Detecting Oxygenator Thrombosis in ECMO: A Review of Current Techniques and an Exploration of Future Directions.

Extracorporeal membrane oxygenation (ECMO) is a life-support technique used to treat cardiac and pulmonary failure, including severe cases of COVID-19 (coronavirus disease 2019) involving acute respiratory distress syndrome. Blood clot formation in the circuit is one of the most common complications in ECMO, having potentially harmful and even fatal consequences. It is therefore essential to regularly monitor for clots within the circuit and take appropriate measures to prevent or treat them. A review of the various methods used by hospital units for detecting blood clots is presented. The benefits and limitations of each method are discussed, specifically concerning detecting blood clots in the oxygenator, as it is concluded that this is the most critical and challenging ECMO component to assess. We investigate the feasibility of solutions proposed in the surrounding literature and explore two areas that hold promise for future research: the analysis of small-scale pressure fluctuations in the circuit, and real-time imaging of the oxygenator. It is concluded that the current methods of detecting blood clots cannot reliably predict clot volume, and their inability to predict clot location puts patients at risk of thromboembolism. It is posited that a more in-depth analysis of pressure readings using machine learning could better provide this information, and that purpose-built imaging could allow for accurate, real-time clotting analysis in ECMO components.

Influence of the Ground Electrode on the Dynamics of Electrowetting.

The ability to manipulate a liquid meniscus using electrowetting has many applications. In any electrowetting design, at least two electrodes are required: one forms the field to change the contact angle and the other functions as a ground electrode. The contribution of the ground electrode (GE) to the dynamics of electrowetting has not yet been thoroughly investigated. In this paper, we discovered that with a bare ground electrode, the contact angle of a sessile drop increases instead of decreases when a direct current (DC) voltage varying from zero to the threshold voltage is applied. This phenomenon is opposite to what occurs when the GE is coated with a dielectric, where the contact-angle change follows the Lippmann-Young equation above the threshold voltage of electrowetting. However, this behaviour is not observed with either a dielectric-coated electrode using direct current (DC) or a bare ground electrode using alternating current (AC) voltage electrowetting. This study explains this phenomenon with finite element simulation and theory. From previous research work, the ground electrode configuration is inconsistent. In some studies, the ground electrode is exposed to water; in other studies, the ground electrode is covered with dielectric. This study identified that an exposed ground electrode is not required in electrowetting. Moreover, this research work suggests that for applications where precise control of the contact angle is paramount, a dielectric-coated ground electrode should be used since it prevents the increase in the contact angle when increasing the applied potential from zero to the threshold voltage. This study also identified that contact angle hysteresis is lower with a Cytop-coated ground electrode and DC voltage than with a bare ground electrode using AC or DC voltages.

A spatiotemporally resolved infection risk model for airborne transmission of COVID-19 variants in indoor spaces.

The classic Wells-Riley model is widely used for estimation of the transmission risk of airborne pathogens in indoor spaces. However, the predictive capability of this zero-dimensional model is limited as it does not resolve the highly heterogeneous spatiotemporal distribution of airborne pathogens, and the infection risk is poorly quantified for many pathogens. In this study we address these shortcomings by developing a novel spatiotemporally resolved Wells-Riley model for prediction of the transmission risk of different COVID-19 variants in indoor environments. This modelling framework properly accounts for airborne infection risk by incorporating the latest clinical data regarding viral shedding by COVID-19 patients and SARS-CoV-2 infecting human cells. The spatiotemporal distribution of airborne pathogens is determined via computational fluid dynamics (CFD) simulations of airflow and aerosol transport, leading to an integrated model of infection risk associated with the exposure to SARS-CoV-2, which can produce quantitative 3D infection risk map for a specific SARS-CoV-2 variant in a given indoor space. Application of this model to airborne COVID-19 transmission within a hospital ward demonstrates the impact of different virus variants and respiratory PPE upon transmission risk. With the emergence of highly contagious SARS-CoV-2 variants such as the Delta and Omicron strains, respiratory PPE alone may not provide effective protection. These findings suggest a combination of optimal ventilation and respiratory PPE must be developed to effectively control the transmission of COVID-19 in healthcare settings and indoor spaces in general. This generalised risk estimation framework has the flexibility to incorporate further clinical data as such becomes available, and can be readily applied to consider a wide range of factors that impact transmission risk, including location and movement of infectious persons, virus variant and stage of infection, level of PPE and vaccination of infectious and susceptible individuals, impacts of coughing, sneezing, talking and breathing, and natural and mechanised ventilation and filtration.

Microfluidic Obstacle Arrays Induce Large Reversible Shape Change in Red Blood Cells.

Red blood cell (RBC) shape change under static and dynamic shear stress has been a source of interest for at least 50 years. High-speed time-lapse microscopy was used to observe the rate of deformation and relaxation when RBCs are subjected to periodic shear stress and deformation forces as they pass through an obstacle. We show that red blood cells are reversibly deformed and take on characteristic shapes not previously seen in physiological buffers when the maximum shear stress was between 2.2 and 25 Pa (strain rate 2200 to 25,000 s-1). We quantify the rates of RBC deformation and recovery using Kaplan-Meier survival analysis. The time to deformation decreased from 320 to 23 milliseconds with increasing flow rates, but the distance traveled before deformation changed little. Shape recovery, a measure of degree of deformation, takes tens of milliseconds at the lowest flow rates and reached saturation at 2.4 s at a shear stress of 11.2 Pa indicating a maximum degree of deformation was reached. The rates and types of deformation have relevance in red blood cell disorders and in blood cell behavior in microfluidic devices.

Effect of inhalation on oropharynx collapse via flow visualisation.

Computational fluid dynamics (CFD) modelling has made significant contributions to the analysis and treatment of obstructive sleep apnoea (OSA). While several investigations have considered the flow field within the airway and its effect on airway collapse, the effect of breathing on the pharynx region is still poorly understood. We address this gap via a combined experimental and numerical study of the flow field within the pharynx and its impacts upon airway collapse. Two 3D experimental models of the upper airway were constructed based upon computerised tomography scans of a specific patient diagnosed with severe OSA; (i) a transparent, rigid model for flow visualisation, and (ii) a semi-flexible model for understanding the effect of flow on pharynx collapse. Validated simulation results for this geometry indicate that during inhalation, negative pressure (with respect to atmospheric pressure) caused by vortices drives significant narrowing of the pharynx. This narrowing is strongly dependent upon whether inhalation occurs through the nostrils. Thus, the methodology presented here can be used to improve OSA treatment by improving the design methodology for personalised, mandibular advancement splints (MAS) that minimise OSA during sleep.

A Novel Hexagonal Beam Steering Electrowetting Device for Solar Energy Concentration.

Traditional tracking devices for solar energy applications have several disadvantages, such as bulky mechanical structure, large wind loads, and ease of misalignment. This study aims to design a flat, thin, and adaptive beam steering device to eliminate these drawbacks. A proof of concept device was fabricated to demonstrate this design. The novelty of the proof of concept device is the hexagonal structure of the electrowetting cell design. The hexagonal cell was dosed with two immiscible liquids with different refractive indices. The hypothesis of this design is that by deforming the liquid shape with the application of voltage, light can be steered and concentrated for solar energy applications. A maximum contact angle change of 44° was observed with the application of 26 V to one of the electrodes of the hexagonal cell. The device demonstrated a 4.5° change of laser beam path with only a 0.2 refractive index difference of the liquids. The 3D simulation model developed in this study shows that a tilted and flat interface can be achieved using higher dielectric constant dielectric materials. The device can facilitate the planer steering and concentration of sunlight for rooftop applications without moving mechanical parts.

A luminescent solar concentrator ray tracing simulator with a graphical user interface: features and applications.

A Monte-Carlo ray tracing simulator with a graphical user interface (MCRTS-GUI) has been developed to provide a quantitative description, performance evaluation and photon loss analysis of luminescent solar concentrators (LSCs). The algorithm is applied to several practical LSC device structures including multiple dyes in the same waveguiding layer, and structures where a dye layer is sandwiched between clear substrates. The effect of the host matrix absorption and the influence of the neighboring layers are investigated. Validations demonstrate that the MCRTS-GUI developed provides a reliable and accurate description of LSC performance. Code for the mixed-dye single layer configuration is converted into a ray-tracing package with a user-friendly interface and is made available as open source software.

Impact of sleeping position, gravitational force & effective tissue stiffness on obstructive sleep apnoea.

Accurate prediction of deformation and collapse of the upper airway during breathing is required for effective and personalised treatment of obstructive sleep apnoea (OSA). While numerical modelling techniques such as fluid-structure interaction (FSI) are promising, an outstanding challenge is to accurately predict the deformation of the airway during breathing and thus the occurrence of OSA. These difficulties arise because the effective stiffness of the soft tissue in the human upper airway varies due to neuromuscular effects on the stiffness of the underlying muscles. In addition, both the elasticity and anisotropy of the soft tissues along the upper airway are poorly characterised. Finally, gravitational effects on anatomic features are yet to be considered. In this study, a validated FSI technique is introduced that allows prediction of the extent and position of the major deformation in the upper airway. This technique is used to analyse the behaviour of the upper airway in the two most common sleeping positions and for a range of effective tissue stiffnesses. The results demonstrate that sleeping position, gravity and soft tissue stiffness (used here as a proxy for neuromuscular effects) are the main factors that affect upper airway collapse. Therefore, this study provides new insights into the mechanisms of OSA and a new methodology that significantly advances the patient-specific treatment of OSA.

Compact, semi-passive beam steering prism array for solar concentrators.

In order to maximize solar energy utilization in a limited space (e.g., rooftops), solar collectors should track the sun. As an alternative to rotational tracking systems, this paper presents a compact, semi-passive beam steering prism array which has been designed, analyzed, and tested for solar applications. The proposed prism array enables a linear concentrator system to remain stationary so that it can integrate with a variety of different solar concentrators, and which should be particularly useful for systems which require a low profile (namely rooftop-mounted systems). A case study of this prism array working within a specific rooftop solar collector demonstrates that it can boost the average daily optical efficiency of the collector by 32.7% and expand its effective working time from 6 h to 7.33 h. Overall, the proposed design provides an alternative way to "follow" the sun for a wide range of solar thermal and photovoltaic concentrator systems.

Controlled Electrochemical Deformation of Liquid-Phase Gallium.

Pure gallium is a soft metal with a low temperature melting point of 29.8 °C. This low melting temperature can potentially be employed for creating optical components with changeable configurations on demand by manipulating gallium in its liquid state. Gallium is a smooth and highly reflective metal that can be readily maneuvered using electric fields. These features allow gallium to be used as a reconfigurable optical reflector. This work demonstrates the use of gallium for creating reconfigurable optical reflectors manipulated through the use of electric fields when gallium is in a liquid state. The use of gallium allows the formed structures to be frozen and preserved as long as the temperature of the metal remains below its melting temperature. The lens can be readily reshaped by raising the temperature above the melting point and reapplying an electric field to produce a different curvature of the gallium reflector.

An investigation on platelet transport during thrombus formation at micro-scale stenosis.

This paper reports on an investigation of mass transport of blood cells at micro-scale stenosis where local strain-rate micro-gradients trigger platelet aggregation. Using a microfluidic flow focusing platform we investigate the blood flow streams that principally contribute to platelet aggregation under shear micro-gradient conditions. We demonstrate that relatively thin surface streams located at the channel wall are the primary contributor of platelets to the developing aggregate under shear gradient conditions. Furthermore we delineate a role for red blood cell hydrodynamic lift forces in driving enhanced advection of platelets to the stenosis wall and surface of developing aggregates. We show that this novel microfluidic platform can be effectively used to study the role of mass transport phenomena driving platelet recruitment and aggregate formation and believe that this approach will lead to a greater understanding of the mechanisms underlying shear-gradient dependent discoid platelet aggregation in the context of cardiovascular diseases such as acute coronary syndromes and ischemic stroke.

Simulation of upper airway occlusion without and with mandibular advancement in obstructive sleep apnea using fluid-structure interaction.

Obstructive Sleep Apnea (OSA) is a common sleep disorder characterized by repetitive collapse of the upper airway (UA). One treatment option is a mandibular advancement splint (MAS) which protrudes the lower jaw, stabilizing the airway. However not all patients respond to MAS therapy and individual effects are not well understood. Simulations of airway behavior may represent a non-invasive means to understand OSA and individual treatment responses. Our aims were (1) to analyze UA occlusion and flow dynamics in OSA using the fluid structure interaction (FSI) method, and (2) to observe changes with MAS. Magnetic resonance imaging (MRI) scans were obtained at baseline and with MAS in a known treatment responder. Computational models of the patients' UA geometry were reconstructed for both conditions. The FSI model demonstrated full collapse of the UA (maximum 5.83mm) pre-treatment (without MAS). The UA collapse was located at the oropharynx with low oropharyngeal pressure (-51.18Pa to -39.08Pa) induced by velopharyngeal jet flow (maximum 10.0m/s). By comparison, simulation results from the UA with MAS, showed smaller deformation (maximum 2.03mm), matching the known clinical response. Our FSI modeling method was validated by physical experiment on a 1:1 flexible UA model fabricated using 3D steriolithography. This is the first study of airflow dynamics in a deformable UA structure and inspiratory flow. These results expand on previous UA models using computational fluid dynamics (CFD), and lay a platform for application of computational models to study biomechanical properties of the UA in the pathogenesis and treatment of OSA.

Cardiac-like flow generator for long-term imaging of endothelial cell responses to circulatory pulsatile flow at microscale.

In vitro models of circulatory hemodynamics are required to mimic the microcirculation for study of endothelial cell responses to pulsatile shear stress by live cell imaging. This study reports the design, fabrication and characterisation of a microfluidic device that generates cardiac-like flow in a continuous culture system with a circulatory volume of only 2-3 µL. The device mimics a single chamber heart, with the following cardiac phases: (1) closure of the ventricle inlet valve, (2) contraction of the ventricle (systole) followed by opening of the outlet valve and (3) relaxation of the ventricle (diastole) with opening of the inlet valve whilst the outlet valve remains closed. Periodic valve states and ventricular contractions were actuated by microprocessor controlled pneumatics. The time-dependent velocity-field was characterised by micro-particle image velocimetry (µ-PIV). µ-PIV observations were used to help tune electronic timing of valve states and ventricular contractions for synthesis of an arterial pulse waveform to study the effect of pulsatile shear stress on bovine artery endothelial cells (BAECs). BAECs elongated and aligned with the direction of shear stress after 48 h of exposure to a pulsatile waveform with a maximum shear stress of 0.42 Pa. The threshold for BAECs alignment and elongation under steady (non-pulsatile) flow reported by Kadohama et al. (2006) is 0.7-1.4 Pa. These cells respond to transient shear stress because the time average shear stress of the pulse waveform to generate this morphological response was only 0.09 Pa, well below the steady flow threshold. The microfluidic pulse generator can simulate circulatory hemodynamics for live cell imaging of shear-induced signalling pathways.

Feasibility of nanofluid-based optical filters.

In this article we report recent modeling and design work indicating that mixtures of nanoparticles in liquids can be used as an alternative to conventional optical filters. The major motivation for creating liquid optical filters is that they can be pumped in and out of a system to meet transient needs in an application. To demonstrate the versatility of this new class of filters, we present the design of nanofluids for use as long-pass, short-pass, and bandpass optical filters using a simple Monte Carlo optimization procedure. With relatively simple mixtures, we achieve filters with <15% mean-squared deviation in transmittance from conventional filters. We also discuss the current commercial feasibility of nanofluid-based optical filters by including an estimation of today's off-the-shelf cost of the materials. While the limited availability of quality commercial nanoparticles makes it hard to compete with conventional filters, new synthesis methods and economies of scale could enable nanofluid-based optical filters in the near future. As such, this study lays the groundwork for creating a new class of selective optical filters for a wide range of applications, namely communications, electronics, optical sensors, lighting, photography, medicine, and many more.

Computational fluid dynamics for the assessment of upper airway response to oral appliance treatment in obstructive sleep apnea.

Mandibular advancement splints (MAS), which protrude the lower jaw during sleep, are recognized as an effective treatment for obstructive sleep apnea (OSA) through their action of enlarging the airway space and preventing upper airway collapse. However a clinical challenge remains in preselecting patients who will respond to this form of therapy. We aimed to use computational fluid dynamics (CFD) in conjunction with patient upper airway scans to understand the upper airway response to treatment. Seven OSA patients were selected based on their varied treatment response (assessed by the apnea-hypopnoea index (AHI) on overnight polysomnography). Anatomically-accurate upper airway computational models were reconstructed from magnetic resonance images with and without MAS. CFD simulations of airflow were performed at the maximum flow rate during inspiration. A physical airway model of one patient was fabricated and the CFD method was validated against the pressure profile on the physical model. The CFD analysis clearly demonstrated effects of MAS treatment on the patient's UA airflow patterns. The CFD results indicated the lowest pressure often occurs close to the soft palate and the base of the tongue. Percentage change in the square root of airway pressure gradient with MAS (Δsqrt(ΔP(Max))%) was found to have the strongest relationship with treatment response (ΔAHI%) in correlation analysis (r=0.976, p=0.000167). Changes in upper airway geometry alone did not significantly correlate with treatment response. We provide further support of CFD as a potential tool for prediction of treatment outcome with MAS in OSA patients without requiring patient specific flow rates.

Structural and hydrodynamic simulation of an acute stenosis-dependent thrombosis model in mice.

Platelet activation under blood flow is thought to be critically dependent on the autologous secretion of soluble platelet agonists (chemical activators) such as ADP and thromboxane. However, recent evidence challenging this model suggests that platelet activation can occur independent of soluble agonist signalling, in response to the mechanical effects of micro-scale shear gradients. A key experimental tool utilized to define the effect of shear gradients on platelet aggregation is the murine intravital microscopy model of platelet thrombosis under conditions of acute controlled arteriolar stenosis. This paper presents a computational structural and hydrodynamic simulation of acute stenotic blood flow in the small bowel mesenteric vessels of mice. Using a homogeneous fluid at low Reynolds number (0.45) we investigated the relationship between the local hydrodynamic strain-rates and the severity of arteriolar stensosis. We conclude that the critical rates of blood flow acceleration and deceleration at sites of artificially induced stenosis (vessel side-wall compression or ligation) are a function of tissue elasticity. By implementing a structural simulation of arteriolar side wall compression, we present a mechanistic model that provides accurate simulations of stenosis in vivo and allows for predictions of the effects on local haemodynamics in the murine small bowel mesenteric thrombosis model.

Microwell perfusion array for high-throughput, long-term imaging of clonal growth.

Continuous cell tracking by time-lapse microscopy has led to detailed study of cell differentiation pathways using single cell fate maps. There are a multitude of cell fate outcomes, so hundreds of clonal division histories are required to measure these stochastic branching processes. This study examines the principle of condensing cell imaging information into a relatively small region to maximize live cell imaging throughput. High throughput clonal analysis of non-adherent cells by continuous live cell tracking was possible using a microwell perfusion array with an internal volume of 16 µl and 600 microwells at the base. This study includes examination of biocompatibility of buffer systems, connecting tubing, cell culture substrates, and media degradation. An intermittent perfusion protocol was selected for long-term time-lapse imaging of KG1a cells in the microwell array; 1500 clones were simultaneously cultured and scanned every 3 min at 100 × magnifications for 6 days. The advantages of perfusion microwell culture are continuous long-term cell tracking, higher cell imaging throughput, and greater control over cell microenvironment. Microwell devices facilitate high throughput analysis of cell lineage development and measurement of the probability distribution for cell life events such as mitosis.

Diatoms: self assembled silica nanostructures, and templates for bio/chemical sensors and biomimetic membranes.

In this review we highlight recent advances in the understanding of biosilica production, biomodification of diatom frustules and their subsequent applications in bio/chemical sensors, and as a model membrane for filtration and separation.

A microfluidics device to monitor platelet aggregation dynamics in response to strain rate micro-gradients in flowing blood.

This paper reports the development of a platform technology for measuring platelet function and aggregation based on localized strain rate micro-gradients. Recent experimental findings within our laboratories have identified a key role for strain rate micro-gradients in focally triggering initial recruitment and subsequent aggregation of discoid platelets at sites of blood vessel injury. We present the design justification, hydrodynamic characterization and experimental validation of a microfluidic device incorporating contraction-expansion geometries that generate strain rate conditions mimicking the effects of pathological changes in blood vessel geometry. Blood perfusion through this device supports our published findings of both in vivo and in vitro platelet aggregation and confirms a critical requirement for the coupling of blood flow acceleration to downstream deceleration for the initiation and stabilization of platelet aggregation, in the absence of soluble platelet agonists. The microfluidics platform presented will facilitate the detailed analysis of the effects of hemodynamic parameters on the rate and extent of platelet aggregation and will be a useful tool to elucidate the hemodynamic and platelet mechano-transduction mechanisms, underlying this shear-dependent process.

Fluorescence correlation spectroscopy to study diffusion through diatom nanopores.

The intricate pore architecture of diatom frustules has been extensively studied mainly as the basis of diatom classification. There have, however, been very few reports on understanding the effect of the pore architecture on the movement of molecules through the pores. Information on molecular transport though diatom membrane pores has the potential to help develop more efficient membrane filtration systems. In this paper the transport of molecules through individual diatom nanopores is investigated. Fluorescence correlation spectroscopy (FCS) is used to determine diffusion coefficients. Thus, for the very first time, we measure the effect of the three dimensional pore structure of the diatom Coscinodiscus wailesii, on the mean diffusion coefficient through the pores. The results show almost a 50% decrease in the diffusion coefficient relative to that in the free solution.