Focusing Of Microparticles Research Articles

High-Efficiency Small Sample Microparticle Fractionation on a Femtosecond Laser-Machined Microfluidic Disc.

The fabrication and testing of microfluidic spinning compact discs with embedded trapezoidal microchambers for the purpose of inertial microparticle focusing is reported in this article. Microparticle focusing channels require small features that cannot be easily fabricated in acrylic sheets and are complicated to realize in glass by traditional lithography techniques; therefore, the fabrication of microfluidic discs with femtosecond laser ablation is reported for the first time in this paper. It could be demonstrated that high-efficiency inertial focusing of 5 and 10 µm particles is achieved in a channel with trapezoidal microchambers regardless of the direction of disc rotation, which correlates to the dominance of inertial forces over Coriolis forces. To achieve the highest throughput possible, the suspension concentration was increased from 0.001% (w/v) to 0.005% (w/v). The focusing efficiency was 98.7% for the 10 µm particles and 93.75% for the 5 µm particles.

Two-dimensional concentration of microparticles using bulk acousto-microfluidics

In this Letter, we report two-dimensional focusing of microparticles in a glass capillary whose cross section is square outside and round inside using bulk acousto-microfluidics. An imaging system allowing measurements of three-dimensional microparticle acoustophoresis is designed to simultaneously present the two-dimensional focusing processes from combinations of vertical and lateral views in a same frame. The underlying mechanisms of microparticle acoustophoresis in the glass capillary device are explained by a full-device numerical model, which solves the coupling of ultrasonic transducer, glass, and fluid layers of the experimental device. We show here that decent two-dimensional microparticle focusing can be achieved when acoustic pressure nodal lines are generated on cross sections of the fluid channel from the excitation of a single ultrasonic transducer. Based on the developed understanding, we further demonstrate here robust two-dimensional focusing of microparticles by creating an acoustic pressure node point at the channel center from excitations of two orthogonally placed ultrasonic transducers.

Continuous sheath-free focusing of microparticles in viscoelastic and Newtonian fluids

A simple microfluidic device is reported for continuous, sheath-free focusing of microparticles in both viscoelastic and Newtonian fluids. Gradually contracted and suddenly expanded structures in the flow direction were designed on one side of the microchannel to induce asymmetric distribution of the elastic force on the cross section in the viscoelastic fluid. Driven by the elastic force and the viscous drag force, microparticles were focused in a single position located near the straight wall of the channel. In the Newtonian fluid, these contracted and expanded structures were utilized to generate highly curved streamlines which induced momentum-change-induced inertial force on particles. Under the combined effect of this force and the inertial lift force, the particles were also focused in a single stream in the Newtonian fluid. The influences of flow rate, particle size, polymer concentration, fluid viscosity and channel geometry on the particle focusing were investigated in the paper. In comparison with other particle focusing devices, the present microchannel can focus microparticles in a single stream in both the viscoelastic and the Newtonian fluids in a short channel length without the aid of sheath flow. With simple structure and easy operation, this device could be potentially utilized in a variety of particle focusing processes in biomedical applications, such as the enrichment of cells.

Dielectrophoresis Multipath Focusing of Microparticles through Perforated Electrodes in Microfluidic Channels.

This paper presents focusing of microparticles in multiple paths within the direction of the flow using dielectrophoresis. The focusing of microparticles is realized through partially perforated electrodes within the microchannel. A continuous electrode on the top surface of the microchannel is considered, while the bottom side is made of a circular meshed perforated electrode. For the mathematical model of this microfluidic channel, inertia, buoyancy, drag and dielectrophoretic forces are brought up in the motion equation of the microparticles. The dielectrophoretic force is accounted for through a finite element discretization taking into account the perforated 3D geometry within the microchannel. An ordinary differential equation is solved to track the trajectories of the microparticles. For the case of continuous electrodes using the same mathematical model, the numerical simulation shows a very good agreement with the experiments, and this confirms the validation of focusing of microparticles within the proposed perforated electrode microchannel. Microparticles of silicon dioxide and polystyrene are used for this analysis. Their initial positions and radius, the Reynolds number, and the radius of the pore in perforated electrodes mainly conduct microparticles trajectories. Moreover, the radius of the pore of perforated electrode is the dominant factor in the steady state levitation height.

New insights into the physics of inertial microfluidics in curved microchannels. II. Adding an additive rule to understand complex cross-sections.

Curved microchannels allow controllable microparticle focusing, but a full understanding of particle behavior has been limited-even for simple rectangular and trapezoidal shapes. At present, most microfluidic particle separation literature is dedicated to adding "internal" complexity (via sheath flow or obstructions) to relatively simple cross-sectional channel shapes. We propose that, with sufficient understanding of particle behavior, an equally viable pathway for microparticle focusing could utilize complex "external" cross-sectional shapes. By investigating three novel, complex spiral microchannels, we have found that it is possible to passively focus (6, 10, and 13 μm) microparticles in the middle of a convex channel. Also, we found that in concave and jagged channel designs, it is possible to create multiple, tight focusing bands. In addition to these performance benefits, we report an "additive rule" herein, which states that complex channels can be considered as multiple, independent, simple cross-sectional shapes. We show with experimental and numerical analysis that this new additive rule can accurately predict particle behavior in complex cross-sectional shaped channels and that it can help to extract general inertial focusing tendencies for suspended particles in curved channels. Overall, this work provides simple, yet reliable, guidelines for the design of advanced curved microchannel cross sections.

Efficient Micro/Nanoparticle Concentration using Direct Current-Induced Thermal Buoyancy Convection for Multiple Liquid Media.

Thermal-based microparticle focusing has recently received increasing attention due to its noninvasive nature and simple manipulation mechanism. However, its further application is limited by current complicated fluid heating systems and low particle focusing velocity. Using simple indium tin oxide-made microheaters, herein we propose a flexible and novel approach for efficient particle focusing based on direct current-induced thermal buoyancy convection. Importantly, for avoiding possible electrochemical reactions on the electrode, the microheaters are isolated from the granular fluids of interest by a thin glass slide. The concentration performance of the designed chip was first demonstrated by statically focusing 4-μm silica particles, yeast cells, silica particles in insulating buffer, and 100-nm copper microspheres. Also the trapping of a mixture of 5-μm and 2-μm polystyrene microbeads indicated that the chip can either simultaneously concentrate two kinds of particles or selectively focus the heavier ones by adjusting the voltages. Then the different concentration patterns of microbeads exhibited that the microspheres can be flexibly manipulated by changing the configurations of microheaters. Furthermore, for the first time, we achieved thermal-based continuous particle focusing in both conducting and insulating solutions using buoyancy convection, demonstrating that this method can be utilized to achieve both static and continuous particle manipulations in multiple liquid media. Finally, the feasibility of this device in effective wear measurement of machines was demonstrated by conducting systematic experiments of focusing nanocopper particles in the hydraulic oil. Therefore, this presented approach would be promising for a broad range of on-chip applications.

Enhanced inertial focusing of microparticles and cells by integrating trapezoidal microchambers in spiral microfluidic channels.

In this work, manipulating width and equilibrium position of fluorescent microparticles in spiral microchannel fractionation devices by embedding microchambers along the last turn of a spiral is reported. Microchambers with different shapes and sizes were tested at Reynolds numbers between 15.7 and 156.6 (100–1000 μL min−1) to observe focusing of 2, 5 and 10 μm fluorescent microparticles. This paper also discusses the fabrication process of the microfluidic chips with femtosecond laser ablation on glass wafers, as well as a particle imaging velocimetry (μPIV) study of microparticle trajectories inside a microchamber. It could be demonstrated with an improved final design with inclined microchamber side walls, that the 2 μm particle equilibrium position is shifted towards the inner wall by ∼27 μm and the focusing line's width is reduced by ∼18 μm. Finally, Saccharomyces cerevisiae yeast cells were tested in the final chip and a cell focusing efficiency of 99.1% is achieved.

Continuous Focusing of Microparticles in Horizontally Actuated Rectangular Channels

We present a device to continuously focus microparticles in a liquid-filled open channel subjected to lateral vibration at frequencies of the order of 10 Hz. The vibration generates a capillary wave at the liquid-air interface. This capillary wave leads to a net motion of microparticles over multiple cycles, causing collection under the displacement nodes of the capillary wave. These accumulated particles are observed as a concentrated stream in the presence of a continuous flow along the open channel, which means that the channel can be designed such that the focused particle stream exits through one outlet, while the filtrate is removed via interspaced outlets on each side of the particle stream. A numerical model is proposed, which superimposes the periodic flow field due to the capillary wave and the inlet-induced transverse flow field between the inlet and the outlet. The model is utilized to predict the smallest distance from the inlet at which the focused stream of particles is obtained, termed here the collection length. In addition, experiments are performed for different channel and inlet sizes, vibration actuation amplitudes, flow rates, and particle sizes. By considering the design factors extracted from the modeling data, we demonstrate that the resulting device is capable of continuous particle collection down to 1 μm diameter, at flow rates of up to 1.2 ml/min.

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.

Single particle train ordering in microchannel based on inertial and vortex effects

A new microfluidic device for microparticle focusing and ordering in a single particle train is reported. The particle focusing and ordering are based on inertial and vortex effects in a microchannel with a series of suddenly contracted and widely expanded structures on one side. In the suddenly contracted regions, particles located near the contracted structures are subjected to a strong wall-effect lift force and momentum-change-induced inertial force due to the highly curved trajectory, migrating to the straight wall. A horizontal vortex is generated downstream of the contracted structure, which prevents the particle from getting close to the wall. In the widely expanded regions, the streamline is curved and no vortex is generated. The shear-gradient lift force and the momentum-change-induced inertial force are dominant for particle lateral migration, driving particles towards the wall of the expanded structures. Eventually, particles are focused and ordered in a single particle train by the combination effects of the inertial forces and the vortex. In comparison with other single-stream particle focusing methods, this device requires no sheath flow, is easy for fabrication and operation, and can work over a wide range of Reynolds numbers from 19.1–142.9. The highly ordered particle chain could be potentially utilized in a variety of lab-chip applications, including micro-flow cytometer, imaging and droplet-based cell entrapment.

Design of a Single-Layer Microchannel for Continuous Sheathless Single-Stream Particle Inertial Focusing.

High-throughput, high-precision single-stream focusing of microparticles has a potentially wide range of applications in biochemical analysis and clinical diagnosis. In this work, we develop a sheathless three-dimensional (3D) particle-focusing method in a single-layer microchannel. This novel microchannel consists of periodic high-aspect-ratio curved channels and straight channels. The proposed method takes advantage of both the curved channels, which induce Dean flow to promote particle migration, and straight channels, which suppress the remaining stirring effects of Dean flow to stabilize the achieved particle focusing. The 3D particle focusing is demonstrated experimentally, and the mechanism is analyzed theoretically. The effects of flow rate, particle size, and cycle number on the focusing performance were also investigated. The experimental results demonstrate that polystyrene particles with diameters of 5-20 μm can be focused into a 3D single file within seven channel cycles, with the focusing accuracy up to 98.5% and focusing rate up to 98.97%. The focusing throughput could reach up to ∼105 counts/min. Furthermore, its applicability to biological cells is also demonstrated by 3D focusing of HeLa and melanoma cells and bovine blood cells in the proposed microchannel. The proposed sheathless passive focusing scheme, featuring a simple channel structure, small footprint (9 mm × 1.2 mm), compact layout, and uncomplicated fabrication procedure, holds great promise as an efficient 3D focusing unit for the development of next-generation on-chip flow cytometry.

A numerical study on dynamic inertial focusing of microparticles in a confined flow

Inertial microfluidics is regarded as a promising approach to facilitate precise, robust and continuous manipulation of particles through inertial focusing of particles in microchannels. Although there is a need to gain rich insights into the focusing dynamics of particles, it has been hardly studied numerically. In this study, the complex focusing dynamics of particles is simulated numerically for multi-particle suspensions in confined microchannels. To this end, we develop a new method that couples the discrete element method (DEM) with the direct numerical simulation (DNS). This method is referred to as the DEM–DNS method. In order to validate the DEM–DNS method, we then investigate complex dependence of particle behaviour on Reynolds number and channel geometries. With good agreement between the numerical results and existing observations, it is shown for the first time that the DEM–DNS method can simulate the counterintuitive focusing dynamics of particles. This study thus establishes that the DEM–DNS method is a powerful tool to examine the focusing dynamics of particles in inertial microfluidics.

Sheathless Microflow Cytometry Using Viscoelastic Fluids

Microflow cytometry is a powerful technique for characterization of particles suspended in a solution. In this work, we present a microflow cytometer based on viscoelastic focusing. 3D single-line focusing of microparticles was achieved in a straight capillary using viscoelastic focusing which alleviated the need for sheath flow or any other actuation mechanism. Optical detection was performed by fiber coupled light source and photodetectors. Using this system, we present the detection of microparticles suspended in three different viscoelastic solutions. The rheological properties of the solutions were measured and used to assess the focusing performance both analytically and numerically. The results were verified experimentally, and it has been shown that polyethlyene oxide (PEO) and hyaluronic acid (HA) based sheathless microflow cytometer demonstrates similar performance to state-of-the art flow cytometers. The sheathless microflow cytometer was shown to present 780 particles/s throughput and 5.8% CV for the forward scatter signal for HA-based focusing. The presented system is composed of a single capillary to accommodate the fluid and optical fibers to couple the light to the fluid of interest. Thanks to its simplicity, the system has the potential to widen the applicability of microflow cytometers.

Inertial particle dynamics in the presence of a secondary flow

An experimental investigation in a novel tangential flow filtration geometry at a moderate Reynolds number reveals how the presence of a secondary flow can can modify inertial migration and focusing of microparticles.

Formation of inverse Chladni patterns in liquids at microscale: roles of acoustic radiation and streaming-induced drag forces

While Chladni patterns in air over vibrating plates at macroscale have been well studied, inverse Chladni patterns in water at microscale have recently been reported. The underlying physics for the focusing of microparticles on the vibrating interface, however, is still unclear. In this paper, we present a quantitative three-dimensional study on the acoustophoretic motion of microparticles on a clamped vibrating circular plate in contact with water with emphasis on the roles of acoustic radiation and streaming-induced drag forces. The numerical simulations show good comparisons with experimental observations and basic theory. While we provide clear demonstrations of three-dimensional particle size-dependent microparticle trajectories in vibrating plate systems, we show that acoustic radiation forces are crucial for the formation of inverse Chladni patterns in liquids on both out-of-plane and in-plane microparticle movements. For out-of-plane microparticle acoustophoresis, out-of-plane acoustic radiation forces are the main driving force in the near-field, which prevent out-of-plane acoustic streaming vortices from dragging particles away from the vibrating interface. For in-plane acoustophoresis on the vibrating interface, acoustic streaming is not the only mechanism that carries microparticles to the vibrating antinodes forming inverse Chladni patterns: In-plane acoustic radiation forces could have a greater contribution. To facilitate the design of lab-on-a-chip devices for a wide range of applications, the effects of many key parameters, including the plate radius R and thickness h and the fluid viscosity μ, on the microparticle acoustophoresis are discussed, which show that the threshold in-plane and out-of-plane particle sizes balanced from the acoustic radiation and streaming-induced drag forces scale linearly with R and sqrt mu, but inversely with sqrt h.

High-throughput sheathless and three-dimensional microparticle focusing using a microchannel with arc-shaped groove arrays

Sheathless particle focusing which utilises the secondary flow with a high throughput has great potential for use in microfluidic applications. In this work, an innovative particle focusing method was proposed. This method makes use of a mechanism that takes advantage of secondary flow and inertial migration. The device was a straight channel with arrays of arc-shaped grooves on the top surface. First, the mechanism and expected focusing phenomenon are explained using numerical simulation of the flow field and force balance. A simulation of particle trajectories was conducted as a reference, and then a series of experiments was designed and the effects of changes in particle size, flow rate and quantity of the groove structure were discussed. The microscopic images show that this particle focusing method performed well for different size particles, and the results agreed well with the theory and simulated results. Finally, the channel successfully concentrated Jurkat cells, which showed a good compatibility in the biological assay field. In this work, the arc-shaped groove channel was demonstrated to have the ability to achieve high-throughput, sheathless and three-dimensional particle focusing with simple operations.

A low-cost, plug-and-play inertial microfluidic helical capillary device for high-throughput flow cytometry.

Glass capillary tubes have been widely used in microfluidics for generating microdroplets and microfibers. Here, we report on the application of glass capillary to inertial focusing of microparticles and cells for high-throughput flow cytometry. Our device uses a commercially available capillary tube with a square cross-section. Wrapping the tube into a helical shape induces the Dean vortices that aid focusing of cells or microbeads into a single position. We investigated the inertial focusing of microbeads in the device at various Re and concentrations and demonstrated 3D focusing with ∼100% efficiency for a wide range of microparticle diameters. We integrated the device with a laser counting system and demonstrated continuous counting of 10 μm microbeads with a high throughput of 13 000 beads/s as well as counting of fluorescently labeled white blood cells in the diluted whole blood. The helical capillary device offers a number of key advantages, including rapid and ultra-low-cost plug-and-play fabrication, optical transparency, and full compatibility with bright field or fluorescent imaging, easy re-configurability of the device radius for tuning focusing behavior, and ability to rotate for easy side-wall observation. With precise and consistent 3D focusing of microbeads and cells with a wide range of sizes at high throughput and without the use of sheath flows, we envision that this simple capillary-based inertial microfluidic device will create new opportunities for this technique to be widely adopted in the laboratory research.

Inertial Focusing of Microparticles in Curvilinear Microchannels.

A passive, continuous and size-dependent focusing technique enabled by “inertial microfluidics”, which takes advantage of hydrodynamic forces, is implemented in this study to focus microparticles. The objective is to analyse the decoupling effects of inertial forces and Dean drag forces on microparticles of different sizes in curvilinear microchannels with inner radius of 800 μm and curvature angle of 280°, which have not been considered in the literature related to inertial microfluidics. This fundamental approach gives insight into the underlying physics of particle dynamics and offers continuous, high-throughput, label-free and parallelizable size-based particle separation. Our design allows the same footprint to be occupied as straight channels, which makes parallelization possible with optical detection integration. This feature is also useful for ultrahigh-throughput applications such as flow cytometers with the advantages of reduced cost and size. The focusing behaviour of 20, 15 and 10 μm fluorescent polystyrene microparticles was examined for different channel Reynolds numbers. Lateral and vertical particle migrations and the equilibrium positions of these particles were investigated in detail, which may lead to the design of novel microfluidic devices with high efficiency and high throughput for particle separation, rapid detection and diagnosis of circulating tumour cells with reduced cost.

Inertial focusing of microparticles and its limitations

Microfluidic devices are useful tools for healthcare, biological and chemical analysis and materials synthesis amongst fields that can benefit from the unique physics of these systems.In this paper we studied inertial focusing as a tool for hydrodynamic sorting of particles by size. Theory and experimental results are provided as a background for a discussion on how to extend the technology to submicron particles. Different geometries and dimensions of microchannels were designed and simulation data was compared to the experimental results.

Role of shear induced diffusion in acoustophoretic focusing of dense suspensions

We investigate the interplay between acoustic and shear induced diffusion (SID) forces in acoustophoretic focusing of dense suspensions in a microchannel. A theoretical model is presented which accurately predicts the width of the focused band in terms of shear rate, acoustic energy density, and particle concentration. The role of SID is clearly demonstrated by switching off the acoustic field, which leads to the instantaneous spreading of the focused band. At a given acoustic energy density and particle concentration, there exists a critical shear rate Γcr above which the focusing of microparticles is prevented. For Γ<Γcr, an equilibrium focused band is formed whose width remains constant downstream.