of Viral DNA/RNA.

Rapid and precise nucleic acid testing at the point-of-care (POC) is essential for effective screening and management of infectious diseases. Current polymerase-based molecular diagnostics often suffer from potential cross-contamination issues, particularly in POC settings. Here, we introduce DECODE, a contamination-free nucleic acid detection platform integrating digital microfluidics (DMF) for nucleic acid extraction and a digital CRISPR amplification-free assay for pathogen detection. The digital CRISPR assay demonstrates sensitivity, detecting target DNA and RNA in the reaction mixture at concentrations of 10 and 5 copies/µL, respectively. Leveraging DMF-extracted samples enhances the performance of the digital CRISPR amplification-free assay. DECODE offers a sample-to-result workflow of 75 min using compact devices. Validation studies using clinical samples confirm DECODE's robust performance, achieving 100% sensitivity and specificity in detecting HPV18 from cervical epithelial cells and influenza A from nasal swabs. DECODE represents a versatile, contamination-free detection platform poised to enhance integrated public health surveillance efforts.

Measuring Concentration of Nanoparticles in Polydisperse Mixtures Using Interferometric Nanoparticle Tracking Analysis.

Quantitative measurements of nanoparticle concentration in liquid suspensions are in high demand, for example, in the medical and food industries. Conventional methods remain unsatisfactory, especially for polydisperse samples with overlapping size ranges. Recently, we introduced interferometric nanoparticle tracking analysis (iNTA) for high-precision measurement of nanoparticle size and refractive index. Here, we show that by counting the number of trajectories that cross the focal plane, iNTA can measure concentrations of subpopulations in a polydisperse mixture in a quantitative manner and without the need for a calibration sample. We evaluate our method on both monodisperse samples and mixtures of known concentrations. Furthermore, we assess the concentration of SARS-CoV-2 in supernatant samples obtained from infected cells.

A mechanistic kinetic model for lipid oxidation in Tween 20-stabilized O/W emulsions.

Models predicting lipid oxidation in oil-in-water (O/W) emulsions are a requirement for developing effective antioxidant solutions. Existing models do, however, not include explicit equations that account for composition and structural features of O/W emulsions. To bridge this gap, a mechanistic kinetic model for lipid oxidation in emulsions is presented, describing the emulsion as a one-dimensional three phase (headspace, water, and oil) system. Variation in oil droplet sizes, overall surface area of oil/water interface, oxidation of emulsifiers, and the presence of catalytic transition metals were accounted for. For adequate predictions, the overall surface area of oil/water interface needs to be determined from the droplet size distribution obtained by dynamic and static light scattering (DLS, SLS). The kinetic model predicted well the formation of oxidation products in both mono- and polydisperse emulsions, with and without presence of catalytic transition metals.

Modeling the Temperature-Dependent Size Change of Polydisperse Nano-objects using a Deep Generative Model.

Modern microscopy techniques can be used to investigate soft nano-objects at the nanometer scale. However, time-consuming microscopy measurements combined with low numbers of observable polydisperse objects often limit the statistics. We propose a method for identifying the most representative objects from their respective point clouds. These point cloud data are obtained, for example, through the localization of single emitters in super-resolution fluorescence microscopy. External stimuli, such as temperature, can cause changes in the shape and properties of adaptive objects. Due to the demanding and time-consuming nature of super-resolution microscopy experiments, only a limited number of temperature steps can be performed. Therefore, we propose a deep generative model that learns the underlying point distribution of temperature-dependent microgels, enabling the reliable generation of unlimited samples with an arbitrary number of localizations. Our method greatly cuts down the data collection effort across diverse experimental conditions, proving invaluable for soft condensed matter studies.

Wet scavenging of multi-mode 137Cs aerosols following the Fukushima accident: Size-resolved microphysics modeling with observed diameters.

Wet scavenging was critical in the atmospheric transport of 137Cs aerosols following the Fukushima accident. The aerosol size diversity and related microphysical processes produce complex behaviors during wet scavenging. Such behaviors are difficult to investigate using traditional simplified size distributions, resulting in inaccurate modeling. This study establishes an improved size-resolved wet scavenging model that considers the activation process. Using this model, five monodisperse simulations with five representative observed diameters with realistic solubility setting are performed to investigate the spatiotemporal wet scavenging behaviors of 137Cs aerosols. One polydisperse simulation with an empirical size distribution is also validated against the observation. The results reveal that 137Cs aerosols with diameters of 0.6 and 2.0 µm are mainly subject to below-cloud scavenging, which makes a significant contribution to low-deposition areas (<300 kBq/m2). For 137Cs aerosols with diameters of 6.4, 15, and 30 µm, in-cloud scavenging dominates, and the resulting depositions make significant contributions in high-deposition areas. The polydisperse results satisfy the criteria for good performance and better agree with the size, and deposition observations than the five monodisperse simulations, whereas for the concentration, the results show a similar RANK2 with the best mono1 and mono2 cases and reach the satisfactory criteria. These findings reveal the complex behavior and wet scavenging process of multi-mode 137Cs aerosols, improving our understanding and modeling.

Effect of Polydispersity on the Structural and Magnetic Properties of a Magnetopolymer Composite.

When using magnetopolymer composites in high-precision industrial and biomedical technologies, the problem of predicting their properties in an external magnetic field arises. In this work, we study theoretically the influence of the polydispersity of a magnetic filler on a composite's equilibrium magnetization and on the orientational texturing of magnetic particles formed during polymerization. The results are obtained using rigorous methods of statistical mechanics and Monte Carlo computer simulations in the framework the bidisperse approximation. It is shown that by adjusting the dispersione composition of the magnetic filler and the intensity of the magnetic field at which the sample's polymerization occurs, it is possible to control the composite's structure and magnetization. The derived analytical expressions determine these regularities. The developed theory takes into account dipole-dipole interparticle interactions and therefore can be applied to predict the properties of concentrated composites. The obtained results are a theoretical basis for the synthesis of magnetopolymer composites with a predetermined structure and magnetic properties.

Parameterization of below-cloud scavenging for polydisperse fine mode aerosols as a function of rain intensity.

The below-cloud aerosol scavenging process by precipitation is one of the most important mechanisms to remove aerosols from the atmosphere. Due to its complexity and dependence on both aerosol and raindrop sizes, wet scavenging process has been poorly treated, especially during the removal of fine particles. This makes the numerical simulation of below-cloud scavenging in large-scale aerosol models unrealistic. To consider the slip effects of submicron particles, a simplified expression for the diffusion scavenging was developed by approximating the Cunningham slip correction factor. The derived analytic solution was parameterized as a simple power function of rain intensity under the assumption of the lognormal size distribution of particles. The resultant approximated expression was compared to the observed data and the results of previous studies including a 3D atmospheric chemical transport model simulation. Compared with the default GEOS-Chem coefficient of 0.00106R0.61 and the observation-based coefficient of 0.0144R0.9268, the coefficient of a and b in Λm = aRb spread in the range of 0.0002- 0.1959 for a and 0.3261- 0.525 for b over a size distribution of GSD of 1.3-2.5 and a geometric mean diameter of 0.01- 2.5 µm. Overall, this study showed that the scavenging coefficient varies widely by orders of magnitude according to the size distribution of particles and rain intensity. This study also demonstrated that the obtained simplified expression could consider the theoretical approach of aerosol polydispersity. Our proposed analytic approach showed that results can be effectively applied for reduced computational burden in atmospheric modeling.

A new modelling approach for dissolution of polydisperse powders.

A new modelling approach for dissolution of polydisperse powders is developed within the framework of the classical Noyes-Whitney/Nernst-Brunner analysis. Its distinguishing feature is that the underlying continuous particle-size distribution is retained. Two different but related dependencies of the diffusion-layer thickness on particle size are considered. First, a power-law dependence that interpolates between a thickness that is proportional to (or equals) the particle radius (obtained when the exponent equals 1) and a constant thickness (obtained when the exponent is 0). Second, a piecewise linear function such that the thickness equals the particle radius for sufficiently small particles and is constant for larger ones. The modelling approach is exemplified by consideration of a lognormal particle-size distribution. Highly accurate closed-form expressions for the fraction of dissolved drug are obtained for dissolution under sink conditions (which are exact if the diffusion-layer thickness is radius-independent). Moreover, it is demonstrated that any result derived under sink conditions can be reused to determine the fraction of dissolved/absorbed drug under non-sink conditions, using the concept of a retarded time. Comparison with literature data and experiments are used to validate the modelling approach and to demonstrate its usefulness in a practical context.

Product Quality Research for Developing and Assessing Regulatory Submissions for Generic Cyclosporine Ophthalmic Emulsions.

Approval of the first generic 0.05% cyclosporine ophthalmic emulsion (COE) in the U.S. represents a milestone achievement of the science and research program in the U.S. Food and Drug Administration's Center for Drug Evaluation and Research (CDER). COE is a locally acting complex drug product indicated to increase tear production in patients whose production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. The path to approval required overcoming numerous scientific challenges to determining therapeutic equivalence to the reference listed drug. Researchers in CDER's Office of Pharmaceutical Quality and Office of Generic Drugs developed a quality by design approach to understand the effects of process and formulation variables on the product's critical quality attributes, including globule size distribution (GSD), turbidity, viscosity, zeta potential, surface tension, and osmolality. CDER researchers explored multiple techniques to perform physicochemical characterization and analyze the GSD including laser diffraction, nanoparticle tracking analysis, cryogenic transmission electron microscopy, dynamic light scattering, asymmetric field flow fractionation, and two-dimensional diffusion ordered spectroscopy nuclear magnetic resonance. Biphasic models to study drug transfer kinetics demonstrated that COEs with qualitative and quantitative sameness and comparable GSDs, analyzed using earth mover's distance, can be therapeutic equivalents. This body of research facilitated the review and approval of the first U.S. generic COE. In addition, the methods and fundamental understanding developed from this research may support the development and assessment of other complex generics. The approval of a generic COE should improve the availability of this complex drug product to U.S. patients.

Disentangling polydisperse biomolecular systems by Chemometrics decomposition of SAS data.

The structural characterization of polydisperse systems consisting of multiple coexisting species or conformations is very challenging or impossible with classical approaches. As a consequence, the structural bases of relevant questions related to protein folding, transient partner recognition, conformational transitions or fibrillation remain poorly understood. Small-Angle Scattering (SAS) techniques structurally probe species present in solution in a population-weighted manner, enabling the inspection of polydisperse systems. However, decomposition of these data to derive the contribution of individual components is not straightforward and requires the acquisition of large SAS datasets and adapted mathematical tools. Here, we present a detailed procedure for the usage of the program COSMiCS for the decomposition of SAS datasets. COSMiCS adapts the popular MCR-ALS chemometrics routine to the specificities of scattering data. Through the use of multiple SAS representations, the appropriate scaling of the data and the possibility to simultaneously decompose multiple orthogonal datasets, COSMiCS efficiently disentangles mixtures and provides species-specific structural and thermodynamic/kinetic information of the process under investigation. Although exemplified for a transient biomolecular interaction, our chemometrics strategy can be applied to many other biological processes that can be straightforwardly probed in last generation SAS beamlines. Indeed, recent experimental setups, including microfluidics and stop-flow devices, coupled to fast-reading detectors can yield large concentration or time-dependent datasets that can be decomposed with COSMiCS. Importantly, as an open-source code, previously known features of the system of interest can be introduced as constraints in the optimization, producing robust solutions for biological systems of increasing complexity.

Two-way coupling and Kolmogorov scales on inhaler spray plume evolutions from Ventolin, ProAir, and Qvar.

Previous numerical studies of pulmonary drug delivery using metered-dose inhalers (MDIs) often neglected the momentum transfer from droplets to fluid. However, Kolmogorov length scales in MDI flows can be comparable to the droplet sizes in the orifice vicinity, and their interactions can modify the spray behaviors. This study aimed to evaluate the two-way coupling effects on spray plume evolutions compared to one-way coupling. The influences from the mass loading, droplet size, and inhaler type were also examined. Large-eddy simulation and Lagrangian approach were used to simulate the flow and droplet motions. Two-way coupled predictions appeared to provide significantly improved predictions of the aerosol behaviors close to the Ventolin orifice than one-way coupling. Increasing the applied MDI dose mass altered both the fluid and aerosol dynamics, notably bending the spray plume downward when applying a dose ten times larger. The droplet size played a key role in spray dynamics, with the plume being suppressed for 2-µm aerosols and enhanced for 20-µm aerosols. The Kolmogorov length scale ratio dp/η correlated well with the observed difference in spray plumes, with suppressed plumes when dp/η < 0.1 and enhanced plumes when dp/η > 0.1. For the three inhalers considered (Ventolin, ProAir, and Qvar), significant differences were predicted using two-way and one-way coupling despite the level and manifestation of these differences varied. Two-way coupling effects were significant for MDI sprays and should be considered in future numerical studies.

Count- and mass-based dosimetry of MDI spray droplets with polydisperse and monodisperse size distributions.

Most previous numerical studies of inhalation drug delivery used monodisperse aerosols or quantified deposition as the ratio of deposited particle number over the total number of released particles (i.e., count-based). These practices are reasonable when the aerosols have a sufficiently narrow size range. However, spray droplets from metered-dose inhalers (MDIs) are often polydisperse with a wide size range, so using monodisperse aerosols and/or count-based deposition quantification may lead to significant errors. The objective of this study was to develop a mass-based dosimetry method and evaluate its performance in lung delivery in a mouth-lung (G9) geometry with an albuterol-CFC inhaler. The conventional practices (monodisperse and polydisperse-count-based) were also simulated for comparison purposes. The MDI actuation in the open space was studied using both high-speed imaging and LES-Lagrangian simulations. Experimentally measured spray velocities and size distribution were implemented in the computational model as boundary conditions. Good agreement was achieved between recorded and simulated spray plume evolution spatially and temporally. The polydisperse-mass-based predictions of MDI doses compared favorably with the measurements in all three regions considered (device, mouth-throat, and lung). Significant errors in MDI regional deposition were predicted using the monodisperse and count-based methods. The new polydisperse-mass-based method also predicted local deposition hot spots that were one order of magnitude higher in intensity than the two conventional methods. The results of this study highlighted that a presentative polydisperse size distribution and appropriate deposition quantification method should be applied to reliably predict the MDI drug delivery in the human respiratory tract.

Characterising sedimentation velocity of primary waste water solids and effluents.

Sedimentation in waste water is a heavily studied topic, but mainly focused on hindered and compression settling in secondary sludge, a largely monodispersed solids, where bulk sedimentation velocity is effectively described by functions such as double Vesilind (Takacs). However, many waste water solids, including primary sludge and anaerobic digester effluent are polydispersed, for which application of velocity functions is not well understood. These systems are also subject to large concentration gradients, and poor availability of settling velocity functions has limited design and computational fluid dynamic (CFD) analysis of these units. In this work, we assess the use of various sedimentation functions in single and multi-dimensional domains, comparing model results against multiple batch settling tests at a range of high and low concentrations. Both solids concentration and sludge bed height (interface) over time are measured and compared. The method incorporates uncertainty analysis using Monte Carlo regression, DIRECT (dividing rectangles), and Newton optimisation. It was identified that a double Vesilind (Takacs) model was most effective in the dilute regime (<1%v/v), but could not effectively fit high solids concentrations (>1%v/v) without a substantial (50%) decrease in effective maximum sedimentation velocity (V0). Other parameters (Rh, Rp) did not change. A power law velocity model (Diehl) was significantly less predictive at low concentrations, and not significantly better at higher concentrations. The optimised model (with reduction in V0) was tested vs a standard (optimised) double Vesilind velocity model in a simple primary sedimentation unit, and resulted in deviation from -12% to +18% in solids capture prediction from underload to overload (washout) conditions, indicating that the effect is important in CFD based analysis of these systems.

Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model.

Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation-inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI-mouth-lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth-throat, and lung. Concerning the device-patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth-throat loss and increased lung doses in both the central and peripheral regions.

Analysis of improved oral drug delivery with different helical stream inhalation modes.

A challenging aspect of pulmonary drug delivery devices, e.g., metered dose inhalers (MDIs), is to deliver therapeutic drugs to prescribed target locations at the required dosage level. In this study, validated computer simulations of micron-drug inhalation with angled or radially positioned helical fluid-particle streams are simulated and analyzed. For a suitable swirl number significant improvements in drug delivery, especially to deeper lung regions, have been achieved. Specifically, considering realistic polydisperse particle distributions at the mouth inlet for a subject-specific upper lung airway geometry, a 10-degree angled helical stream increased the local efficacy by up to 26% in comparison to a conventional helical stream, causing an overall dosage of about 60% to the deep lung. Considering lobe-specific drug targeting scenarios, while using an off-center, i.e., radially well positioned, helical-flow mouthpiece, the local particle-deposition efficacy increased from 9% to 24% in the left lobe and from 25% to 38% in the right lobe in comparison to conventional drug-aerosol stream released from the central position. The efficacy of helical streams for pulmonary drug delivery applications has been established.

Using ultrasonic attenuation in cortical bone to infer distributions on pore size.

In this work we infer the underlying distribution on pore radius in human cortical bone samples using ultrasonic attenuation data. We first discuss how to formulate polydisperse attenuation models using a probabilistic approach and the Waterman Truell model for scattering attenuation. We then compare the Independent Scattering Approximation and the higher-order Waterman Truell models' forward predictions for total attenuation in polydisperse samples. Following this, we formulate an inverse problem under the Prohorov Metric Framework coupled with variational regularization to stabilize this inverse problem. We then use experimental attenuation data taken from human cadaver samples and solve inverse problems resulting in nonparametric estimates of the probability density function on pore radius. We compare these estimates to the "true" microstructure of the bone samples determined via microCT imaging. We find that our methodology allows us to reliably estimate the underlying microstructure of the bone from attenuation data.

Design and experimental investigation of a novel spiral microfluidic chip to separate wide size range of micro-particles aimed at cell separation.

Isolation of microparticles and biological cells on microfluidic chips has received considerable attention due to their applications in numerous areas such as medical and engineering fields. Microparticles separation is of great importance in bioassays due to the need for smaller sample and device size and lower manufacturing costs. In this study, we first explain the concepts of separation and microfluidic science along with their applications in the medical sciences, and then, a conceptual design of a novel inertial microfluidic system is proposed and analyzed. The PDMS spiral microfluidic device was fabricated, and its effects on the separation of particles with sizes similar to biological particles were experimentally analyzed. This separation technique can be used to separate cancer cells from the normal ones in the blood samples. These components required for testing were selected, assembled, and finally, a very affordable microfluidic kit was provided. Different experiments were designed, and the results were analyzed using appropriate software and methods. Separator system tests with polydisperse hollow glass particles (diameter 2-20 µm), and monodisperse Polystyrene particles (diameter 5 & 15 µm), and the results exhibit an acceptable chip performance with 86% of efficiency for both monodisperse particles and polydisperse particles. The microchannel collects particles with an average diameter of 15.8, 9.4, and 5.9 µm at the proposed reservoirs. This chip can be integrated into a more extensive point-of-care diagnostic system to test blood samples.

MATSAS: a small-angle scattering computing tool for porous systems.

MATSAS is a script-based MATLAB program for analysis of X-ray and neutron small-angle scattering (SAS) data obtained from various facilities. The program has primarily been developed for sedimentary rock samples but is equally applicable to other porous media. MATSAS imports raw SAS data from .xls(x) or .csv files, combines small-angle and very small angle scattering data, subtracts the sample background, and displays the processed scattering curves in log-log plots. MATSAS uses the polydisperse spherical (PDSP) model to obtain structural information on the scatterers (scattering objects); for a porous system, the results include specific surface area (SSA), porosity (Φ), and differential and logarithmic differential pore area/volume distributions. In addition, pore and surface fractal dimensions (D p and D s, respectively) are obtained from the scattering profiles. The program package allows simultaneous and rapid analysis of a batch of samples, and the results are then exported to .xlsx and .csv files with separate spreadsheets for individual samples. MATSAS is the first SAS program that delivers a full suite of pore characterizations for sedimentary rocks. MATSAS is an open-source package and is freely available at GitHub (https://github.com/matsas-software/MATSAS).

Effect of ultrasonic frequency and surfactant addition on microcapsule destruction.

In a previous study, we found that cavitation bubbles cause the ultrasonic destruction of microcapsules containing oil in a shell made of melamine resin. The cavitation bubbles can be smaller or larger than the resonance size; smaller bubbles cause Rayleigh contraction, whereas larger bubbles are not involved in the sonochemical reaction. The activity in and around the bubble (e.g., shear stress, shock wave, microjet, sonochemical reaction, and sonoluminescence) varies substantially depending on the bubble size. In this study, we investigated the mechanism of the ultrasonic destruction of microcapsules by examining the correlations between frequency and microcapsule destruction rate and between microcapsule size and cavitation bubble size. We evaluated the bubbles using multibubble sonoluminescence and the bubble size was changed by adding a surfactant to the microcapsule suspension. The microcapsule destruction was frequency dependent. The main cause of microcapsule destruction was identified as mechanical resonance, although the relationship between bubble size and microcapsule size suggested that bubbles smaller than or equal to the microcapsule size may also destroy microcapsules by applying shear stress locally.