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.     

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.     

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.     

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.     

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.     

Sheathless microfluidic particle focusing technique using slanted microstructure array

This paper proposes a microfluidic channel for particle focusing that uses a microstructure on the bottom of the channel. Particles can be effectively focused in channels with bottom structures because of microvortex induced by the structure. Microchannels with top structures (top type) and bottom structures (bottom type) were fabricated. The focusing ratios in the focusing region (one-eighth of the channel width) were 86 % in top type and 89 % in bottom type at a flow rate of 1 μl/min. When the flow rate was increased to 5 μl/min, particles in top type were barely focused, whereas particles in bottom type were focused with a focusing ratio of approximately 80 %. We also evaluated the effect of a slanted angle for the microstructures. The comparative experiment was conducted with microstructures fabricated at slanted angle intervals of 20° (20°, 40°, 60°, and 80°) and 10°. The results indicated that the slanted angle (20°) required a small number of microstructures to direct the sample to the focusing region. For microstructures with a 20° slanted angle, the sample was focused after passing through 20 microstructures (10 mm). However, microstructures with an angle of 80° needed over 70 microstructures (over 23 mm) to direct the particle. In this sense, a microchannel with microstructures slanted at 20° is applicable to miniaturized devices. These results show that the microchannel with bottom structures slanted 20° can be used to effectively focus samples with advantages of applying various ranges of flow rates and miniaturizing devices.     

Two- and three-dimensional lattice Boltzmann simulations of particle migration in microchannels

The use of two-dimensional (2D) numerical simulations with a reduced particle-based Reynolds number (Re) for studying particle migration in a microchannel with equally spaced multiple constrictions was investigated. 2D and 3D colloidal lattice Boltzmann (LB) models were used to simulate particle-fluid hydrodynamics. Experiments were conducted with inert microparticles in a creeping flow in a microflow channel with symmetric wall obstacles. Lowering Re in 2D simulations by a factor of R (the dimensionless particle radius in LB simulations) resulted in a close match between numerically computed and experimentally obtained particle velocities, indicating that Re-based dimensional scaling was needed to capture the 3D particle flow dynamics in 2D simulations of experimental data. We captured particle displacement motion in a microchannel with symmetric inline obstacles in 2D simulations, where symmetry in the flow field was broken by local disturbances in the flow field due to particle motion, indicating that asymmetry in channel geometry is not the sole cause for particle displacement motion. Particle acceleration/deceleration around each constriction followed the same pattern, but each constriction acted like a particle accelerator in 2D and 3D simulations, in which particles exhibited progressively higher velocities in each subsequent constriction. Particles migrated across multiple streamlines in converging and diverging flow zones in a creeping flow, which calls into question the use of steady streamlines for calculating transient particle flow. Monotonicity in particle acceleration toward the constriction and deceleration beyond the constriction was broken by interparticle hydrodynamic interactions leading to more pronounced particle migration across multiple streamlines.     

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.     

Inertial particle focusing dynamics in a trapezoidal straight microchannel: application to particle filtration

Inertial microfluidics has emerged recently as a promising tool for high-throughput manipulation of particles and cells for a wide range of flow cytometric tasks including cell separation/filtration, cell counting, and mechanical phenotyping. Inertial focusing is profoundly reliant on the cross-sectional shape of channel and its impacts on not only the shear field but also the wall-effect lift force near the wall region. In this study, particle focusing dynamics inside trapezoidal straight microchannels was first studied systematically for a broad range of channel Re number (20 < Re < 800). The altered axial velocity profile and consequently new shear force arrangement led to a cross-lateral movement of equilibration toward the longer side wall when the rectangular straight channel was changed to a trapezoid; however, the lateral focusing started to move backward toward the middle and the shorter side wall, depending on particle clogging ratio, channel aspect ratio, and slope of slanted wall, as the channel Reynolds number further increased (Re > 50). Remarkably, an almost complete transition of major focusing from the longer side wall to the shorter side wall was found for large-sized particles of clogging ratio K ~ 0.9 (K = a/H_min) when Re increased noticeably to ~ 650. Finally, based on our findings, a trapezoidal straight channel along with a bifurcation was designed and applied for continuous filtration of a broad range of particle size (0.3 < K < 1) exiting through the longer wall outlet with ~ 99% efficiency (Re < 100).     

Inertial migration of single particle in a square microchannel over wide ranges of <Emphasis Type="Italic">Re</Emphasis> and particle sizes

Inertial migration of particles has been widely used in inertial microfluidic systems to passively manipulate cells/particles. However, the migration behaviors and the underlying mechanisms, especially in a square microchannel, are still not very clear. In this paper, the immersed boundary-lattice Boltzmann method (IB-LBM) was introduced and validated to explore the migration characteristics and the underlying mechanisms of an inertial focusing single particle in a square microchannel. The grid-independence analysis was made first to highlight that the grid number across the thin liquid film (between a particle and its neighboring channel wall) was of significant importance in accurately capturing the migrating particle’s dynamics. Then, the inertial migration of a single particle was numerically investigated over wide ranges of Reynolds number (Re, from 10 to 500) and particle sizes (diameter-to-height ratio a/H, from 0.16 to 0.5). It was interesting to find that as Re increased, the channel face equilibrium (CFE) position moved outward to channel walls at first, and then inflected inwards to the channel center at high Re (Re?>?200). To account for the physical mechanisms behind this behavior, the secondary flow induced by the inertial focusing single particle was further investigated. It was found that as Re increased, two vortices appeared around the particle and grew gradually, which pushed the particle away from the channel wall at high Re. Finally, a correlation was proposed based on the numerical data to predict the critical length L_c (defined to describe the size of fluid domain that was strongly influenced by the particle) according to the particle size a/H and Re.     

Experimental and numerical investigation on particle–particle interaction of multi-particle separation in an alternating and repetitive microchannel

Inertial focusing plays a major role in size-based cell separation or enrichment for microfluidic applications in many medical areas such as diagnostics and treatment. These applications often deal with suspensions of different particles which cause interactions between particles with different diameters such as particle–particle collision. In this study, particle–particle interaction in a laminar flow through a low aspect ratio alternating and repetitive microchannel is investigated both numerically and experimentally. It is revealed that particle–particle collision affects high quality particle focusing. computational fluid dynamics simulations are conducted for demonstrating the effect of the flow field in the transverse cross-section on the focusing quality and position. The experiments and simulations both revealed that if the flow is seeded with a mixture of particles of 3.3 and 9.9 µm diameters, the quality of focusing intensity is degenerated compared to the focusing features obtained by particles with a diameter of 9.9 µm solely. The results clearly show that particle–particle collision between the 3.3 and 9.9 µm particles has a negative effect on particle focusing behavior of the 9.9 µm particles.

     

Lateral migration of particles suspended in viscoelastic fluids in a microchannel flow

In this work, we investigated the lateral migration of microparticles suspended in two different viscoelastic fluids with or without the second normal stress difference. For the viscoelastic fluid without the second normal stress difference, competing forces existed between microfluidic inertia and the first normal stress difference (N ₁), which resulted in a synergetic effect of particle focusing. For the fluid with the second normal stress difference (N ₂), particles were greatly affected by a N ₂-induced secondary flow, and the competition among the inertia, N ₁, and N ₂ determined the lateral migration trajectories of the particles. The obtained results were delineated with the blockage ratio, which showed good agreement with the results of a recent numerical study (Villone et al. in J Non Newton Fluid Mech 195:1–8, 2013). The present study also examined the possibility of particle separation in a size-dependent manner using the N ₂-induced secondary flow in microchannel flow.     

Inertial effects on cylindrical particle migration in linear shear flow near a wall

Micro-/nanoparticle-based systems are regarded as one of the possible candidates due to the engineerability and multifunctionality to maximize the accumulation of the nano-/microparticle-based drug delivery system on the target. Recent advances in nanotechnology enable the fabrication of diverse particle shapes from simple spherical particles to more complex shapes. The particle dynamics in blood flow and endocytosis characteristics of non-spherical particles change as the non-sphericity effect increases. We used a numerical approach to investigate the particle dynamics in linear shear flow near a wall. We examined the dynamics of slender cylindrical particles with aspect ratio γ = 5.0 in terms of particle trajectory, velocity, and force variation for different Stokes numbers over time. We identified the rotating inertia of particle near a wall as the source of inertial migration toward the wall. The drift velocity of slender cylindrical particles is comparable to that of discoidal particles. We discuss the possibilities and limitations of using slender cylindrical particles as a drug delivery system.     

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.     

Flow-induced particle migration in microchannels for improved microfiltration processes

Microchannels can be used to induce migration phenomena of micron sized particles in a fluid. Separation processes, like microfiltration, could benefit from particle migration phenomena. Currently, microfiltration is designed around maximum flux, resulting in accumulation of particles in and on the membrane. In this paper it is shown that starting the design at the particle level will result in a new microfiltration process. The behaviour of suspensions between 9 and 38 volume% was studied by confocal scanning laser microscopy; migration as a result of shear-induced diffusion was observed in a rectangular microchannel with nonporous walls. Particles segregated on size within the first 10 cm of the channel. To illustrate this, at 20 volume% of small (1.53 μm) and large (2.65 μm) particles each, the larger particles migrated to the middle of the channel, while the small particles had high concentrations near the walls. The small particles could then be collected from their position close to the permeable walls, e.g. membranes, where the pore size of the membrane is no longer the determining factor for separation. Guidelines for using this phenomenon in a microfiltration process were derived and the selectivity of the process was experimentally evaluated. The small droplets could be removed from the mixtures with a membrane having pores 3.7 times larger than the droplets, thereby minimizing accumulation of droplets in and on the membrane. As long as the process conditions are chosen appropriately, no droplet deposition takes place and high fluxes (1.7 × 10³ L h^?1 m^?² bar^?1) can be maintained.     

Predicting different adhesive regimens of circulating particles at blood capillary walls

A fundamental step in the rational design of vascular targeted particles is the firm adhesion at the blood vessel walls. Here, a combined lattice Boltzmann–immersed boundary model is presented for predicting the near-wall dynamics of circulating particles. A moving least squares algorithm is used to reconstruct the forcing term accounting for the immersed particle, whereas ligand-receptor binding at the particle–wall interface is described via forward and reverse probability distributions. First, it is demonstrated that the model predicts with good accuracy the rolling velocity of tumor cells over an endothelial layer in a microfluidic channel. Then, particle–wall interactions are systematically analyzed in terms of particle geometries (circular, elliptical with aspect ratios 2 and 3), surface ligand densities (0.3, 0.5, 0.7 and 0.9), ligand-receptor bond strengths (1 and 2) and Reynolds numbers (Re = 0.01, 0.1 and 1.0). Depending on these conditions, four different particle–wall interaction regimens are identified, namely not adhering, rolling, sliding and firmly adhering particles. The proposed computational strategy can be efficiently used for predicting the near-wall dynamics of particles with arbitrary geometries and surface properties and represents a fundamental tool in the rational design of particles for the specific delivery of therapeutic and imaging agents.     

Experimental observations of bands of suspended colloidal particles subject to shear flow and steady electric field

Manipulating suspended colloidal particles flowing through a microchannel is of interest in microfluidics and nanotechnology. However, the flow itself can affect the dynamics of these suspended particles via wall-normal “lift” forces. The near-wall dynamics of particles suspended in shear flow and subject to a dc electric field was quantified in combined Poiseuille and EO flow through a?~?30 μm deep channel. When the two flows are in opposite directions, the particles are attracted to the wall. They then assemble into very high aspect ratio structures, or concentrated streamwise “bands,” above a minimum electric field magnitude, and, it appears, a minimum near-wall shear rate. These bands only exist over the few micrometers next to the wall and are roughly periodic in the cross-stream direction, although there are no external forces along this direction. Experimental observations and dimensional analysis of the time for the first band to form and the number of bands over a field of view of ~?200 μm are presented for dilute suspensions of polystyrene particles over a range of particle radii, concentrations, and zeta potentials. To our knowledge, there is no theoretical explanation for band assembly, but the results presented here demonstrate that it occurs over a wide range of different particle and flow parameters.     

A microfluidic device for thermal particle detection

We demonstrate the use of heat to count microscopic particles. A thermal particle detector (TPD) was fabricated by combining a 500-nm-thick silicon nitride membrane containing a thin-film resistive temperature detector with a silicone elastomer microchannel. Particles with diameters of 90 and 200 μm created relative temperature changes of 0.11 and ?0.44 K, respectively, as they flowed by the sensor. A first-order lumped thermal model was developed to predict the temperature changes. Multiple particles were counted in series to demonstrate the utility of the TPD as a particle counter.     

Improving particle detection sensitivity of a microfluidic resistive pulse sensor by a novel electrokinetic flow focusing method

A novel and simple method of improving the particle detection sensitivity of a microfluidic resistive pulse sensor was presented in this paper. This novel electrokinetic flow focusing method utilizes a focusing solution (with high resistivity) flowing from the upstream focusing channel to the downstream focusing channel. The focusing solution in the sensing gate works like a virtual insulation wall that greatly narrows the gate and thus improves the detection sensitivity. An equation was derived to relate the magnitude of the output signal to the resistivity and the width of the focusing solution. The width of the focused particle solution under different voltages was numerically predicted. The results show that the magnitude of output signal increases with the decrease in the width of the focused particle stream. More importantly, the detection sensitivity can be improved by decreasing the space occupied by the focusing solution in the upstream and downstream channels as much as possible. Detection of 1 μm particle with a sensing gate of 30 × 40 × 10 μm (width × length × height) was successfully achieved. The proposed method is simple and advantageous in detecting smaller particles without fabricating a small sensing gate.     

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.