Numerical investigation of ternary particle separation in a microchannel with a wall-mounted obstacle using dielectrophoresis.

In recent years, microfluidic-based particle/cell manipulation techniques have catalyzed significant advances in several fields of science. As an efficient, precise, and label-free particle/cell manipulation technique, dielectrophoresis (DEP) has recently attracted widespread attention. This paper presents the design and investigation of a straight sheathless 3D microchannel with a wall-mounted trapezoidal obstacle for continuous-flow separation of three different populations of polystyrene (PS) particles (5, 10 and 20 µm) using DEP. An OpenFOAM code is developed to simulate and investigate the movement of particles in the microchannel. Then, the code is validated by performing various experimental tests using a microdevice previously fabricated in our lab. By comparing the numerical simulation results with the experimental tests, it can be claimed that the newly developed solver is highly accurate, and its results agree well with experimental tests. Next, the effect of various operational and geometrical parameters such as obstacle height, applied voltage, electrode pairs angle, and flow rate on the efficient focusing and separation of particles are numerically investigated. The results showed that efficient particle separation could only be achieved for obstacle heights of more than 350 µm. Furthermore, the appropriate voltage range for efficient particle separation is increased by decreasing the electrode angle as well as increasing the flow rate. Moreover, the results showed that by employing the appropriate channel design and operational conditions, at a maximum applied voltage of 10V, a sample flow rate of 2.5µL/min could be processed. The proposed design can be beneficial for integrating with lab-on-a-chip and clinical diagnosis applications due to advantages, such as simple design, no need for sheath flow, the simultaneous ternary separation of particles, and providing precise particle separation.

Numerical and Experimental Analysis of Drug Inhalation in Realistic Human Upper Airway Model.

The demand for a more efficient and targeted method for intranasal drug delivery has led to sophisticated device design, delivery methods, and aerosol properties. Due to the complex nasal geometry and measurement limitations, numerical modeling is an appropriate approach to simulate the airflow, aerosol dispersion, and deposition for the initial assessment of novel methodologies for better drug delivery. In this study, a CT-based, 3D-printed model of a realistic nasal airway was reconstructed, and airflow pressure, velocity, turbulent kinetic energy (TKE), and aerosol deposition patterns were simultaneously investigated. Different inhalation flowrates (5, 10, 15, 30, and 45 L/min) and aerosol sizes (1, 1.5, 2.5, 3, 6, 15, and 30 µm) were simulated using laminar and SST viscous models, with the results compared and verified by experimental data. The results revealed that from the vestibule to the nasopharynx, the pressure drop was negligible for flow rates of 5, 10, and 15 L/min, while for flow rates of 30 and 40 L/min, a considerable pressure drop was observed by approximately 14 and 10%, respectively. However, from the nasopharynx and trachea, this reduction was approximately 70%. The aerosol deposition fraction alongside the nasal cavities and upper airway showed a significant difference in pattern, dependent on particle size. More than 90% of the initiated particles were deposited in the anterior region, while just under 20% of the injected ultrafine particles were deposited in this area. The turbulent and laminar models showed slightly different values for the deposition fraction and efficiency of drug delivery for ultrafine particles (about 5%); however, the deposition pattern for ultrafine particles was very different.

Continuous size-based DEP separation of particles using a bi-gap electrode pair.

A novel microfluidic device containing a bi-gap electrode pair is presented in this paper, and it is capable of continuously separating three different populations of particles using dielectrophoresis. A mixture of 5, 10, and 20 µm polystyrene particles is focused by a sheath flow and then separated based on size after flowing over a bi-gap electrode pair. A new solver is developed in OpenFOAM to investigate the effects of various parameters such as the flow rate, gaps, and electrode pair angles to achieve an appropriate configuration of the bi-gap electrode pair for efficient particle separation. Based on the numerical simulation results, three different configurations of bi-gap electrode pairs are fabricated. The paths of three populations of polystyrene particles under various operating conditions are experimentally examined and compared with numerical results. Then, by examining the purity of the separated particles with three different electrode configurations at different flow rates, the performance of the device is experimentally investigated. The results showed that by employing the proposed electrode configuration, at a maximum flow rate of 100 µL h-1 (25 µL h-1 for the sample), particles are separated precisely (with more than 99% purity for all particles at desired outlets) using a 20 Vpp sinusoidal electric potential with a frequency of 100 kHz. This novel microfluidic device is thus a practical device for continuously separating three different populations of particles/cells according to size in a heterogeneous admixture.

Application of level-set method in simulation of normal and cancer cells deformability within a microfluidic device.

Application of microfluidic systems for the study of cellular behaviors has been a flourishing area of research in the past decade. In the process of probing cell biomechanics the passage of a cell through a narrow microchannel or a small pore has attracted much attention during the recent years. And the study of cellular deformability and transportability using these systems with enhanced resolution and accuracy has opened a new paradigm for high-throughput characterization of both healthy and diseased cell populations.Here we use the level-set method to explore the relationship between the transit time and mechanical properties of normal white blood cells (WBCs) and breast cancer epithelial cells (MCF7) under different microenvironmental parameters (i.e., pressure difference, cell size, effective cell surface tension, constriction size and taper angle) in a 2-D computational domain by considering the cell as a viscous drop. The novel biomechanical relations are obtained for each cell type by the Response Surface Method (RSM), relating microenvironmental parameters to the dimensionless entry time of the normal and cancer cells. Our results revealed that MCF7 cells show asignificantly different behavior (a bifurcating behavior when the pressure difference of inlet/outlet increases) in regards to the dimensionless entry time as a function of microchannel taper angle in comparison with the WBC. These results suggest that the microenvironmental parameters have a significant effect on the transportability of the cells and different cells have different behaviors in response to a specific microenvironmental parameter. Finally, it can be claimed that this method can be also utilized to distinguish between benign and cancerous cells or even to probe tumor heterogeneity toward high throughput cell cytometry.

Investigation of blood flow rheology using second-grade viscoelastic model (Phan-Thien-Tanner) within carotid artery.

PURPOSE: Hemodynamic factors, such as Wall Shear Stress (WSS), play a substantial role in arterial diseases. In the larger arteries, such as the carotid artery, interaction between the vessel wall and blood flow affects the distribution of hemodynamic factors. The fluid is considered to be non-Newtonian, whose flow is governed by the equation of a second-grade viscoelastic fluid and the effects of viscoelastic on blood flow in carotid artery is investigated. METHODS: Pulsatile flow studies were carried out in a 3D model of carotid artery. The governing equations were solved using finite volume C++ based on open source code, OpenFOAM. To describe blood flow, conservation of mass and momentum, a constitutive relation of simplified Phan-Thien-Tanner (sPTT), and appropriate relations were used to explain shear thinning behavior. RESULTS: The first recirculation was observed at t = 0.2 s, in deceleration phase. In the acceleration phase from t = 0.3 s to t = 0.5 s, vortex and recirculation sizes in bulb regions in both ECA and ICA gradually increased. As is observed in the line graphs based on extracted data from ICA, at t = 0.2 s, τyy is the maximum amount of wall shear stress and τxy the minimum one. The maximum shear stress occurred in the inner side of the main branch (inner side of ICA and ECA) because the velocity of blood flow in the inner side of the bulb region was maximum due to the created recirculation zone in the opposite side in this area. CONCLUSIONS: The rheology of blood flow and shear stress in various important parts (the area that are in higher rates of WSS such as bifurcation region and the regions after bulb areas in both branches, Line1-4 in Fig. 7) were also analyzed. The investigation of velocity stream line, velocity profile and shear stress in various sections of carotid artery showed that the maximum shear stress occurred in acceleration phase and in the bifurcation region between ECA and ICA which is due to velocity gradients and changes in thinning behavior of blood and increasing strain rate in Newtonian stress part.

Magnetic nanoparticles and blood flow behavior in non-Newtonian pulsating flow within the carotid artery in drug delivery application.

Nanoparticles play an important role in the molecular diagnosis, treatment, and monitoring therapeutic outcomes in various diseases. Magnetic nanoparticles are being of great interest due to their unique purposes, especially medicine, in which the application of magnetic nanoparticles is much promising. Magnetic nanoparticles have been actively investigated as the next generation of targeted drug delivery for more than three decades. This article is devoted to study on the magnetic drug targeting technique by particle tracking in the presence of a magnetic field in the carotid artery. The results showed that applying a magnetic field on the secondary branch of the external carotid artery in a pulsating non-Newtonian flow drove nanoparticles inside this sub-branch, while none of them entered that branch in the absence of magnetic field on the internal carotid artery. Wall shear stress distributions showed that high shear stress occurs near the bifurcation region, and its maximum value belongs to the junction of internal carotid artery and external carotid artery.