Download user presentations that focus on microfluidic applications of FLOW-3D from past users conferences.
Numerical modeling of microfluidics cells
Julien Bœuf, Roche Diagnostics GmbH
Alastair Laing, John Willems, Matt Griebel, and Evan Graves, Roche Tissue Diagnostics
Alexander Meier, Roche Diagnostics International AG
Roche Tissue Diagnostics platforms perform assays on histological and cytological samples which are placed upon glass microscope slides in order to enable a pathologist to diagnose cancerous and possibly other diseased tissue states. In order to develop new advanced staining systems, this project considered a new platform in which glass microscope slides containing samples are inserted into disposable microfluidics cell devices. To select the best flow-cell technology, different designs were evaluated, both experimentally and theoretically. The fluid dynamics were analyzed theoretically by Computational Fluid Dynamics (CFD) technology using FLOW-3D. As a first step, the plausibility of the models was investigated by comparison to videos. Both fluid exchange process and the primary filling process, including fluid/air interface, were considered for three different cell designs. The calculation results show very good quantitative agreement with the experiments. For the fluid exchange calculation, the rapidity of the exchange and the homogeneity of the interface between the two fluids were calculated. This allowed the ranking of the three designs. For the primary filling process, bubble formation was predicted, and the resulting risk of inhomogeneous staining was analyzed.
The importance of valve dynamics in the lymphangion fluid-dynamic: A computational CFD investigation with FLOW-3D
Nicholas Mattia Marazzi and Giovanna Guidoboni, Department of Electric and Computer Engineering, University of Missouri
Riccardo Sacco, Department of Mathematics, Politecnico di Milano
Raul Pirovano and Paolo Airoldi, XC Engineering SRL
The lymphatic system plays a crucial role in maintaining the overall fluid balance in the human body by returning the extracellular fluid from the tissue space in the blood system. Although impaired lymphatic function can lead to pathological conditions, such as lymphedema or tumor metastases, the lymphatic system has received less scientific attention, and several mechanisms of this system still need to be elucidated. Currently, it is widely accepted that the role played by the pumping mechanism occurring in the lymphangion is fundamental for lymphatic system function. By means of spontaneous contraction, the lymphangions are capable of propelling the fluid unidirectionally and returning it to the blood circulation. However, the mechanisms controlling activity of lymphangions are not fully characterized. To help clarify this issue, a CFD simulation was developed with the commercial software FLOW-3D aimed at investigating the fluid-dynamic behavior of the lymphangions. As a first step, a 3D simulation of a single lymphangion was implemented. The results highlight a tight relationship between the time rate of change of pressure in the lymphangion and valve dynamics. Based on the simulation results, a mechanistic assumption regarding valve movement has been proposed and tested within a computational framework composed of several lymphangions. The simulation results are consistent with the experimental measurements reported in the literature, thereby proving the capability of the proposed model to describe a physiological condition in a lymphangion chain. Our study demonstrated the importance of valve dynamics which (i) determine the time rate of change of intra-lymphangion pressure and (ii) allow for the formation and maintenance of a favorable pressure gradient through the lymphangion chain. The model developed with FLOW-3D holds promise as a virtual laboratory, where lymphangion activity can be investigated and characterized to elucidate functional mechanisms of the lymphatic system in health and disease.
Modeling of a printing head
Shmuel Olek, J-ROM Ltd.
A Drop-On Demand (DOD) type printing head has been simulated using FLOW-3D. This kind of printing head includes a piezoelectric push-mode, which acts on a membrane to create pressure pulses causing ejection of individual droplets when needed. The piezoelectric and membrane components of the printing head are not physically modeled. Rather, rectangular pressure pulses are applied at the support component in the zone of the piezoelectric component. A number of cases with different data and assumptions are examined. Using the TruVOF method, simulation results are shown to compare favorably with experimental data.
Flow in a Peristaltic Pump: Two-Fluids Approach
Julien Bœuf, Roche Diagnostics GmbH
Peristaltic pumps are commonly used in the pharmaceutical industry. However, in case of high sensibility to shear forces of the dispensed biopharmaceutical solution, limitations in process parameters must be carefully considered. For example, denaturing of protein during processing (aggregation, unfolding, fibril formation, loss of activity, etc.) can occur at a too high or a too long shearing. CFD models basically allow a better theoretical understanding of the flow and of the shear stress applied to the proteins. In a peristaltic pump, the fluid is contained within a flexible tube. The tube is occluded by a solid part, forcing the fluid to be pumped to move through the tube. Of course, this is basically an FSI problem with high deformation of the solid (tube), and the structural mechanical part of the problem is not fully covered by the current FLOW-3D software version. However, because the only physical aspect of interest is the fluid flow, the tube deformation can be roughly modeled using a visco-elastic fluid in a two-fluids approach. The delivered precision of the tube deformation is sufficient for the purpose of this study. Within this modeling approach, the shear rate field of different processes can be compared. In this presentation, commercial linear and radial peristaltic pumps are considered. To evaluate the ability of the devices to dispense small volumes of pharmaceutical solution, the flow and the resulting shear rates are analyzed. The numerical models are described, the strength and limits of this numerical approach are discussed, and the main results reviewed.
Multiphysics CFD: Challenges and applications
Edward Furlani, University at Buffalo, SUNY
The interest in fluids and related transport phenomena has grown dramatically in recent years as applications have broadly proliferated. At the same time, advances in computational fluid dynamics (CFD) combined with ever increasing computational power at reduced cost have enabled unprecedented understanding of fluidic behavior and the rational design of novel commercial technologies. In this presentation, challenges and applications of multiphysics CFD are discussed. The applications range in scope from nanoscale photothermal bubble nucleation for cancer therapy, to magnetically-based microfluidic biosorting, to inkjet technology and liquid metal 3D printing, among others. The discussion will be reinforced with results from case studies.
Winner of the Best Presentation Award
Computational analysis of pinch-off dynamics and printability of simple and complex fluids
Vivek Sharma and Jelena Dinic, University of Illinois at Chicago, IL
Drop formation and liquid transfer in jetting, printing, coating, and spraying as well as microfluidic drop/particle formation applications are accompanied by the formation of unstable columnar liquid necks that undergo surface tension driven thinning and pinch-off. Advances in high-speed imaging and visualization methods, coupled with advances in theory and simulation methods for free surface flows, have resulted in a fairly comprehensive characterization and understanding of capillary-thinning dynamics for simple, Newtonian fluids. For Newtonian fluids, the complex interplay of inertial, viscous and capillary stresses before and after breakup leads to neck thinning dynamics that can often be described by universal scaling laws, and selfsimilar neck evolution manifested in experiments. In rheologically-complex fluids, extra elastic stresses as well as non-Newtonian shear and extensional viscosity dramatically alter the nonlinear dynamics. Stream-wise velocity-gradients associated with extensional flows arise in thinning liquid necks spontaneously formed during printing, spraying and atomization, and fiber spinning. Complex fluids exhibit a much larger resistance to elongational flow than simple fluids with the same zero shear viscosity, leading to delayed pinch-off and dramatically changing the shape of the neck as well as rate of neck thinning, satellite drop formation and printability. Using the Volume-of-Fluid approach implemented in FLOW-3D, we simulate the free surface flows within columnar necks or stretched liquid bridges formed by dripping, by applying step strain to fluid between two parallel plates, and by dripping-onto substrate. Using these three prototypical cases, we simulate free-surface flows realized in printing as well as in extensional rheometry devices used for studying pinch-off dynamics and the influence of microstructure and viscoelasticity. In contrast with often-used 1D or 2D models, FLOW-3D allows a robust evaluation of the magnitude of the underlying stresses and extensional flow field (both uniformity and magnitude). We contrast our results with 1D and 2D models, and show that shape evolution dynamics, finite-time singularities, and satellite formation can be probed remarkably well with the CFD simulations in FLOW-3D. We find that the simulated radius evolution profiles match the scaling laws and pinch-off dynamics that are experimentally-observed and theoretically-predicted for Newtonian fluids. Finally, we describe our experiments and FLOW-3D simulations to elucidate how viscoelasticity modeled using the Oldroyd-B constitutive model influences interfacial and nonlinear flows underlying pinch-off dynamics, extensional rheometry and printability of polymeric complex fluids.
Optofluidics: Modeling L2 lens
Adwaith Gupta and Ioannis Karampelas, Flow Science and Justin Kitting, University of New Mexico
This presentation describes the modeling of dynamically reconfigurable liquid-core liquid-cladding (L2) lens in a microfluidic channel using FLOW-3D, followed by quantitative validation against the experimental results. The lens is formed in a microchannel by three laminar streams of fluids with different refractive indices. The core stream, which is sandwiched between the cladding streams, has a higher refractive index, causing the light to bend while passing through the layers of microfluidic streams. Based on the relative flow magnitudes of the core flow rates and the cladding flow rates, different lens shapes (defined by the curvatures) are formed. Each curvature leads to a different focal length, thus governing the path of light rays passing through the microchannel. The case study is divided into two parts – constant cladding flow rates and constant core flow rates. Also, a technique is devised in FlowSight to find the curvatures of each lens. Finally, the results are validated against the experimental results.
Winner of the Best Presentation Award
Optimization of magnetic blood cleansing microdevices
Jenifer Gómez-Pastora, University of Cantabria
The use of magnetic particles has recently expanded for a process known as detoxification in which different toxins are captured from the bloodstream of septic patients. Due to the laminar flow developed in microfluidic devices, the particle separation after the toxin capture can be carried out in a continuous mode by using multiphase microfluidic channels. In this work, the design for a two-phase continuous-flow microseparator and an optimization study for the separation of magnetic beads from blood are presented. The numerical method includes a combination of magnetic and fluidic computational models that were solved using FLOW-3D’s TruVOF method, whereas an external Fortran subroutine was employed for the calculation of the magnetic fields and forces. For optimization purposes, a dimensionless number J is introduced and results show that complete and safe separation is achieved only for a certain value of J (≈0.3). This is the first computational study of the interaction between two different fluids flowing simultaneously in the device that takes into account two-way coupled particle-fluid interactions in the flow field and the particle motion effects as they cross the interface between the fluids under various magnetic field intensities.
CFD modelling of droplet formation in microarrays
Julien Bœuf, Roche Diagnostics GmbH
Alexander Meier, Roche Diagnostics International AG
In microfluidic applications, a two fluid system is usually used to distribute and separate the fluid of interest using the second fluid within the microfluidic chip. The behavior of the interface between the two phases (e.g., air/liquid or liquid/liquid interfaces) has a large impact on the performance of such devices. CFD models allow a better theoretical understanding of the flow and of the formation of the interface. At microfluidic scales the shape of the interface is mainly governed by surface tension and the contact angle of the two fluids with the walls of the device. The process robustness can be analyzed by the design or the process parameter variations. Similarly, properties of fluid or substrate surface can be easily modified in the model and their influence on the process analyzed. In this presentation, a typical microwell biochip application is considered. This microfluidic application allows droplet generation by separating the water based fluid of interest in a well array using a second non miscible fluid. CFD models using FLOW-3D are described and the main results reviewed.
Pinch-off dynamics, extensional rheometry and printability of simple and complex fluids
Jelena Dinic and Vivek Sharma, University of Illinois at Chicago
Liquid transfer and drop formation/deposition processes underlying printing involve complex free-surface flows, including the formation of columnar necks that undergo spontaneous capillary-driven instability, thinning and pinch-off. For simple (Newtonian and inelastic) fluids, a complex interplay of capillary, inertial and viscous stresses determines the nonlinear dynamics underlying finite-time singularity, satellite drop formation as well as self-similar capillary thinning and pinch-off dynamics. In rheologically-complex fluids, extra elastic stresses as well as non-Newtonian shear and extensional viscosity dramatically alter the nonlinear dynamics. Stream-wise velocity gradients that arise within the thinning columnar neck create an extensional flow field, and complex fluids exhibit a much larger resistance to elongational flow than simple fluids with the same zero shear viscosity. Using FLOW-3D, we simulate flows within columnar necks or stretched liquid bridges formed by dripping, by applying step strain to fluid between two parallel plates, and by dripping-onto substrate. Using these three prototypical cases, we simulate free-surface flows realized in printing as well as in extensional rheometry devices used for studying pinch-off dynamics and the influence of microstructure and viscoelasticity. In contrast with often-used 1D or 2D models, FLOW-3D allows a robust evaluation of the magnitude of the underlying stresses and extensional flow field (both uniformity and magnitude). We find that the simulated radius evolution profiles match the scaling laws and pinch-off dynamics that are experimentally-observed and theoretically-predicted for Newtonian fluids. Finally, we describe our experiments and FLOW-3D simulations to elucidate how viscoelasticity as well as non-Newtonian shear and extensional viscosity influence interfacial and nonlinear flows underlying pinch-off dynamics, extensional rheometry and printability of complex fluids.
CFD modelling of dispensing processes in different medical devices
Julien Bœuf, Roche Diagnostics GmbH
Among production processes in the diagnostics and pharmaceutical branch, dispensing processes of liquid are very common: Drugs are filled in vials or syringes, reactive chemistry is dispensed in vessels or onto unconventional substrates like Lab-on-chip. Those processes are physically analogous but require different dispensing devices and process parameters due to the different scales and amount of dispensed fluid. CFD models allow a better theoretical understanding of the flow and formation of free surfaces. The process robustness can be analyzed by the design or the process parameter variations. Similarly, properties of fluid or substrate surface can be easily modified in the model and their influence on the process analyzed. Different criteria for process robustness can be considered: precision of dispensed fluid amount, precision of its localization, process duration, etc. Furthermore, the exposure to shear stress during the process can be estimated, which can be relevant in the case of sensitive bio-pharmaceuticals regarding degradation of proteins. In this presentation, different applications of FLOW-3D to dispensing processes are overviewed. All models have to take account for large free surfaces, which strongly develop over time. But, depending on both time and space scales, Capillary or Weber numbers are quite different and the specific numerical options have to be adapted to each specific configuration.
A CFD approach for predicting magnetic field-directed particle-transport and self-assembly in microfluidic systems
Xiaozheng Xue1, Chenxu Liu1, and Edward P. Furlani1,2
1Dept. of Chemical and Biological Engineering, University at Buffalo SUNY, 2Dept. of Electrical Engineering, University at Buffalo SUNY
Magnetic particles are finding increasing use in microfluidic systems to selectively separate and sort biomaterial from a specimen for a broad range of biomedical applications. They are also commonly used to adaptively control rheology in fluid-based mechanical applications such as vibration dampers. Computational models are needed for the rational design of such applications. However, to date, much of the theoretical work in this field has been based on simplified one-way particle-fluid coupling wherein the fluid flow affects particle motion, but the flow itself is independent of the particle dynamics. Relatively few studies have taken into account two-way particle-fluid coupling wherein momentum is transferred from the particles to the fluid, thereby altering the flow. Moreover, magnetic dipole-dipole interactions, which cause aggregation and self-assembly, are often also neglected. In this presentation a computational method is presented for predicting the field-directed transport, sorting and self-assembly of magnetic particles in microfluidic systems. Custom-developed Fortran-based subroutines have been integrated into FLOW-3D that take into account the force on the particles due to an applied field, interparticle magnetic dipole-dipole interactions and Brownian motion. Fully-coupled particle-fluid transport is computed using the FLOW-3D general moving object (GMO) capability. The model is demonstrated via application to various magnetic sorting and self-assembly applications.
Analysis of venous blood flow at intra-venous drug delivery
Bettina Willinger, Bastian Schöneberger, and Antonio Delgado, Institute of Fluid Mechanics, Friedrich-Alexander University of Erlangen-Nuremberg
In hospitals it is standard that infusions supply patients with drugs and liquids. The infusion is normally induced in the vein, but only the transport behind the heart in the arteries has been investigated in detail until nowadays. Thus the intention of this work is to contribute to a better understanding of the fluid flow and the mixing behavior of an anesthetic induced in the vein on its way towards the heart. The geometry of the vein is reproduced as a stiff tube. In the simulations venous valves are included and modeled as coupled moving semicircular plates. For the needle a second stiff tube is centered in the vein. To reduce free space around the vein, the mesh grid is defined in cylindrical coordinates. It is important that the needle and the venous valves have their own mesh grids, to simulate the moving of the medical fluid and the moving of the valves. The venous tube is completely filled with a fluid with blood characteristics and the needle with a medical fluid. An analysis of the flow shows that the mixing of both fluids is mainly achieved by the movement of the venous valves which is caused by the pressure changes in the vein. The valves also extend the time of the fluid flow to the heart.
Computational modelling a microcarrier bioreactor system for stem cell culture performance analysis
Koushik Ponnuru1, Ioannis H. Karampelas1, Jincheng Wu1, Preeti Ashok1, Emmanuel S. Tzanakakis1,3,4,5,6 and Edward P. Furlani1, 2
1Dept. of Chemical and Biological Engineering, University at Buffalo SUNY
2Dept. of Electrical Engineering, University at Buffalo SUNY
3Dept. of Biomedical Engineering, University at Buffalo SUNY
4New York State Center of Excellence in Bioinformatics and Life Sciences
5Western New York Stem Cell Culture and Analysis Center
6Genetics, Genomics and Bioinformatics, University at Buffalo SUNY
In recent years, there has been a proliferation of research in human pluripotent stem cells (hPSCs). A key feature of these cells is that they are capable of differentiating into all somatic cell types and, therefore, hold great potential for future clinical applications. Cell culture studies in stirred tank bioreactors suggest that mechanical forces occurring from the interaction of stem cells with turbulent eddies significantly affect their differentiation propensity. The magnitude of shear is directly related to the size of turbulent eddies formed in the bioreactor relative to the size of the microcarrier particles. It has been reported that cell mechanical damage could be prevented provided that the particle size is smaller than the size of the smallest eddy, as characterized by the Kolmogorov length scale for turbulence. Hence, the Kolmogorov length scale is a key determinant of the differentiation outcome of cultured stem cells. The objective of our current work is to determine the effects of the turbulent shear stress on cell culture performance through a synergistic combination of CFD-based simulations and experiments. The impact of variable parameters such as impeller speed, culture medium fluid properties and cell size on the steady-state shear stress acting on the cell-laden microcarrier particles in the bioreactor are studied using FLOW-3D. This computational modelling is used to predict the precise shear levels experienced by cells and identify optimum operating conditions so as to prevent potential turbulent shear damage. In addition, the effect of shear on the pluripotency of hPSCs is studied by determining the percentage of cells carrying the pluripotency markers Oct4, Sox2 and Nanog using flow cytometry and quantitative PCR. The cell cycle of hPSCs under different shear stress conditions is also studied to determine the doubling time and the length of the G phase of the cells.