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.

Recent Progress in Micro- and Nanotechnology-Enabled Sensors for Biomedical and Environmental Challenges.

Micro- and nanotechnology-enabled sensors have made remarkable advancements in the fields of biomedicine and the environment, enabling the sensitive and selective detection and quantification of diverse analytes. In biomedicine, these sensors have facilitated disease diagnosis, drug discovery, and point-of-care devices. In environmental monitoring, they have played a crucial role in assessing air, water, and soil quality, as well as ensured food safety.

An extensional strain sensing mechanosome drives adhesion-independent platelet activation at supraphysiological hemodynamic gradients.

Background: Supraphysiological hemodynamics are a recognized driver of platelet activation and thrombosis at high-grade stenosis and in blood contacting circulatory support devices. However, whether platelets mechano-sense hemodynamic parameters directly in free flow (in the absence of adhesion receptor engagement), the specific hemodynamic parameters at play, the precise timing of activation, and the signaling mechanism(s) involved remain poorly elucidated.

Results: Using a generalized Newtonian computational model in combination with microfluidic models of flow acceleration and quasi-homogenous extensional strain, we demonstrate that platelets directly mechano-sense acute changes in free-flow extensional strain independent of shear strain, platelet amplification loops, von Willebrand factor, and canonical adhesion receptor engagement.

Extremely Sensitive Microwave Microfluidic Dielectric Sensor Using a Transmission Line Loaded with Shunt LC Resonators.

In this paper, a very high sensitivity microwave-based planar microfluidic sensor is presented. Sensitivity enhancement is achieved and described theoretically and experimentally by eliminating any extra parasitic capacitance not contributing to the sensing mechanism. The sensor consists of a microstrip transmission line loaded with a series connected shunt LC resonator.

Magnetic actuation and deformation of a soft shuttle.

Here, we describe the magnetic actuation of soft shuttles for open-top microfluidic applications. The system is comprised of two immiscible liquids, including glycerol as the soft shuttle and a suspension of iron powder in sucrose solution as the magnetic drop. Permanent magnets assembled on 3D printed motorized actuators were used for the actuation of the magnetic drop, enabling the glycerol shuttle to be propelled along customized linear, circular, and sinusoidal paths.

Droplet on Soft Shuttle: Electrowetting-on-Dielectric Actuation of Small Droplets.

Here, we introduce the novel concept of a "soft shuttle" for transportation, manipulation, and diffusion studies of small liquid droplets using electrowetting on the dielectric mechanism. This method enables manipulation of droplets several times smaller than the electrode size and, importantly, minimizes evaporation, contamination, and exposure of the sample to high voltages. We demonstrate various modes of droplet loading, transporting, and unloading.

A Microfluidic System for Studying the Effects of Disturbed Flow on Endothelial Cells.

Arterial endothelium experience physical stress associated with blood flow and play a central role in maintaining vascular integrity and homeostasis in response to hemodynamic forces. Blood flow within vessels is generally laminar and streamlined. However, abrupt changes in the vessel geometry due to branching, sharp turns or stenosis can disturb the laminar blood flow, causing secondary flows in the form of vortices.

Application of a strain rate gradient microfluidic device to von Willebrand's disease screening.

Von Willebrand's disease (VWD) is the most common inherited bleeding disorder caused by either quantitative or qualitative defects of von Willebrand factor (VWF). Current tests for VWD require relatively large blood volumes, have low throughput, are time-consuming, and do not incorporate the physiologically relevant effects of haemodynamic forces. We developed a microfluidic device incorporating micro-contractions that harnesses well-defined haemodynamic strain gradients to initiate platelet aggregation in citrated whole blood.

Dynamic drag force based on iterative density mapping: A new numerical tool for three-dimensional analysis of particle trajectories in a dielectrophoretic system.

Dielectrophoresis is a widely used means of manipulating suspended particles within microfluidic systems. In order to efficiently design such systems for a desired application, various numerical methods exist that enable particle trajectory plotting in two or three dimensions based on the interplay of hydrodynamic and dielectrophoretic forces. While various models are described in the literature, few are capable of modeling interactions between particles as well as their surrounding environment as these interactions are complex, multifaceted, and computationally expensive to the point of being prohibitive when considering a large number of particles.

Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells.

Mechanosensitive ion channels are implicated in the biology of touch, pain, hearing and vascular reactivity; however, the identity of these ion channels and the molecular basis of their activation is poorly understood. We previously found that transient receptor potential vanilloid 4 (TRPV4) is a receptor operated ion channel that is sensitised and activated by mechanical stress. Here, we investigated the effects of mechanical stimulation on TRPV4 localisation and activation in native and recombinant TRPV4-expressing cells.

Continuous transfer of liquid metal droplets across a fluid-fluid interface within an integrated microfluidic chip.

Micro scale liquid metal droplets have been hailed as the potential key building blocks of future micro-electro-mechanical systems (MEMS). However, most of the current liquid metal enabled systems involve millimeter scale droplets, which are manually injected onto the desired locations of the microchip. Despite its simplicity, this method is impractical for patterning large arrays or complex systems based on micro scale droplets.

Nonlinear Dynamic Modelling of Platelet Aggregation via Microfluidic Devices.

The recent application of new microfluidic technologies and methods has facilitated significant progress in the understanding of the fundamental mechanisms governing blood platelet function and how these parameters affect pathological thrombus formation. In-line with these new bioengineering approaches, the application of nonlinear dynamic systems analysis holds particular potential to extend our understanding of the complex interplay between mechanical and biochemical factors that underlie this complex biological phenomenon. In this paper we propose a simple mathematical model of the main dynamics of platelet aggregation/disaggregation observed experimentally in a novel microfluidic device that approximates a severe arterial stenosis.

Examination of the role of transient receptor potential vanilloid type 4 in endothelial responses to shear forces.

Shear stress is the major mechanical force applied on vascular endothelial cells by blood flow, and is a crucial factor in normal vascular physiology and in the development of some vascular pathologies. The exact mechanisms of cellular mechano-transduction in mammalian cells and tissues have not yet been elucidated, but it is known that mechanically sensitive receptors and ion channels play a crucial role. This paper describes the use of a novel and efficient microfluidic device to study mechanically-sensitive receptors and ion channels in vitro, which has three independent channels from which recordings can be made and has a small surface area such that fewer cells are required than for conventional flow chambers.

Finite-element analysis of the effect of basic hip movements on the mechanical stimulus within a proximal femur.

Osteoporosis is a serious and multifactorial disease. The number of people affected with osteoporosis is increasing due to the lengthening of life expectancy. Currently, unlike the genetic, nutritional and hormonal factors that have been the focus of most studies of osteoporosis, mechanical stimuli that potentially can produce an increase in bone strength have not been well studied.

Dielectrophoresis with 3D microelectrodes fabricated by surface tension assisted lithography.

This paper demonstrates the utilization of 3D semispherical shaped microelectrodes for dielectrophoretic manipulation of yeast cells. The semispherical microelectrodes are capable of producing strong electric field gradients, and in turn dielectrophoretic forces across a large area of channel cross-section. The semispherical shape of microelectrodes avoids the formation of undesired sharp electric fields along the structure and also minimizes the disturbance of the streamlines of nearby passing fluid.

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.

A multimode-TIRFM and microfluidic technique to examine platelet adhesion dynamics.

Fluorescence microscopy techniques have provided important insights into the structural and signalling events occurring during platelet adhesion under both static and blood flow conditions. However, due to limitations in sectioning ability and sensitivity these techniques are restricted in their capacity to precisely image the adhesion footprint of spreading platelets. In particular, investigation of platelet adhesion under hemodynamic shear stress requires an imaging platform with high spatial discrimination and sensitivity and rapid temporal resolution.

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.

Particle trapping using dielectrophoretically patterned carbon nanotubes.

This study presents the dielectrophoretic (DEP) assembly of multi-walled carbon nanotubes (MWCNTs) between curved microelectrodes for the purpose of trapping polystyrene microparticles within a microfluidic system. Under normal conditions, polystyrene particles exhibit negative DEP behaviour and are repelled from microelectrodes. Interestingly, the addition of MWCNTs to the system alters this situation in two ways: first, they coat the surface of particles and change their dielectric properties to exhibit positive DEP behaviour; second, the assembled MWCNTs are highly conductive and after the deposition serve as extensions to the microelectrodes.

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.

Dielectrophoretic manipulation and separation of microparticles using curved microelectrodes.

This paper presents the development and experimental analysis of a dielectrophoresis (DEP) system, which is used for the manipulation and separation of microparticles in liquid flow. The system is composed of arrays of microelectrodes integrated to a microchannel. Novel curved microelectrodes are symmetrically placed with respect to the centre of the microchannel with a minimum gap of 40 microm.

A shear gradient-dependent platelet aggregation mechanism drives thrombus formation.

Platelet aggregation at sites of vascular injury is essential for hemostasis and arterial thrombosis. It has long been assumed that platelet aggregation and thrombus growth are initiated by soluble agonists generated at sites of vascular injury. By using high-resolution intravital imaging techniques and hydrodynamic analyses, we show that platelet aggregation is primarily driven by changes in blood flow parameters (rheology), with soluble agonists having a secondary role, stabilizing formed aggregates.