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.     

Particle inertial focusing and its mechanism in a serpentine microchannel

Particle inertial focusing in a curved channel promises a big potential for lab-on-a-chip applications. This focusing concept is usually based on the balance of inertial lift force and the drag of secondary flow. This paper proposes a new focusing concept independent of inertial lift force, relying solely on secondary flow drag and particle centrifugal force. Firstly, a focusing mechanism in a serpentine channel is introduced, and some design considerations are described in order to make the proposed focusing concept valid. Then, numerical modelling based on the proposed focusing mechanism is conducted, and the numerical results agree well with the experimental ones, which verify the rationality of proposed mechanism. Thirdly, the effects of flow condition and particle size on the focusing performance are studied. The effect of particle centrifugal force on particle focusing in a serpentine microchannel is carefully evaluated. Finally, the speed of focussed particles at the outlet is measured by a micro-PIV, which further certifies the focusing positions of particles within the cross section. Our study provides insights into the role of centrifugal force on inertial focusing. This paper demonstrates for the first time that a single focusing streak can be achieved in a symmetric serpentine channel. The simple serpentine microchannel can easily be implemented in a single-layer microfluidic device. No sheath flow or external force field is needed allowing a simple operation in a more complex lab-on-a-chip system.     

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.     

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.     

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.     

Cluster formation and growth in microchannel flow of dilute particle suspensions

The lifetime of microfluidic devices depends on their ability to maintain flow without interruption. Certain applications require microdevices for transport of liquids containing particles. However, microchannels are susceptible to blockage by solid particles. Therefore, in this study, the phenomenon of interest is the formation and growth of clusters on a microchannel surface in the flow of a dilute suspension of hard spheres. Based on the present experiments, aggregation of clusters was observed for particle-laden flows in microchannels with particle void fraction as low as 0.001 and particle diameter to channel height ratio as low as 0.1. The incipience and growth of a single cluster is discussed, and the spatial distribution and time evolution of clusters along the microchannel are presented. Although the cluster size seems to be independent of location, more clusters are found at the inlet/outlet regions than in the microchannel center. Similarly as for an individual cluster, as long as particle–cluster interaction is the dominant mode, the total cluster area in the microchannel grows almost linearly in time. The effects of flow rate, particle size, and concentration are also reported.     

Design optimization of capillary-driven micromixer with square-wave microchannel for blood plasma mixing

A numerical and experimental investigation is performed into the flow characteristics and mixing performance of three microfluidic polydimethylsiloxane blood plasma mixing devices incorporating square-wave, curved and zigzag microchannels, respectively. For each device, the plasma is introduced into the microfluidic channel under the effects of capillary action alone. Of the three devices, that with the square-wave microchannel is found to yield the best mixing performance, and is therefore selected for design optimization. Four microfluidic micromixers incorporating square-wave microchannels with different widths in the x- and y-directions are fabricated using conventional photolithography techniques. The mixing performance of the four microchannels is investigated both numerically and experimentally. The results show that given an appropriate specification of the microchannel geometry, a mixing efficiency of approximately 76 % can be obtained within 4 s. The practical feasibility of the micromixer is demonstrated by performing prothrombin time (PT) tests using a total liquid volume of 4.0 μL (2.0 μL of plasma and 2.0 μL of PT reagent). It is shown that the mean time required to complete the entire PT test (including loading, mixing and coagulation) is less than 30 s.

     

Valves for autonomous capillary systems

Autonomous capillary systems (CSs) are microfluidic systems inside which liquids move owing to capillary forces. CSs can in principle bring the high-performances of microfluidic-based analytical devices to near patient and environmental testing applications. In this paper, we show how wettable capillary valves can enhance CSs with novel functionalities, such as delaying and stopping liquids in microchannels. The valves employ an abruptly changing geometry of the flow path to delay a moving liquid filling front in a wettable microchannel. We show how to combine delay valves with capillary pumps, prevent shortcuts of liquid along the corners of microfluidic channels, stop liquids filling microchannels from a few seconds to over 30 min, trigger valves using two liquid fronts merging, and time a liquid using parallel microfluidic paths converging to a trigger valve. All together, these concepts should add functionality to passive microfluidic systems without departing from their initial simplicity of use. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Fluid rheological effects on particle migration in a straight rectangular microchannel

There has recently been a significantly increasing interest in the passive manipulation of particles in the flow of non-Newtonian fluids through microchannels. However, an accurate and comprehensive understanding of the various fluid rheological effects on particle migration is still largely missing. We present in this work a systematic experimental study of both the individual and the combined effects of fluid inertia, elasticity, and shear thinning on the motion of rigid spherical particles in a straight rectangular microchannel. We first study the sole effect of each of these rheological properties in a Newtonian fluid, purely elastic (i.e., Boger) fluid, and purely shear-thinning (i.e., pseudoplastic) fluid, respectively. We then study the combined effects of two or all of these rheological properties in a pseudoplastic fluid and two types of elastic shear-thinning fluids, respectively. We find that the fluid elasticity effect directs particles toward the centerline of the channel while the fluid shear-thinning effect causes particle migration toward both the centerline and corners. These two effects are combined with the fluid inertial effect to understand the particle migration in inertial pseudoplastic and viscoelastic fluid flows.     

Axial particle displacements in fluid slugs after passing a simple serpentiform microchannel

In this work, we designed a simple microchannel to separate particles in fluids by size. We found that mixtures of polystyrene 2 and 0.5 μm particles in a fluid slug can be differentiated by size after passing a long serpentiform microchannel. In contrast to the tubular pinch effect, which separates the particle in radial direction, we found that the particle suspensions in fluid slugs are displaced along the flow directions. The separation performance increases with the increasing flow velocity. The feature of differentiation along the flow directions in our device leads to the result that the separation process can be easily improved by stretching the slug before cutting the slug into pieces. Furthermore, the alternative air slugs between working fluid slugs can also prevent clogging inside the microchannels.     

Modeling, analysis and design of centrifugal force driven transient filling flow into rectangular microchannel

Recently, centrifugal pumping has been discovered to be an excellent alternative method for controlling the fluid flow inside microchannels. In this paper, we have developed the physical modeling and carried out the analysis for the centrifugal force driven transient filling flow into a rectangular microchannel. Two types of analytic solutions for the transient flow were obtained: (1) a pseudo-static approximate solution, and (2) an exact solution. Analytic solutions include expressions for flow front advancement, detailed velocity profile and pressure distribution. The obtained analytical results show that the filling flow driven by centrifugal force is affected by three dimensionless parameters which combine fluid properties, rectangular channel geometry and processing condition of rotational speed. Effects of inertia, viscous and centrifugal forces were also discussed based on the parametric study. Furthermore, we have also successfully provided a simple and convenient analytical design tool for such rectangular microchannels, demonstrating two design application examples.     

Particle handling in straight microfluidic channels via opposing electroosmotic and pressure-driven flows

The current study presents a method for producing recirculation zones in a straight microchannel using opposing pressure-driven and electrokinetically driven flows. The interaction of these two flow streams causes flow recirculation structures, which restricts the flow passage within the microchannel and causes a nozzle-like effect, thereby increasing the separation distance between particles in the fluid stream. Theoretical and experimental investigations are performed to investigate the effects of the applied electrical field intensity on the flow recirculation size, and the nozzle-like effect, respectively. In general, the results confirm that the proposed approach provides an effective means of achieving particle acceleration and separation distance within straight microchannels, and therefore provides a viable technique for improving particle manipulation and optical detection in conventional microfluidic devices. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Acoustofluidic separation: impact of microfluidic system design and of sample properties

We describe the results of a numerical study about the separation of fluid-suspended microsamples (as microbeads and cells) by acoustophoresis. A microfluidic channel with rectangular cross section is considered, and we investigate the impact on particle separation of many different parameters, dividing them in two groups: sample’s intrinsic factors (own properties of the sample) and extrinsic factors (related to the microfluidic system design and operation). Differently from what is usually done, we include in our study the impact of the initial sample position, which always has a certain variability in real experiments, and we introduce several new parameters allowing to assess system performance and to optimize the microchip separation efficiency. The obtained results show the importance of two design parameters that are generally overlooked: the channel width and the offset between the channel border and the input of the target samples in the microchannel. Additionally, the analysis method we describe and the new parameters we introduce to study the system can be beneficially used in almost any study of acoustophoretic-based separation system.     

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.     

In-channel focusing of flowing microparticles utilizing hydrodynamic filtration

We present herein microfluidic systems to continuously focus the positions of flowing particles onto the center of a microchannel, which is indispensable to various applications for manipulating particles or cells such as flow cytometry and particle-based bioassay. A scheme called ‘hydrodynamic filtration’ is employed to repeatedly split fluid flows from a main stream, while remaining particles in the main stream. By re-injecting the split flows into the main channel, these flows work as sheath flows, focusing the positions of the particles onto the center of the microchannel without the help of sheath flows or complicated devices generating physical forces. In this study, we proposed two schemes, and compared the focusing efficiencies between the two schemes using particles 5.0 μm in diameter. Also, we confirmed that the flow speed did not affect the focusing efficiency, demonstrating the versatility and applicability of the presented systems. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

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.     

Predictive model on micro droplet generation through mechanical cutting

We describe the step-by-step formation process of picoliter to femtoliter volume of microdroplets by using a mechanical valve. An experiment-based theoretical model has been proposed through a parametric study of droplet formation in a microchannel with variations of the channel height, the working pressure to drive the liquids in the microchannels, and the viscosity of the dispensed phase. Three steps in the process of droplet generation have been depicted. The present study provides a clear understanding of the droplet generation process based on physical cutting method by using a mechanical valve and could be applied to advanced design for highly flexible droplet-based microfluidic systems. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. W. S. Lee, S. Jambovane and D. Kim contributed equally to this work.     

Effects of channel surface finish on blood flow in microfluidic devices

The behaviour of blood flow in relation to microchannel surface roughness has been investigated. Special attention was focused on the techniques used to fabricate the microchannels and on the apparent viscosity of the blood as it flowed through these microchannels. For the experimental comparison of smooth and rough surface channels, each channel was designed to be 10 mm long and rectangular in cross-section with aspect ratios of ≥100:1 for channel heights of 50 and 100 μm. Polycarbonate was used as the material for the device construction. The shims, which created the heights of the channels, were made of polyethylene terephthalate. Surface roughnesses of the channels were varied from R _z of 60 nm to 1.8 μm. Whole horse blood and filtered water were used as the test fluids and differential pressures ranged from 200 to 5,000 Pa. The defibrinated horse blood was treated further to prevent coagulation. The results indicate that a surface roughness above an unknown value lowers the apparent viscosity of blood dramatically due to boundary effects. Furthermore, the roughness seemed to influence both water and whole blood almost equally. A set of design rules for channel fabrication is also presented in accordance with the experiments performed.     

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 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.