Continuous dielectrophoretic separation of particles in a spiral microchannel

Particle separation is a fundamental operation in the areas of biology and physical chemistry. A variety of force fields have been used to separate particles in microfluidic devices, among which electric field may be the most popular one due to its general applicability and adaptability. So far, however, electrophoresis‐based separations have been limited primarily to batchwise processes. Dielectrophoresis (DEP)‐based separations require in‐channel micro‐electrodes or micro‐insulators to produce electric field gradients. This article introduces a novel particle separation technique in DC electrokinetic flow through a planar double‐spiral microchannel. The continuous separation arises from the cross‐stream dielectrophoretic motion of particles induced by the non‐uniform electric field inherent to curved channels. Specifically, particles are focused by DEP to one sidewall of the first spiral, and then dielectrophoretically deflected toward the other sidewall of the second spiral at a particle‐dependent rate, leading to focused particle streams along different flow paths. This DEP‐based particle separation technique is demonstrated in an asymmetric double‐spiral microchannel by continuously separating a mixture of 5/10 μm particles and 3/5 μm particles.     

Continuous dielectrophoretic particle separation via isomotive dielectrophoresis with bifurcating stagnation flow

We present a novel technique for continuous label‐free separation of particles based on their dielectrophoretic crossover frequencies. Our technique relies on our unique microfluidic geometry which performs hydrodynamic focusing, generates a stagnation flow with two outlets, and simultaneously produces an isomotive dielectrophoretic field via wall‐situated electrodes. To perform particle separation, we hydrodynamically focus particles onto stagnation streamlines and use isomotive dielectrophoretic force to nudge the particles off these streamlines and direct them into appropriate outlets. Focusing particles onto stagnation streamlines obviates the need for large forces to be applied to the particles and therefore increases system throughput. The use of isomotive (spatially uniform) dielectrophoretic force increases system reliability. To guide designers, we develop and describe a simple scaling model for the particle separation dynamics of our technique. The model predicts the range of particle sizes that can be separated as well as the processing rate that can be achieved as a function of system design parameters: channel size, flow rate, and applied potential. Finally, as a proof‐of‐principle, we use this technique to separate polystyrene bead and cell mixtures of the same diameters as well as mixtures of both particles with varying diameters.     

Dielectrophoresis switching with vertical sidewall electrodes for microfluidic flow cytometry

A novel dielectrophoresis switching with vertical electrodes in the sidewall of microchannels for multiplexed switching of objects has been designed, fabricated and tested. With appropriate electrode design, lateral DEP force can be generated so that one can dynamically position particulates along the width of the channel. A set of interdigitated electrodes in the sidewall of the microchannels is used for the generation of non-uniform electrical fields to generate negative DEP forces that repel beads/cells from the sidewalls. A countering DEP force is generated from another set of electrodes patterned on the opposing sidewall. These lateral negative DEP forces can be adjusted by the voltage and frequency applied. By manipulating the coupled DEP forces, the particles flowing through the microchannel can be positioned at different equilibrium points along the width direction and continue to flow into different outlet channels. Experimental results for switching biological cells and polystyrene microbeads to multiple outlets (up to 5) have been achieved. This novel particle switching technique can be integrated with other particle detection components to enable microfluidic flow cytometry systems.     

Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics

We propose here a new method for continuous concentration and classification of particles in microfluidic devices, named hydrodynamic filtration. When a particle is flowing in a microchannel, the center position of the particle cannot be present in a certain distance from sidewalls, which is equal to the particle radius. The proposed method utilizes this fact, and is performed using a microchannel having multiple side branch channels. By withdrawing a small amount of liquid repeatedly from the main stream through the side channels, particles are concentrated and aligned onto the sidewalls. Then the concentrated and aligned particles can be collected according to size through other side channels (selection channels) in the downstream of the microchannel. Therefore, continuous introduction of a particle suspension into the microchannel enables both particle concentration and classification at the same time. In this method, the flow profile inside a precisely fabricated microchannel determines the size limit of the filtered substances. So the filtration can be performed even when the channel widths are much larger than the particle size, without the problem of channel clogging. In this study, concentrations of polymer microspheres with diameters of 1-3 microm were increased 20-50-fold, and they were collected independently according to size. In addition, selective enrichment of leukocytes from blood was successfully performed.     

Separation of mixtures of particles in a multipart microdevice employing insulator-based dielectrophoresis

Dielectrophoresis is the electrokinetic movement of particles due to polarization effects in the presence of non-uniform electric fields. In insulator-based dielectrophoresis (iDEP) regions of low and high electric field intensity, i.e. non-uniformity of electric field, are produced when the cross-sectional area of a microchannel is decreased by the presence of electrical insulating structures between two electrodes. This technique is increasingly being studied for the manipulation of a wide variety of particles, and novel designs are continuously developed. Despite significant advances in the area, complex mixture separation and sample fractionation continue to be the most important challenges. In this work, a microchannel design is presented for carrying out direct current (DC)-iDEP for the separation of a mixture of particles. The device comprises a main channel, two side channels and two sections of cylindrical posts with different diameters, which will generate different non-uniformities in the electric field on the main channel, designed for the discrimination and separation of particles of two different sizes. By applying an electric potential of 1000 V, a mixture of 1 and 4 μm polystyrene microspheres were dielectrophoretically separated and concentrated at the same time and then redirected to different outlets. The results obtained here demonstrate that, by carefully designing the device geometry and selecting operating conditions, effective sorting of particle mixtures can be achieved in this type of multi-section DC-iDEP devices.     

Analytical solutions and validation of electric field and dielectrophoretic force in a bio-microfluidic channel

In a microbiological device, cell or particle manipulation and characterization require the use of electric field on different electrodes in several configurations and shapes. To efficiently design microelectrodes within a microfluidic channel for dielectrophoresis focusing, manipulation and characterization of cells, the designer will seek the exact distribution of the electric potential, electric field and hence dielectrophoresis force exerted on the cell within the microdevice. In this paper we describe the approach attaining the analytical solution of the dielectrophoretic force expression within a microchannel with parallel facing same size electrodes present on the two faces of channel substrates, with opposite voltages on the pair electrodes. Simple Fourier series mathematical expressions are derived for electric potential, electric field and dielectric force between two distant finite‐size electrodes. Excellent agreement is found by comparing the analytical results calculated using MATLAB? with numerical ones obtained by Comsol. This analytical result can help the designer to perform simple design parametric analysis. Bio‐microdevices are also designed and fabricated to illustrate the theoretical solution results with the experimental data. Experiments with red blood cells show the dielectrophoretic force contour plots of the analytical data matched to the experimental results.     

Recent advances in direct current electrokinetic manipulation of particles for microfluidic applications

Microfluidic devices have been extensively used to achieve precise transport and placement of a variety of particles for numerous applications. A range of force fields have thus far been demonstrated to control the motion of particles in microchannels. Among them, electric field‐driven particle manipulation may be the most popular and versatile technique because of its general applicability and adaptability as well as the ease of operation and integration into lab‐on‐a‐chip systems. This article is aimed to review the recent advances in direct current (DC) (and as well DC‐biased alternating current) electrokinetic manipulation of particles for microfluidic applications. The electric voltages are applied through electrodes that are positioned into the distant channel‐end reservoirs for a concurrent transport of the suspending fluid and manipulation of the suspended particles. The focus of this review is upon the cross‐stream nonlinear electrokinetic motions of particles in the linear electroosmotic flow of fluids, which enable the diverse control of particle transport in microchannels via the wall‐induced electrical lift and/or the insulating structure‐induced dielectrophoretic force.     

Focused electrophoretic motion and selected electrokinetic dispensing of particles and cells in cross-microchannels

The electrokinetic focusing and the resultant accelerated electrophoretic motion of polystyrene particles and red blood cells were visualized in microfluidic cross-channels. The experimentally measured width of the focused stream and the measured velocity increase of particles and cells at different voltage ratios follow the proposed analytical formula within the experimental error. The attained velocity increase is insensitive to the particle size, particle property (i.e., particle or cell), and particle trajectory. By solving the electrical potential field in the cross-channel at the experimental conditions, we demonstrate that the squeezed electrical field lines in the channel intersection determine the shape of the focused stream, and the nonuniform distribution of axial electrical field strength underlies the variation of particle/cell electrophoretic velocity through the focusing region. However, the dielectrophoretic force resulting from the nonuniform electrical field in the intersection seems to push the acceleration region of particles and cells slightly in the downstream direction. We have also achieved the single particle/cell dispensing by instantly triggering an electrical pulse perpendicular to the focused particulate flow in a double-cross microchannel. The electrokinetic manipulation of particle/cell in microchannels demonstrated in this work can be used for developing integrated lab-on-a-chip devices for studies of cells.     

Focusing particles by induced charge electrokinetic flow in a microchannel

A novel method of sheathless particle focusing by induced charge electrokinetic flow in a microchannel is presented in this paper. By placing a pair of metal plates on the opposite walls of the channel and applying an electrical field, particle focusing is achieved due to the two pairs of vortex that constrain the flow of the particle solution. As an example, the trajectories of particles under different electrical fields with only one metal plate on one side channel wall were numerically simulated and experimentally validated. Other flow focusing effects, such as the focused width ratio (focused width/channel width) and length ratio (focused length/half‐length of metal plate) of the sample solution, were also numerically studied. The results show that the particle firstly passes through the gaps between the upstream vortices and the channel walls. Afterwards, the particle is focused to pass through the gap between the two downstream vortices that determine the focused particle position. Numerical simulations show that the focused particle stream becomes thin with the increases in the applied electrical field and the length of the metal plates. As regards to the focused length ratio of the focused stream, however, it slightly increases with the increase in the applied electrical field and almost keeps constant with the increase in the length of the metal plate. The size of the focused sample solution, therefore, can be easily adjusted by controlling the applied electrical field and the sizes of the metal plates.     

Electrothermal flow effects in insulating (electrodeless) dielectrophoresis systems

We simulate electrothermally induced flow in polymeric, insulator-based dielectrophoresis (iDEP) systems with DC-offset, AC electric fields at finite thermal Péclet number, and we identify key regimes where electrothermal (ET) effects enhance particle deflection and trapping. We study a single, two-dimensional constriction in channel depth with parametric variations in electric field, channel geometry, fluid conductivity, particle electrophoretic (EP) mobility, and channel electroosmotic (EO) mobility. We report the effects of increasing particle EP mobility, channel EO mobility, and AC and DC field magnitudes on the mean constriction temperature and particle behavior. Specifically, we quantify particle deflection and trapping, referring to the deviation of particles from their pathlines due to dielectrophoresis as they pass a constriction and the stagnation of particles due to negative dielectrophoresis near a constriction, respectively. This work includes the coupling between fluid, heat, and electromagnetic phenomena via temperature-dependent physical parameters. Results indicate that the temperature distribution depends strongly on the fluid conductivity and electric field magnitude, and particle deflection and trapping depend strongly on the channel geometry. Electrothermal (ET) effects perturb the EO flow field, creating vorticity near the channel constriction and enhancing the deflection and trapping effects. ET effects alter particle deflection and trapping responses in insulator-based dielectrophoresis devices, especially at intermediate device aspect ratios (2 ≤ r ≤ 7) in solutions of higher conductivity (σ m ≥ 1 × 10(-3)S/m). The impact of ET effects on particle deflection and trapping are diminished when particle EP mobility or channel EO mobility is high. In almost all cases, ET effects enhance negative dielectrophoretic particle deflection and trapping phenomena.     

Nanoparticles in nematic liquid crystals: interactions with nanochannels

A mesoscale theory for the tensor order parameter Q is used to investigate the structures that arise when spherical nanoparticles are suspended in confined nematic liquid crystals (NLCs). The NLC is "sandwiched" between a wall and a small channel. The potential of mean force is determined between particles and the bottom of the channels or between several particles. Our results suggest that strong NLC-mediated interactions between the particles and the sidewalls of the channels, on the order of hundreds of k(B)T, arise when the colloids are inside the channels. The magnitude of the channel-particle interactions is dictated by a combination of two factors, namely, the type of defect structures that develop when a nanoparticle is inside a channel, and the degree of ordering of the nematic in the region between the colloid and the nanochannel. The channel-particle interactions become stronger as the nanoparticle diameter becomes commensurate with the nanochannel width. Nanochannel geometry also affects the channel-particle interactions. Among the different geometries considered, a cylindrical channel seems to provide the strongest interactions. Our calculations suggest that small variations in geometry, such as removing the sharp edges of the channels, can lead to important reductions in channel-particle interactions. Our calculations for systems of several nanoparticles indicate that linear arrays of colloids with Saturn ring defects, which for some physical conditions are not stable in a bulk system, can be stabilized inside the nanochannels. These results suggest that nanochannels and NLCs could be used to direct the assembly of nanoparticles into ordered arrays with unusual morphologies.     

Lateral and cross-lateral focusing of spherical particles in a square microchannel

The inertial migration of particles in micro-scale flows has received much attention due to its promising applications, such as the membrane-free passive separation of particles or cells. The particles suspended in rectangular channels are known to be focused near the center of each channel face as the channel Reynolds number (R(C)) increases due to the lift force balance and the hydrodynamic interactions of the particles with the wall. In this study, the three-dimensional positions of neutrally buoyant spherical particles inside a square microchannel are measured using the digital holographic microscopy technique, and a transition from the lateral tubular pinch to the cross-lateral focusing with increasing R(C) is reported. The particles are found to migrate first in the lateral direction and then cross-laterally toward the four equilibrium positions. A general criterion that can be used to secure the fully developed state of particle focusing in Lab-on-a-Chip applications is also derived. This criterion could be helpful for the accurate estimation of the design parameters of inertial microfluidic devices, such as R(C), channel length and width, and particle diameter.     

Different elution modes and field programming in gravitational field-flow fractionation. 2. Experimental verification of the range of conditions for flow-rate and carrier liquid density programming

Gravitational field-flow fractionation utilises the Earth's gravitational field as an external force that causes the settlement of particles towards the channel accumulation wall. Hydrodynamic lift forces oppose this action by elevating of particles from the channel accumulation wall. Therefore there are several possibilities to modulate the resulting force field acting on particles in gravitational field-flow fractionation. Regarding the force field programming in gravitational field-flow fractionation, this work focused on two topics: changes of the difference between particle density and carrier liquid density in Brownian and focusing elution modes and influencing of lift forces achieved by changing the flow-rate in focusing elution mode. We have found and described the experimental conditions applicable to force field programming in the case of separations of silica gel particles by gravitational field-flow fractionation. It was shown that the effect of carrier liquid viscosity in the water-methanol system is implemented as an additional factor enhancing the desired effect of carrier liquid density. Some other forces influencing the retention behaviour of the model particles are discussed.     

Fabrication and evaluation of a ratchet type dielectrophoretic device for particle analysis

Dielectrophoresis is an electrokinetic phenomenon that utilizes an asymmetric electric field to separate analytes based on differences in their polarizabilities relative to that of the suspending medium. One dielectrophoretic device architecture that offers interesting possibilities for particle transport without the use of external flow is the ratchet geometry. This paper describes the fabrication and evaluation of a novel dielectrophoretic ratchet device using a series of fine particles as test probes. The asymmetrical electric field required to selectively transport target analytes was produced using electroformed electrodes which offer the possibility of reducing convective heating and which can be used to construct a device in which all particles located within the fluidic channel are exposed to the applied field. Initial tests of this device were conducted using magnetite and polystyrene fine particles to demonstrate selective particle collection and a separation based on differences in the electrical properties of the analytes employed.     

Enhanced viscoelastic focusing of particle in microchannel

A novel method is reported to enhance the focusing of microparticle in the viscoelastic fluid. Gradually contracted geometry is designed in microchannel, which changes the distribution of the elastic lift force on the cross section. Additionally, it induces the viscous drag force and the Saffman lift force in the lateral direction. Under the combined effect of these forces, microparticles fast migrate to the center of the channel. In comparison to the channel with constant cross section, the present channel significantly enhances the particle's lateral migration, leading to efficient viscoelastic particle focusing in a short channel length. The influence of flow rate, channel length, particle size and fluid property on the particle focusing is also investigated. With simple structure, small footprint and perfect particle focusing performance, the present device has great potential in the particle focusing processes in various lab-on-a-chip applications.     

Manipulating particles in microfluidics by floating electrodes

Various particle manipulations including enrichment, movement, trapping, separation, and focusing by floating electrodes attached to the bottom wall of a straight microchannel under an imposed DC electric field have been experimentally demonstrated. In contrast to a dielectric microchannel possessing a nearly uniform surface charge (or ζ potential), the metal strip (floating electrode) is polarized under the imposed electric field, resulting in a nonuniform distribution of the induced surface charge with a zero net surface charge along the floating electrode's surface, and accordingly induced-charge electroosmotic flow near the metal strip. The induced induced-charge electroosmotic flow can be regulated by controlling the strength of the imposed electric field and affects both the hydrodynamic field and the particle's motion. By using a single floating electrode, charged particles could be locally concentrated in a section of the channel or in an end-reservoir and move toward either the anode or the cathode by controlling the strength of the imposed electric field. By using double floating electrodes, negatively charged particles could be concentrated between the floating electrodes, subsequently squeezed to a stream flowing in the center region of the microchannel toward the cathodic reservoir, which can be used to focus particles.     

On the effect of thermophoretic force,gravitational force,and particle–particle interactions in field-flow fractionation

The theoretical calculations confirmed that the gravitational force cannot be neglected in all field-flow fractionation techniques separating nanometer-sized colloidal particles whenever particle diameter is approximately 200?nm and larger. Particle–particle repulsive interactions, mostly electrostatic repulsions, influence substantially concentration distribution established by any effective field acting across the fractionation channel, as confirmed explicitly for thermophoretic force generated by temperature gradient in microthermal field-flow fractionation. The ionic strength of the carrier liquid causes the screening of the electrostatic double layer around the dispersed particles and thus influences the retention. The attractive particle–particle forces occur when the zeta potential of the particles approaches to 0?mV, the electrostatic repulsions are screened, and the aggregation of the particles is observed. The pH influences differently the size and zeta potential of the plain polystyrene latex particles and of the particles modified on the surface by the groups –COOH and –NH₂. The role of a detergent in carrier liquid is non-negligible, as demonstrated by its presence or absence in carrier liquid.     

Low-capacity channel designed for particle separation with controlled electric fields and evaluation of involved forces

Electric field is one of the suitable physical fields applicable to particle separations. Although long rectangular channel is used for particle separation in usual electrical field flow fractionation (FFF), a short low-capacity channel can replace it if the field is precisely controlled. Several separation principles are proposed with this channel. The elution behavior of particles has revealed that the gravitational, diffusion, and hydrodynamic lift force (HLF) play important roles in the determination of the elution behavior of particles. The elution threshold voltage (V(th)) was defined and experimentally determined for various system configurations and particles. The electric force no longer overcomes the other forces, and particles are taken off the wall, when the applied voltage becomes lower than V(th). V(th) values have allowed us not only to estimate surface charge density of a particle but also to evaluate the hydrodynamic lift force against particle.     

Microdevices for manipulation and accumulation of micro- and nanoparticles by dielectrophoresis

Microfluidic devices with three-dimensional (3-D) arrays of microelectrodes embedded in microchannels have been developed to study dielectrophoretic forces acting on synthetic micro- and nanoparticles. In particular, so-called deflector structures were used to separate particles according to their size and to enable accumulation of a fraction of interest into a small sample volume for further analysis. Particle velocity within the microchannels was measured by video microscopy and the hydrodynamic friction forces exerted on deflected particles were determined according to Stokes law. These results lead to an absolute measure of the dielectrophoretic forces and allowed for a quantitative test of the underlying theory. In summary, the influence of channel height, particle size, buffer composition, electric field, strength and frequency on the dielectrophoretic force and the effectiveness of dielectrophoretic deflection structures were determined. For this purpose, microfluidic devices have been developed comprising pairs of electrodes extending into fluid channels on both top and bottom side of the microfluidic channels. Electrodes were aligned under angles varying from 0 to 75 degrees with respect to the direction of flow. Devices with channel height varying between 5 and 50 microm were manufactured. Fabrication involved a dedicated bonding technology using a mask aligner and UV-curing adhesive. Particles with radius ranging from 250 nm to 12 microm were injected into the channels using aqueous buffer solutions.     

Measurement of mobility of adsorbed colloids by lateral force microscopy

The surface mobility of colloidal latex particles adsorbed on mica was measured by moving the particles with an AFM tip in the lateral force microscopy mode. The same particle was repeatedly scanned while the normal force was gradually increased, until the particle was displaced from its location on the substrate. The lateral (friction) force curve obtained for that scan was then used to determine the force needed to displace the particle. The data accumulated for approximately 100 particles indicate a wide distribution in the lateral force required. However, the data show that the mean lateral force is proportional to the particle diameter, with the effect of electrostatic interactions on the mobility of adsorbed particles seen to be weak. These results are consistent with classical theories of friction in macroscopic systems.