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.     

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.     

High-throughput,single-stream microparticle focusing using a microchannel with asymmetric sharp corners

A new microfluidic device for fast and high-throughput particle focusing is reported. The particle focusing is based on the combination of inertial lift force effect and centrifugal force effect generated in a microchannel with a series of repeated asymmetric sharp corners on one side of the channel wall. The inertial lift force induces two focused particle streams in the microchannel, and the centrifugal force generated at the sharp corner structures tends to drive the particles laterally away from the corner. With the use of a series of repeated asymmetric sharp corner structures, a single and highly focused particle stream was achieved near the straight channel wall at a wide range of flow rate. In comparison with other hydrodynamic particle focusing methods, this method is less sensitive to the flow rate and can work at a higher flow rate (up to 700 μL/min) and Reynolds number (Re = 129.5). With its simple structure and operation, and high throughput, this method can be potentially used in particle focusing processes in a variety of lab-on-a-chip applications.     

Inertial focusing of microparticles in curvilinear microchannels with different curvature angles

Inertial microfluidics has become one of the emerging topics due to potential applications such as particle separation, particle enrichment, rapid detection and diagnosis of circulating tumor cells. To realize its integration to such applications, underlying physics should be well understood. This study focuses on particle dynamics in curvilinear channels with different curvature angles (280°, 230°, and 180°) and different channel heights (90, 75, and 60 µm) where the advantages of hydrodynamic forces were exploited. We presented the cruciality of the three-dimensional particle position with respect to inertial lift forces and Dean drag force by examining the focusing behavior of 20 µm (large), 15 µm (medium) and 10 µm (small) fluorescent polystyrene microparticles for a wide range of flow rates (400–2700 µL/min) and corresponding channel Reynolds numbers. Migration of the particles in lateral direction and their equilibrium positions were investigated in detail. In addition, in the light of our findings, we described two different regions: transition region, where the inner wall becomes the outer wall and vice versa, and the outlet region. The maximum distance between the tight particle stream of 20 and 15 µm particles was obtained in the 90 high channel with curvature angle of 280° at Reynolds number of 144 in the transition region (intersection of the turns), which was the optimum condition/configuration for focusing.     

Inertial microfluidics for continuous particle filtration and extraction

In this paper, we describe a simple passive microfluidic device with rectangular microchannel geometry for continuous particle filtration. The design takes advantage of preferential migration of particles in rectangular microchannels based on shear-induced inertial lift forces. These dominant inertial forces cause particles to move laterally and occupy equilibrium positions along the longer vertical microchannel walls. Using this principle, we demonstrate extraction of 590 nm particles from a mixture of 1.9 μm and 590 nm particles in a straight microfluidic channel with rectangular cross-section. Based on the theoretical analysis and experimental data, we describe conditions required for predicting the onset of particle equilibration in square and rectangular microchannels. The microfluidic channel design has a simple planar structure and can be easily integrated with on-chip microfluidic components for filtration and extraction of wide range of particle sizes. The ability to continuously and differentially equilibrate particles of different size without external forces in microchannels is expected to have numerous applications in filtration, cytometry, and bioseparations.     

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.     

Design of new microchannel to reduce applied voltage for microparticles separation using dielectrophoresis method

This paper presents a new structure of microchannel in order to reduce the applied voltage using dielectrophoresis (DEP). DEP is one of the most popular techniques to separate microparticles which needs an electric field in microfluidic devices. In this study, the AC-DEP sidewall electrodes are used. The novelty of this research is to change the outlet microchannel size which effectively reduces applied voltage. In previous work, in order to separate particles with 3.5 and 4 µm diameters, 4.5 V was needed. In new design, we keep all effective parameters constant and change one of the outlet microchannel size from 50 to 60, 70 and 80 µm. Therefore, in order to separate the microparticles, we need only 3, 2 and 1.3 V, respectively.

     

Quantitative characterization of the focusing process and dynamic behavior of differently sized microparticles in a spiral microchannel

In this paper, a spiral microchannel was fabricated to systematically investigate particle dynamics. The focusing process or migration behavior of different-sized particles in the outlet region was presented. Specifically, for focused microparticles, quantitative characterization and analysis of how particles migrate towards the equilibrium positions with the increase in flow rate (De = 0.31–3.36) were performed. For unfocused microparticles, the particle migration behavior and the particle-free region’s formation process were characterized over a wide range of flow rates (De = 0.31–4.58), and the emergence of double particle-free regions was observed at De ≥ 3.36. These results provide insights into the design and operation of high-throughput particle/cell filtration and separation. Furthermore, using the location markers pre-fabricated along with the microchannel structures, the focusing or migration dynamics of different-sized particles along the spiral microchannel was systematically explored. The particle migration length effects on focusing degree and particle-free region width were analyzed. These analyses may be valuable for the optimization of microchannel structures. In addition, this device was successfully used to efficiently filter rare particles from a large-volume sample and separate particles of two different sizes according to their focusing states.     

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.     

Sedimentation pinched-flow fractionation for size- and density-based particle sorting in microchannels

A simple and efficient device for density-based particle sorting is in high demand for the purification of specific cells, bacterium, or environmental particles for medical, biochemical, and industrial applications. Here we present microfluidic systems to achieve size- and density-based particle separation by adopting the sedimentation effect for a size-based particle sorting technique utilizing microscale hydrodynamics, called ??pinched-flow fractionation (PFF).?? Two schemes are presented: (a) the particle inertia scheme, which utilizes the inertial force of particle movement induced by the momentum change in the curved microchannel, and (b) the device rotation scheme, in which rotation of the microdevice exerts centrifugal force on the flowing particles. In the experiments, we successfully demonstrated continuous sorting of microparticles according to size and density by using these two schemes, and showed that the observed particle movements were in good agreement with the theoretical estimations. The presented schemes could potentially become one of the functional components for integrated bioanalysis systems that can manipulate/separate small amount of precious biological samples.     

Arrays of high aspect ratio magnetic microstructures for large trapping throughput in lab-on-chip systems

Here we report a novel technology to obtain arrays of highly efficient magnetic micro-traps that relies on simple fabrication process. Developed micro-traps consist in chains of iron particles diluted in polydimethylsiloxane (PDMS). We analyzed the microstructure of the composite membrane by X-ray tomography. It revealed the predominance of aligned chain-like agglomerates. Largest traps, with diameter ranging from 4 to 11 µm, are found to be the most efficient. The trap arrays were characterized by a density of 1300 magnetic micro-traps/mm², an average nearest neighbor distance of 21 µm. Implemented in a microfluidic channel operating at a relatively high flow rate of 0.97 µL/s—a flow velocity of 8.3 mm/s—we measured a trapping efficiency of more than 99.7%, with a throughput of up to 7100 trapped beads/min. These performances are competitive with other approaches like hydrodynamic trapping. The strengths of this technology are its simple fabrication and easy handling.     

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.     

A novel microfluidic high-throughput resistive pulse sensing device for cells analysis

Microfluidic impedance-based devices offer a simple method for counting and sizing particles and cells in fields of biomedical research and clinical diagnosis. In this work, we present design, fabrication and operational characteristics of a novel high throughput original MEMS-based Coulter counter. This microfluidic device possesses two sub channels including two pairs of coplanar Au/Cr electrodes in each channels which allows double detection of the particles simultaneously and increases the throughput. The present design provides minimizing the cross talk and obviating the need for hydrodynamic focusing of the sample particles by adjusting Y shape insulation obstacle in direction of flow. Moreover, reducing coincidence events and removing electrode polarization effect were purposed by applying optimum sizes for electrodes considering the ease of fabrication and low costs. The reliability of the novel device was evaluated for polystyrene particles and cancer cells in conductive solutions. Results, which were recorded as relative resistance pulses across four sensing zones, illustrate the capability of the double-channel proposed device in detecting, counting and sizing 10 and 20 µm polystyrene particles. The superiority of present design was proved by relative counting error of below 3 and 11% for the 10 µm and 20 µm particles, respectively and a throughput of hundreds particles per second. Aiming at demonstrating the functionality of the proposed device in the biomedical area, counting of SP2/0 cells was performed. The measured counting outputs for cells in the size range of 5.63–17.6 µm were validated with results of hemocytometer cell counter, with relative error less than 7%.

     

Liquid flow through a diverging microchannel

In this work, experiments and three-dimensional numerical calculations of fluid flow through diverging microchannels were carried out with the aim of bringing out differences between flow in uniform and nonuniform passages. Deionized water was used as the working fluid in the experiments where the effects of mass flow rate (8.33 × 10^?6 to 8.33 × 10^?5 kg/s), microchannel hydraulic diameter (118–177 µm), length (10–30 mm) and divergence angle (4°–16°) on pressure drop were studied. The results are analyzed in detail with the help of numerical data. The pressure drop exhibits a linear dependence on the mass flow rate, whereas it is inversely proportional to the divergence angle and square of the hydraulic diameter. The pressure drop increases anomalously at 16°, suggesting that flow reversal occurs between 12° and 16°, which agrees with the corresponding value at the conventional scale. For the purpose of predicting pressure drop using straight microchannel theory, an equivalent hydraulic diameter was defined. It is observed that the equivalent hydraulic diameter, located at one-third of the diverging microchannel length from the inlet, becomes mostly independent of the mass flow rate, microchannel hydraulic diameter, length and divergence angle. The pressure drop for a diverging microchannel becomes equal to an equivalent hydraulic diameter uniform cross-section microchannel, suggesting that conventional correlations for straight microchannels can also be applied to diverging microchannels. The data presented in this work are of fundamental importance and can help in optimization of diffuser design used for example in valveless micropumps.     

Microcapillary electrophoresis chip with a bypass channel for autonomous compensation of hydrostatic pressure flow

The application of chip-based microcapillary electrophoresis (µCE) to determine the electrophoretic mobility of molecules and particles has been intensively studied in the last two decades. Balancing the hydrostatic pressure between both ends of the microchannel is essential for free-zone electrophoresis and highly accurate measurement. This balancing operation appears simple on a macroscale (e.g., >?10^?3 m); however, on a microscale (e.g., 10^?6–10^?3 m), it is not straightforward because of the complexity of the interface dynamics at the meniscus. The hydrostatic pressure flow is unstable because of the small size of the microchannel, which is smaller than a single droplet of water. In this study, a µCE chip design was proposed by adding an extra bypass channel to balance the fluid level of the two open reservoirs and inhibit the generation of hydrostatic pressure flow within the microchannel. The fluid behaviors in the microchannel and current and voltage (I–V) characterization were experimentally studied. In addition, a numerical simulation of the electroosmotic flow and hydrostatic flow in the µCE chip was performed. The comparison between the µCE chip with and without the bypass channel showed that the bypass channel did not produce a disturbance in the microchannel for the electrophoretic measurement. The simple microchannel design enabled autonomous compensation of the hydrostatic pressure from the instability of the meniscus, and thus improved the usability of the chip-based µCE chip and the accuracy in the electrophoretic measurement.     

Sorting algal cells by morphology in spiral microchannels using inertial microfluidics

Sub-millimetre phytoplankton (here referred to as algae) exist in a wide variety of shapes and sizes. Measuring algae morphology can be a useful tool for understanding the species dynamics in a body of water, and size-sorting in general is a valuable first step in automated species identification. Here, we demonstrate the sorting of algae by shape and size in a spiral microchannel, in which lift forces and Dean flow drag forces combine to position the cells in a shape-dependent location in the channel cross section. Three species were used for experiments: the high-aspect-ratio cylindrical Monoraphidium griffithii, the prolate spheroidal Cyanothece aeruginosa, and the small spherical Chlorella vulgaris. These results are compared with the sorting of similarly sized polystyrene latex microspheres in the same device over the same range of flow rates. Tests were done at conditions which yielded average Dean numbers over the channel length of 3 < De < 30. At 1.6 mL/min, the 10- and 20-µm microspheres could be separated with an efficiency of 96 %. The best sorting results for the algae were obtained at a flow rate of 3.2 mL/min, which yielded an average Dean number of De = 25 over the channel length. These conditions led to the separation of the Monoraphidium from the differently shaped Cyanothece; these two species could be sorted with a 77 % separation efficiency despite the relatively high polydispersity in cell sizes within each species. The elegance and simplicity of inertial microfluidics make it appropriate for the high-throughput pre-sorting of algae cells upstream of other integrated sensing modalities in a field-deployable device.     

Continuous-flow ferrohydrodynamic sorting of particles and cells in microfluidic devices

A new sorting scheme based on ferrofluid hydrodynamics (ferrohydrodynamics) was used to separate mixtures of particles and live cells simultaneously. Two species of cells, including Escherichia coli and Saccharomyces cerevisiae, as well as fluorescent polystyrene microparticles were studied for their sorting throughput and efficiency. Ferrofluids are stable magnetic nanoparticles suspensions. Under external magnetic field gradients, magnetic buoyancy forces exerted on particles and cells lead to size-dependent deflections from their laminar flow paths and result in spatial separation. We report the design, modeling, fabrication and characterization of the sorting device. This scheme is simple, low-cost and label-free compared to other existing techniques.     

An efficient micromixer actuated by induced-charge electroosmosis using asymmetrical floating electrodes

Efficient microfluid mixing is an important process for various microfluidic-based biological and chemical reactions. Herein we propose an efficient micromixer actuated by induced-charge electroosmosis (ICEO). The microchannel of this device is easy to fabricate for its simple straight channel structure. Importantly, unlike previous design featuring complicated three-dimensional conducting posts, we utilize the simpler asymmetrical planar floating-electrodes to induce asymmetrical microvortices. For evaluating the mixing performance of this micromixer, we conducted a series of simulations and experiments. The mixing performance was quantified using the mixing index, specifically, the mixing efficiency can reach 94.7% at a flow rate of 1500 µm/s under a sinusoidal wave with a peak voltage of 14 V and a frequency of 400 Hz. Finally, we compared this micromixer with different micromixing devices using a comparative mixing index, demonstrating that this micromixer remains competitive among these existing designs. Therefore, the method proposed herein can offer a simple solution for efficient fluids mixing in microfluidic systems.     

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.     

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.