Numerical investigation of LDL nanoparticle collision in coronary artery grafts with porous wall and different implantation angles and two state of inlet velocity.

This study aimed to reduce the risk of graft occlusion by evaluating the two-phase flow of blood and LDL nanoparticles in coronary artery grafts. The study considered blood as an incompressible Newtonian fluid, with the addition of LDL nanoparticles, and the artery wall as a porous medium. Two scenarios were compared, with constant inlet velocity (CIV) and other with pulsatile inlet velocity (PIV), with LDL nanoparticles experiencing drag, wall-induced lift, and induced Saffman lift forces, or drag force only. The study also evaluated the concentration polarization of LDLs (CP of LDLs) near the walls, by considering the artery wall with and without permeation. To model LDL nanoparticles, the study randomly injected 100, 500, and 1000 nanoparticles in three release states at each time step, using different geometries. Numerical simulations were performed using COMSOL software, and the results were presented as relative collision of nanoparticles to the walls in tables, diagrams, and shear stress contours. The study found that a graft implantation angle of 15° had the most desirable conditions compared to larger angles, in terms of nanoparticle collision with surfaces and occlusion. The nanoparticle release modes behaved similarly in terms of collision with the surfaces. A difference was observed between CIV and PIV. Saffman lift and wall-induced lift forces having no effect, possibly due to the assumption of a porous artery wall and perpendicular outlet flow. In case of permeable artery walls, relative collision of particles with the graft wall was larger, suggesting the effect of CP of LDLs.

Investigating the temperature distribution behavior and flow parameters of argon fluid in a nanochannel with changing dimensions of the obstacle using the molecular dynamics (MD) method.

This article, examines the flow of argon inside a nanochannel with respect to the molecular dynamics (MD) in the free molecular flow regime using LAMMPS software. The nanochannel is made of copper featuring a square cross-section and obstacles of varying dimensions and values. In this study, the flow of argon fluid is three-dimensional. To gain a deeper understanding of the effect of solid walls within the nanochannel and their influence on flow behavior, the research is simulated in a nanochannel with all side walls for the 3D model and without side walls for the 2D model. This research assesses the effect of the obstacles' dimensions and values on the nanochannel wall surface and areas above the wall surface. The total dimensions of all simulated two- and three-dimensional atomic structures with a square cross-section are assumed to be 60 × 60 × 100 Å3. and the presence of square obstacles (with dimensions of 8 × 8 × 8 Å3) and rectangular obstacles (with dimensions of 8 × 18 × 8 Å3) is examined. This study seeks to understand the influence on flow behavior, temperature distribution, density, heat flux, velocity, and thermal conductivity coefficient. This study is simulated using a time step of 1 fs for 10,000 time steps, involving approximately 10,000-15,000 argon and copper atoms. The results of this research indicate that obstacles with structures of P and R and larger dimensions increase the number of solid atoms exhibiting stronger attractive forces. Compared to a smooth nanochannel, the thermal exchange between fluid and solid atoms results in a density increase of 17.5 % and 17.3 %, respectively. On the other hand, in the 3D nanochannel, the sidewalls of the nanochannel have reduced the effect of the presence of R and P obstacles with larger dimensions, which comparing to a smooth nanochannel, have increased the density by 8.21 % and 7.53 %, respectively. The obstacles with different spatial positions (P and R structures) in the two-dimensional nanochannel cause a rise in the thermal conductivity coefficient. The P structure obstacles have a better effect on the thermal conductivity coefficient in the 2D nanochannel compared to the R structure. In the three-dimensional nanochannel, utilizing smaller obstacles proves to be more effective because it results in better atom distribution or temperature distribution due to increased atomic collisions in the central region compared to the wall regions.

Effect of process parameters on separation efficiency in a deterministic lateral displacement device.

Deterministic lateral displacement (DLD) is a hydrodynamic method known for its high-resolution sorting of particles. It achieves this through a periodic array of obstacles and laminar flow that passively directs particles along in two different directions depending on the particles' diameter. Many prior publications have been dedicated to the structural and geometrical development of DLD arrays to improve separation performance; however, a successful separation requires much more than a well-designed array. This paper shows how separation performance is affected by process parameters. For this purpose, the design and fabrication of a DLD device are described. Then three experiments show how process parameters affect the performance of the device. The first experiment uses dye solutions to visualize the formation of a hydrodynamically focused sample stream. The second experiment shows that the particle separation performance (of 7- & 15-µm particles) is affected by the way output fluids are collected. Finally, the third experiment looks at the particle separation efficiency as the input flow rates and the ratio of buffer to sample are changed. The results show that the proper range for buffer and sample flow rate in this device is 1-10 and 0.1-1 (µl/min), respectively. The buffer to sample flow rate ratio of 10 gives the highest separation efficiency, but at a lower sample throughput. The optimized values are specific for our device but demonstrate processes that we believe are universal for DLD separations.

Mathematical simulation and prediction of tumor volume using RBF artificial neural network at different circumstances in the tumor microenvironment.

Uncontrolled proliferation of cells in a tissue caused by genetic mutations inside a cell is referred to as a tumor. A tumor which grows rapidly encounters a barrier when it grows to a certain size in presence of preexisting vasculature. This is the time when it has to find a way to go on the growth. The tumor starts to secrete tumor angiogenic factors (TAFs) and stimulate preexisting vessels to grow new sprouts. These new sprouts will find their way to the tumor in the extracellular matrix (ECM) by the gradient of TAF. As these new capillaries anastomose and reach tumor, fresh oxygen is available for the tumor and it will reinitiate the growth. Number of initial sprouts, distance of initial tumor cells from the vessel(s) and initial density of the tumor at the time of sprout formation are questions which are to be investigated. In the present study, the aim is to find the response of tumor cells and vessels to the reciprocal effects of each other in different circumstances in the tissue. Together with a mathematical formulation, a radial basis function (RBF) neural network is established to predict the number of tumor cells at different circumstances including size and distance of initial tumors from the parent vessel. A final formulation is given for the final number of tumor cells as a function of initial tumor size and distance between a parent vessel and a tumor. Results of this simulation demonstrate that, increasing the distance between a tumor and a parent vessel decreases the number of final tumor cells. Specially, this decrement becomes faster beyond a certain distance. Moreover, initial tumors in bigger domains must become much bigger before inducing angiogenesis which makes it harder for them to survive.

A Quantitative Study of the Secondary Acoustic Radiation Force on Biological Cells during Acoustophoresis.

We investigate cell-particle secondary acoustic radiation forces in a plain ultrasonic standing wave field inside a microfluidic channel. The effect of secondary acoustic radiation forces on biological cells is measured in a location between a pressure node and a pressure anti-node and the result is compared with theory by considering both compressibility and density dependent effects. The secondary acoustic force between motile red blood cells (RBCs) and MCF-7 cells and fixed 20 µm silica beads is investigated in a half-wavelength wide microchannel actuated at 2 MHz ultrasonic frequency. Our study shows that the secondary acoustic force between cells in acoustofluidic devices could play an important role for cell separation, sorting, and trapping purposes. Our results also demonstrate the possibility to isolate individual cells at trapping positions provided by silica beads immobilized and adhered to the microchannel bottom. We conclude that during certain experimental conditions, the secondary acoustic force acting on biological cells can dominate over the primary acoustic radiation force, which could open up for new microscale acoustofluidic methods.

Mathematical modeling reveals how the density of initial tumor and its distance to parent vessels alter the growth trend of vascular tumors.

OBJECTIVES: The aim of this study was to investigate the response of a tumor and parent vessels to stimulating factors in the tumor microenvironment in different configurations. How a tumor grows and induces angiogenesis in different distances of a parent vessel is investigated. Moreover, interstitial fluid pressure and its effects on tumor cell phenotype are considered in the model. METHODS: A multiscale continuum-discrete model of a vascular tumor is utilized to simulate the growth of a cluster of tumor cells positioned in different distances of parent vessels. An agent-based probabilistic angiogenesis model is coupled to a discrete tumor model to simulate branching, anastomosis, blood flow, wall shear stress, and interstitial tumor pressure in which tumor cells are divided to necrotic, hypoxic, and proliferative. RESULTS: Starting the simulations from 9 initial tumor cells, the model proved that tumors grow to a certain size and also reach to a certain distance before being able to induce sprouting. For tumors placed 2 and 2.5 mm away from a parent vessel, initiation of angiogenesis is delayed significantly in comparison with closer distances. For the initial cluster positioned in a distance of 2.5 mm away, first sprout is seen after 47 days. Moreover, dendritic shape of the tumor is seen prior to angiogenesis which is a sign of cells being starved and wandered in the domain to reach the oxygen source. The trend of tumor growth obeys power law function which aligns with the experimental results. DISCUSSION: The mathematical model revealed the importance of geometry and position of an initial tumor cluster in determining the behavior and final architecture of a vascular tumor. As a tumor cell appears in farther distances from a parent vessel, duration of its growth and inducing angiogenesis becomes longer and the chance of suppressing the tumor in the initial days of growth is higher. Also, the importance of angiogenesis in making tumors devastating is again corroborated by mathematical models.

Acoustic dipole and monopole effects in solid particle interaction dynamics during acoustophoresis.

A method is presented for measurements of secondary acoustic radiation forces acting on solid particles in a plain ultrasonic standing wave. The method allows for measurements of acoustic interaction forces between particles located in arbitrary positions such as in between a pressure node and a pressure antinode. By utilizing a model that considers both density- and compressibility-dependent effects, the observed particle-particle interaction dynamics can be well understood. Two differently sized polystyrene micro-particles (4.8 and 25 µm, respectively) were used in order to achieve pronounced interaction effects. The particulate was subjected to a 2-MHz ultrasonic standing wave in a microfluidic channel, such as commonly used for acoustophoresis. Observation of deflections in the particle pathways shows that the particle interaction force is not negligible under this circumstance and has to be considered in accurate particle manipulation applications. The effect is primarily pronounced when the distance between two particles is small, the sizes of the particles are different, and the acoustic properties of the particles are different relative to the media. As predicted by theory, the authors also observe that the interaction forces are affected by the angle between the inter-particle centerline and the axis of the standing wave propagation direction.

Mathematical Modeling of the Function of Warburg Effect in Tumor Microenvironment.

Tumor cells are known for their increased glucose uptake rates even in the presence of abundant oxygen. This altered metabolic shift towards aerobic glycolysis is known as the Warburg effect. Despite an enormous number of studies conducted on the causes and consequences of this phenomenon, little is known about how the Warburg effect affects tumor growth and progression. We developed a multi-scale computational model to explore the detailed effects of glucose metabolism of cancer cells on tumorigenesis behavior in a tumor microenvironment. Despite glycolytic tumors, the growth of non-glycolytic tumor is dependent on a congruous morphology without markedly interfering with glucose and acid concentrations of the tumor microenvironment. Upregulated glucose metabolism helped to retain oxygen levels above the hypoxic limit during early tumor growth, and thus obviated the need for neo-vasculature recruitment. Importantly, simulating growth of tumors within a range of glucose uptake rates showed that there exists a spectrum of glucose uptake rates within which the tumor is most aggressive, i.e. it can exert maximal acidic stress on its microenvironment and most efficiently compete for glucose supplies. Moreover, within the same spectrum, the tumor could grow to invasive morphologies while its size did not markedly shrink.

Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy.

Intraperitoneal (IP) chemotherapy has revived hopes during the past few years for the management of peritoneal disseminations of digestive and gynecological cancers. Nevertheless, a poor drug penetration is one key drawback of IP chemotherapy since peritoneal neoplasms are notoriously resistant to drug penetration. Recent preclinical studies have focused on targeting the aberrant tumor microenvironment to improve intratumoral drug transport. However, tumor stroma targeting therapies have limited therapeutic windows and show variable outcomes across different cohort of patients. Therefore, the development of new strategies for improving the efficacy of IP chemotherapy is a certain need. In this work, we propose a new magnetically assisted strategy to elevate drug penetration into peritoneal tumor nodules and improve IP chemotherapy. A computational model was developed to assess the feasibility and predictability of the proposed active drug delivery method. The key tumor pathophysiology, including a spatially heterogeneous construct of leaky vasculature, nonfunctional lymphatics, and dense extracellular matrix (ECM), was reconstructed in silico. The transport of intraperitoneally injected magnetic nanoparticles (MNPs) inside tumors was simulated and compared with the transport of free cytotoxic agents. Our results on magnetically assisted delivery showed an order of magnitude increase in the final intratumoral concentration of drug-coated MNPs with respect to free cytotoxic agents. The intermediate MNPs with the radius range of 200-300 nm yield optimal magnetic drug targeting (MDT) performance in 5-10 mm tumors while the MDT performance remains essentially the same over a large particle radius range of 100-500 nm for a 1 mm radius small tumor. The success of MDT in larger tumors (5-10 mm in radius) was found to be markedly dependent on the choice of magnet strength and tumor-magnet distance while these two parameters were less of a concern in small tumors. We also validated in silico results against experimental results related to tumor interstitial hypertension, conventional IP chemoperfusion, and magnetically actuated movement of MNPs in excised tissue.

Translational models of tumor angiogenesis: A nexus of in silico and in vitro models.

Emerging evidence shows that endothelial cells are not only the building blocks of vascular networks that enable oxygen and nutrient delivery throughout a tissue but also serve as a rich resource of angiocrine factors. Endothelial cells play key roles in determining cancer progression and response to anti-cancer drugs. Furthermore, the endothelium-specific deposition of extracellular matrix is a key modulator of the availability of angiocrine factors to both stromal and cancer cells. Considering tumor vascular network as a decisive factor in cancer pathogenesis and treatment response, these networks need to be an inseparable component of cancer models. Both computational and in vitro experimental models have been extensively developed to model tumor-endothelium interactions. While informative, they have been developed in different communities and do not yet represent a comprehensive platform. In this review, we overview the necessity of incorporating vascular networks for both in vitro and in silico cancer models and discuss recent progresses and challenges of in vitro experimental microfluidic cancer vasculature-on-chip systems and their in silico counterparts. We further highlight how these two approaches can merge together with the aim of presenting a predictive combinatorial platform for studying cancer pathogenesis and testing the efficacy of single or multi-drug therapeutics for cancer treatment.

Numerical Study of Turbulent Pulsatile Blood Flow through Stenosed Artery Using Fluid-Solid Interaction.

The turbulent pulsatile blood flow through stenosed arteries considering the elastic property of the wall is investigated numerically. During the numerical model validation both standard k-ε model and RNG K-ε model are used. Compared with the RNG K-ε model, the standard K-ε model shows better agreement with previous experimental results and is better able to show the reverse flow region. Also, compared with experimental data, the results show that, up to 70% stenosis, the flow is laminar and for 80% stenosis the flow becomes turbulent. Assuming laminar or turbulent flow and also rigid or elastic walls, the results are compared with each other. The investigation of time-averaged shear stress and the oscillatory shear index for 80% stenosis show that assuming laminar flow will cause more error than assuming a rigid wall. The results also show that, in turbulent flow compared with laminar flow, the importance of assuming a flexible artery wall is more than assuming a rigid artery wall.