scholarly journals Numerical Model to Predict Hemolysis and Transport in a Membrane-Based Microfluidic Device

2020 ◽  
Author(s):  
Matthew D Poskus ◽  
Thomas R Gaborski ◽  
Steven W Day

AbstractMicrofluidic devices may overcome the limitations of conventional hemodialysis and oxygenation technology to improve patient outcomes. Namely, the small form of this technology and parallel development of highly permeable membranes may facilitate the development of portable, low-volume, and efficient alternatives to conventional membrane-based equipment. However, the characteristically small dimensions of these devices may also inhibit transport and may also induce flow-mediated nonphysiologic shear stresses that may damage red blood cells (RBCs). In vitro testing is commonly used to quantify these phenomenon, but is costly and only characterizes bulk device performance. Here we developed a computational model that predicts the blood damage and solute transport for an abitrary microfluidic geometry. We challenged the predictiveness of the model with three geometric variants of a prototype design and validated hemolysis predictions with in vitro blood damge of prototype devices in a recirculating loop. We found that six of the nine tested damage models statistically agree with the experimental data for at least one geometric variant. Additionally, we found that one geometrical variant, the herringbone design, improved toxin (urea) transport to the dialysate by 38% in silico at the expense of a 50% increase in hemolysis. Our work demonstrates that computational modeling may supplement in vitro testing of prototype microdialyzer/micro-oxygenators to expedite the design optimization of these devices. Furthermore, the low device-induced blood damage measured in our study at physiologically relevant flow rates is promising for the future development of microfluidic dialyzers and oxygenators.

Author(s):  
Yertay Mendygarin ◽  
Luis R. Rojas-Solórzano ◽  
Nurassyl Kussaiyn ◽  
Rakhim Supiyev ◽  
Mansur Zhussupbekov

Cardiovascular Diseases, the common name for various Heart Diseases, are responsible for nearly 17.3 million deaths annually and remain the leading global cause of death in the world. It is estimated that this number will grow to more than 23.6 million by 2030, with almost 80% of all cases taking place in low and middle income countries. Surgical treatment of these diseases involves the use of blood-wetted devices, whose relatively recent development has given rise to numerous possibilities for design improvements. However, blood can be damaged when flowing through these devices due to the lack of biocompatibility of surrounding walls, thermal and osmotic effects and most prominently, due to the excessive exposure of blood cells to shear stress for prolonged periods of time. This extended exposure may lead to a rupture of membrane of red blood cells, resulting in a release of hemoglobin into the blood plasma, in a process called hemolysis. Moreover, exposure of platelets to high shear stresses can increase the likelihood of thrombosis. Therefore, regions of high shear stress and residence time of blood cells must be considered thoroughly during the design of blood-contacting devices. Though laboratory tests are vital for design improvements, in-vitro experiments have proven to be costly, time-intensive and ethically controversial. On the other hand, simulating blood behavior using Computational Fluid Dynamics (CFD) is considered to be an inexpensive and promising tool to help predicting blood damage in complex flows. Nevertheless, current state-of-the-art CFD models of blood flow to predict hemolysis are still far from being fully reliable and accurate for design purposes. Previous work have demonstrated that prediction of hemolysis can be dramatically improved when using a multiphase (i.e., phases are plasma, red blood cells and platelets) model of the blood instead of assuming the blood as a homogeneous mixture. Nonetheless, the accurate determination of how the cells segregate becomes the critical issue in reaching a truthful prediction of blood damage. Therefore, the attempt of this study is to develop and validate a numerical model based on Granular Kinetic Theory (GKT) for solid phases (i.e., cells treated as particles) that provides an improved prediction of blood cells segregation within the flow in a microtube. Simulations were based on finite volume method using Eulerian-Eulerian modeling for treatment of three-phase (liquid-red blood cells and platelets) flow including the GKT to deal with viscous properties of the solid phases. GKT proved to be a good model to predict particle concentration and pressure drop by taking into account the contribution of collisional, kinetic and frictional effects in the stress tensor of the segregated solid phases. Preliminary results show that the improved segregated model leads to a better prediction of spatial distribution of blood cells. Simulations were performed using ANSYS FLUENT platform.


2019 ◽  
Vol 42 (12) ◽  
pp. 735-747 ◽  
Author(s):  
Benjamin Torner ◽  
Lucas Konnigk ◽  
Frank-Hendrik Wurm

The blood damage prediction in rotary blood pumps is an important procedure to evaluate the hemocompatibility of such systems. Blood damage is caused by shear stresses to the blood cells and their exposure times. The total impact of an equivalent shear stress can only be taken into account when turbulent stresses are included in the blood damage prediction. The aim of this article was to analyze the influence of the turbulent stresses on the damage prediction in a rotary blood pump’s flow. Therefore, the flow in a research blood pump was computed using large eddy simulations. A highly turbulence-resolving setup was used in order to directly resolve most of the computed stresses. The simulations were performed at the design point and an operation point with lower flow rate. Blood damage was predicted using three damage models (volumetric analysis of exceeded stress thresholds, hemolysis transport equation, and hemolysis approximation via volume integral) and two shear stress definitions (with and without turbulent stresses). For both simulations, turbulent stresses are the dominant stresses away from the walls. Here, they act in a range between 9 and 50 Pa. Nonetheless, the mean stresses in the proximity of the walls reach levels, which are one order of magnitude higher. Due to this, the turbulent stresses have a small impact on the results of the hemolysis prediction. Yet, turbulent stresses should be included in the damage prediction, since they belong to the total equivalent stress definition and could impact the damage on proteins or platelets.


Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 762
Author(s):  
Taylor Morrisette ◽  
Sara Alosaimy ◽  
Jacinda C. Abdul-Mutakabbir ◽  
Razieh Kebriaei ◽  
Michael J. Rybak

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with substantial morbidity and mortality. Vancomycin (VAN) has been used as the gold standard treatment for invasive MRSA infections for decades but, unfortunately, the reliance of VAN as the primary treatment option against these infections has led to a reduction in VAN susceptibility in MRSA isolates. Although daptomycin (DAP) is another common treatment option against invasive MRSA infections, it has been shown that the development of VAN resistance can lead to DAP nonsusceptibility. VAN or DAP backbone regimens in combination with other antibiotics has been advocated as an alternative approach to improve patient outcomes in VAN/DAP-susceptible infections, enhance outcomes in infections caused by isolates with reduced VAN/DAP susceptibility, and/or prevent the emergence of VAN/DAP resistance or further resistance. A peer-reviewed literature search was conducted using Medline, Google Scholar and PubMed databases. The primary purpose of this review is to describe the mechanisms and epidemiology of MRSA isolates with a reduction in VAN and/or DAP susceptibility, evaluate in vitro and in vivo literature describing combination therapy (CT) against MRSA isolates with reduced VAN and/or DAP susceptibility and describe studies involving the clinical outcomes of patients treated with CT against invasive MRSA infections.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Abraham Otero ◽  
Andrey Apalkov ◽  
Roemi Fernández ◽  
Manuel Armada

Urine output (UO) is usually measured manually each hour in acutely ill patients. This task consumes a substantial amount of time. Furthermore, in the literature there is evidence that more frequent (minute-by-minute) UO measurement could impact clinical decision making and improve patient outcomes. However, it is not feasible to manually take minute-by-minute UO measurements. A device capable of automatically monitoring UO could save precious time of the healthcare staff and improve patient outcomes through a more precise and continuous monitoring of this parameter. This paper presents a device capable of automatically monitoring UO. It provides minute by minute measures and it can generate alarms that warn of deviations from therapeutic goals. It uses a capacitive sensor for the measurement of the UO collected within a rigid container. When the container is full, it automatically empties without requiring any internal or external power supply or any intervention by the nursing staff. In vitro tests have been conducted to verify the proper operation and accuracy in the measures of the device. These tests confirm the viability of the device to automate the monitoring of UO.


1991 ◽  
Vol 14 (11) ◽  
pp. 716-720 ◽  
Author(s):  
S. Einav ◽  
H. Reul ◽  
G. Rau ◽  
D. Elad

Blood flowing through a prosthetic heart valve can be damaged by flow-induced shear forces. Fluid dynamics variables and geometric factors play an important role in the evaluation of shear-stress-related blood damage. Central-flow prosthetic valves have been considered as an optimal replacement for mechanical and biological valves. Recently it was shown that shear stress distribution along the surface of a polyurethane cusp reaches values that can damage the blood elements. A mathematical model correlating the effects of shear stresses on blood corpuscles with clinical findings was employed in vitro. The model can be applied to the effects of blood-surface interaction and is of clinical relevance


2015 ◽  
Vol 137 (4) ◽  
Author(s):  
Sivakkumar Arjunon ◽  
Pablo Hidalgo Ardana ◽  
Neelakantan Saikrishnan ◽  
Shalv Madhani ◽  
Brent Foster ◽  
...  

Due to expensive nature of clinical trials, implantable cardiac devices should first be extensively characterized in vitro. Prosthetic heart valves (PHVs), an important class of these devices, have been shown to be associated with thromboembolic complications. Although various in vitro systems have been designed to quantify blood-cell damage and platelet activation caused by nonphysiological hemodynamic shear stresses in these PHVs, very few systems attempt to characterize both blood damage and fluid dynamics aspects of PHVs in the same test system. Various numerical modeling methodologies are also evolving to simulate the structural mechanics, fluid mechanics, and blood damage aspects of these devices. This article presents a completely hemocompatible small-volume test-platform that can be used for thrombogenicity studies and experimental fluid mechanics characterization. Using a programmable piston pump to drive freshly drawn human blood inside a cylindrical column, the presented system can simulate various physiological and pathophysiological conditions in testing PHVs. The system includes a modular device-mounting chamber, and in this presented case, a 23 mm St. Jude Medical (SJM) Regents® mechanical heart valve (MHV) in aortic position was used as the test device. The system was validated for its capability to quantify blood damage by measuring blood damage induced by the tester itself (using freshly drawn whole human blood). Blood damage levels were ascertained through clinically relevant assays on human blood while fluid dynamics were characterized using time-resolved particle image velocimetry (PIV) using a blood-mimicking fluid. Blood damage induced by the tester itself, assessed through Thrombin-anti-Thrombin (TAT), Prothrombin factor 1.2 (PF1.2), and hemolysis (Drabkins assay), was within clinically accepted levels. The hydrodynamic performance of the tester showed consistent, repeatable physiological pressure and flow conditions. In addition, the system contains proximity sensors to accurately capture leaflet motion during the entire cardiac cycle. The PIV results showed skewing of the leakage jet, caused by the asymmetric closing of the two leaflets. All these results are critical to characterizing the blood damage and fluid dynamics characteristics of the SJM Regents® MHV, proving the utility of this tester as a precise system for assessing the hemodynamics and thrombogenicity for various PHVs.


2018 ◽  
Vol 42 (3) ◽  
pp. 125-132 ◽  
Author(s):  
Leonid Goubergrits ◽  
Ulrich Kertzscher ◽  
Michael Lommel

Anatomic pathologies such as stenosed or regurgitating heart valves and artificial organs such as heart assist devices or heart valve prostheses are associated with non-physiological flow. This regime is associated with regions of spatially high-velocity gradients, high-velocity and/or pressure fluctuations as well as neighbouring regions with stagnant flow associated with high residence time. These hemodynamic conditions cause destruction and/or activation of blood components and their accumulation in regions with high residence time. The development of next-generation artificial organs, which allow long-term patient care by reducing adverse events and improve quality of life, requires the development of blood damage models serving as a cost function for device optimization. We summarized the studies underlining the key findings with subsequent elaboration of the requirements for blood damage models as well as a decision tree based on the classification of existing blood damage models. The four major classes are Lagrangian or Eulerian approaches with stress- or strain-based blood damage. Key challenges were identified and future steps towards the translation of blood damage models into the device development pipeline were formulated. The integration of blood damage caused by turbulence into models as well as in vitro and in vivo validation of models remain the major challenges for future developments. Both require the development of novel experimental setups to provide reliable and well-documented experimental data.


Author(s):  
Sheri Palejwala ◽  
Jonnae Barry ◽  
Crystal Rodriguez ◽  
Chandni Parikh ◽  
Stephen Goldstein ◽  
...  

2012 ◽  
Vol 9 (2) ◽  
pp. 96-98
Author(s):  
Brian A Bruckner ◽  
Matthias Loebe

Patients undergoing re-operative cardiac surgical procedures present a great challenge with regard to obtaining hemostasis in the surgical field. Adhesions are ever-present and these patients are often on oral anti-coagulants and platelet inhibitors. As part of a well-planned surgical intervention, a systematic approach to hemostasis should be employed to decrease blood transfusion requirement and improve patient outcomes. Topical hemostatic agents can be a great help to the surgeon in achieving surgical field hemostasis and are increasingly being employed. Our approach, to these difficult patients, includes the systematic and planned use of AristaAH, which is a novel hemostatic agent whose use has proven safe and efficacious in our patient population.


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