Analytical model of microfluidic transport of non-magnetic particles in ferrofluids under the influence of a permanent magnet

This study describes an analytical model and experimental verifications of transport of non-magnetic spherical microparticles in ferrofluids in a microfluidic system that consists of a microchannel and a permanent magnet. The permanent magnet produces a spatially non-uniform magnetic field that gives rise to a magnetic buoyancy force on particles within ferrofluid-filled microchannel. We obtained trajectories of particles in the microchannel by (1) calculating magnetic buoyancy force through the use of an analytical expression of magnetic field distributions and a nonlinear magnetization model of ferrofluids, (2) deriving governing equations of motion for particles through the use of analytical expressions of dominant magnetic buoyancy and hydrodynamic viscous drag forces, (3) solving equations of motion for particles in laminar flow conditions. We studied effects of particle size and flow rate in the microchannel on the trajectories of particles. The analysis indicated that particles were increasingly deflected in the direction that was perpendicular to the flow when size of particles increased, or when flow rate in the microchannel decreased. We also studied ??wall effect?? on the trajectories of particles in the microchannel when surfaces of particles were in contact with channel wall. Experimentally obtained trajectories of particles were used to confirm the validity of our analytical results. We believe this study forms the theoretical foundation for size-based particle (both synthetic and biological) separation in ferrofluids in a microfluidic device. The simplicity and versatility of our analytical model make it useful for quick optimizations of future separation devices as the model takes into account important design parameters including particle size, property of ferrofluids, magnetic field distribution, dimension of microchannel, and fluid flow rate.     

Stepwise gray-scale light-induced electric field gradient for passive and continuous separation of microparticles

This article presents a gray-scale light-induced dielectrophoresis (GS-LIDEP) method that induces the lateral displacements normal to the through-flow for continuous and passive separation of microparticles. In general, DEP force only can affect the particles within very local areas due to the electric field is exponentially decayed by the distance away from the electrodes. Unlike with conventional LIDEP, a broad-ranged electrical field gradient can easily be created by GS pattern illumination, which induces DEP forces with two directions for continuous separation of particles to their specific sub-channels. Candia albicans were effectively guided to the specific outlet with the efficiency of 90% to increase the concentration of the sample below the flow rate of 0.6?μl/min. 2 and 10?μm polystyrene particles can also be passively and well separated using the multi-step GS pattern through positive and negative DEP forces, respectively, under an applied voltage of 36?V_p–p at the frequency of 10?kHz. GS-LIDEP generated a wide-ranged DEP force that is capable of working on the entire area of the microchannel, and thus the mix of particles can be passively and continuously separated toward the opposite directions by the both positive and negative GS-LIDEP forces. This simple, low cost, and flexible separation/manipulation platform could be very promising for many applications, such as in-field detections/pretreatments.     

Inertially focused diamagnetic particle separation in ferrofluids

Continuous flow separation of target particles from a mixture is essential to many chemical and biomedical applications. There has recently been an increasing interest in the integration of active and passive particle separation techniques for enhanced sensitivity and flexibility. We demonstrate herein the proof-of-concept of a ferrofluid-based hybrid microfluidic technique that combines passive inertial focusing with active magnetic deflection to separate diamagnetic particles by size. The two operations take place in series in a continuous flow through a straight rectangular microchannel with a nearby permanent magnet. We also develop a three-dimensional numerical model to simulate the transport of diamagnetic particles during their inertial focusing and magnetic separation processes in the entire microchannel. The predicted particle trajectories are found to be approximately consistent with the experimental observations at different ferrofluid flow rates and ferrofluid concentrations.     

Improved concentration and separation of particles in a 3D dielectrophoretic chip integrating focusing, aligning and trapping

This article presents a dielectrophoresis (DEP)-based microfluidic device with the three-dimensional (3D) microelectrode configuration for concentrating and separating particles in a continuous throughflow. The 3D electrode structure, where microelectrode array are patterned on both the top and bottom surfaces of the microchannel, is composed of three units: focusing, aligning and trapping. As particles flowing through the microfluidic channel, they are firstly focused and aligned by the funnel-shaped and parallel electrode array, respectively, before being captured at the trapping unit due to negative DEP force. For a mixture of two particle populations of different sizes or dielectric properties, with a careful selection of suspending medium and applied field, the population exhibits stronger negative DEP manipulated by the microelectrode array and, therefore, separated from the other population which is easily carried away toward the outlet due to hydrodynamic force. The functionality of the proposed microdevice was verified by concentrating different-sized polystyrene (PS) microparticles and yeast cells dynamically flowing in the microchannel. Moreover, separation based on size and dielectric properties was achieved by sorting PS microparticles, and isolating 5 μm PS particles from yeast cells, respectively. The performance of the proposed micro-concentrator and separator was also studied, including the threshold voltage at which particles begin to be trapped, variation of cell-trapping efficiency with respect to the applied voltage and flow rate, and the efficiency of separation experiments. The proposed microdevice has various advantages, including multi-functionality, improved manipulation efficiency and throughput, easy fabrication and operation, etc., which shows a great potential for biological, chemical and medical applications.     

Magnetic particle dosing and size separation in a microfluidic channel

Separation of functional magnetic particles or magnetically labeled entities is a key feature for bioanalytical or biomedical applications and therefore also an important component of lab-on-a-chip devices for biological applications. We present a novel integrated microfluidic magnetic bead manipulation device, comprising dosing of magnetic particles, controlled release and subsequent magnetophoretic size separation with high resolution. The system is designed to meet the requirements of specific bioassays, in particular of on-chip agglutination assays for the detection of rare analytes by particle coupling as doublets. Integrated soft-magnetic microtips with different shapes provide the magnetic driving force of the bead manipulation protocol. The magnetic tips that serve as field concentrators of an external electromagnetic field, are positioned in close contact to a microfluidic channel in order to generate high magnetic actuation forces. Mixtures of 1.0 μm and 2.8 μm superparamagnetic beads have been used to characterize the system. Magnetophoretic size separation with high resolution was performed in static conditions and in continuous flow mode. In particular, we could demonstrate the separation of 1.0 μm single beads and doublets in a sample flow.     

Flow rate-insensitive microparticle separation and filtration using a microchannel with arc-shaped groove arrays

Inertial microfluidics can separate microparticles in a continuous and high-throughput manner, and is very promising for a wide range of industrial, biomedical and clinical applications. However, most of the proposed inertial microfluidic devices only work effectively at a limited and narrow flow rate range because the performance of inertial particle focusing and separation is normally very sensitive to the flow rate (Reynolds number). In this work, an innovative particle separation method is proposed and developed by taking advantage of the secondary flow and particle inertial lift force in a straight channel (AR = 0.2) with arc-shaped groove arrays patterned on the channel top surface. Through the simulation results achieved, it can be found that a secondary flow is induced within the cross section of the microchannel and guides different-size particles to the corresponding equilibrium positions. On the other hand, the effects of the particle size, flow rate and particle concentration on particle focusing and separation quality were experimentally investigated. In the experiments, the performance of particle focusing, however, was found relatively insensitive to the variation of flow rate. According to this, a separation of 4.8 and 13 µm particle suspensions was designed and successfully achieved in the proposed microchannel, and the results show that a qualified particle separation can be achieved at a wide range of flow rate. This flow rate-insensitive microfluidic separation (filtration) method is able to potentially serve as a reliable biosample preparation processing step for downstream bioassays.     

Dean flow focusing and separation of small microspheres within a narrow size range

Rapid, selective particle separation and concentration within the bacterial size range (1–3 μm) in clinical or environmental samples promises significant improvements in detection of pathogenic microorganisms in areas including diagnostics and bio-defence. It has been proposed that microfluidic Dean flow-based separation might offer simple, efficient sample clean-up: separation of larger, bioassay contaminants to prepare bioassay targets including spores, viruses and proteins. However, reports are limited to focusing spherical particles with diameters of 5 μm or above. To evaluate Dean flow separation for (1–3 μm) range samples, we employ a 20 μm width and depth, spiral microchannel. We demonstrate focusing, separation and concentration of particles with closely spaced diameters of 2.1 and 3.2 μm, significantly smaller than previously reported as separated in Dean flow devices. The smallest target, represented by 1.0 μm particles, is not focused due to the high pressures associated with focussing particles of this size; however, it is cleaned of 93 % of 3.2 μm and 87 % of 2.1 μm microparticles. Concentration increases approaching 3.5 times, close to the maximum, were obtained for 3.2 μm particles at a flow rate of 10 μl min^?1. Increasing concentration degraded separation, commencing at significantly lower concentrations than previously predicted, particularly for particles on the limit of being focused. It was demonstrated that flow separation specificity can be fine-tuned by adjustment of output pressure differentials, improving separation of closely spaced particle sizes. We conclude that Dean flow separation techniques can be effectively applied to sample clean-up within this significant microorganism size range.     

A dielectrophoretic barrier-based microsystem for separation of microparticles

This paper presents a microfluidic system for separation of microparticles based on the use of dielectrophoretic barriers, which are constructed by aligning two layers of microelectrode structure face-to-face on the top and bottom sides of the microchannel. The energized barriers tend to prevent the particles in the flow from passing through. However, particles may penetrate the barriers if a sufficiently high flow rate is used. The flow velocity at which the particles begin to penetrate the barrier is defined as threshold velocity. Different particles are of different threshold velocities so that they can be separated. In this paper, the electrodes are configured with open ends and aligned with a certain angle to the direction of the flow. Polystyrene microbeads of different sizes (i.e., 9.6 and 16 μm in diameter) are studied in the tests. Under the experimental conditions, two particle trajectories are observed: the 9.6 μm beads penetrate the barriers and move straightly toward the fluidic outlet, while the 16 μm beads snake their way along the electrode edges at a relatively low speed. The two subpopulations of particles are separated into spatial distance of ∼10 mm within tens of seconds. The system presents a rapid and dynamic separation process within a continuous flow.     

Continuous-flow particle and cell separations in a serpentine microchannel via curvature-induced dielectrophoresis

Particle and cell separations are critical to chemical and biomedical analyses. This study demonstrates a continuous-flow electrokinetic separation of particles and cells in a serpentine microchannel through curvature-induced dielectrophoresis. The separation arises from the particle size-dependent cross-stream dielectrophoretic deflection that is generated by the inherent electric field gradients within channel turns. Through the use of a sheath flow to focus the particle mixture, we implement a continuous separation of 1 and 5 μm polystyrene particles in a serpentine microchannel under a 15 kV/m DC electric field. The effects of the applied DC voltages and the serpentine length on the separation performance are examined. The same channel is also demonstrated to separate yeast cells (range in diameter between 4 and 8 μm) from 3 μm particles under an electric field as low as 10 kV/m. The observed focusing and separation processes for particles and cells in the serpentine microchannel are reasonably predicted by a numerical model.     

Enhancement of separation efficiency on continuous magnetophoresis by utilizing L/T-shaped microchannels

In this article a novel design of on-chip continuous magnetophoretic separator was proposed by utilizing the magnetic field and L-turning/T-junction effect of the flow field for high throughput applications. The motion of the magnetic bead was simulated based on Lagrangian tracking method and the separation efficiency was calculated according to the trajectories. Impact parameters including geometrical configuration, fluid velocity, magnetic flux density, magnetic bead size, and temperature on separation efficiency were discussed. The results show that both the L- and T-microchannel separators have higher separation efficiency as compared with the conventional straight-microchannel separator because of the L-turning/T-junction effect of the flow field. The separation efficiencies for L- and T-microchannel separators are 63.4 and 100%, respectively, while it is only 43.7% for straight-microchannel separator at the same conditions. Above a critical flow rate the separation efficiency drops drastically from nearly 100% to zero while this decrease is much slower for T-shaped configurations. The separation efficiency increases initially with the increase of the external magnetic flux density and keeps nearly constant at high magnetic flux density owing to saturated magnetization of the beads. It is also found that both the magnetic bead diameter and fluid temperature have great effect on the separation efficiency. The L/T-microchannel separators presented in this article are simple and efficient for magnetophoretic separation at high flow rates and thus useful for the high-efficiency on-chip enrichment of analytes with very low concentrations.     

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.     

Precisely sized separation of multiple particles based on the dielectrophoresis gradient in the z-direction

We present a new 3D dielectrophoresis-field-flow fraction (DEP-FFF) concept to achieve precise separation of multiple particles by using AC DEP force gradient in the z-direction. The interlaced electrode array was placed at the upstream of the microchannel, which not only focused the particles into a single particle stream to be at the same starting position for further separation, but also increased the spacing between each particle by the retard effect to reduce particle–particle aggregation. An inclined electrode was also designed in back of the focusing component to continuously and precisely separate different sizes of microparticles. Different magnitudes of DEP force are induced at different positions in the z-direction of the DEP gate, which causes different penetration times and positions of particles along the inclined DEP gate. 2, 3, 4, and 6?μm polystyrene beads were precisely sized fractionation to be four particle streams based on their different threshold DEP velocities that were induced by the field gradient in the z-direction when a voltage of 6.5?V_p–p was applied at a flow rate of 0.6?μl/min. Finally, Candida albicans were also sized separated to be three populations for demonstrating the feasibility of this platform in biological applications. The results showed that a high resolution sized fractionation (only 25% size difference) of multiple particles can be achieved in this DEP-based microfluidic device by applying a single AC electrical signal.     

Multiplex Inertio-Magnetic Fractionation (MIMF) of magnetic and non-magnetic microparticles in a microfluidic device

Separation of multiple microparticles at high throughput is highly required in different applications such as diagnostics and immunomagnetic detection. We present a microfluidic device for multiplex (i.e., duplex to fourplex) fractionation of magnetic and non-magnetic microparticles using a novel hybrid technique based on interactions between flow-induced inertial forces and countering magnetic forces in a simple expansion microchannel with a side permanent magnet. Separation of more than two types of particles solely by inertia or magnetic forces in a straight microchannel is challenging due to the inherent limitations of each technique. By combining inertial and magnetic forces in a straight microchannel and addition of a downstream expansion hydrodynamic separator, we overcame these limitations and achieved duplex to fourplex fractionation of magnetic and non-magnetic microparticles with high throughput and efficiency. Particle fractionation performance in our device was first optimized with respect to parameters such as flow rate and aspect ratio of the channel to attain coexistence of inertial and magnetic focusing of particles. Using this scheme, we achieved duplex fractionation of particles at high throughput of 10⁹ particles per hour. Further, we conducted experiments with three magnetic particles (5, 11 and 35 µm) to establish their size-dependent ordering in the device under combined effects of magnetic and inertial forces. We then used the findings for fourplex fractionation of 5, 11 and 35 µm magnetic particles from non-magnetic particles of various sizes (10–19 µm). This Multiplex Inertio-Magnetic Fractionation (MIMF) technique offers a simple tool to handle complex and heterogeneous samples and can be used for affinity-based immunomagnetic separation of multiple biological substances in fluidic specimens in the future.     

集成惯性聚焦结构的介电泳微流控芯片的粒子连续分离

设计并制造了一种带有惯性聚焦结构的介电泳微流控芯片,以实现不同介电性质的粒子连续分离.采用MEMS工艺制作了介电泳微流控芯片:通道入口侧壁设置一对梯形结构使经过的粒子受惯性升力的作用聚焦到通道两侧;通道底部光刻一组夹角为90°的倾斜叉指电极产生非均匀电场,利用介电泳力和流体曳力的合力使通道两侧不同的粒子发生角度不同的偏转进入不同通道,从而实现分离.将酵母菌细胞和聚苯乙烯小球作为实验样本,分析了流速和交流电压对分离的影响,确定了二者分离的最优条件并进行分离.实验结果表明,将电导率为20μS/cm的样本溶液以5μL/min的流速注入到通道中,施加6 Vp-p、10 kHz的正弦信号,酵母菌细胞沿电极运动至夹角处后沿通道中心排出,聚苯乙烯小球沿通道两侧排出,成功实现分离,平均分离效率达92.8％、平均分离纯度达90.7％.     

Particle streaming and separation using dielectrophoresis through discrete periodic microelectrode array

This study presents a particle manipulation and separation technique based on dielectrophoresis principle by employing an array of isosceles triangular microelectrodes on the bottom plate and a continuous electrode on the top plate. These electrodes generate non-uniform electric fields transversely across the microchannel. The particles within the flowing fluid experience a dielectrophoretic force perpendicular to the fluid flow direction due to the non-uniform electric fields. The isosceles triangular microelectrodes were designed to continuously exert a small dielectrophoretic force on the particles. Particles experiencing a larger dielectrophoretic force would move further in the perpendicular direction to the fluid flow as they traveled past each microelectrode. Polystyrene microspheres were used as the model particles, with particles of ∅20 μm employed for studying the basic characteristics of this technique. Particle separation was subsequently demonstrated on ∅10 and ∅15 μm microspheres. Using an applied sinusoidal voltage of 20 V_pp and frequency of 1 MHz, a mean separation distance of 0.765 mm between them was achieved at a flow rate of 3 μl/min (~1 mm/s), an important consideration for high throughput separation capability in a micro-scale technology device. This unique isosceles triangular microelectrodes design allows heterogeneous particle populations to be separated into multiple streams in a single continuous operation.     

Particle focusing in a contactless dielectrophoretic microfluidic chip with insulating structures

The focusing of biological and synthetic particles in microfluidic devices is a crucial step for the construction of many microstructured materials as well as for medical applications. The present study examines the feasibility of using contactless dielectrophoresis (cDEP) in an insulator-based dielectrophoretic (iDEP) microdevice to effectively focus particles. Particles 10?μm in diameter were introduced into the microchannel and pre-confined hydrodynamically by funnel-shaped insulating structures near the inlet. The particles were repelled toward the center of the microchannel by the negative DEP forces generated by the insulating structures. The microchip was fabricated based on the concept of cDEP. The electric field in the main microchannel was generated using electrodes inserted into two conductive micro-reservoirs, which were separated from the main microchannel by 20-μm-thick insulating barriers made of polydimethylsiloxane (PDMS). The impedance spectrum of the thin insulating PDMS barrier was measured to investigate its capacitive behavior. Experiments employing polystyrene particles were conducted to demonstrate the feasibility of the proposed microdevice. Results show that the particle focusing performance increased with increasing frequency of the applied AC voltage due to the reduced impedance of PDMS barriers at high frequencies. When the frequency was above 800?kHz, most particles were focused into a single file. The smallest width of focused particles distributed at the outlet was about 13.1?μm at a frequency of 1?MHz. Experimental results also show that the particle focusing performance improved with increasing applied electric field strength and decreasing inlet flow rate. The usage of the cDEP technique makes the proposed microchip mechanically robust and chemically inert.     

Continuous size-based focusing and bifurcating microparticle streams using a negative dielectrophoretic system

Dielectrophoresis (DEP) is an electrokinetic phenomenon which is used for manipulating micro- and nanoparticles in micron-sized devices with high sensitivity. In recent years, electrode-based DEP by patterning narrow oblique electrodes in microchannels has been used for particle manipulation. In this theoretic study, a microchannel with triangular electrodes is presented and a detailed comparison with oblique electrodes is made. For each shape, the behavior of particles is compared for three different configurations of applied voltages. Electric field, resultant DEP force, and particle trajectories for configurations are computed by means of Rayan native code. The separation efficiency of the two systems is assessed and compared afterward. The results demonstrate higher lateral DEP force, responsible for particle separation, distributed wider across the channel width for triangular shape electrodes in comparison with the oblique ones. The proposed electrode shape also shows the ability of particle separation by attracting negative DEP particles to or propelling them from the flow centerline, according to the configuration of applied voltages. A major deficiency of the oblique electrodes, which is the streamwise variation of the lateral DEP force direction near the electrodes, is also eliminated in the proposed electrode shape. In addition, with a proper voltages configuration, the triangular electrodes require lower voltages for particle focusing in comparison with the oblique ones.     

Viscosity-difference-induced asymmetric selective focusing for large stroke particle separation

We developed a new approach for particle separation by introducing viscosity difference of the sheath flows to form an asymmetric focusing of sample particle flow. This approach relies on the high-velocity gradient in the asymmetric focusing of the particle flow to generate a lift force, which plays a dominated role in the particle separation. The larger particles migrate away from the original streamline to the side of the higher relative velocity, while the smaller particles remain close to the streamline. Under high-viscosity (glycerol–water solution) and low-viscosity (PBS) sheath flows, a significant large stroke separation between the smaller (1.0 μm) and larger (9.9 μm) particles was achieved in a sample microfluidic device. We demonstrate that the flow rate and the viscosity difference of the sheath flows have an impact on the interval distance of the particle separation that affects the collected purity and on the focusing distribution of the smaller particles that affects the collected concentration. The interval distance of 293 μm (relative to the channel width: 0.281) and the focusing distribution of 112 μm (relative to the channel width: 0.107) were obtained in the 1042-μm-width separation area of the device. This separation method proposed in our work can potentially be applied to biological and medical applications due to the wide interval distance and the narrow focusing distribution of the particle separation, by easy manufacturing in a simple device.     

Magnetofluidic spreading in microchannels

We investigate the spreading phenomena caused by the interaction between a uniform magnetic field and a magnetic fluid in microchannels. The flow system consists of two liquids: a ferrofluid and a mineral oil. The ferrofluid consists of superparamagnetic nanoparticles suspended in an oil-based carrier. Under a uniform magnetic field, the superparamagnetic particles are polarized and represent magnetic dipoles. The magnetization of the magnetic nanoparticles leads to a force resulting in the change of diffusion behavior inside the microchannel. Mixing due to secondary flow close to the interface also contributes to the spreading of the ferrofluid. The magnetic force acting on the liquid/liquid interface is caused by the mismatch of magnetization between the nanoparticles and surrounding liquid in a multiphase flow system. This paper examines the roles of magnetic force in the observed spreading phenomena. The effect of particles on the flow field is also considered. These phenomena would allow simple wireless control of a microfluidic system without changing the flow rates. These phenomena can potentially be used for focusing and sorting in cytometry.     

Development of micro-vibrating flow pumps using MEMS technologies

In the present paper, we propose a micro-vibrating flow pump (micro-VFP), which is a novel micropump. The micro-VFP is constructed using an actively vibrating valve that has a cantilever-like structure fixed on a wall of a microchannel and a slit orifice downstream. The slit orifice is designed to make the flow asymmetric around the vibrating valve and to effectively generate a net flow in one direction. At the same time, the valve works as an actuator to induce liquid flow in the microchannel. Since the valve is made of a flexible material including magnetic particles, it is manipulated by changing the magnetic field from outside the micro-VFP. This design allows external operation of the micro-VFP without any electrical or mechanical connections. In addition, the micro-VFP, which realizes pumping with a chamber free design, is advantageous for implementation in a small space. In order to demonstrate its basic pumping performance, a prototype micro-VFP was fabricated in a microchannel with a cross section of 240?μm?×?500?μm using microelectromechanical systems technologies. The vibration characteristics of the valve were investigated using a high-speed camera. The pump performance at various actuation frequencies in the range of 5 to 25?Hz was evaluated by measuring the hydrostatic head and the flow rate. The proposed micro-VFP design exhibited an increase in performance with the driving frequency and had a maximum shut-off pressure of 3.8?±?0.4?Pa and a maximum flow rate of 0.38?±?0.02?μl/min at 25?Hz. Furthermore, in order to clarify the detailed pumping process, the flow characteristics around the vibrating valve were investigated by analyzing the velocity field based on micron-resolution particle image velocimetry (micro-PIV). The validity of the hydrostatic measurement was confirmed by comparing the volume flow rate with that estimated from micro-PIV data. The present study revealed the basic performance of the developed micro-VFP.