Maximizing flow rate in single paper layer, rapid flow microfluidic paper-based analytical devices.

Small, single-layer microfluidic paper-based analytical devices (µPADs) offer potential for a range of point-of-care applications; however, they have been limited to low flow rates. Here, we investigate the role of laser cutting paper channels in maximizing flow rate in small profile devices with limited fluid volumes. We demonstrate that branching, laser-cut grooves can provide a 59.23-73.98% improvement in flow rate over a single cut, and a 435% increase over paper alone. These design considerations can be applied to more complex microfluidic devices with the aim of increasing the flow rate, and could be used in stand-alone channels for self-pumping. Supplementary Information: The online version contains supplementary material available at 10.1007/s10404-023-02679-8.

Wall shear rates in human and mouse arteries: Standardization of hemodynamics for in vitro blood flow assays: Communication from the ISTH SSC subcommittee on biorheology.

Hemodynamics play a central role in hemostasis and thrombosis by affecting all aspects linked to platelet functions and coagulation. In vitro flow devices are extensively used in basic research, pharmacological studies, antiplatelet agent screening, and development of diagnostic tools. Because hemodynamic conditions vary tremendously throughout the vascular tree and among different (patho)physiological processes, it is important to use flow conditions based on relevant biorheological reference ranges. Surprisingly, it is particularly difficult to find a concise overview of relevant hemodynamic parameters in various human and mouse vessels. To our knowledge, this is the first time an inventory of flow conditions in healthy, non-diseased, human and mouse vessels has been created. The objective of providing such a repertoire is to aid researchers in the field of hemostasis and thrombosis in choosing rheological conditions relevant in in vitro flow experiments and to promote harmonization of flow-based assays to facilitate comparative evaluations between studies. With reference to the human, we discuss relevant similarities and discrepancies in wall shear rates in the mouse, which are typically one order of magnitude greater in agreement with allometric scaling laws between species. Importantly, we bring the attention of the researchers to the fact that the relevant range of average wall shear rates in human arteries where clinically relevant arterial thrombosis occurs may fall as low as 100 to 200 s-1, thus significantly overlapping with what are considered "venous" shear rates. The same range for the murine arteries used for arterial thrombosis models may significantly exceed 1000 s-1 reaching values considered to be "pathological."

Impact of superhydrophobicity on the fluid dynamics of a bileaflet mechanical heart valve.

OBJECTIVE: The objective of this study is to evaluate the impact of superhydrophobic coating on the hemodynamics and turbulence characteristics of a bileaflet mechanical valve in the context of evaluating blood damage potential. METHODS: Two 3D printed bileaflet mechanical valves were hemodynamically tested in a pulse duplicator under physiological pressure and flow conditions. The leaflets of one of the two valves were sprayed with a superhydrophobic coating. Particle Image Velocimetry was performed. Pressure gradients (PG), effective orifice areas (EOA), Reynolds shear stresses (RSS) and instantaneous viscous shear stresses (VSS) were calculated. RESULTS: (a) Without SH coating, the PG was found to be 14.53 ± 0.7 mmHg and EOA 1.44 ± 0.06 cm2. With coating, the PG obtained was 15.21 ± 1.7 mmHg and EOA 1.39 ± 0.07 cm2; (b) during peak systole, the magnitude of RSS with SH coating (110Pa) exceeded that obtained without SH coating (40 Pa) with higher probabilities to develop higher RSS in the immediate wake of the leaflet; (c) The magnitudes range of instantaneous VSS obtained with SH coating were slightly larger than those obtained without SH coating (7.0 Pa versus 5.0 Pa). CONCLUSION: With Reynolds Shear Stresses and instantaneous Viscous Shear Stresses being correlated with platelet damage, SH coating did not lead to their decrease. While SH coating is known to improve surface properties such as reduced platelet or clot adhesion, the relaxation of the slip condition does not necessarily improve overall hemodynamic performance for the bileaflet mechanical valve design.

Hemocompatibility of Super-Repellent surfaces: Current and Future.

Virtually all blood-contacting medical implants and devices initiate immunological events in the form of thrombosis and inflammation. Typically, patients receiving such implants are also given large doses of anticoagulants, which pose a high risk and a high cost to the patient. Thus, the design and development of surfaces with improved hemocompatibility and reduced dependence on anticoagulation treatments is paramount for the success of blood-contacting medical implants and devices. In the past decade, the hemocompatibility of super-repellent surfaces (i.e., surfaces that are extremely repellent to liquids) has been extensively investigated because such surfaces greatly reduce the blood-material contact area, which in turn reduces the area available for protein adsorption and blood cell or platelet adhesion, thereby offering the potential for improved hemocompatibility. In this review, we critically examine the progress made in characterizing the hemocompatibility of super-repellent surfaces, identify the unresolved challenges and highlight the opportunities for future research on developing medical implants and devices with super-repellent surfaces.

Effect of Arched Leaflets and Stent Profile on the Hemodynamics of Tri-Leaflet Flexible Polymeric Heart Valves.

Polymeric heart valves (PHV) can be engineered to serve as alternatives for existing prosthetic valves due to higher durability and hemodynamics similar to bioprosthetic valves. The purpose of this study is to evaluate the effect of geometry on PHVs coaptation and hemodynamic performance. The two geometric factors considered are stent profile and leaflet arch length, which were varied across six valve configurations. Three models were created with height to diameter ratio of 0.6, 0.7, and 0.88. The other three models were designed by altering arch height to stent diameter ratio, to be 0, 0.081, and 0.116. Particle image velocimetry experiments were conducted on each PHV to characterize velocity, vorticity, turbulent characteristics, effective orifice area, and regurgitant fraction. This study revealed that the presence of arches as well as higher stent profile reduced regurgitant flow down to 5%, while peak systole downstream velocity reduced to 58% and Reynolds Shear Stress values reduced 40%. Further, earlier reattachment of the forward flow jet was observed in PHVs with leaflet arches. These findings indicate that although both geometric factors help diminish the commissural gap during diastole, leaflet arches induce a larger jet opening, yielding to earlier flow reattachment and lower energy dissipation.

Hemodynamic Performance and Thrombogenic Properties of a Superhydrophobic Bileaflet Mechanical Heart Valve.

In this study, we explore how blood-material interactions and hemodynamics are impacted by rendering a clinical quality 25 mm St. Jude Medical Bileaflet mechanical heart valve (BMHV) superhydrophobic (SH) with the aim of reducing thrombo-embolic complications associated with BMHVs. Basic cell adhesion is evaluated to assess blood-material interactions, while hemodynamic performance is analyzed with and without the SH coating. Results show that a SH coating with a receding contact angle (CA) of 160° strikingly eliminates platelet and leukocyte adhesion to the surface. Alternatively, many platelets attach to and activate on pyrolytic carbon (receding CA = 47), the base material for BMHVs. We further show that the performance index increases by 2.5% for coated valve relative to an uncoated valve, with a maximum possible improved performance of 5%. Both valves exhibit instantaneous shear stress below 10 N/m2 and Reynolds Shear Stress below 100 N/m2. Therefore, a SH BMHV has the potential to relax the requirement for antiplatelet and anticoagulant drug regimens typically required for patients receiving MHVs by minimizing blood-material interactions, while having a minimal impact on hemodynamics. We show for the first time that SH-coated surfaces may be a promising direction to minimize thrombotic complications in complex devices such as heart valves.

Reynolds shear stress for textile prosthetic heart valves in relation to fabric design.

The most widely implanted prosthetic heart valves are either mechanical or bioprosthetic. While the former suffers from thrombotic risks, the latter suffers from a lack of durability. Textile valves, alternatively, can be designed with durability and to exhibit hemodynamics similar to the native valve, lowering the risk for thrombosis. Deviations from native valve hemodynamics can result in an increased Reynolds Shear Stress (RSS), which has the potential to instigate hemolysis or shear-induced thrombosis. This study is aimed at characterizing flow in multiple textile valve designs with an aim of developing a low profile valve. Valves were created using a shaping process based on heating a textile membrane and placed within a left heart simulator. Turbulence and bulk hemodynamics were assessed through particle imaging velocimetry, along with flow and pressure measurements. Overall, RSS was reduced for low profile valves relative to high profile valves, but was otherwise similar among low profile valves involving different fabric designs. However, leakage was found in 3 of the 4 low profile valve designs driving the fabric design for low profile valves. Through textile design, low profile valves can be created with favorable hemodynamics.

The Impact of Fluid Inertia on In Vivo Estimation of Mitral Valve Leaflet Constitutive Properties and Mechanics.

We examine the influence of the added mass effect (fluid inertia) on mitral valve leaflet stress during isovolumetric phases. To study this effect, oscillating flow is applied to a flexible membrane at various frequencies to control inertia. Resulting membrane strain is calculated through a three-dimensional reconstruction of markers from stereo images. To investigate the effect in vivo, the analysis is repeated on a published dataset for an ovine mitral valve (Journal of Biomechanics 42(16): 2697-2701). The membrane experiment demonstrates that the relationship between pressure and strain must be corrected with a fluid inertia term if the ratio of inertia to pressure differential approaches 1. In the mitral valve, this ratio reaches 0.7 during isovolumetric contraction for an acceleration of 6 m/s(2). Acceleration is reduced by 72% during isovolumetric relaxation. Fluid acceleration also varies along the leaflet during isovolumetric phases, resulting in spatial variations in stress. These results demonstrate that fluid inertia may be the source of the temporally and spatially varying stiffness measurements previously seen through inverse finite element analysis of in vivo data during isovolumetric phases. This study demonstrates that there is a need to account for added mass effects when analyzing in vivo constitutive relationships of heart valves.

Platelet transport rates and binding kinetics at high shear over a thrombus.

Thrombus formation over a ruptured atherosclerotic plaque cap can occlude an artery with fatal consequences. We describe a computational model of platelet transport and binding to interpret rate-limiting steps seen in experimental thrombus formation over a collagen-coated stenosis. The model is used to compute shear rates in stenoses with growing boundaries. In the model, moving erythrocytes influence platelet transport based on shear-dependent enhanced diffusivity and a nonuniform platelet distribution. Adhesion is modeled as platelet-platelet binding kinetics. The results indicate that observed thrombus growth rates are limited by platelet transport to the wall for shear rates up to 6000 s(-1). Above 7000 s(-1), the thrombus growth rate is likely limited by binding kinetics (10(-4) m/s). Thrombus growth computed from these rate-limiting steps match the thrombus location and occlusion times for experimental conditions if a lag time for platelet activation is included. Using fitted parameters, the model is then used to predict thrombus size and shape at a higher Reynolds number flow consistent with coronary artery disease.

Correlation of thrombosis growth rate to pathological wall shear rate during platelet accumulation.

Local hemodynamics may strongly influence atherothrombosis, which can lead to acute myocardial infarction and stroke. The relationship between hemodynamics and thrombosis during platelet accumulation was studied through an in vitro flow system consisting of a stenosis. Specifically, wall shear rates (WSR) ranging from 0 to 100,000 s(-1) were ascertained through computations and compared with thrombus growth rates found by image analysis for over 5,000 individual observation points per experiment. A positive correlation (P < 0.0001) was found between thrombus accumulation rates and WSR up to 6,000 s(-1), with a decrease in growth rates at WSR >6,000 s(-1) (P < 0.0001). Furthermore, growth rates at pathological shear rates were found to be two to four times greater than for physiological arterial shear rates below 400 s(-1). Platelets did not accumulate for the first minute of perfusion. The initial lag time, before discernible thrombus growth could be found, diminished with shear (P < 0.0001). These studies show the quantitative increase in thrombus growth rates with very high shear rates in stenoses onto a collagen substrate.

Wall shear over high degree stenoses pertinent to atherothrombosis.

Atherothrombosis can induce acute myocardial infarction and stroke by progressive stenosis of a blood vessel lumen to full occlusion. Since thrombus formation and embolization may be shear-dependent, we quantify the magnitude of shear rates in idealized severely stenotic coronary arteries (≥75% by diameter) using computational fluid dynamics to characterize the shear environment that may exist during atherothrombosis. Maximum shear rates in severe short stenoses were found to exceed 250,000s(-1) (9500dynes/cm(2)) and can reach a peak value of 425,000s(-1) for a 98% stenosis. These high shear rates exceed typical shear used for in vitro blood flow experiments by an order of magnitude, indicating the need to examine thrombosis at very high shear rates. Pulsatility and stenosis eccentricity were found to have minor effects on the maximum wall shear rates in severe stenoses. In contrast, increases in the stenosis length reduced the maximum shear to 107,000s(-1) (98% stenosis), while surface roughness could increase focal wall shear rates to a value reaching 610,000s(-1) (90% stenosis). The "shear histories" of circulating platelets in these stenoses are far below reported activation thresholds. Platelets may be required to form bonds in 5µs and resist shear forces reaching 8000pN per platelet. Arterial thrombosis occurs in the face of pathological high shear stress, creating rapid and strong bonds without prior activation of circulating platelets.