Magnetohydrodynamic flow with slippage in an annular duct for microfluidic applications

In this paper, we investigate theoretically the 3D laminar flow of an electrolyte in an annular duct driven by a Lorentz force. The duct is formed by two concentric electrically conducting cylinders limited by insulating bottom and top walls. A uniform magnetic field acts along the axial direction, while a potential difference is applied between the cylinders so that a radial electric current traverses the fluid. The interaction of the current and the magnetic field produces a Lorentz force that drives an azimuthal flow. The steady flow is solved using a Galerkin method with Bessel–Fourier series in the radial direction and trigonometric series along the vertical direction, allowing different combinations of slip conditions at the walls. The orthogonality of both series with the general boundary conditions of the third kind is used to find an analytic approximation. Velocity patterns and flow rates are explored by varying the aspect ratio of the duct and the gap between the cylinders, as well as the slippage at the walls. Results can provide useful information for optimization and design of annular microfluidic devices.     

Microfluidic effects of transporting signaling components in cell coculture chips

A theoretical model has been developed to investigate the microfluidic transport of the signaling chemicals in the cell coculture chips. Using an epidermal growth factor (EGF)-like growth factor as the sample chemical, the effects of velocities and channel geometry were studied for the continuous-flow microchannel bioreactors. It is found that different perfusion velocities must be applied in the parallel channels to facilitate the communication, i.e., transport of the signaling component, between the coculture channels. Such communication occurs in a unidirectional way because the signaling chemicals can only flow from the high velocity area to the low velocity area. Moreover, the effect of the transport of the signaling component between the coculture channels on the growth of the monolayer cells and the multicellular tumor spheroid (MTS) in the continuous-flow coculture environment were simulated using 3D models. The numerical results demonstrated that the concentration gradients will induce the heterogeneous growth of the cells and the MTSs, which should be taken into account in designing the continuous-flow perfusion bioreactor for the cell coculture research.     

Microvalve and liquid membrane double-controlled integrated microfluidics for observing the interaction of breast cancer cells

The methodical development of cell biology has resulted in significant advancements in the study of breast tumors. However, the dynamic investigation of the self-seeding process remains largely out of reach. In the present study, we describe a microvalve and liquid membrane double-controlled integrated microfluidic device that provides for the versatile assessment of breast tumor cell invasion dynamics. The liquid membrane formation was first optimized to obtain a high level of control, and was then applied to different types of homotypic and heterotypic cell seeding with precise selective positioning for monoculture and coculture. Using this device, the interaction between breast cancer cells MDA231-LM2 and MDA-MB231 was successfully observed to investigate self-seeding dynamics, including migration, infiltration, and coexistence. The results quantitatively demonstrate the mutual signal-induced attraction between MDA-MB231 and MDA231-LM2 cells, as well as the progressive infiltration of MDA231-LM2 cells into the MDA-MB231 cell population. These results are valuable in the development of spatiotemporal-controlled microfluidic systems and to many microscale-based biological and diagnostic studies involving cell growth, cell differentiation, cell interaction, and cell signal.     

Numerical investigation of dynamics of elliptical magnetic microparticles in shear flows

We study the rotational dynamics of magnetic prolate elliptical particles in a simple shear flow subjected to a uniform magnetic field, using direct numerical simulations based on the finite element method. Focusing on paramagnetic and ferromagnetic particles, we investigate the effects of the magnetic field strength and direction on their rotational dynamics. In the weak field regime (below a critical field strength), the particles are able to perform complete rotations, and the symmetry property of particle rotational speed is influenced by the direction and strength of the magnetic field. In the strong field regime (above a critical strength), the particles are pinned at steady angles. The steady angle depends on both the direction and strength of the magnetic field. Our results show that paramagnetic and ferromagnetic particles exhibit markedly different rotational dynamics in a uniform magnetic field. The numerical findings are in good agreement with theoretical prediction. Our numerical investigation further reveals drastically different lateral migration behaviors of paramagnetic and ferromagnetic particles in a wall-bounded simple shear flow under a uniform magnetic field. These two kinds of particles can thus be separated by combining a shear flow and a uniform magnetic field. We also study the lateral migration of paramagnetic and ferromagnetic particles in a pressure-driven flow (a more practical flow configuration in microfluidics), and observe similar lateral migration behaviors. These findings demonstrate a simple but useful way to manipulate non-spherical microparticles in microfluidic devices.     

Computational and performance analysis of a continuous magnetophoretic bioseparation chip with alternating magnetic fields

This paper presents the modeling and optimization of a magnetophoretic bioseparation chip for isolating cells, such as circulating tumor cells from the peripheral blood. The chip consists of a continuous-flow microfluidic platform that contains locally engineered magnetic field gradients. The high-gradient magnetic field produced by the magnets is spatially non-uniform and gives rise to an attractive force on magnetic particles flowing through a fluidic channel. Simulations of the particle–fluid transport and the magnetic force are performed to predict the trajectories and capture lengths of the particles within the fluidic channel. The computational model takes into account key forces, such as the magnetic and fluidic forces and their effect on design parameters for an effective separation. The results show that the microfluidic device has the capability of separating various cells from their native environment. An experimental study is also conducted to verify and validate the simulation results. Finally, to improve the performance of the separation device, a parametric study is performed to investigate the effects of the magnetic bead size, cell size, number of beads per cell, and flow rate on the cell separation performance.     

Detection of Cellular Parameters Using a Microfluidic Chip-Based System

Lab-on-a-chip technology achieves a reduction of sample and reagent volume and automates complex laboratory processes. Here, we present the implementation of cell assays on a microfluidic platform using disposable microfluidic chips. The applications are based on the controlled movement of cells by pressure-driven flow inside networks of microfluidic channels. Cells are hydrodynamically focused and pass the fluorescence detector in single file. Initial applications are the determination of protein expression and apoptosis parameters. The microfluidic system allows unattended measurement of six samples per chip. Results obtained with the microfluidic chips showed good correlation with data obtained using a standard flow cytometer.     

Numerical simulations of particle migration in a viscoelastic fluid subjected to shear flow

Particle migration is a relevant transport mechanism whenever suspensions flow in channels with gap size comparable to particle dimensions (e.g. microfluidic devices). Several theoretical as well as experimental studies have been performed on this topic, showing that the occurring of this phenomenon and the migration direction are related to particle size, flow rate, and the nature of the suspending liquid.In this work we perform a systematic analysis on the migration of a single particle in a sheared viscoelastic fluid through 2D finite element simulations in a Couette planar geometry. To focus on the effects of viscoelasticity alone, inertia is neglected. The suspending medium is modeled as a Giesekus fluid.An ALE particle mover is combined with a DEVSS/SUPG formulation with a log-representation of the conformation tensor giving stable and convergent results up to high flow rates. To optimize the computational effort and reduce the remeshing and projection steps, needed as soon as the mesh becomes too distorted, a ‘backprojection’ of the flow fields is performed, through which the particle in fact moves along the cross-streamline direction only, and the mesh distortion is hence drastically reduced.Our results, in agreement with recent experimental data, show a migration towards the closest walls, regardless of the fluid and geometrical parameters. The phenomenon is enhanced by the fluid elasticity, the shear thinning and strong confinements. The migration velocity trends show the existence of a master curve governing the particle dynamics in the whole channel. Three different regimes experienced by the particle are recognized, related to the particle-wall distance. The existence of a unique migration behavior and its qualitative aspects do not change by varying the fluid parameters or the particle size.     

Numerical study on the cell motility interacting with the chemical flow in microchannels

Beneficial to the steady control of flow properties and concentration gradient profiles, quantification of cell chemotaxis based on microfluidic devices could achieve on the scale of a single cell. However, normal experimental studies assumed that the concentration field was not affected by the existing cell or by the impact of the cell motion. The present paper systematically simulated the interactions of the cell translational and rotational movements with its chemical gradient flow by both 2D and 3D models. The influences of the chemical flow Peclet number, cell’s translational velocity, cell’s rotational velocity and direction on the sensed chemical gradient were investigated. Results showed that both the cell’s translational and rotational movements disturbed its surrounding chemical distribution and affect chemotactic speed and direction later on. Rotating cell brings in flow circulation with it, and consequently the sensed chemical gradient dramatically deviates from the original direction. The cell’s two contrary rotational directions lead to contrary results. 2D model with circular cell is practically feasible due to simplicity, while 3D model with spherical cell is closer to reality. Numerical comparison showed that the 2D model can be used to analyze the cell’s chemotactic tendency, but it also amplifies the cell’s perturbation and then separation to its surrounding chemical flow. Finally, a single cell’s interactive chemotaxis in a micro chamber was simulated based on experimental measured chemotactic coefficient. The interactive chemotactic cell kept moving slightly upstream instead of upright crossing the interface. This work may contribute to the development of chemotactic measurement method and precise evaluation on the cell’s chemotactic sensitivity.     

3D printing: an emerging tool for novel microfluidics and lab-on-a-chip applications

In the past few years, 3D printing technology has witnessed an explosive growth, penetrating various aspects of our lives. Current best-in-class 3D printers can fabricate micrometer scale objects, which has made fabrication of microfluidic devices possible. The highest achievable resolution is already at nanometer scale, which is continuing to drop. Since geometric complexity is not a concern for 3D printing, novel 3D microfluidics and lab-on-a-chip systems that are otherwise impossible to produce with traditional 2D microfabrication technology have started to emerge in recent years. In this review, we first introduce the basics of 3D printing technology for the microfluidic community and then summarize its emerging applications in creating novel microfluidic devices. We foresee widespread utilization of 3D printing for future developments in microfluidic engineering and lab-on-a-chip technology.     

Lab-on-PCB-based micro-cytometer for circulating tumor cells detection and enumeration

Impedance-based microfluidic cytometer has been introduced to provide a companion diagnostic platform in biological cells analysis. In the conventional way, microfluidic impedance cytometer requires accurately patterning metal electrodes in the corresponding location on silicon/glass substrate, which is expensive and time-consuming. In this short communication, we demonstrate a disposable impedance-based microfluidic cytometer above the commercially available printed circuit board (PCB) with pre-deposited copper electrode, which is reusable. In this experiment, red blood cells (RBCs) and mixture of RBCs, white blood cells (WBCs), and circulating tumor cells (CTCs) are utilized to test the function of the proposed device, which indicated that it can differentiate the WBCs and CTCs from the mixture of the three types of cells. After each sample test, the upper microfluidic cytometer is disposed which shows the great commercial potential in point-of-care test for clinical application.     

A novel three-dimensional microfluidic platform for on chip multicellular tumor spheroid formation and culture

The formation of three-dimensional (3D) multicellular cell spheroids such as microspheres and embryoid bodies has recently gained much attention as a useful cell culture technique, but few studies have investigated the suitability of glass for spheroids formation and culture. In this work, we present a novel three-dimensional microfluidic device made of poly(dimethylsiloxane) (PDMS) and glass for the easy and rapid synthesis and culture of tumor spheroid. The cell culture unit is composed of an array of microwells on the bottom of a glass plate, bigger microwells and elastomeric microchannels on the top of a PDMS plate. Cell suspension can be easily introduced into the cell culture unit and exchange with the external liquid environment by the microfluidic channels. A single tumor spheroid can be formed and cultured in each glass cell culture chamber, the surface of which was modified with poly(vinyl alcohol) to render it to be resistant to cell adhesion. As the cell culture medium could be replaced, spheroids of the human breast cancer (MCF-7) cells were cultured on the chip for 3 days, reaching the diameters of about 150 μm. Furthermore, the MCF-7 cells were successfully cultured on the chip in 2D and 3D culture modes. Results have shown that glass is well suitable for multicellular tumor spheroids culture. The established platform provides a convenient and rapid method for tumor spheroid culture, which is also adaptable for anticancer drug screening and fundamental biomedical research in cell biology.     

Microfluidic device for continuous magnetophoretic separation of white blood cells

This paper presents a microfluidic device for magnetophoretic separation of red blood cells from blood under continuous flow. The separation method consists of continuous flow of a blood sample (diluted in PBS) through a microfluidic channel which presents on the bottom “dots” of ferromagnetic layer. By applying a magnetic field perpendicular on the flowing direction, the ferromagnetic “dots” generate a gradient of magnetic field which amplifies the magnetic force. As a result, the red blood cells are captured on the bottom of the microfluidic channel while the rest of the blood is collected at the outlet. Experimental results show that an average of 95% of red blood cells is trapped in the device.     

Miniaturized flow cytometer with 3D hydrodynamic particle focusing and integrated optical elements applying silicon photodiodes

In this study, the design, realization and measurement results of a novel optofluidic system capable of performing absorbance-based flow cytometric analysis is presented. This miniaturized laboratory platform, fabricated using SU-8 on a silicon substrate, comprises integrated polymer-based waveguides for light guiding and a biconcave cylindrical lens for incident light focusing. The optical structures are detached from the microfluidic sample channel resulting in a significant increase in optical sensitivity. This allows the application of standard solid-state laser and standard silicon-based photodiodes operated by lock-in-amplification resulting in a highly practical and effective detection system. The easy-to-fabricate single-layer microfluidic structure enables independently adjustable 3D hydrodynamic sample focusing to an arbitrary position in the channel. To confirm the fluid dynamics and raytracing simulations and to characterize the system, different sets of microparticles and T-lymphocyte cells (Jurkat cell line) for vital staining were investigated by detecting the extinction (axial light loss) signal. The analytical classification via signal peak height/width demonstrates the high sensitivity and sample discrimination capability of this compact low-cost/low-power microflow cytometer.     

Design optimization of micromixer with square-wave microchannel on compact disk microfluidic platform

This paper presents a passive micromixer on a compact disk (CD) microfluidic platform that performs plasma mixing function. The driving force of CD microfluidic platform including, the centrifugal force due to the system rotation, the Coriolis force as a function of the rotation angular frequency and velocity of liquid. Numerical simulations are performed to investigate the flow characteristics and mixing performance of three CD microfluidic mixers with square-wave, curved and zig-zag microchannels, respectively. Of the three microchannels, the square-wave microchannel is found to yield the best mixing performance, and is therefore selected for design optimization. Four CD microfluidic micromixers incorporating square-wave PDMS microchannels with different widths in the x- and y-directions are fabricated using conventional photolithography techniques. The mixing performance of the four microchannels is investigated both numerically and experimentally. The results show that given an appropriate specification of the microchannel geometry and a CD rotation speed of 2,000 rpm, a mixing efficiency of more than 93 % can be obtained within 5 s.     

Flow control for cell growth by movement of magnetic particles utilizing electromagnetic force

Three-dimensional (3D) cell structures are required to fabricate artificial organ. Inkjet technology is applied for fabrication of 3D cell structures in order to fabricate artificial organ and investigate biochemical characteristics of cells in 3D cell structures. Usually cells located inside 3D cell structures get nutrition via blood vessels. In case that there are no blood vessels in the 3D cell structures, cells located inside the 3D cell structures will die of nutrition shortage. So, blood vessels are essential to fabricate 3D cell structures. When the amount and flow of nutrition is controlled, growth speed of cells will be changed. We control the flow around the cells utilizing magnetic particles and magnetic force. The magnetic particles are installed in the dish that is filled with medium, nutrition and living cells. When the magnetic particles are trapped and transported by magnetic force, the cell growth will be controlled. In this paper, we challenge to control the flow utilizing magnetic particles and magnetic force.     

High-throughput electrokinetic bioparticle focusing based on a travelling-wave dielectrophoretic field

This study presents a sheathless and portable microfluidic chip that is capable of high-throughput focusing bioparticles based on 3D travelling-wave dielectrophoresis (twDEP). High-throughput focusing is achieved by sustaining a centralized twDEP field normal to the continuous through-flow direction. Two twDEP electrode arrays are formed from upper and lower walls of the microchannel and extend to its center, which induce twDEP forces to provide the lateral displacements in two directions for focusing the bioparticles. Bioparticles can be focused to the center of the microchannel effectively by twDEP conveyance when the characteristic time due to twDEP conveying in the y direction is shorter than the residence time of the particles within twDEP electrode array. Red blood cells can be effectively focused into a narrow particle stream (~10 μm) below a critical flow rate of 10 μl/min (linear flow velocity ~5 mm/s), when under a voltage of 14 V_p–p at a frequency of 500 kHz is applied. Approximately 90% focusing efficiency for red blood cells can be achieved within two 6-mm-long electrode arrays when the flow rate is below 12 μl/min. Blood cells and Candida cells were also focused and sorted successfully based on their different twDEP mobilities. Compared to conventional 3D-paired DEP focusing, velocity is enhanced nearly four folds of magnitude. 3D twDEP provides the lateral displacements of particles and long residence time for migrating particles in a high-speed continuous flow, which breaks through the limitation of many electrokinetic cell manipulation techniques.     

Quantitative analysis of sperm rheotaxis using a microfluidic device

Quite puzzling issue in biology is how sperm cells are selected naturally where human sperm has to maintain a correct swimming behavior during the various stages of reproduction process. In nature, sperm has to compete a long journey from cervix to oocyte to stand a chance for fertilization. Although various guidance mechanisms such as chemical and thermal gradients are proposed previously, these mechanisms may only be relevant as sperm reaches very close to the oocyte. Rheotaxis, a phenomenon where sperm cells swim against the flow direction, is possibly the long-range sperm guidance mechanism for successful fertilization. A little is known quantitatively about how flow shear effects may help guide human sperm cells over long distances. Here, we have developed microfluidic devices to quantitatively investigate sperm rheotaxis at various physiological flow conditions. We observed that at certain flow rates sperm actively orient and swim against the flow. Sperm that exhibit positive rheotaxis show better motility and velocity than the control (no-flow condition), however, rheotaxis does not select sperm based on hyaluronic acid (HA) binding potential and morphology. Morphology and HA binding potential may not be a significant factor in sperm transport in natural sperm selection.     

Development of a biological detection platform utilizing a modular microfluidic stack

The goal of this project is to build a miniaturized, user-friendly cytometry setup (Datta et al. in Microfluidic platform for education and research. COMS, Baton Rouge, 2008; Frische et al. in Development of an miniaturized flow cytometry setup for visual cell inspection and sorting. Baton Rouge, Project Report, 2008) by combining a customized, microfluidic device with visual microscope inspection to detect and extract specific cells from a continuous sample flow. We developed a cytological tool, based on the Coulter particle counter principle, using a microelectrode array patterned on a borosilicate glass chip as electrical detection set-up which is fully embedded into a polymeric multi-layer microfluidic stack. The detection takes place between pairs of coplanar Cr/Au microelectrodes by sensing an impedance change caused by particles continuously carried within a microfluidic channel across the detection area under laminar flow conditions. A wide frequency range available for counting provides information on cell size, membrane capacitance, cytoplasm conductivity and is potentially of interest for in-depth cell diagnostic e.g. to detect damaged or cancerous cells and select them for extraction and further in-depth analysis.     

Physical stimulation of mammalian cells using micro-bead impact within a microfluidic environment to enhance growth rate

Various cell stimulation experiments have been traditionally conducted regarding observation of cells to specific stimulative factors, and in light of this area of study, we report a new method by utilizing micro-beads. HeLa cells and MC3T3 cells are cultured in straight PDMS (polydimethylsiloxane) microfluidic devices and are stimulated by sterilized polystyrene micro-beads. Cell culture medium either with or without micro-beads are introduced in microfluidic cell culturing chambers at a specific time interval, and stimulated cells are observed using an inverted microscope. The results show that cells exposed under micro-bead stimulation perform at a higher growth rate than those under normal conditions. This paper demonstrates that micro-beads can be used as a physical stimulation factor and affect cell growth behaviors.     

Three-dimensional and analytical modeling of microfluidic particle transport in magnetic fluids

We present an analytical model that can predict the three-dimensional (3D) transport of non-magnetic particles in magnetic fluids inside a microfluidic channel coupled with permanent magnets. The magnets produce a spatially non-uniform magnetic field that gives rise to a magnetic buoyancy force on the particles. Resulting 3D trajectories of the particles are obtained by (1) calculating the 3D magnetic buoyancy force exerted on the particles via an analytical distribution of magnetic fields as well as their gradients, together with a nonlinear magnetization model of the magnetic fluids, (2) deriving the 3D hydrodynamic viscous drag force on the particles with an analytical velocity profile of a low Reynolds number ferrohydrodynamic flow in the channel including “wall effect” and magnetoviscous effect of the magnetic fluids, and (3) constituting and solving the governing equations of motion for the particles using the analytical expressions of magnetic buoyancy force and hydrodynamic viscous drag force. We use such a model to study the particles’ trajectories in the channel and investigate the magnitude of their deflections at different flow rates, with different properties of magnetic fluids and different geometrical parameters of the system.