Physics of Fluids

Aerosols and droplets generated from expiratory events play a critical role in the transmission of infectious respiratory viruses. Increasingly robust evidence has suggested the crucial role of fine aerosols in airborne transmission of respiratory diseases, which is now widely regarded as an important transmission path of COVID-19. In this report, we used CFD modelling to investigate the efficiency of using portable air purifiers containing HEPA filters to reduce airborne aerosols in hospitals and serve as a potential retrofit mitigation strategy. We used a consulting room to set up our simulations because currently the clearance time between consultations is the controlling factor that limits the patient turnover rate. The results suggest the inlet/suction of the air purifier unit should be lifted above the floor to achieve better clearance efficiency, with up to 40% improvement possible. If multiple air purifiers are used, the combined efficiency can increase to 62%. This work provides practical guidance on a mitigation strategy that can be easily implemented in an expedient, cost-effective and rapid manner, and paves the way for developing more science-informed strategies to mitigate the airborne transmission of respiratory infections in hospitals.

In this study we assessed the effect of ethanol on the filtering properties of FFP2 masks. The permeability of parts of a FFP2 mask was measured before and after six cleanings with ethanol. As for any porous medium, the filtering properties of a mask are related to the size and tortuosity of the pores of the filter, and are quantified by its permeability. Any damage to the filter will change its permeability. We show here that after six cleaning cycles, the permeability remains very close to the permeability before cleaning. Amid the COVID-19 pandemic and the shortage of protective masks, this study suggests that ethanol could be used to sanitize a FFP2 mask without significantly altering its filtering properties. Additional measurements on FFP2 and N95 masks from different manufacturers need to be performed to validate this study.

We present a simple method to generate discrete aerodynamic gust under controlled laboratory condition in the form of a vortex ring which, unlike conventional methods of perturbation, is well studied and highly controllable. We characterized the flow properties of the vortex ring using flow visualization and novel light bead method. Reynolds number of the vortex ring, based on its average propagation velocity and nozzle exit diameter, was 16000. We demonstrate this method by studying the impact of head-on gust on freely flying soldier flies, Reynolds number of which, based on its wingtip velocity and mean wing chord, was 1100. We also present simple theoretical models to characterize the vortex ring based on generating conditions. The device can also be used to generate continuous gust in any direction and can be applied, in general, to study the gust response of natural fliers and swimmers, man-made micro aerial vehicles and aquatic plant lives.

There exists an ongoing need to improve the validity and accuracy of computational fluid dynamics (CFD) simulations of turbulent airflows in the extra-thoracic and upper airways. Yet, a knowledge gap remains in providing experimentally-resolved 3D flow benchmarks with sufficient data density and completeness for useful comparison with widely-employed numerical schemes. Motivated by such shortcomings, the present work details to the best of our knowledge the first attempt to deliver in vitro-in silico correlations of 3D respiratory airflows in a generalized mouth-throat model and thereby assess the performance of Large Eddy Simulations (LES) and Reynolds-Averaged Numerical Simulations (RANS). Numerical predictions are compared against 3D volumetric flow measurements using Tomographic Particle Image Velocimetry (TPIV) at three steady inhalation flowrates varying from shallow to deep inhalation conditions. We find that a RANS k-{omega} SST model adequately predicts velocity flow patterns for Reynolds numbers spanning 1500 to 7000, supporting results in close proximity to a more computationally-expensive LES model. Yet, RANS significantly underestimates turbulent kinetic energy (TKE), thus underlining the advantages of LES as a higher-order turbulence modeling scheme. In an effort to bridge future endevours across respiratory research disciplines, we provide end users with the present in vitro -in silico correlation data for improved predictive CFD models towards inhalation therapy and therapeutic or toxic dosimetry endpoints. Author SummaryThe dispersion and ensuing deposition of inhaled airborne particulate matter in the lungs are strongly influenced by the dynamics of turbulent respiratory airflows in the mouth-throat region during inhalation. To cirumvent costly in vitro experimental measurement resources, fluid dynamics (CFD) simulations are widely sought to predict deposition outcomes but often lack detailed experimental data to first validate the three-dimensional (3D) flow structures anticipated to arise in the upper respiratory tract. In an effort to reconcile such data scarcity, we deliver experimental-numerical correlations of 3D respiratory airflows in an idealized 3D printed mouth-throat model against two widely-established numerical schemes with varying computational costs, namely coarse RANS and finer LES technique. Our time-resolved 3D flow data underline the complexity of these physiological inhalation flows, and discuss advantages and drawbacks of the different numerical techniques. With an outlook on future respiratory applications geared towards broad preclinical inhaled aerosol deposition studies, our open source data are made available for future benchmark comparisons for a broad range of end users in the respiratory research community.

An instrument-free particle-templated droplet formation can be achieved upon simple mixing of amphiphilic particles with aqueous and oil phases in a well plate by using a common lab pipette. Here, a two-dimensional, two-phase flow model was established using a finite element method to mimic the droplet formation within a concentric amphiphilic particle, which consisted of an outer hydrophobic layer and an inner hydrophilic layer. Immiscible water and oil phases selectively interacted with the hydrophilic and hydrophobic layers of the particle, respectively, to form an isolated aqueous compartment within a cavity. Three extreme models were also simulated, including completely hydrophilic, completely hydrophobic, and oppositely amphiphilic particle, which indicated that a right order of the particle layers was necessary to capture the droplet inside the cavity. Moreover, we performed a systematic study of particle-templated droplet formation by varying the individual layer thicknesses of particle, particle height, interfacial tension between water and oil, contact angle of interface with different surfaces, velocity of incoming oil media, and distance between neighboring particles. The volume fraction of water droplet trapped within the target cavity region was calculated to characterize the droplet formation. Our work will help to optimize the particle fabrication process, predict the experiment droplet formation, and explain the physical mechanism underlying compartmentalization phenomena.

The complex undulated geometry of seal whiskers has been shown to substantially modify the turbulent structures directly downstream, resulting in a reduction of hydrodynamic forces as well as modified vortex-induced-vibration response when compared with smooth whiskers. Although the unique hydrodynamic response has been well documented, an understanding of the fluid flow effects from each geometric feature remains incomplete. In this computational investigation, nondimensional geometric parameters of the seal whisker morphology are defined in terms of their hydrodynamic relevance, such that wavelength, aspect ratio, undulation amplitudes, symmetry and undulation off-set can be varied independently of one another. A two-factor fractional factorial design of experiments procedure is used to create 16 unique geometries, each of which dramatically amplifies or attenuates the geometric parameters compared with the baseline model. The flow over each unique topography is computed with a large-eddy simulation at a Reynolds number of 500 with respect to the mean whisker thickness and the effects on force and frequency are recorded. The results determine the specific fluid flow impact of each geometric feature which will inform both biologists and engineers who seek to understand the impact of whisker morphology or lay out a framework for biomimetic design of undulated structures.

The authors present an easily manufactured modification of Getinge Groups Maquet Flow-i anaesthesia machine that gives it potential to be used long-term as an Intensive Care ventilator for emergency circumstances. There are some 7000 such machines in use worldwide, which could assist in increasing ICU ventilated bed capacity in a number of nations. The authors believe this modification has potential as a solution to increasing ventilator numbers for the COVID-19 pandemic, in hospitals where the Flow-i is underutilised for its designed purpose during this emergency. The technical drawing files are downloadable on the GrabCAD website and are Creative Commons (CC-BY 4.0) licensed to allow local manufacture of the modification. We welcome other Flow-i users and engineers to join us in troubleshooting this project on the associated GrabCAD discussion group during this pre-print phase of research.

Drug delivery for viral respiratory infections, such as SARS-CoV-2, can be enhanced significantly by targeting the nasopharynx, which is the dominant initial infection site in the upper airway, for example by nasal sprays. However, under the standard recommended spray usage protocol ("Current Use", or CU), the nozzle enters the nose almost vertically, resulting in sub-optimal deposition of drug droplets at the nasopharynx. Using computational fluid dynamics simulations in two anatomic nasal geometries, along with experimental validation of the generic findings in a different third subject, we have identified a new "Improved Use" (or, IU) spray protocol. It entails pointing the spray bottle at a shallower angle (almost horizontally), aiming slightly toward the cheeks. We have simulated the performance of this protocol for conically injected spray droplet sizes of 1 - 24 m, at two breathing rates: 15 and 30 L/min. The lower flowrate corresponds to resting breathing and follows a viscous-laminar model; the higher rate, standing in for moderate breathing conditions, is turbulent and is tracked via Large Eddy Simulation. The results show that (a) droplets sized between [~] 6 - 14 m are most efficient at direct landing over the nasopharyngeal viral infection hot-spot; and (b) targeted drug delivery via IU outperforms CU by approximately 2 orders-of-magnitude, under the two tested inhalation conditions. Also quite importantly, the improved delivery strategy, facilitated by the IU protocol, is found to be robust to small perturbations in spray direction, underlining the practical utility of this simple change in nasal spray administration protocol.

Protist cells are typically manipulated through either centrifugation or membrane filtration, which can damage these fragile cell types. Use of microfluidic devices could greatly aid in the separation and concentration of protist cells with significantly less damage. Recent developments have enabled passive cell separation and consequent concentration based only on cell size. We utilize these advances to show that a passive spiral microfluidic device can effectively concentrate marine nanoflagellates within the 3-20 micron size range without harm to cells, while reducing background bacteria levels. The ability to concentrate these cell types appears only dependent on cell size, despite complicated cell surface geometries and motility. We anticipate that this approach will greatly aid researchers who require an ability to manipulate fragile cell types as well as reduce bacteria concentrations for experimental setups and cell isolation.

This work presents the development of a novel approach to model the dynamics of cancer cells in microcirculation. We investigate the role the membrane elasticity, and cancer cell shape on deformation dynamics under the shear and pressure forces in a micro-channel. The proposed numerical model is based on a hybrid continuum-particle approach. The cancer cell model includes the cell membrane, nucleus, cytoplasm and the cytoskeleton. The Dissipative Particle Dynamics method was employed to simulate the mechanical components. The blood plasma is modeled as a Newtonian incompressible fluid. A Fluid-Structure Interaction coupling, leveraging the Immersed Boundary Method is developed to simulate the cells response to flow dynamics. We quantify how subtle variations in these biophysical properties alter deformation indices such as sphericity and aspect ratio, and stress distributions on the membrane of the cancer cell. Our findings align well with existing computational and experimental studies. Results reveal that increased membrane stiffness reduces overall deformation as well as the total distance traveled. Similarly, cell geometry strongly influences flow-structure interactions: near-spherical morphologies exhibit stable deformation with minimal sensitivity to shear variations, whereas elongated geometries show pronounced orientation and stretching effects. Collectively, these findings highlight the critical importance of cell-specific heterogeneity in governing cell dynamics in microvascular flows. Furthermore, the intracellular and extracellular dynamics response of the cancer cell are intrinsically linked to their shape, in which certain morphologies displayed strong resistance to the fluid-induced forces and the ability to migrate in various directions. The insights obtained provide a mechanistic framework for understanding circulating tumor cell transport in shear-dominated environments during metastasis. Our work may inform the design of biomimetic microfluidic systems and therapeutic strategies targeting cancer cell detection and cancer prognosis.

Fluidic habitats are very common to bacterial life, however, very little is known about the effect of the flow stresses on the virulence of the bacteria. In the present work, we conduct microfluidic experiments to understand the consequence of stresses generated by flowing fluid on the bacterial morphology and virulence. We consider Klebsiella pneumoniae (KP), an ESKAPE pathogen as the model bacteria that are responsible for blood stream infections like bacteremia apart from pneumonia, urinary tract infections and more. We generate four different stress conditions by changing the flow rate and channel geometry subsequently altering the shear rate and stressing time ({tau}). We observe significant changes in the structural aspects of the stressed bacteria. With an increase in stressing parameters, the viability of the bacterial sample deteriorated. Most importantly, these stressed samples proliferate much more than unstressed samples inside the RAW264.7 murine macrophages. The results shed light on the complex relationship between flow stresses and bacterial virulence. Furthermore, we challenge the bacterial samples with ciprofloxacin to see how they behave under different stress conditions. The present study can be extended to model deadly diseases like bacteremia using organ-on-a-chip technology and help understand bacterial pathogenicity under realistic environments. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/558194v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1111ea1org.highwire.dtl.DTLVardef@f20494org.highwire.dtl.DTLVardef@10ac86dorg.highwire.dtl.DTLVardef@ec6eb1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure:C_FLOATNO A schematic representation of the present work. Figure created with BioRender (www.biorender.com) C_FIG

Mucus is a viscoelastic gel secreted by the pulmonary epithelium in the tracheobronchial region of the lungs. The coordinated beating of cilia in contact with the gel layer moves mucus upwards towards pharynx, removing inhaled pathogens and particles from the airways. The efficacy of this clearance mechanism depends primarily on the rheological properties of mucus. Here we use a magnetic wire based microrheology technique to study the viscoelastic properties of human mucus collected from human bronchus tubes. The response of wires between 5 and 80 {micro}m in length to a magnetic rotating field is monitored by optical time-lapse microscopy and analyzed using constitutive equation models of rheology, including Maxwell and Kelvin-Voigt. The static shear viscosity and elastic modulus can be inferred from low frequency (10-3 - 10 rad s-1) measurements, leading to the evaluation of the mucin network relaxation time. This relaxation time is found to be widely distributed, from one to several hundred seconds. Mucus is identified as a viscoelastic liquid with an elastic modulus of 2.5 {+/-} 0.5 Pa and a static viscosity of 100 {+/-} 40 Pa s. Our work shows that beyond the established spatial variations in rheological properties due to microcavities, mucus exhibits secondary inhomogeneities associated with the relaxation time of the mucin network that may be important for its flow properties.

The composition of respiratory fluids influences the stability of viruses in exhaled aerosol particles and droplets, though the role of respiratory organics in modulating virus stability remains poorly understood. This study investigates the effect of organic compounds on the stability of influenza A virus (IAV) in deposited droplets. We compare the infectivity loss of IAV at different relative humidities (RH) over the course of one hour in 1-l droplets consisting of phosphate-buffered saline (without organics), synthetic lung fluid, or nasal mucus (both containing organics). We show that IAV stability increases with increasing organic:salt ratios. Among the various organic species, proteins are identified as the most protective component, with smaller proteins stabilizing IAV more efficiently at the same mass concentration. Organics act by both increasing the efflorescence RH and shortening the drying period until efflorescence at a given RH. This research advances our mechanistic understanding of how organics stabilize exhaled viruses and thus influence their inactivation in respiratory droplets.

Droplet-based microfluidics is the study of microfluidic device, where droplets are generated mainly using two methods i.e., active, and passive methods. The manipulation of these droplets in microfluidic channels is an immensely useful technology in various scientific fields such as biological, biomedical studies, and drug delivery. Recently droplets with a core-shell structure have achieved considerable interest due to their unique properties and varied applications. Droplet splitting as an important feature of droplet-based microfluidic systems has been widely used. In the present paper, two-dimensional numerical simulations have been done to examine the droplet splitting process in an E Junction geometry microchannel. The two-phase level set method (LSM) has been used to analyze the mechanism of droplet formation and droplet splitting in an immiscible liquid/liquid two-phase flow. Governing equations on the flow field have been studied and solved using COMSOL Multiphysics software. The model was developed to simulate the mechanism of droplet splitting at the E-junction microchannel. This study provides a passive technique to split up microdroplets at the E-junction.

This paper presents a proof-of-concept study establishing effectiveness of the Active Plasma Sterilizer (APS) for sterilization in planetary protection. The APS uses Compact Portable Plasma Reactors (CPPRs) to produce surface dielectric barrier discharge, a type of cold plasma, using ambient air to generate and distribute reactive species like ozone used for decontamination. Sterilization tests were performed with pathogenic bacteria (Escherichia coli and Bacillus subtilis) on materials (Aluminum, Polycarbonate, Kevlar and Orthofabric) relevant to space missions. Results show that the APS can achieve 4 to 5 log reductions of pathogenic bacteria on four selected materials, simultaneously at 11 points within 30 minutes, using power of 13.2 {+/-} 2.22 W. Spatial sterilization data shows the APS can uniformly sterilize several areas of a contaminated surface within 30 minutes. Ozone penetration through Kevlar and Orthofabric layers was achieved using the CPPR with no external agent assisting penetration. Preliminary material compatibility tests with SEM analysis of the APS exposed materials showed no significant material damage. Thus, this study shows the potential of the APS as a light-weight sustainable sterilization technology for planetary protection with advantages of uniform spatial decontamination, low processing temperatures, low exposure times, material compatibility and the ability to disinfect porous surfaces.

To compare the transport of respiratory pathogens, computational fluid dynamics (CFD) simulations were performed to track particles released by coughing from a passenger on a Boeing 737 aircraft, and by a person in a comparable indoor commercial space. Simulation data were post-processed to calculate the amounts of particles inhaled by nearby persons in both environments. The effects of different airflow rates, placement of air inlets, positioning and distances between index (coughing) and susceptible (inhaling) persons were also analyzed. The removal of airborne particles from the indoor environment, due ventilation and deposition onto surfaces, was compared to that of an aircraft cabin. In an aircraft cabin 80% of the particles were removed 5 to 12 times faster than in the indoor commercial space; ultimately resulting in 7 times less particulate mass inhaled in the aircraft cabin.

For many of the one billion sufferers of respiratory diseases worldwide, managing their disease with inhalers improves their ability to breathe. Poor disease management and rising pollution can trigger exacerbations which require urgent relief. Higher drug deposition in the throat instead of the lungs limits the impact on patient symptoms. To optimise delivery to the lung, patient-specific computational studies of aerosol inhalation can be used. How-ever in many studies, inhalation modelling does not represent an exacerbation, where the patients breath is much faster and shorter. Here we compare differences in deposition of inhaler particles (10, 4 {micro}m) in the airways of a healthy male, female lung cancer and child cystic fibrosis patient. We aimed to evaluate deposition differences during an exacerbation compared to healthy breathing with image-based healthy and diseased patient models. We found that the ratio of drug in the lower to upper lobes was 35% larger during healthy breathing than an exacerbation. For smaller particles the upper airway deposition was similar in all patients, but local deposition hotspots differed in size, location and intensity. Our results identify that image-based airways must be used in respiratory modelling. Various inhalation profiles should be tested for optimal prediction of inhaler deposition. HighlightsO_LIRegional and local drug deposition was modelled in three patients during normal, sinusoidal inhalation and an exacerbation. C_LIO_LILocal drug deposition changes with airway shape and inhalation profile, even when regional deposition is similar. C_LIO_LIImage-based models were combined with highly-resolved particle tracking including particle contact and cohesion. C_LIO_LIFluid model validated by comparing gas velocity field with in vitro experiments. C_LI

Complex fluid systems can exhibit highly non-linear and time-dependent flow behaviors that arise from microscale reorganization. Rheological measurements to understand these flow-induced properties in soft condensed matter and biology are critical to optimize manufacturing processes that rely upon the use of complex fluids, such as the creation of viscoelastic bioinks for 3D bioprinting. While typical rheological characterizations are performed on bulky and expensive rheometers, these options do not readily enable in situ microscopic visualization of flow behavior, which can provide microstructural insights into the mechanisms and patterns of yielding. To address these limitations, we present a visual, inexpensive (approximately $200), and wireless capillary rheometer (VIEWR) assembled from chiefly 3D printed components. We validate the accuracy and reliability of the portable rheometer by comparing measurements of multiple rheological parameters, including viscosity and yield stress, with measurements obtained from a commercial oscillatory rheometer. At its core, VIEWR employs an easily interchangeable glass capillary channel to enable real-time microscopic observation under flow conditions. To facilitate various experimental conditions, a communication protocol based on Internet of Things (IoT) is adapted to support wireless transmission of data. This unique rheometer design can be used for characterizing and visualizing numerous living and non-living complex fluids. Specifications table O_TBL View this table: org.highwire.dtl.DTLVardef@1be2128org.highwire.dtl.DTLVardef@172d43eorg.highwire.dtl.DTLVardef@1cc6eaforg.highwire.dtl.DTLVardef@76c6f5org.highwire.dtl.DTLVardef@3882_HPS_FORMAT_FIGEXP M_TBL C_TBL

The potential for characterizing aerosol generating procedures (AGPs) using background oriented schlieren (BOS) flow visualization was investigated in two clinical situations. A human-scale BOS system was used on a manikin simulating jet ventilation and extubation. A novel approach to representation of the BOS images using line integral convolution allows direct evaluation of both magnitude and direction of the refractive index gradient field. Plumes issuing from the manikins mouth were clearly visualized and characterized in both experiments, and it is recommended that BOS be adapted into a clinical tool for risk evaluation in clinical environments.

Culture medium is frequently modelled as water in computational fluid dynamics (CFD) analysis of in vitro culture systems involving flow, such as bioreactors and organ-on-chips. However, culture medium can be expected to have different properties to water due to its higher solute content. Furthermore, cellular activities such as metabolism and secretion of ECM proteins alter the composition of culture medium and therefore its properties during culture. As these properties directly determine the hydromechanical stimuli exerted on cells in vitro, these, along with any changes during culture must be known for CFD modelling accuracy and meaningful interpretation of cellular responses. In this study, the density and dynamic viscosity of DMEM and RPMI-1640 media supplemented with typical concentrations of foetal bovine serum (0, 5, 10 and 20% v/v) were measured to serve as a reference for computational design analysis. Any changes in the properties of medium during culture were also investigated with NCI-H460 and HN6 cell lines. The density and dynamic viscosity of the media increased proportional to the % volume of added foetal bovine serum (FBS). Importantly, the viscosity of 5% FBS-supplemented RPMI-1640 was found to increase significantly after 3 days of culture of NCI-H460 and HN6 cell lines, with distinct differences between magnitude of change for each cell line. Finally, these experimentally-derived values were applied in CFD analysis of a simple microfluidic device, which demonstrated clear differences in maximum wall shear stress and pressure between fluid models. Overall, these results highlight the importance of characterizing model-specific properties for CFD design analysis of cell culture systems.