Low Shear Conditions Research Articles

Enhancement of Tissue Factor Expression in Monocyte-Derived Dendritic Cells by Pentraxin 3 and Its Modulation by C1 Esterase Inhibitor

Background: We have previously shown that human monocyte-derived dendritic cells (moDCs) may participate in immune system-mediated hypercoagulable state through enhanced tissue factor (TF) expression and that the complement system may be involved in this process. Objectives: The aim of this study was to explore the role of pentraxin 3 (PTX3) and the complement system in enhanced TF expression in moDCs. Methods: moDCs were generated from isolated human monocytes. PTX3 levels in whole human blood supplemented with moDCs were determined after lipopolysaccharide (LPS) stimulation. PTX3 release by the generated moDCs upon LPS stimulation was also assessed. The effect of PTX3 on whole blood coagulation was investigated using thromboelastometric analysis. TF expression in stationary moDCs treated with LPS and/or PTX3 was determined by measuring TF activity. The effect of complement inhibitors on TF activity in moDCs treated with LPS and/or PTX3 under low-shear conditions was evaluated. Results: PTX3 levels were higher in whole blood supplemented with moDCs than in the presence of monocytes and were further elevated by LPS stimulation. PTX3 release from generated moDCs was also increased by LPS stimulation. PTX3 reduced whole blood coagulation time in a dose-dependent manner. However, PTX3 did not increase TF expression in stationary moDCs. Under low-shear conditions, PTX3 increased TF expression in moDCs. C1 esterase inhibitor (C1-inh) suppressed this effect. Conclusions: PTX3 might have a thrombophilic activity and enhance TF expression in moDCs under low-shear conditions. Furthermore, suppression of moDC-associated hypercoagulability by C1-inh might be partly ascribed to its inhibitory effect on PTX3.

Antimicrobial efficacy of Thymbra capitata (L.) Cav. essential oil loaded in self-assembled zein nanoparticles in combination with heat

This study reports on the chemical composition of Thymbra capitata essential oil (TCEO) and its antimicrobial activity when applied with heat either as a suspension (s-TCEO) or loaded in self-assembled zein nanoparticles (zn-TCEO). Zein, a plant protein isolated from corn and maize, is proposed as natural, and biocompatible carrier. TCEO composition was analysed by GC–MS, and 35 components were identified. Carvacrol, a monoterpenoid, was the major constituent (73.8%). zn-TCEO were prepared under low shear conditions and characterized according to droplet size (<180 nm) and encapsulation efficiency (77.8%). The two TCEO formulations (s-TCEO and zn-TCEO) were compared in terms of antibacterial activity against Escherichia coli O157:H7 Sakai and Listeria monocytogenes EGD-e. The zn-TCEO displayed a greater bacteriostatic activity than s-TCEO, probably due to their improved dispersion in the growth media. However, zn-TCEO exerted a lower bactericidal activity than s-TCEO, probably due to the EO progressive release. The combination of TCEO and heat (53 °C) exerted valuable synergistic lethal effects, causing the death of up to 5 log10 cycles of both microorganisms. The effectiveness of zn-TCEO was especially improved at pH 4.0. Therefore, the application of this new delivery system, designed to encapsulate and protect EOs, and ensure their controlled release, might represent an advantageous alternative for food, cosmetic or pharmaceutical industries to improve the efficacy of higienization processes or surface cleaning and disinfection procedures when combined with mild heat.

MESSENGER Observations and Global Simulations of Highly Compressed Magnetosphere Events at Mercury

AbstractWe identify and examine all MErcury Surface Space ENvironment, GEochemistry, and Ranging (MESSENGER) crossings of Mercury's dayside magnetopause with magnetospheric field intensities ≥300 nT. The eight such events, which occurred under highly compressed magnetosphere conditions, are analyzed in the identical manner utilized by Slavin et al. (2014, https://doi.org/10.1002/2014JA020319). The results suggest that the eight highly compressed magnetosphere events represent the highest solar wind dynamic pressures for which the MESSENGER's orbit still passed below the magnetopause and provided measurements of the dayside magnetosphere. Using the magnetohydrodynamic model by Jia et al. (2015, https://doi.org/10.1002/2015JA021143) that electromagnetically couples Mercury's interior with its magnetosphere, a series of global simulations are conducted to quantitatively characterize the response of Mercury's magnetosphere to solar wind forcing. Combining the MESSENGER observations with the simulations, we have obtained a consistent picture of how Mercury's dayside magnetospheric configuration is controlled, separately and in combination, by induction‐driven shielding and reconnection‐driven erosion. For solar wind pressures of ∼40–90 nPa, compared with the average ∼10–15 nPa at Mercury's orbit, the shielding effects of induction in Mercury's core in standing‐off the solar wind typically exceed the erosion of the dayside magnetosphere due to reconnection for these events, most of which occurred under low magnetic shear conditions. For high magnetic shear across the magnetopause our simulation predicts that reconnection would dominate. Mercury's effective magnetic moment as inferred from magnetopause standoff distance ranges from 170 to 250 for these events. These findings are of crucial importance for understanding the space weathering at Mercury and its contribution to the generation of Mercury's exosphere.

Influence of Impeller Geometry on Hydromechanical Stress in Stirred Liquid/Liquid Dispersions

Hydromechanical stress is a crucial parameter for a broad range of multiphase processes in the field of (bio)chemical engineering. The effect of impeller type and geometry on hydromechanical stress in stirred tanks is important. The present study aims at characterizing conventional and new impeller types in terms of particle stress. A two-phase liquid/liquid noncoalescing dispersion system is employed, and the drop breakage is monitored in-line in a stirred tank. The published effects of agitation on drop deformation are confirmed and expanded significantly for five modified new impeller types. Radial impellers are advantageous for applications where low shear conditions are desired. A modified propeller with a peripheral ring and the developed wave-ribbon impellers present remarkable results by producing significantly low and high hydromechanical stress, respectively. The results obtained are correlated in terms of mean and maximum energy dissipation rate, as well as circulation frequency in the impeller...

Stratification in the physical structure and cohesion of membrane biofilms — Implications for hydraulic resistance

This study aimed at evaluating stratification of hydraulic resistance over the depth of membrane biofilms developed during gravity driven membrane (GDM) ultrafiltration. Biofilms were grown in membrane fouling simulators (MFS) for 25 days under 3 contrasting influent conditions: nutrient enriched, phosphorus limiting, and river water influent. Shear rheology was used to determine the biofilms material characteristics (e.g., elasticity, yield stress). Optical coherence tomography (OCT) was used to determine the response of the biofilms physical structure (e.g., thickness) to increased hydraulic shear stress from 0 up to 2.6 Pa. Stratification was observed in nutrient enriched and river water biofilms and which partially detached by erosion of their rough top layer under low shear conditions. A cohesive base layer remained attached to the membrane surface under high shear conditions, indicating stratification in cohesion over the biofilms depth. Erosion of the top layer only resulted in a slight decrease in the biofilm hydraulic resistance indicating that the very cohesive and thin base layer also represent significant hydraulic resistance. Conversely, P limiting biofilms had uniform structural and mechanical characteristics, detaching by sloughing and peeling at low and high shear stress respectively. Biofilms formed under phosphorus limiting conditions had equal elasticity, yet a lower yield stress compared to nutrient enriched and river water biofilms respectively and were more susceptible to detachment. The scientific implication of the presented work demonstrates that biofilm detachment is influenced by both the structural (surface heterogeneity) and material characteristics (e.g., yield stress), with practical relevance for hydraulic resistance during GDM filtration.

Blood rheology during normal pregnancy.

Recent studies have shown increased RBC aggregation and no difference in plasma viscosity in the presence of markedly lower hematocrit in women at term compared to non-pregnant women. Little is known about the outcome of blood rheological parameters and red blood cell (RBC) deformability particularly in the course of normal pregnancy. During a 36 months interval 1.913 blood samples were randomly collected from a total of 945 pregnant women in the course of their pregnancy (n = 1.259) and during puerperium (upto 1 week; n = 654). Next to the blood count, hemorheological parameters including red blood cell (RBC) -aggregation (stasis E0; low shear E1), -deformability (low, moderate and high shear conditions) and plasma viscosity (pv) were assessed. Plasma viscosity (pv) was examined using KSPV 1 Fresenius, RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne and RBC deformability (def) was determined by Rheodyn SSD Diffractometer, Myrenne, Roetgen, Germany were tested. In some of these women laboratory results prior to pregnancy (n = 145) were available which were compared with those during pregnancy. Mean maternal pv remained unchanged within each trimester and compared to the values before pregnancy and during early puerperium (Range of means: 1.18-1.20 mPa S). In contrast, RBC agg (E0 and E1) was markedly higher in the 2nd (21.8 ± 7.0 and 28.9 ± 9.4; p < 0.001) and 3rd trimester (18.74 ± 8.4 and 28.2 ± 9.4; p < 0.01) compared to the values before pregnancy (16.4 ± 6.4 and 20 ± 7.5) and during 1st trimester (17.49 ± 6.5 and 22.4 ± 7.4). There was a stat. significant temporary reduction in RBC def. under all shear rate conditions during 2nd trimester compared to the values before pregnancy which remained significantly lower during 3rd trimester only under high shear rates.An increase RBC agg was stat. significantly inversely correlated with reduced RBC def being most pronounced under low shear rate conditions. While RBC rigidity was stat. significantly correlated with higher hematocrit values there was only a weak correlation between RBC agg and haematocrit (E0: r = -0.084; p = 0.03; E1: r = -0.06; p = 0.1). Pv was not correlated with haematocrit or RBC def but stat. significantly correlated with RBC agg. Blood rheological changes manifest during 1st trimester, and fairly remain unchanged during 2nd trimester until term. Physiologic hemodilution and increasing hypercoagulability is accompanied by high RBC -aggregation and - rigidity during 2nd trimester while plasma viscosity remains nearly unaffected throughout normal pregnancy.

Coarse-Grain Modeling of Shear-Induced Binding between von Willebrand Factor and Collagen

Von Willebrand factor (VWF) is a large multimeric protein that aids in blood clotting. Near injury sites, hydrodynamic force from increased blood flow elongates VWF, exposing binding sites for platelets and collagen. To investigate VWF binding to collagen that is exposed on injured arterial surfaces, Brownian dynamics simulations are performed with a coarse-grain molecular model. Accounting for hydrodynamic interactions in the presence of a stationary surface, shear flow conditions are modeled. Binding between beads in coarse-grain VWF and collagen sites on the surface is described via reversible ligand-receptor-type bond formation, which is governed via Bell model kinetics. For conditions in which binding is energetically favored, the model predicts a high probability for binding at low shear conditions; this is counter to experimental observations but in agreement with what prior modeling studies have revealed. To address this discrepancy, an additional binding criterion that depends on the conformation of a submonomer feature in the model local to a given VWF binding site is implemented. The modified model predicts shear-induced binding, in very good agreement with experimental observations; this is true even for conditions in which binding is significantly favored energetically. Biological implications of the model modification are discussed in terms of mechanisms of VWF activity.

In vitro measurement of platelet adhesion to intact endothelial cells under low shear conditions.

Prediction of thrombus formation at intact arterial walls under low shear flow conditions is clinically important particularly for better prognoses of embolisation in cerebral aneurysms. Although a new mathematical model for this purpose is necessary, little quantitative information has been known about platelet adhesion to intact endothelial cells. The objective of this study is to measure the number of platelets adhering to intact endothelial cells with a focus upon the influence of the shear rate. Endothelial cells disseminated in μ-slides were exposed to swine whole blood at different shear rates. Adenosine diphosphate (ADP) was used as an agonist. Adherent platelets were counted by means of scanning electron microscopy. At an ADP concentration of 1µM, 20.8 ± 3.1 platelets per 900µm2 were observed after 30-minute perfusion at a shear rate of 0.8s-1 whereas only 3.0 ± 1.4 per 900µm2 at 16.8s-1. The number of adherent platelets is determined by a balance between the shear and the degree of stimulation by the agonist. At an ADP concentration of 1µM, a limit to the shear rate at which platelets can adhere to intact endothelial cells is considered to be slightly higher than 16.8s-1.

Design of intelligent surfaces for energy intensive processing industry

There are three different factors that can affect adhesion: the process fluid, the processing conditions and the surface of the processing equipment. Of these three factors, the surface properties of the processing equipment are the factor that offers the greatest opportunity for manipulation. The two key surface properties that have been identified to reduce adhesion are the surface energy and the surface topography. The surface energy of a material determines its degree of wettability and, a surface's affinity for water. In previous studies the surface energy of materials have been leveraged in order to create a surface with reduced levels of fouling through surface modification or the addition of polymer coatings with varying degrees of hydrophobicity. In addition, the topography of surfaces has been modified to reduce the level of particle adhesion. These modifications involve creating either a structured or random porous microstructure on the surface. Additional methods identified to reduce fouling include the application of liquid infused porous surfaces at low shear conditions and the use of non-contact heating through techniques such as microwave processing.

Dynamics of an n = 1 explosive instability and its role in high-β disruptions

Some low-n kink-ballooning modes not far from marginal stability are shown to exhibit a bifurcation between two very distinct nonlinear paths that depends sensitively on the background transport levels and linear perturbation amplitudes. The particular instability studied in this work is an mode dominated by an component. It is driven by a large pressure gradient in weak magnetic shear and can appear in various high- hybrid/advanced scenarios. Here it is investigated in reversed shear equilibria where the region around the safety-factor minimum provides the low-shear conditions necessary for instability. For a certain range of parameters, a relatively benign path results in a saturated ‘long-lived mode’ (LLM) that causes little confinement degradation. At the other extreme, the quadrupole geometry of the perturbed pressure field evolves into a ballooning finger that subsequently transitions from exponential to explosive growth. The finger eventually leads to a fast disruption with precursors too short for any mitigation effort. Interestingly, the saturated LLM state is found to be metastable; it also can be driven explosively unstable by finite-amplitude perturbations. Similarities to some high-β disruptions in reversed-shear discharges are discussed.

Energetic-ion excited internal kink modes with weak magnetic shear in tokamak plasmas**Project supported by the National Natural Science Foundation of China (Grant No. 11261140326).

The energetic particle driven internal kink mode is investigated in this paper for tokamak plasma with weak magnetic shear. With the effect of energetic particles, the internal mode structure in tokamak plasma does not appear as a rigid step-function when safety factor passes through q = 1 rational surface. It is found that even when the rational surface is removed, the mode may be still unstable under the low magnetic shear condition if the energetic particle drive is strong enough; with the low shear region of safety factor profile widening, the mode becomes more unstable with its growth-rate increasing. Furthermore, we find that the existence of the q = 1 rational surface does not have a significant effect on the stability of the plasma if energetic particles are present, which is very different from the scenarios of the ideal-MHD modes.

The Impact of Biophysical Properties of Erythrocytes on their Aggregation

Erythrocytes aggregation takes places under low shear conditions or at stasis. All suggested mechanisms of erythrocytes aggregation indicated the importance role of fibrinogen and other blood proteins in enhanced erythrocyte aggregation. Recently a special attention is given to the cellular factors that may effect on erythrocytes aggregation. The present study inferred the effect of the cellular properties of erythrocytes on their aggregation. In the present study, aggregation index was calculated by a simple microscopic method. Correlations between erythrocytes aggregation index and mean cell volume, osmotic fragility, electrophoretic mobility, and magnetophoretic mobility were studied. The findings of this study indicated that the aggregation index is significatly correlated to mean cell volume, magnetophoretic mobility, osmotic fragility and electrophoretic mobility. Thus, It is concluded that cellular factors should be taken into consideration when studying the mechanism of erythrocytes aggregation.

Activated FVIII Released from FVIII/VWF Complex Facilitates Thrombus Development Under High Shear Flow Condition

Activated FVIII Released from FVIII/VWF Complex Facilitates Thrombus Development Under High Shear Flow Condition

Effect of Shear Stress on Pseudomonas aeruginosa Isolated from the Cystic Fibrosis Lung.

ABSTRACTChronic colonization of the lungs by Pseudomonas aeruginosa is one of the major causes of morbidity and mortality in cystic fibrosis (CF) patients. To gain insights into the characteristic biofilm phenotype of P. aeruginosa in the CF lungs, mimicking the CF lung environment is critical. We previously showed that growth of the non-CF-adapted P. aeruginosa PAO1 strain in a rotating wall vessel, a device that simulates the low fluid shear (LS) conditions present in the CF lung, leads to the formation of in-suspension, self-aggregating biofilms. In the present study, we determined the phenotypic and transcriptomic changes associated with the growth of a highly adapted, transmissible P. aeruginosa CF strain in artificial sputum medium under LS conditions. Robust self-aggregating biofilms were observed only under LS conditions. Growth under LS conditions resulted in the upregulation of genes involved in stress response, alginate biosynthesis, denitrification, glycine betaine biosynthesis, glycerol metabolism, and cell shape maintenance, while genes involved in phenazine biosynthesis, type VI secretion, and multidrug efflux were downregulated. In addition, a number of small RNAs appeared to be involved in the response to shear stress. Finally, quorum sensing was found to be slightly but significantly affected by shear stress, resulting in higher production of autoinducer molecules during growth under high fluid shear (HS) conditions. In summary, our study revealed a way to modulate the behavior of a highly adapted P. aeruginosa CF strain by means of introducing shear stress, driving it from a biofilm lifestyle to a more planktonic lifestyle.

Molecular Dynamics Simulations of Glycerol Monooleate Confined between Mica Surfaces.

The structure and frictional properties of glycerol monooleate (GMO) in organic solvents, with and without water impurity, confined and sheared between two mica surfaces are examined using molecular dynamics simulations. The structure of the fluid is characterized in various ways, and the differences between systems with nonaggregated GMO and with preformed GMO reverse micelles are examined. Preformed reverse micelles are metastable under static conditions in all systems. In n-heptane under shear conditions, with or without water, preformed GMO reverse micelles remain intact and adsorb onto one surface or another, becoming surface micelles. In dry toluene, preformed reverse micelles break apart under shear, while in the presence of water, the reverse micelles survive and become surface micelles. In all systems under static and shear conditions, nonaggregated GMO adsorbs onto both surfaces with roughly equal probability. Added water is strongly associated with the GMO, irrespective of shear or the form of the added GMO. In all cases, with increasing shear rate, the GMO molecules flatten on the surface, and the kinetic friction coefficient increases. Under low-shear conditions, the friction is insensitive to the form of the GMO added, whereas the presence of water is found to lead to a small reduction in friction. Under high-shear conditions, the presence of reverse micelles leads to a significant reduction in friction, whereas the presence of water increases the friction in n-heptane and decreases the friction in toluene.

Antimicrobial activity of a bioelectric dressing using an in vitro wound pathogen colony drip-flow reactor biofilm model.

We performed in vitro antibiofilm testing of a silver and zinc containing microcurrent generating bioelectric dressing (BED) against clinical wound pathogens to determine its efficacy in preventing biofilm formation under low shear and continuous flow conditions, simulating wound infection environments. We customised an in vitro colony drip-flow reactor (DFR) biofilm model for efficacy evaluation of BED. Each bacterial pathogen was diluted to 104CFU/ml and inoculated on the polycarbonate filter membrane as an abiotic support. BED and controls (no treatment, gauze, and blank polyester with no silver and zinc) were applied directly on the membranes where bacterial cultures were inoculated. Biofilms were continuously developed onto the membranes for 72 hours at room temperature. Biofilm formation was confirmed by crystal violet staining and microscopic observation. Through vigorous shaking and sonication, the released bacteria were serially diluted, plated, and incubated for 24 hours at 37°C to determine the numbers of surviving bacteria. Biofilms were well developed onto blank polyesters, but not the BED after 72 hours incubation. Crystal violet staining from the blank polyesters showed large and fully grown biofilms. We observed an inhibition in bacterial growth on BED treatment. The antibiofilm activity of the BED against each of eight monospecies biofilms showed a 1- or 2 log10 (or 10- or 100-fold) reduction in bacterial numbers compared with those of controls. Our results demonstrated that colony DFR biofilm model was an appropriate for testing the antibiofilm efficacy of BED under low shear and continuous flow conditions for simulating clinical wound environments. The bioelectric currents generated from the silver and zinc active ingredients in the dressing resulted in antibiofilm activity of this wound care device. The opinions or assertions contained herein are the private views of the authors, based on scientific investigation, and are not to be construed as official or as reflecting the views of the Department of Defense, the United States Government or any of the authors' employers. Dr. Mina Izadjoo has served as a consultant to Vomaris Innovations Inc.

The utility of thromboelastography in inherited and acquired bleeding disorders.

Thromboelastography (TEG) was first described by Hartert in 1948, and was designed to monitor viscoelastic clot strength in whole blood in real time. The current TEG method and Rotational Thromboelastometry (ROTEM) were subsequently developed from the original principles. Both of the modern methods provide data by measuring changes in the viscoelastic strength of a small sample of clotting blood in response to a constant rotational force. The important advantage of these techniques is to visually observe and quantify blood coagulation including the propagation, stabilization and dissolution phases of clot formation under low shear conditions. Analysis of the results provides detailed kinetic data on fibrin generation, clot strength and fibrinolysis. These TEG/ROTEM analyses therefore enable evaluation of global clotting function and the monitoring of haemostatic treatment in various clinical situations, not only in patients with genetic bleeding disorders, such as haemophilia, but also in patients undergoing cardiac surgery, liver transplantation or suffering from traumatic injury. Some evidence suggests that haemostatic management using TEG/ROTEM leads to a reduction in total transfusions of whole blood or clotting factors. Wider clinical application of this technology seems likely.

Succinic Acid Production by Actinobacillus Succinogenes in Chemostat and Biofilm Cultures

Previously published results from a novel, homogeneously distributed shear, tubular fermenter used to study continuous chemostat (high shear) and biofilm (low shear) fermentations (Brink and Nicol, 2014a), were compared to results obtained in the same reactor at intermediate shear conditions as well as batch (biofilm) fermentations of Actinobacillus succinogenes.It was found that the steady-state volumetric production rates increased by nearly an order of magnitude (1.8 g.L-1.h-1 vs 15–17 g.L-1.h-1) as the shear was reduced from the chemostat (1.83 m.s-1) to the lower shear biofilm conditions. The biofilm results indicated similar volumetric production rates for the different shear conditions, while the measured extracellular polymeric substances (EPS) in the biofilm exhibited a significant shear dependence; EPS fractions of 0.50 ± 0.05 g.g-1 vs. 0.16 ± 0.02 g.g-1 for the low and intermediate shear conditions respectively. The cell-based biofilm production rates were shown to be dependent on shear conditions at succinic acid titres less than the growth-maintenance boundary (10 g.L-1), with a reduction in cellular production rate associated with an increase in shear. Under maintenance conditions the cell-based production rates appeared independent of the shear conditions in the fermenter, with the cell-based production rates decreasing with increasing succinic acid titres. The industrial implications are that for succinic acid titres in excess of 10 g.L-1, the same mass of biomass under intermediate shear conditions should exhibit a greater volumetric production rate due to the higher fraction of cells as opposed to EPS.The initial values for the batch cell-based succinic acid production rates corresponded to the steady-state values for biofilms grown under the same continuous conditions. However, during transient operation the production rates exceeded the steady-state values; a lag in the product inhibition response was observed. The transient production rates eventually ceased at succinic acid titres in excess of approximately 60–72 g.L-1; a residual glucose concentration of 20 g.L-1 was measured at the highest succinic acid titre (72 g.L-1), indicating product related inhibition as opposed to substrate depletion. The transient results indicate that a larger average cell- based production rate can be obtained during transient operation when compared to the steady fermentation conditions due to a lag in the succinic acid inhibition during transient operation.

Microfluidic approaches for the assessment of blood cell trauma: a focus on thrombotic risk in mechanical circulatory support devices.

Mechanical circulatory support devices (MCSDs) are emerging as a valuable therapeutic option for the management of end-stage heart failure. However, although recipients are routinely administered with anti-thrombotic (AT) drugs, thrombosis persists as a severe post-implant complication. Conventional clinical assays and coagulation markers demonstrate partial ability in preventing the onset of thrombosis. Through years, different laboratory techniques have been proposed as potential tools for the evaluation of platelets' hemostatic response in MCSD recipients. Most rely on platelet aggregation tests; they are performed in static or low shear conditions, neglecting the prominent contribution of MCSD shear-induced mechanical load in enhancing platelet activation (PA). On the other hand, those tests able to account for shear-induced PA have limited possibility of effective clinical translation. Advances on this side have been addressed by microfluidic technology. Microfluidic devices have been developed for AT drug monitoring under flow, able to replicate physiological and/or constant shear flow conditions in vitro. In this paper, we present a newly developed microfluidic platform able to expose platelets to MCSD-specific dynamic shear stress patterns. We performed in vitro tests circulating human platelets in the microfluidic platform and quantifying the dynamics of PA by means of the Platelet Activity State (PAS) assay. Our results prove the feasibility of using microfluidics for the diagnosis of MCSD-related thrombotic risk. This study paves the way for the development of a miniaturized point-of-care device for monitoring AT drug regimen. Such a system may have significant impact on limiting the incidence of thrombosis in MCSD recipients.

Sensing Electrostatic Charge Generation During Granular Flow of Pharmaceutical Powders in a Flow Tester

The purpose of this study is to investigate the triboelectrification of pharmaceutical powders during continuous flow in terms of electrostatic charge accumulation and dissipation as the powder tumbles in a rotating cylinder. The intensity of electrostatic signal output, its frequency during particle interactions as the powder flows, and the dependency of particle charge on the shear rate which was captured by varying the rotational speed of the cylinder were studied. Various pharmaceutical blends were run at different rotational speeds in a flow tester and their charge accumulations and dissipations during the powder flow were captured using an electrometer and an oscilloscope. An interesting finding showed that the charge frequency generated during the powder flow was related to the powder flowability. The deterioration of powder flow was found to increase the frequency of voltage spikes. Voltage frequency from charge accumulations during powder flow increased with a corresponding increase in rotational speed of the cylinder. At low shear conditions, cohesive powder exhibited higher voltage peak intensity than the free flowing powder. The voltage charge intensity measured from the powder bed correlated to the powder flow of pure component powders. Voltage peak intensity for cohesive powders was found to decrease with time but remained stable for free flowing powders. Interestingly, voltage peak intensity for cohesive powders decreased with rotational speed but increased in the case of free flowing powders. A stronger correlation between electrostatic charge and powder flow existed in pure component powders than formulations containing additives.