Low Shear Flow Research Articles

Flexible non-Brownian filament in intensified shear flow

The behavior of a three-dimensional, non-Brownian flexible filament in a low Reynolds number shear flow was investigated through theoretical and numerical analyses. In the phase plane with Reynolds number Re∈[0.03,8] and flow intensity Z∈[800,35 000], four primary motion modes of the filament were identified: rigid, C-buckling, U-turn, and S-turn. By employing the principle of symmetry, a theoretical model was developed to explain the S-turn mode, and we discovered that the critical flow strength for the transition from U-turn to S-turn was approximately Zc=4900. Our numerical simulations confirmed this transition value. In a system devoid of thermal fluctuations, it was observed that the mode transitions of microscale filament precisely corresponded to the abrupt scale rate changes in the non-Newtonian behavior of the macroscopic solution. Although the polymer stress under different modes has distinct underlying causes, they can all be predicted by the generalized Hooke's law.

Janus nanoparticles as efficient interface compatibilizer in blends of polylactide and elastomers: Importance of interfacial relaxation on toughening

For blending immiscible polymers, such as in the toughening modification of polylactide (PLA) via blending with rubbery materials, interfacial compatibilization is of great significance while the mechanism, especially the role of interfacial rheology, remains elusive. In this study, styrene-butadiene block copolymer elastomer (SBC) was employed to toughen PLA and a dumbbell-shaped Janus nanoparticle (JNP) consisting of polymethyl methacrylate and polystyrene spheres with equal size (∼80 nm) was used as the compatibilizer. Located at the interface, JNPs exhibited a great compatibilization efficiency in PLA/SBC blends, as demonstrated by the good morphology stabilization against droplet coalescence under static annealing and low shear flow conditions, as well as by the resistance against droplet breakup under high shear flow conditions. Moreover, as revealed from the linear viscoelasticity of JNP compatibilized blends, when JNP loading is more than 2 phr, aside from shape relaxation, an interfacial relaxation dominated by Marangoni stress was observed, indicating the possibility of particle redistribution on droplet surfaces. However, when loading is more than 4 phr, relaxations in the terminal zone no longer exist, implying the possible formation of a particle network on the droplet surface. This is consistent with the mechanical properties. The blend shows the greatest toughness at JNP loading around 3 phr, while the toughness is very poor when JNP loading is either too low or too high. This suggests interfacial relaxation to be crucial to guarantee a good toughening effect of SBC in PLA.

Subjects with carotid webs demonstrate pro-thrombotic hemodynamics compared to subjects with carotid atherosclerosis

Carotid artery webs (CaW) are non-atherosclerotic projections into the vascular lumen and have been linked to up to one-third of cryptogenic strokes in younger patients. Determining how CaW affects local hemodynamics is essential for understanding clot formation and stroke risk. Computational fluid dynamics simulations were used to investigate patient-specific hemodynamics in carotid artery bifurcations with CaW, bifurcations with atherosclerotic lesions having a similar degree of lumen narrowing, and with healthy carotid bifurcations. Simulations were conducted using segmented computed tomography angiography geometries with inlet boundary conditions extracted from 2D phase contrast MRI scans. The study included carotid bifurcations with CaW (n = 13), mild atherosclerosis (n = 7), and healthy bifurcation geometries (n = 6). Hemodynamic parameters associated with vascular dysfunction and clot formation, including shear rate, oscillatory shear index (OSI), low velocity, and flow stasis were calculated and compared between the subject groups. Patients with CaW had significantly larger regions containing low shear rate, high OSI, low velocity, and flow stasis in comparison to subjects with mild atherosclerosis or normal bifurcations. These abnormal hemodynamic metrics in patients with CaW are associated with clot formation and vascular dysfunction and suggest that hemodynamic assessment may be a tool to assess stroke risk in these patients.

Detecting normal and cancer skin cells via glycosylation and adhesion signatures: A path to enhanced microfluidic phenotyping

Recruiting circulating cells based on interactions between surface receptors and corresponding ligands holds promise for capturing cells with specific adhesive properties. Our study investigates the adhesion of skin cells to specific lectins, particularly focusing on advancements in lectin-based biosensors with diagnostic potential. We explore whether we can successfully capture normal skin (melanocytes and keratinocytes) and melanoma (WM35, WM115, WM266-4) cells in a low-shear flow environment by coating surfaces with lectins. Specifically, we coated surfaces with Dolichos biflorus (DBA) and Maackia Amurensis (MAL) lectins, which were used to detect and capture specific skin cells from the flow of cell mixture. Alterations in glycan expression (confirmed by fluorescent microscopy) demonstrated that DBA binds predominantly to normal skin cells, while MAL interacts strongly with melanoma cells. Assessing adhesion under static and dynamic low-shear stress conditions (up to 30 mPa) underscores the reliability of DBA and MAL as markers for discriminating specific cell type. Melanocytes and keratinocytes adhere to DBA-coated surfaces, while melanoma cells prefer MAL-coated surfaces. A comprehensive analysis encompassing cell shape, cytoskeleton, and focal adhesions shows the independence of our approach from the inherent characteristics of cells, thus demonstrating its robustness. Our results carry practical implications for lectin-biosensor designs, emphasizing the significance of glycan-based discrimination of pathologically altered cells. Combined with microfluidics, it demonstrates the value of cell adhesion as a discriminant of cancer-related changes, with potential applications spanning diagnostics, therapeutic interventions, and advanced biomedical technologies.

Instability of Jeffrey Fluid Throughflow in a Porous Layer Induced by Heat Source and Soret Effect

Abstract In this study, we investigated the instability of thermosolutal convection of Jeffrey fluid in a porous layer with internal heating and the Soret effect. The layer is bounded by two fixed permeable parallel plates which are assumed to be isothermal and isosolutal. An existing initial flow in the vertical direction is passing the layer at a constant speed. The flow fields are adequately presented by PDEs and transformed into dimensionless forms. A small perturbation to the basic flow profiles with linear stability analysis results the problem in an eigenvalue problem. The Runge-Kutta method is used to derive the numerical value of the critical thermal Rayleigh number. The convective instability for asymptotic cases for Le = 1 and Pe = 0 are also examined as special cases. The analysis reveals that for a non-positive Soret parameter, the flow is stable for all Lewis numbers and independent of the heat source. But with a positive Soret parameter in the absence of a heat source, the fluid flow is stable for Le = 3 while the influence of a heat source destabilizes the flow for Le > 2. In high and low shear flows with increasing solutal gradient, the solutal Rayleigh number shows a highly destabilizing nature for all Le. Moreover, smaller relaxation and higher retardation time are the most unstable characteristics of the heat source system. In convective longitudinal rolls, the uni-cellular streamline patterns tend to become bi-cellular by the influence of positive Soret parameters and energy sources.

Shear rheology of a dilute suspension of thin rings

The rheology of suspensions of rings (tori) rotating in an unbounded low Reynolds number simple shear flow is calculated using numerical simulations at dilute particle number densities ( n ≪ 1 ). Suspensions of non-Brownian rings are studied by computing pair interactions that include hydrodynamic interactions modeled using slender body theory and particle collisions modeled using a short-range repulsive force. Particle contact and hydrodynamic interactions were found to have comparable influences on the steady-state Jeffery orbit distribution. The average tilt of the ring away from the flow-vorticity plane increased during pairwise interactions compared to the tilt associated with Jeffery rotation and the steady-state orbit distribution. Particle stresses associated with the increased tilt during the interaction were found to be comparable to the stresses induced directly by particle contact forces and the hydrodynamic velocity disturbances of other particles. The hydrodynamic diffusivity coefficients in the gradient and vorticity directions were also obtained and were found to be two orders of magnitude larger than the corresponding values in fiber suspensions at the same particle concentrations. Rotary Brownian dynamics simulations of isolated Brownian rings were used to understand the shear rate dependence of suspension rheology. The orbit distribution observed in the regime of weak Brownian motion, P e ≫ ϕ T − 3, was surprisingly similar to that obtained from pairwise interaction calculations of non-Brownian rings. Here, the Peclet number P e is the ratio of the shear rate and the rotary diffusivity of the particle and ϕ T is the effective inverse-aspect ratio of the particle (approximately equal to 2 π times the inverse of its non-dimensional Jeffery time period). Thus, the rheology results obtained from pairwise interactions should retain accuracy even for weakly Brownian rings ( n ≪ 1 and ϕ T − 3 ≪ P e ).

The effect of drainage cannula tip position on risk of thrombosis during venoarterial extracorporeal membrane oxygenation

Background and objectivesVenoarterial extracorporeal membrane oxygenation (VA ECMO) is able to support critically ill patients undergoing refractory cardiopulmonary failure. It relies on drainage cannulae to extract venous blood from the patient, but cannula features and tip position may impact flow dynamics and thrombosis risk. Therefore, this study aimed to investigate the effect of tip position of single-stage (SS) and multi-stage (MS) VA ECMO drainage cannulae on the risk of thrombosis. MethodsComputational fluid dynamics was used to model flow dynamics within patient-specific geometry of the venous vasculature. The tip of the SS and MS cannula was placed in the superior vena cava (SVC), SVC-Right atrium (RA) junction, mid-RA, inferior vena cava (IVC)-RA junction, and IVC. The risk of thrombosis was assessed by measuring several factors. Blood residence time was measured via an Eulerian approach through the use of a scalar source term. Regions of stagnant volume were recognised by identifying regions of low fluid velocity and shear rate. Rate of blood washout was calculated by patching the domain with a scalar value and measuring the rate of fluid displacement. Lastly, wall shear stress values were determined to provide a qualitative understanding of potential blood trauma. ResultsThrombosis risk varied substantially with position changes of the SS cannula, which was less evident with the MS cannula. The SS cannula showed reduced thrombosis risk arising from stagnant regions when placed in the SVC or SVC-RA junction, whereas an MS cannula was predicted to create stagnant regions during all tip positions. When positioned in the IVC-RA junction or IVC, the risk of thrombosis was higher in the SS cannula than in the MS cannula due to both high and low shear flow. ConclusionTip position of the drainage cannula impacts cannula flow dynamics and, subsequently, the risk of thrombosis. The use of MS cannulae can reduce high shear-related thrombosis, but SS cannulae can eliminate stagnant regions when advanced into the SVC. Therefore, the choice of cannula design and tip position should be carefully considered during cannulation.

Classification of red cell dynamics with convolutional and recurrent neural networks: a sickle cell disease case study

The fraction of red blood cells adopting a specific motion under low shear flow is a promising inexpensive marker for monitoring the clinical status of patients with sickle cell disease. Its high-throughput measurement relies on the video analysis of thousands of cell motions for each blood sample to eliminate a large majority of unreliable samples (out of focus or overlapping cells) and discriminate between tank-treading and flipping motion, characterizing highly and poorly deformable cells respectively. Moreover, these videos are of different durations (from 6 to more than 100 frames). We present a two-stage end-to-end machine learning pipeline able to automatically classify cell motions in videos with a high class imbalance. By extending, comparing, and combining two state-of-the-art methods, a convolutional neural network (CNN) model and a recurrent CNN, we are able to automatically discard 97% of the unreliable cell sequences (first stage) and classify highly and poorly deformable red cell sequences with 97% accuracy and an F1-score of 0.94 (second stage). Dataset and codes are publicly released for the community.

Granular packing in complex flow geometries

We examine the packing fraction and stress ratio in different granular flow geometries. In isochoric systems, we find that the packing fraction response versus inertial number is qualitatively similar to the more well established stress ratio response. As a result, the packing fraction is well-characterized as a local function of stress across a range of geometries and flow conditions. In a non-isochoric system, specifically a hopper, we find the response is more complex. By examining the flow onset in shear cell and chute systems, we attribute the different response in the hopper to the differing time scales for the development of stress versus packing in dense, low shear flow regions.

Rheological investigation of polymer/clay dispersions as potential drilling fluids

The rheological properties of poly(ethylene glycol)(PEG)/Laponite® RD (Lap) and poly(propylene glycol)(PPG)/Lap aqueous dispersions, with 2% polymer and different clay concentrations, were investigated at 25 °C in order to establish the optimal composition to formulate a system applicable as drilling fluid. Some of the most important parameters, such as low shear rate viscosity, plastic viscosity, yield stress and flow behavior index, were determined and discussed. The PEG/Lap and PPG/Lap dispersions containing more than 2.55% and 3.10% clay, respectively, could be considered in the formulation of drilling fluids. The yield point value of dispersions, which is suitable for drilling fluid applications, increased while their plastic viscosity decreased in the presence of NaCl. By addition of NaCl, the complex viscosity of these samples becomes independent of temperature in the range 10 °C – 65 °C. Zeta potential value decreases as the Lap concentration increases up to about 3% clay and, higher clay content no longer affects it. • Laponite® RD (Lap) aqueous dispersions in presence of PEG or PPG were investigated. • Rheological results suggest Lap suitability for drilling fluids. • Effect of salt and temperature on viscoelastic properties was evaluated. • Zeta potential as function of clay content and polymer structure was analysed. • Structure of Lap dispersions in presence/absence of PEG or PPG was discussed.

Tailoring of arteriovenous graft-to-vein anastomosis angle to attenuate pathological flow fields

Arteriovenous grafts are routinely placed to facilitate hemodialysis in patients with end stage renal disease. These grafts are conduits between higher pressure arteries and lower pressure veins. The connection on the vein end of the graft, known as the graft-to-vein anastomosis, fails frequently and chronically due to high rates of stenosis and thrombosis. These failures are widely believed to be associated with pathologically high and low flow shear strain rates at the graft-to-vein anastomosis. We hypothesized that consistent with pipe flow dynamics and prior work exploring vein-to-artery anastomosis angles in arteriovenous fistulas, altering the graft-to-vein anastomosis angle can reduce the incidence of pathological shear rate fields. We tested this via computational fluid dynamic simulations of idealized arteriovenous grafts, using the Bird-Carreau constitutive law for blood. We observed that low graft-to-vein anastomosis angles (<20^{circ }) led to increased incidence of pathologically low shear rates, and that high graft-to-vein anastomosis angles (>40^{circ }) led to increased incidence of pathologically high shear rates. Optimizations predicted that an intermediate (sim 30^circ) graft-to-anastomosis angle was optimal. Our study demonstrates that graft-to-vein anastomosis angles can significantly impact pathological flow fields, and can be optimized to substantially improve arteriovenous graft patency rates.

Mechanotransduction-on-chip: vessel-chip model of endothelial YAP mechanobiology reveals matrix stiffness impedes shear response.

Endothelial mechanobiology is a key consideration in the progression of vascular dysfunction, including atherosclerosis. However mechanistic connections between the clinically associated physical stimuli, vessel stiffness and shear stress, and how they interact to modulate plaque progression remain incompletely characterized. Vessel-chip systems are excellent candidates for modeling vascular mechanobiology as they may be engineered from the ground up, guided by the mechanical parameters present in human arteries and veins, to recapitulate key features of the vasculature. Here, we report extensive validation of a vessel-chip model of endothelial yes-associated protein (YAP) mechanobiology, a protein sensitive to both matrix stiffness and shearing forces and, importantly, implicated in atherosclerotic progression. Our model captures the established endothelial mechanoresponse, with endothelial alignment, elongation, reduction of adhesion molecules, and YAP cytoplasmic retention under high laminar shear. Conversely, we observed disturbed morphology, inflammation, and nuclear partitioning under low, high, and high oscillatory shear. Examining targets of YAP transcriptional co-activation, connective tissue growth factor (CTGF) is strongly downregulated by high laminar shear, whereas it is strongly upregulated by low shear or oscillatory flow. Ankyrin repeat domain 1 (ANKRD1) is only upregulated by high oscillatory shear. Verteporfin inhibition of YAP reduced the expression of CTGF but did not affect ANKRD1. Lastly, substrate stiffness modulated the endothelial shear mechanoresponse. Under high shear, softer substrates showed the lowest nuclear localization of YAP whereas stiffer substrates increased nuclear localization. Low shear strongly increased nuclear localization of YAP across stiffnesses. Together, we have validated a model of endothelial mechanobiology and describe a clinically relevant biological connection between matrix stiffness, shear stress, and endothelial activation via YAP mechanobiology.

Input-output inspired method for permissible perturbation amplitude of transitional wall-bounded shear flows.

The precise set of parameters governing transition to turbulence in wall-bounded shear flows remains an open question; many theoretical bounds have been obtained, but there is not yet a consensus between these bounds and experimental or simulation results. In this work, we focus on a method to provide a provable Reynolds-number-dependent bound on the amplitude of perturbations a flow can sustain while maintaining the laminar state. Our analysis relies on an input-output approach that partitions the dynamics into a feedback interconnection of the linear and nonlinear dynamics (i.e., a Luré system that represents the nonlinearity as static feedback). We then construct quadratic constraints of the nonlinear term that is restricted by system physics to be energy-conserving (lossless) and to have bounded input-output energy. Computing the region of attraction of the laminar state (set of safe perturbations) and permissible perturbation amplitude are then reformulated as linear matrix inequalities, which allows more computationally efficient solutions than prevailing nonlinear approaches based on the sum of squares programming. The proposed framework can also be used for energy method computations and linear stability analysis. We apply our approach to low-dimensional nonlinear shear flow models for a range of Reynolds numbers. The results from our analytically derived bounds are consistent with the bounds identified through exhaustive simulations. However, they have the added benefit of being achieved at a much lower computational cost and providing a provable guarantee that a certain level of perturbation is permissible.

Sublethal Supraphysiological Shear Stress Alters Erythrocyte Dynamics in Subsequent Low-Shear Flows

Blood is a non-Newtonian, shear-thinning fluid owing to the physical properties and behaviors of red blood cells (RBCs). Under increased shear flow, pre-existing clusters of cells disaggregate, orientate with flow, and deform. These essential processes enhance fluidity of blood, although accumulating evidence suggests that sublethal blood trauma—induced by supraphysiological shear exposure—paradoxically increases the deformability of RBCs when examined under low-shear conditions, despite obvious decrement of cellular deformation at moderate-to-higher shear stresses. Some propose that rather than actual enhancement of cell mechanics, these observations are “pseudoimprovements” and possibly reflect altered flow and/or cell orientation, leading to methodological artifacts, although direct evidence is lacking. This study thus sought to explore RBC mechanical responses in shear flow using purpose-built laser diffractometry in tandem with direct optical visualization to address this problem. Freshly collected RBCs were exposed to a mechanical stimulus known to drastically alter cell deformability (i.e., prior shear exposure (PSE) to 100 Pa × 300 s). Samples were subsequently transferred to a custom-built slit-flow chamber that combined laser diffractometry with direct cell visualization. Cell suspensions were sheared in a stepwise manner (between 0.3 and 5.0 Pa), with each step being maintained for 15 s. Deformability and cell orientation indices were recorded for small-scatter Fraunhofer diffraction patterns and also visualized RBCs. PSE RBCs had significantly decreased visualized and laser-derived deformability at any given shear stress ≥1 Pa. Novel, to our knowledge, observations demonstrated that PSE RBCs had increased heterogeneity of direct visualized orientation with flow vector at any shear, which may be due to greater vorticity and thus instability in 5-Pa flow compared with unsheared control. These findings indicate that shear exposure and stress-strain history can alter subsequent RBC behavior in physiologically relevant low-shear flows. These findings may yield insight into microvascular disorders in recipients of mechanical circulatory support and individuals with hematological diseases that alter physical properties of blood.

Beyond oxygen transport: active role of erythrocytes in the regulation of blood flow.

It was classically thought that the function of mammalian red blood cells (RBCs) was limited to serving as a vehicle for oxygen, given the cells' abundance of cytosolic hemoglobin. Over the past decades, however, accumulating evidence indicates that RBCs have the capacity to sense low-oxygen tensions in hypoxic tissues, and, subsequently, release signaling molecules that influence the distribution of blood flow. The precise mechanisms that facilitate RBC modulation of blood flow are still being elucidated, although recent evidence indicates involvement of 1) adenosine triphosphate, capable of binding to purinergic receptors located on the vascular wall before initiating nitric oxide (NO; a powerful vasodilator) production in endothelial cells, and/or 2) nonvascular NO, which is now known to have several modes of production within RBCs, including an enzymatic process via a unique isoform of NO synthase (i.e., RBC-NOS), which has potential effects on the vascular smooth muscle. The physical properties of RBCs, including their tendency to form three-dimensional structures in low shear flow (i.e., aggregation) and their capacity to elongate in high shear flow (i.e., deformability), are only recently being viewed as mechanotransductive processes, with profound effects on vascular reactivity and tissue perfusion. Recent developments in intracellular signaling in RBCs, and the subsequent effects on the mechanical properties of blood, and blood flow, thus present a vivid expansion on the classic perspective of these abundant cells.

Evaluation of clinical severity in patients with type 2N von Willebrand disease using microchip-based flow-chamber system.

Type 2N von Willebrand disease (VWD) is characterized by impaired factor VIII (FVIII) binding to von Willebrand factor (VWF). Type 2N VWD patients generally exhibit mild bleeding tendency, but some exhibit a more severe hemorrhagic pattern. An assay for assessing hemostatic potential and predict clinical severity could significantly improve clinical management in these patients. We examined the relationship between bleeding score (BS) and the potential for thrombus formation in whole blood from type 2N VWD patients with various BS using rotational thromboelastometry (ROTEM) and microchip flow-chamber system (T-TAS®). Collagen-coated PL-chips, or thromboplastin- and collagen-coated AR-chips, were utilized in the T-TAS to assess platelet thrombus formation at high shear flow, or fibrin-rich platelet thrombus formation at low shear flow, respectively. Neither ROTEM nor the T-TAS using PL-chips reflected the BS. The AR-chip parameters in the T-TAS, however, were highly sensitive to different BS levels among these patients, despite similar FVIII/VWF-related measurements including FVIII/VWF binding. Additionally, the results with AR-chip assay were restored to normal after infusions of FVIII/VWF concentrates in the most severe patients. The data indicate that T-TAS using AR-chips may be a useful assay for predicting clinical severity and assessing therapeutic efficiency in type 2N VWD patients.

In Vitro Functionality of hiPSC Derived PLT+: The Utility of Microfluidic Assays in Determining Potency

Introduction: There is a growing shortage of platelets, the principal blood cells responsible for clot formation and blood vessel repair at sites of active bleeding. Platelet BioGenesis (PBG) is developing a commercial-scale, donor-free platelet (PLT+) production process using a cGMP-grade human induced pluripotent stem cell line (hiPSC) to address this issue. The PLT+ activity is being characterized extensively through multiple approaches that measure hemostatic function both in vitro and in vivo, with the ultimate goal of determining a clinical dose in humans. Alongside tests such as the current gold standard thrombin generation assay (TGA), we have developed an in-house microfluidic model to measure the ability of PLT+ to adhere to extracellular proteins under flow. The assay captures the surface receptor dynamics, as well as the ability of PLT+ to initiate coagulation. Materials and Methods: The thrombin generation assays are performed according to manufacturer's instructions. For the in-house microfluidic assay (MFA), fibrillar collagen, fibrinogen, or von Willebrand Factor is patterned in a commercial microfluidic device (Ibidi Slide VI 0.1). PLT+ (DNA-, calcein +, CD61+, CD42a+ cells from our bioreactor) are concentrated in normal pooled plasma, platelet additive solution, or platelet wash buffer to a normalized concentration of 1e8/mL, and are labeled with the mitochondrial dye DiOC6. Calcium chloride (7.5 mM) is added and the solution is perfused with a syringe pump at 50 1/s over the bioactive surface for 10 min. Images are captured every 10 seconds and quantified with ImageJ. After perfusion, the samples are fixed with 4% paraformaldehyde and can be stained for further characterization. Results and Discussion: PLTs+ are functionally non-inferior to human donor (blood) platelets and appear more active than Day 4/5 stored apheresis unit platelets. The TGA of PLT+ shows a more rapid generation of thrombin but similar total potential to donor platelets (Figure A). In the microfluidic assay, PLT+ (green DiOC6, red PAC1, figure B) adhere readily to the collagen surface under low shear flow, but do not adhere to non-functionalized surfaces, indicating GPVI functionality. As measured by surface coverage, the PLT+ resuspended in PAS adhere faster to the surface than either freshly washed donor platelets or apheresis platelets (p=0.01). When the PLT+ are preincubated in normal pooled plasma prior to perfusion, we observe fibrin formation and the aggregates show clot retraction, which supports the TGA results. Adhesion to surface bound fibrinogen and VWF is also comparable to donor platelets (GP IIb/IIa and GPIb function,). Combined, the TGA and MFA data reflect results of traditional more resource intensive assays, suggesting their viability as a rapid and flexible platform to study platelet function and function as release assays for in vitro generated PLTs+ Conclusion: Current work demonstrates that PLT+ are functional and a future alternative to donor derived platelet units. The MFA is a valuable tool for the characterization of this new therapeutic because of its specific control of surface protein-receptor interactions, shear forces, and flexibility to look at multiple markers. Alongside the TGA, the MFA will be a release assay for the PLT+. Figure Disclosures Lehmann: Platelet Biogenesis: Employment. Burton:Platelet Biogenesis: Employment. Szemethy:Platelet Biogenesis: Employment. Valdez:Platelet BioGenesis: Employment. Thon:Platelet BioGenesis: Employment.

Does transcatheter aortic valve alignment matter?

ObjectiveThis study investigates the effect of transcatheter aortic valve (TAV) angular alignment on the postprocedure haemodynamics. TAV implantation has emerged as an effective alternative to surgery when treating valve dysfunction....

Towards Mechanical Clinical Markers in Sickle Cell Disease: Dynamics of Red Blood Cells in Low Shear Flow

Several regimes of motion are evident in red blood cells (RBCs) under shear flow and are known to be controlled by the shear flow rate and by the deformability of the cell. Above a certain shear flow rate, healthy RBCs present a fluidized regime analogous to that of a droplet: the membrane adopts a tank-treading motion, i.e. rotates around the centre of mass of the cell, and its orientation oscillates around a mean value (Fig. 1). This motion is not observed in rigid RBCs which keep the same regime of motion as with low shear flow rate. The transition from one motion to the other depends on several intrinsic parameters including membrane viscosity, elasticity and cytoplasmic viscosity.Sickle cell disease (SCD) is a hereditary hemolytic anemia due to the presence of mutant hemoglobin, Hb S, which tends to polymerize in RBCs, reducing its deformability and resulting ultimately in RBC sickling. We postulate that SCD may affect RBCs capacity to adopt the tank-treading motion.Thanks to microfluidic chips coupled with high speed video, we studied the fraction of RBCs displaying a tank-treading motion (% of TT) at moderate shear stresses (0.4-0.6 Pa), in homozygous SCD patients (n=30) and in normal subjects (n=12). At the time of sampling, SCD patients were in steady state (no vaso-occlusive crisis or other acute complications) and not transfused for at least 3 months. Around 3 microL of total blood were necessary for each measurement. RBCs were studied under atmospheric conditions and exhibited the normal discoid shape.We showed first that the % of TT is significantly different in SCD patients compared to controls, with no overlap between the values of each groups (respectively 70.4±12.9% versus 98.6±0.9%). Second, measurements performed on different cells fractions isolated by cell density or in the presence of different NaCl concentrations, showed that the % of TT cells is sensitive to cell density and hydration status, both in normal subjects and in SCD patients. Finally, we evaluate the % of TT in RBC samples drawn just before or during 10 episodes of vaso-occlusive crisis from 8 different patients. The definition of a vaso-occlusive crisis, for this specific study, was set as an episode with pain in at least 2 different locations requiring hospitalization at least for 24h. The results revealed that, for a given patient, the % of TT cells varies significantly for 12h before as well as during vaso-occlusive crises with kinetics comparable from one patient to another.In conclusion, we described here a new inexpensive biological test able to discriminate healthy RBCs from sickle RBCs, with preliminary results suggesting potential interest for monitoring the clinical status of SCD patients. Further analysis will be necessary to determine if this parameter is suitable for predicting the occurrence of vaso-occlusive crises early enough to allow preventive actions.Fig1: Schematic view of the regime of motion corresponding to tank-treading. Flow direction is from left to right and RBCs are observed from the direction of the shear gradient. The black dot on the RBCs displays the motion of a membrane element on the RBC surface. The axis of symmetry remains in the shear plane, the body of the RBC oscillates slightly as the membrane rotates around it DisclosuresThuret:Addmedica: Research Funding; bluebird bio: Research Funding; Novartis: Research Funding.

Cleaning of Fluid-Infused Surfaces in Microchannels.

When an immiscible fluid is flowing over a fluid-infused surface with transverse grooves in a microchannel, the infused fluid is either left in or cleaned away from the grooves by the flowing fluid. The cleaning status depends on the geometric parameters of the groove and the contact angle of the flowing fluids. The critical width of the grooves for the infused fluid enclosed in or driven out of the grooves is derived. This study helps to understand the stability of the Cassie status in a low-shear flow where the surface tension plays the key role.