Three-dimensional analysis and enhancement of continuous magnetic separation of particles in microfluidics

In continuous magnetic separation process, particles can be deflected and separated from the direction of laminar flow by means of magnetic force depending on their magnetic susceptibility and size as well as the flow rate. To analyze and control dynamic behavior of these particles flowing in microchannels, a three-dimensional numerical model was proposed and solved for obtaining the particle trajectories under the action of a gradient magnetic field and flow field. The magnetic force distribution and particle trajectories obtained were firstly verified by analytical and experimental results. Then, a detailed analysis for the enhancement of the continuous magnetic separation efficiency by optimizing the flow parameters and microchannel configurations was carried out. The results show that the separation efficiency can be greatly improved by controlling the flow rate ratio of the two fluid streams and introducing a broadened segment in the T-shaped microchannel. And it has been demonstrated to be effective through the sorting of 2-μm and 5-μm non-magnetic particles suspended in a dilute ferrofluid by a permanent magnet. The results reported could be encouraging for the design and optimization of efficient microfluidic separation systems.     

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.     

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.     

On-chip manipulation of nonmagnetic particles in paramagnetic solutions using embedded permanent magnets

This study develops a method for embedding permanent magnets into poly(dimethylsiloxane) (PDMS)-based microfluidic chips. Magnets can be brought very close to the planar microchannels for enhanced magnetic field and field gradients, which enables on-chip continuous-flow manipulation of nonmagnetic particles in typical paramagnetic solutions. We performed a systematic study of the transport of polystyrene particles suspended in manganese (II) chloride (MnCl₂) solutions through a rectangular microchannel. Owing to their smaller magnetization than the suspending fluid, particles experience negative magnetophoresis and are deflected away from the magnet. The effects of particle position (relative to the magnet), particle size, MnCl₂ salt concentration, and fluid flow velocity on the horizontal magnetophoretic deflection are examined using a combined experimental and theoretical approach. The experimental results agree quantitatively with the predictions of an analytical model. The demonstrated nonmagnetic particle deflection may be used with the potential to focus and sort cells in lab-on-a-chip for bio-applications.     

Focusing microparticles in a microfluidic channel with ferrofluids

We report a novel on-chip microparticles focusing technique using stable magnetic nanoparticles suspension (i.e., ferrofluids). The principle of focusing is based on magnetic buoyancy forces exerted on non-magnetic particles within ferrofluids under non-uniform magnetic field. The design, modeling, fabrication, and characterization of the focusing scheme are presented. Focusing of 4.8, 5.8, and 7.3 ??m microparticles at various flow rates are demonstrated in a microfluidic channel. Our scheme is simple, low-cost, and label-free compared to other existing techniques.     

Diamagnetic particle focusing using ferromicrofluidics with a single magnet

Focusing particles into a tight stream is critical to many applications such as microfluidic flow cytometry and particle sorting. Current magnetic field-induced particle focusing techniques rely on the use of a pair of repulsive magnets, which makes the device integration and operation difficult. We develop herein a new approach to focusing nonmagnetic particles in ferrofluid flow through a T-microchannel using a single permanent magnet. Particles are deflected across the suspending ferrofluid by negative magnetophoresis and confined by a water flow to the center plane of the microchannel, leading to a focused particle stream flowing near the bottom channel wall. Such three-dimensional diamagnetic particle focusing is demonstrated in a sufficiently diluted ferrofluid through both the top and side views of the microchannel. As the suspended particles can be visualized in bright field, this magnetic focusing method is expected to find applications to label-free (i.e., no magnetic or fluorescent labeling) cellular focusing in lab-on-a-chip devices.     

Magnetic concentration of particles and cells in ferrofluid flow through a straight microchannel using attracting magnets

Concentrating particles to a detectable level is often necessary in many applications. Although magnetic force has long been used to enrich magnetic (or magnetically tagged) particles in suspensions, magnetic concentration of diamagnetic particles is relatively new and little reported. We demonstrate in this work a simple magnetic technique to concentrate polystyrene particles and live yeast cells in ferrofluid flow through a straight rectangular microchannel using negative magnetophoresis. The magnetic field gradient is created by two attracting permanent magnets that are placed on the top and bottom of the planar microfluidic device and held in position by their natural attractive force. The magnet–magnet distance is mainly controlled by the thickness of the device substrate and can be made small, allowing for the use of a dilute ferrofluid in the developed magnetic concentration technique. This advantage not only enables a magnetic/fluorescent label-free handling of diamagnetic particles, but also renders such handling biocompatible.     

Controlled counter-flow motion of magnetic bead chains rolling along microchannels

We demonstrate controlled transport of superparamagnetic beads in the opposite direction of a laminar flow. A permanent magnet assembles 200 nm magnetic particles into about 200 μm long bead chains that are aligned in parallel to the magnetic field lines. Due to a magnetic field gradient, the bead chains are attracted towards the wall of a microfluidic channel. A rotation of the permanent magnet results in a rotation of the bead chains in the opposite direction to the magnet. Due to friction on the surface, the bead chains roll along the channel wall, even in counter-flow direction, up to at a maximum counter-flow velocity of 8 mm s⁻¹. Based on this approach, magnetic beads can be accurately manoeuvred within microfluidic channels. This counter-flow motion can be efficiently be used in Lab-on-a-Chip systems, e.g. for implementing washing steps in DNA purification.     

Rotationally controlled magneto-hydrodynamic particle handling for bead-based microfluidic assays

This work presents a novel magnetic actuation scheme for advanced particle handling on our previously introduced, centrifugal microfluidic platform for array-based analysis of individual cells and beads. The conceptually simple actuation is based on the reciprocating motion of an elastomeric membrane featuring an integrated permanent magnet and a stationary magnet aligned along the orbit of a disc-based chamber. This compression chamber is placed at the downstream end of the particle capture chamber to induce centripetally directed, hydrodynamic lift forces on particles trapped in V-shaped geometrical barriers. Towards high frequencies of rotation, the on-disc magnet ceases to follow the rapidly oscillating magnetic field, so that the magnetic actuator is disabled during the initial, sedimentation-based filling of the trap array. At reduced spin speeds, the residence time of the magnetic actuator is sufficient to displace the magnetic actuator, resulting in a flow through the V-cup array that re-distributes, and eventually fully depletes, the previously trapped beads from the array. The same magnetic deflection scheme is also demonstrated to accelerate mixing, e.g. for upstream sample preparation.     

Microfluidic separation of magnetic particles with soft magnetic microstructures

This paper demonstrates simple and cost-effective microfluidic devices for enhanced separation of magnetic particles by using soft magnetic microstructures. By injecting a mixture of iron powder and polydimethylsiloxane (PDMS) into a prefabricated channel, an iron–PDMS microstructure was fabricated next to a microfluidic channel. Placed between two external permanent magnets, the magnetized iron–PDMS microstructure induces localized and strong forces on the magnetic particles in the direction perpendicular to the fluid flow. Due to the small distance between the microstructure and the fluid channel, the localized large magnetic field gradients result a vertical force on the magnetic particles, leading to enhanced separation of the particles. Numerical simulations were developed to compute the particle trajectories and agreed well with experimental data. Systematic experiments and numerical simulation were conducted to study the effect of relevant factors on the transport of superparamagnetic particles, including the shape of iron–PDMS microstructure, mass ratio of iron–PDMS composite, width of the microfluidic channel, and average flow velocity.     

Size-selective separation of magnetic nanospheres in a microfluidic channel

This paper reported an efficient method to size-selective separate magnetic nanospheres using a self-focusing microfluidic channel equipped with a permanent magnet. Under external magnetic field, the magnetophoresis force exerted on particles leads to size-dependent deflections from their laminar flow paths and results in effective particles separation. By adjusting the distance between magnet and main path of channel, we obtained two monodisperse nanosphere samples (Ca. 90 nm, Ca. 160 nm) from polydispersing particles solution whose diameters varied from 40 to 280 nm. Based on the magnetostatic and laminar flow models, numerical simulations were also used to predict and optimize the nanospheres migrations. Two thresholds of particles diameters were obtained by the simulations and diverse at each position of magnet. Therefore, appropriate position of the magnet could be determined at a certain particle sizes’ range when the flow rate of the two inlets remains unchanged.     

磁塞式油液磨粒在线收集器的结构设计及数值模拟

油液中的磁性颗粒不仅受到传感器探头中永磁体的吸附力,而且还会受到流动油液对其产生的作用力,对油液流场和磁场中的颗粒进行了受力分析,采用有限元数值计算软件ANSYS和Ansoft Maxwell分别对流场和磁场进行了数值仿真,得到了流场中颗粒受力分布及永磁体结构参数对吸附力的影响规律,反映了空心永磁环空间磁场的变化规律,为以后优化设计提供了理论依据。     

A novel type of a microfluidic system using ferrofluids for an application of μ-TAS

This paper shows the novel type of microfluidic system for the purpose of applications to delivery systems, which is the core device of -TAS (micro Total Analysis System) in medicine and biology. The proposed microfluidic control device in this work has been designed for precisely actuating and fast sampling in submicroliter range. Also, the biological liquids have not been contaminated since they have been isolated from the ferrofluids. The magnetic dipoles in ferrofluids line up with the applied field due to the permanent magnet with surface gauss 3400. The maximum net pressure by ferrofluid flows in the rounded microchannel was more than 2 kPa. The device was fabricated by MEMS technology with silicon wafer. The stepping motor with 20 steps was used for the control of delivering the liquids. One step makes the permanent magnet move 18° in the circumferential direction and the liquids can be sampled in nanoliter level. This study presents a significant point that a microfluidic delivery system for sampling biological liquids with high pressure in a microchannels can be integrated in -TAS.This work was supported by the Korea Research Fundation Grant (KRF-2002–005-D00003).     

3D-printed microfluidic manipulation device integrated with magnetic array

This paper reported a transparent, high-precision 3D-printed microfluidic device integrated with magnet array for magnetic manipulation. A reserved groove in the device can well constrain the Halbach array or conventional alternating array. Numerical simulations and experimental data indicate that the magnetic flux density ranges from 30 to 400 mT and its gradient is about 0.2–0.4 T/m in the manipulation channel. The magnetic field parameters of Halbach array in the same location are better than the other array. Diamagnetic polystyrene beads experience a repulsive force and move away from the magnetic field source under the effect of negative magnetophoresis. It is undeniable that as the flow rate increases, the ability of Halbach array to screen particle sizes decreases. Even so, it has a good particle size discrimination at a volumetric flow rate of 1.08 mL/h, which is much larger than that of a conventional PDMS device with a single magnet. The observed particle trajectories also confirm these statements. The deflection angle is related to the magnetic field, flow rate, and particle size. This 3D-printed device integrated with Halbach array offers excellent magnetic manipulation performance.     

A ferrofluidic magnetic micropump

A microfluidic pump is described that uses magnetic actuation to push fluid through a microchannel. Operation relies on the use of magnetically-actuated plugs of ferrofluid, a suspension of nanosize ferromagnetic particles. The ferrofluid contacts but is immiscible with the pumped fluid. The prototype circular design demonstrates continuous pumping by regenerating a translating ferrofluidic plug at the conclusion of each pumping cycle. The flow rate can be controlled by adjusting device dimensions or the velocity of an external permanent magnet that directs the motion of the ferrofluid. The ferrofluidic plugs also serve as valves; if the magnetic actuator is stopped, pressure can be maintained with no power consumption. Flow can also be reversed by switching the direction of actuation. The maximum flow rate achieved with minimal backpressure was 45.8 μl/min. The maximum pressure head achieved was 135 mm water (1.2 kPa)     

Particle flow control by induced dipolar interaction of superparamagnetic microbeads

Magnetic particles diluted in liquid agglomerate in rod-like particle arrays if an external homogeneous magnetic field is applied. This work introduces a method to specifically exploit particle–particle interaction to obtain flow control of magnetic particles without changing the motion state of the carrier liquid. Experiments show the possibility to uncouple the particle flux from the motion state of liquid. We show how this method may be applied to design a microfluidic geometry in which the particle flow in a specific direction is either enabled or suppressed by the relative orientation of the fluid velocity and the external field.     

Experimental characterization of electrical current leakage in poly(dimethylsiloxane) microfluidic devices

Poly(dimethylsiloxane) (PDMS) is usually considered as a dielectric material and the PDMS microchannel wall can be treated as an electrically insulated boundary in an applied electric field. However, in certain layouts of microfluidic networks, electrical leakage through the PDMS microfluidic channel walls may not be negligible, which must be carefully considered in the microfluidic circuit design. In this paper, we report on the experimental characterization of the electrical leakage current through PDMS microfluidic channel walls of different configurations. Our numerical and experimental studies indicate that for tens of microns thick PDMS channel walls, electrical leakage through the PDMS wall could significantly alter the electrical field in the main channel. We further show that we can use the electrical leakage through the PDMS microfluidic channel wall to control the electrolyte flow inside the microfluidic channel and manipulate the particle motion inside the microfluidic channel. More specifically, we can trap individual particles at different locations inside the microfluidic channel by balancing the electroosmotic flow and the electrophoretic migration of the particle.     

Cell separation in a microfluidic channel using magnetic microspheres

Magnetophoretic isolation of biological cells in a microfluidic environment has strong relevance in biomedicine and biotechnology. A numerical analysis of magnetophoretic cell separation using magnetic microspheres in a straight and a T-shaped microfluidic channel under the influence of a line dipole is presented. The effect of coupled particle–fluid interactions on the fluid flow and particle trajectories are investigated under different particle loading and dipole strengths. Microchannel flow and particle trajectories are simulated for different values of dipole strength and position, particle diameter and magnetic susceptibility, fluid viscosity and flow velocity in both the microchannel configurations. Residence times of the captured particles within the channel are also computed. The capture efficiency is found to be a function of two nondimensional parameters, α and β. The first parameter denotes the ratio of magnetic to viscous forces, while the second one represents the ratio of channel height to the distance of the dipole from the channel wall. Two additional nondimensional parameters γ (representing the inverse of normalized offset distance of the dipole from the line of symmetry) and σ (representing the inverse of normalized width of the outlet limbs) are found to influence the capture efficiency in the T-channel. Results of this investigation can be applied for the selection of a wide range of operating and design parameters for practical microfluidic cell separators.     

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.