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.     

AC electrokinetic pumping on symmetric electrode arrays

AC electro-osmotic (ACEO) pumping is experimentally demonstrated on a symmetric gold electrode array. Using asymmetric connection of electrodes to the applied AC voltage, spatial asymmetry along the array is created, which produces unidirectional flow of electrolyte. An aqueous solution of 100 μM KCl is selected as the pumping fluid. The liquid velocity obtained as a function of voltage and frequency is compared to that generated using travelling-wave electroosmosis (TWEO) with the same electrode array. The expected velocities from the linear electrokinetic models of ACEO and TWEO are computed numerically. The comparison shows that TWEO generates greater velocity amplitudes and the streamlines are smoother than those generated by ACEO.     

DC dielectrophoretic focusing of particles in a serpentine microchannel

Focusing particles into a tight stream is usually a necessary step prior to separating and sorting them. We present herein a proof-of-concept experiment of a novel particle focusing technique in DC electrokinetic flow through a planar serpentine microchannel. This focusing stems from the cross-stream dielectrophoretic motion induced within the channel turns. The observed particle focusing behavior is consistent with the predicted particle trajectories from a numerical modeling.     

On-demand particle enrichment in a microfluidic channel by a locally controlled floating electrode

A flexible strategy for the on-demand control of the particle enrichment and positioning in a microfluidic channel is proposed and demonstrated by the use of a locally controlled floating metal electrode attached to the channel bottom wall. The channel is subjected to an axially acting global DC electric field, but the degree of charge polarization of the floating electrode is governed largely by a local control of the voltage applied to two micron-sized control electrodes (CEs) on either side of the floating electrode (FE). This strategy allows an independent tuning of the electrokinetic phenomena engendered by the floating electrode regardless of the global electric field across the channel, thus making the method for particle manipulation far more versatile and flexible. In contrast to a dielectric microchannel wall possessing a nearly uniform surface charge (or zeta potential), the patterned metal strip (floating electrode) is polarized under electric field resulting in a non-uniform distribution of the induced surface charge with a zero net surface charge, and accordingly induced-charge electro-osmotic (ICEO) flow. The ICEO flow can be regulated by the control electric field through tuning the magnitude and polarity of the voltage applied to the CEs, which in turn affects both the hydrodynamic field as well as the particle motion. By controlling the control electric field, on-demand control of the particle enrichment and its position inside a microfluidic channel has been experimentally demonstrated.     

Particle separation in alternating-current electro-osmotic micropumps using field-flow fractionation

This work presents a novel method for continuous particle separation on the microscale by means of field-flow fractionation. It is based on the use of asymmetric interdigitated electrode arrays on the channel bottom, which induce an electro-osmotic channel flow when driven harmonically. Suspended particles are influenced by viscous fluid drag, sedimentation as well as by dielectrophoretic repulsion forces from the driving electrodes due to the emerging electric field. The significant dependance of the present forces on particle properties allows for separation with respect to particle density and size. This work analyzes electric and flow field by means of the finite element method and investigates the size and density dependent particle motion as a function of driving voltage and frequency of the electrode array. Matching these driving parameters permits the separation of sedimenting particles by their density independently from their size as well as the separation by size. Finally, channel designs are proposed which enable standard separation by means of selective particle mobility in the channel, separation in terms of opposing motion directions, as well as continuous lateral separation.     

Electrokinetically driven concentration of particles and cells by dielectrophoresis with DC-offset AC electric field

Insulator-based dielectrophoresis (iDEP) has been successfully used for on-chip manipulations of biological samples. Despite its effectiveness, iDEP typically requires high DC voltages to achieve sufficient electric field; this is mainly due to the coupled phenomena among linear electrokinetics: electroosmosis (EO) and electrophoresis (EP) and nonlinear electrokinetics: dielectrophoresis (DEP). This paper presents a microfluidic technique using DC-offset AC electric field for electrokinetic concentration of particles and cells by repulsive iDEP. This technique introduces AC electric field for producing iDEP which is decoupled from electroosmosis (EO) and electrophoresis (EP). The repulsive iDEP is generated in a PDMS tapered contraction channel that induces non-uniform electric field. The benefits of introducing AC electric field component are threefold: (i) it contributes to DEP force acting on particles, (ii) it suppresses EO flow and (iii) it does not cause any EP motion. As a result, the required DC field component that is mainly used to transport particles on the basis of EO and EP can be significantly reduced. Experimental results supported by numerical simulations showed that the total DC-offset AC electric field strength required to concentrate 15-μm particles is significantly reduced up to 85.9% as compared to using sole DC electric field. Parametric experimental studies showed that the higher buffer concentration, larger particle size and higher ratio of AC-to-DC electric field are favorable for particle concentration. In addition, the proposed technique was demonstrated for concentration of yeast cells.     

Enhancing microcantilever capability with integrated AC electroosmotic trapping

Microcantilevers are finding wide applications in detecting biochemical agents. However, their usage has been limited to highly concentrated samples to ensure sufficient deposition of agents onto cantilevers. A pre-concentration or enrichment step will expand their application range to more dilute, practical samples and real-time detection. This paper reports the integration of in-situ particle concentrators on microcantilevers. Only a thin metal layer on microcantilevers is required to generate microfluidic convection of particles from solution bulk onto microcantilever surfaces, greatly enriching local particle counts and enhancing sensitivity of the system. A working prototype is presented in the paper. Preliminary experiments concentrating latex particles were conducted and the particle concentration effect has been experimentally verified using AFM probes as microcantilevers. As ACEO concentrator has no dependence on particle properties, the method is expected to be applicable to bio-particles collection.     

Electrical measurement of cross-sectional position of particles flowing through a microchannel

The first high-throughput system for the electrical detection of cross-sectional position and velocity of individual particles flowing through a rectangular microchannel is presented. Lateral position (along channel width) and vertical position (along channel height) are measured using two different sets of coplanar electrodes. In particular, the ratio of travel times measured with electrodes generating a current flow transverse or oblique with respect to particle trajectory yields lateral position. The relative prominence and transit time of a bipolar double-Gaussian signal obtained with a suited electrode configuration, respectively, supply vertical position and velocity. The operating principle is presented by means of finite element numerical simulations. The method is experimentally validated by comparing the electrical estimates of position and velocity of polystyrene beads with optical estimates obtained by processing high-speed images. The system is used to observe bead focusing at different particle Reynolds numbers. This system, providing a fully electrical characterization of single-particle motion, represents a powerful tool, e.g. to understand fluid motion at the microscale, in particle separation studies, or to assess the performance of particle focusing devices. Moreover, it can be simultaneously used to perform single-cell impedance spectroscopy, thus achieving an unprecedented multiparamteric characterization.     

Application of astigmatism μ-PTV to analyze the vortex structure of AC electroosmotic flows

The three-dimensional (3D) flow due to AC electroosmotic (ACEO) forcing on an array of interdigitated symmetric electrodes in micro-channels is experimentally analyzed using astigmatism micro-particle tracking velocimetry (astigmatism μ-PTV). Upon application of the AC electric field with a frequency of 1,000 Hz and a voltage of 2 Volts peak–peak, the obtained 3D particle trajectories exhibit a vortical structure of ACEO flow above the electrodes. Two alternating time delays (0.03 and 0.37 s) were used to measure the flow field with a wide range of velocities, including error analysis. Presence and properties of the vortical flow were quantified. The steady nature and the quasi-2D character of the vortices can combine the results from a series of measurements into one dense data set. This facilitates accurate evaluation of the velocity field by data-processing methods. The primary circulation of the vortices due to ACEO forcing is given in terms of the spanwise component of vorticity. The outline of the vortex boundary is determined via the eigenvalues of the strain-rate tensor. Overall, astigmatism μ-PTV is proven to be a reliable tool for quantitative analysis of ACEO flow.     

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.     

Computation and plotting of solid particle flow in rotating cascades

A numerical technique to solve the three dimensional equations of motion of solid particles suspended by a compressible fluid flow in a rotating cascade of a turbomachine is presented. The solution of these equations utilizes the numerically computed nonparticle fluid flow properties through the same cascade channel. It also takes into consideration the experimentally investigated phenomenon of solid particle impingement with the blade surface and turbomachine casing and their subsequent rebound. Computer plottings of the absolute paths of the solid particles, their trajectories relative to the rotor blades, and their velocity distributions in a turbine stator, turbine stage, and a compressor one and one-half stage are given.     

Continuous size-based focusing and bifurcating microparticle streams using a negative dielectrophoretic system

Dielectrophoresis (DEP) is an electrokinetic phenomenon which is used for manipulating micro- and nanoparticles in micron-sized devices with high sensitivity. In recent years, electrode-based DEP by patterning narrow oblique electrodes in microchannels has been used for particle manipulation. In this theoretic study, a microchannel with triangular electrodes is presented and a detailed comparison with oblique electrodes is made. For each shape, the behavior of particles is compared for three different configurations of applied voltages. Electric field, resultant DEP force, and particle trajectories for configurations are computed by means of Rayan native code. The separation efficiency of the two systems is assessed and compared afterward. The results demonstrate higher lateral DEP force, responsible for particle separation, distributed wider across the channel width for triangular shape electrodes in comparison with the oblique ones. The proposed electrode shape also shows the ability of particle separation by attracting negative DEP particles to or propelling them from the flow centerline, according to the configuration of applied voltages. A major deficiency of the oblique electrodes, which is the streamwise variation of the lateral DEP force direction near the electrodes, is also eliminated in the proposed electrode shape. In addition, with a proper voltages configuration, the triangular electrodes require lower voltages for particle focusing in comparison with the oblique ones.     

AC electroosmotic microconcentrator using a face-to-face,asymmetric electrode pair with expanded sections in the bottom electrode

An AC electroosmotic (AC-EO) microconcentrator using a face-to-face, asymmetric electrode pair with expanded sections in the bottom electrode is proposed in this study. The electrode pair of the AC-EO microconcentrator is composed of a larger top electrode (30 mm × 60 mm) and a bottom electrode (containing three slim electrodes and a triangular electrode). In the expanded section at the connection of a slim electrode and the triangular electrode, an electroosmosis flow transports test samples far away from the triangular electrode to the stagnation zone inside the triangular electrode through the slim electrode for concentration. On the three sides of the triangular electrode, vortices bring test samples surrounding the triangular electrode to the stagnation zone. By these two electroosmosis flow fields, the microconcentrator can concentrate test samples near and far from the triangular electrode to its central area, achieving a highly efficient sample concentration. The measured concentration distribution in the vertical electrode direction by confocal microscopy indicates that the concentration process occurs above the electrode surface. The capability of the proposed AC-EO concentrator in the repeated concentration and release of test samples is verified by a reversible switch test. The performance of the proposed AC-EO concentrator in concentrating latex particles and T4 GT7 DNA is better than those reported in the literature under similar average electric field strength. The fluorescence enhancement factor is 3.9–9.1 times better when concentrating latex particles, and the concentration enhance factor is 1.4–5.7 times better when concentrating T4 GT7 DNA.     

Viscosity-difference-induced asymmetric selective focusing for large stroke particle separation

We developed a new approach for particle separation by introducing viscosity difference of the sheath flows to form an asymmetric focusing of sample particle flow. This approach relies on the high-velocity gradient in the asymmetric focusing of the particle flow to generate a lift force, which plays a dominated role in the particle separation. The larger particles migrate away from the original streamline to the side of the higher relative velocity, while the smaller particles remain close to the streamline. Under high-viscosity (glycerol–water solution) and low-viscosity (PBS) sheath flows, a significant large stroke separation between the smaller (1.0 μm) and larger (9.9 μm) particles was achieved in a sample microfluidic device. We demonstrate that the flow rate and the viscosity difference of the sheath flows have an impact on the interval distance of the particle separation that affects the collected purity and on the focusing distribution of the smaller particles that affects the collected concentration. The interval distance of 293 μm (relative to the channel width: 0.281) and the focusing distribution of 112 μm (relative to the channel width: 0.107) were obtained in the 1042-μm-width separation area of the device. This separation method proposed in our work can potentially be applied to biological and medical applications due to the wide interval distance and the narrow focusing distribution of the particle separation, by easy manufacturing in a simple device.     

Size-selective separation of magnetic nanospheres in a microfluidic channel

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

Self-ordered particle trains in inertial microchannel flows

Controlling the transport of particles in flowing suspensions at microscale is of interest in numerous contexts such as the development of miniaturized and point-of-care analytical devices (in bioengineering, for foodborne illnesses detection, etc.) and polymer engineering. In square microchannels, neutrally buoyant spherical particles are known to migrate across the flow streamlines and concentrate at specific equilibrium positions located at the channel centerline at low flow inertia and near the four walls along their symmetry planes at moderate Reynolds numbers. Under specific flow and geometrical conditions, the spherical particles are also found to line up in the flow direction and form evenly spaced trains. In order to statistically explore the dynamics of train formation and their dependence on the physical parameters of the suspension flow (particle-to-channel size ratio, Reynolds number and solid volume fraction), experiments have been conducted based on in situ visualizations of the flowing particles by optical microscopy. The trains form only once particles have reached their equilibrium positions (following lateral migration). The percentage of particles in trains and the interparticle distance in a train have been extracted and analyzed. The percentage of particles organized in trains increases with the particle Reynolds number up to a threshold value which depends on the concentration and then decreases for higher values. The average distance between the surfaces of consecutive particles in a train decreases as the particle Reynolds number increases and is independent of the particles size and concentration, if the concentration remains below a threshold value related to the degree of confinement of the suspension flow.     

Particle method for computer simulation of red blood cell motion in blood flow

A particle method for the computer simulation of blood flow was proposed to analyze the motion of a deformable red blood cell (RBC) in flowing blood plasma. The RBC and plasma were discretized by particles that have the characteristics of an elastic membrane and a viscous fluid, respectively. The membrane particles were connected to their neighboring membrane particles by springs, and the motion of the particles was determined on the basis of the minimum energy principle. The incompressible flow of plasma that was expressed by the motion of the fluid particles was determined by the moving-particle semi-implicit (MPS) method. The RBC motion and plasma flow were weakly coupled. The two-dimensional simulation of blood flow between parallel plates demonstrated the capability of the proposed method to express the blood flow phenomena observed in experiments, such as the downstream motion of the RBC and the deformation of the RBC into a parachute shape.     

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.     

Effect of particle migration on heat transfer in suspensions of nanoparticles flowing through minichannels

Recent work has shown that suspensions of highly thermally conducting nanoparticles with a size considerably smaller than 100 nm have great potential as a high-energy carrier for small channel systems. However, it is also known that particles in a suspension under certain conditions may migrate. This indicates that the efficiency of heat transfer in the small channels may not be as superior as expected, which bears significance to the system design and operation. This work aims at addressing this issue by examining the effect of particle migration on heat transfer under a fully developed laminar flow regime in small channels. This involves the development of both flow and heat transfer models, and a numerical solution to the models. The flow model takes into account the effects of the shear-induced and viscosity-gradient-induced particle migration, as well as self-diffusion due to Brownian motion, which is coupled with an energy equation. The results suggest a significant non-uniformity in particle concentration and, hence, thermal conductivity over the tube cross-section due to particle migration, particularly for large particles at high concentrations. Compared with the constant thermal conductivity assumption, the non-uniform distribution due to particle migration leads to a higher Nusselt number, which depends on the Peclet number and the mean particle concentration. Further improvement of the model is needed to take into account other factors such as entrance effects, as well as the dynamics of particles and particle–wall interactions.     

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.