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.     

Particle focusing in a contactless dielectrophoretic microfluidic chip with insulating structures

The focusing of biological and synthetic particles in microfluidic devices is a crucial step for the construction of many microstructured materials as well as for medical applications. The present study examines the feasibility of using contactless dielectrophoresis (cDEP) in an insulator-based dielectrophoretic (iDEP) microdevice to effectively focus particles. Particles 10?μm in diameter were introduced into the microchannel and pre-confined hydrodynamically by funnel-shaped insulating structures near the inlet. The particles were repelled toward the center of the microchannel by the negative DEP forces generated by the insulating structures. The microchip was fabricated based on the concept of cDEP. The electric field in the main microchannel was generated using electrodes inserted into two conductive micro-reservoirs, which were separated from the main microchannel by 20-μm-thick insulating barriers made of polydimethylsiloxane (PDMS). The impedance spectrum of the thin insulating PDMS barrier was measured to investigate its capacitive behavior. Experiments employing polystyrene particles were conducted to demonstrate the feasibility of the proposed microdevice. Results show that the particle focusing performance increased with increasing frequency of the applied AC voltage due to the reduced impedance of PDMS barriers at high frequencies. When the frequency was above 800?kHz, most particles were focused into a single file. The smallest width of focused particles distributed at the outlet was about 13.1?μm at a frequency of 1?MHz. Experimental results also show that the particle focusing performance improved with increasing applied electric field strength and decreasing inlet flow rate. The usage of the cDEP technique makes the proposed microchip mechanically robust and chemically inert.     

Acoustically induced bubbles in a microfluidic channel for mixing enhancement

Due to small dimensions and low fluid velocity, mixing in microfluidic systems is usually poor. In this study, we report a method of enhancing microfluidic mixing using acoustically induced gas bubbles. The effect of applied frequency on mixing was investigated over the range 0.5–10 kHz. Under either low frequency 0.5 kHz or high frequency 10 kHz, no noticeable improvement in the present mixer was observed. However, a significant increase in the mixing efficiency was achieved within a window of the frequencies between 1.0 and 5.0 kHz. It was found in our present microfluidic structure, single (or multi-) bubble(s) could be acoustically generated under the frequency ranging from 1.0 to 5.0 kHz by a piezoelectric disc. The interaction between bubble and acoustic field causes bubble oscillation which in turn could disturb local flow field to result in mixing enhancement.     

A numerical hydrodynamic and thermal characterization of an inter-strata liquid cooling solution for 3D ICs

A novel integrated thermal management solution is proposed to alleviate hot spots in a contemporary 3D IC architecture. The solution employs a series of integrated microchannels, interconnected through each stratum by through silicon fluidic vias (TSFVs), and permits the transfer of heat, via a coolant, from hot to cold zones. This microfluidic system is driven by an integrated AC electrokinetic pump embedded in the channel walls. Recent advancements in electrokinetic micropump technology have allowed greater increases in fluid velocity (mm/s) while operating within the voltage constraints of a 3D IC. This paper presents a 2D simulation of an electrokinetic micropump operating at V_pp = 1.5 V in a 40 μm channel and examines its velocity profile for six frequencies in the range 100 ≤ ω ≤ 100 MHz. An optimum frequency of 100 kHz was established within this range and this was further examined with a constant heat flux of 186 W/cm2 imposed on the wall for an inlet fluid temperature of 40°C. Temperature profiles are presented at the channel-silicon interface and compared with theory.     

High-throughput electrokinetic bioparticle focusing based on a travelling-wave dielectrophoretic field

This study presents a sheathless and portable microfluidic chip that is capable of high-throughput focusing bioparticles based on 3D travelling-wave dielectrophoresis (twDEP). High-throughput focusing is achieved by sustaining a centralized twDEP field normal to the continuous through-flow direction. Two twDEP electrode arrays are formed from upper and lower walls of the microchannel and extend to its center, which induce twDEP forces to provide the lateral displacements in two directions for focusing the bioparticles. Bioparticles can be focused to the center of the microchannel effectively by twDEP conveyance when the characteristic time due to twDEP conveying in the y direction is shorter than the residence time of the particles within twDEP electrode array. Red blood cells can be effectively focused into a narrow particle stream (~10 μm) below a critical flow rate of 10 μl/min (linear flow velocity ~5 mm/s), when under a voltage of 14 V_p–p at a frequency of 500 kHz is applied. Approximately 90% focusing efficiency for red blood cells can be achieved within two 6-mm-long electrode arrays when the flow rate is below 12 μl/min. Blood cells and Candida cells were also focused and sorted successfully based on their different twDEP mobilities. Compared to conventional 3D-paired DEP focusing, velocity is enhanced nearly four folds of magnitude. 3D twDEP provides the lateral displacements of particles and long residence time for migrating particles in a high-speed continuous flow, which breaks through the limitation of many electrokinetic cell manipulation techniques.     

Liquid�Cliquid fluorescent waveguides using microfluidic-drifting-induced hydrodynamic focusing

We demonstrate fluorescent liquid-core/liquid-cladding (L ²) waveguides focused in three-dimensional (3-D) space based on a 3-D hydrodynamic focusing technique. In the proposed system, the core and vertical cladding streams are passed through a curved 90° corner in a microfluidic channel, leading to the formation of a pair of counter rotating vortices known as the Dean vortex. As a result, the core fluid is completely confined within the cladding fluid and does not touch the top and bottom poly(dimethylsiloxane) (PDMS) surfaces of the microfluidic channel. Because the core stream was not in contact with the PDMS channel, whose refractive index contrast and optical smoothness with the core fluid are lower than that between the core and the cladding fluids, the 3-D focused L ² waveguide exhibited a higher captured fraction (η) and lower propagation loss when compared to conventional two-dimensional (2-D) focused L ² waveguides. Because the proposed 3-D focused L ² waveguides can be generated in planar PDMS microfluidic devices, such optofluidic waveguides can be integrated with precise alignment together with other in-plane microfluidic and optical components to achieve micro-total analysis systems (μ-TAS).     

Scaling the formation of slug bubbles in microfluidic flow-focusing devices

The present study aims at scaling the formation of slug bubbles in flow-focusing microfluidic devices using a high-speed digital camera and a micro particle image velocimetry (μ-PIV) system. Experiments were conducted in two different polymethyl methacrylate square microchannels of respectively 600 × 600 and 400 × 400 μm. N₂ bubbles were generated in glycerol–water mixtures with several concentrations of surfactant sodium dodecyl sulfate. The influence of gas and liquid flow rates, the viscosity of the liquid phase and the width of the microchannel on the bubble size were explored. The bubble size was correlated as a function of the width of the microchannel W _c, the ratio of the gas/liquid flow rates Q _g/Q _l and the liquid Reynolds number. During the pinch-off stage, the variation of the minimum width of the gaseous thread W _m with the remaining time could be scaled as _boxclose_boxclose ()^ - 0.15 (T - t)^1/3 . W_{\text{m}} \propto ({\frac{{Q_{\text{g}} }}{{Q_{\text{l}} }}})^{ - 0.15} (T - t)^{1/3} . The velocity fields in the liquid phase around the thread, determined by μ-PIV measurements, were obtained around a forming bubble to reveal the role of the liquid phase.     

Experimental study of the separation behavior of nanoparticles in micro- and nanochannels

In this article, we investigate the effects of pH, ionic strength, and channel height on the mobility and diffusivity of charged spherical particles within planar microfluidic channels. Specifically, we report results of a broad experimental study on the transport and separation behavior of 50 and 100 nm spherical carboxylated polystyrene nanoparticles, confined in 20 μm, 1 μm, and 250 nm deep fluidic channels. We find that pH, ionic strength, and channel height have coupled impacts on mobility changes. In particular, we show that, depending on pH, the dependence of particle mobility on channel size can have opposing behavior. In addition, we also show that at the nanoscale, at lower ionic strengths, there is a substantial increase in mobility, due to enhanced electric fields within the nanochannels. These effects are important to understand in order to avoid potential downfalls in terms of separation efficiency as well as design for better tuning of separation performance in micro- and nanochannels. Finally, we propose a method to estimate the effective zeta potential of spherical particles from measured electrophoretic mobility data. This could prove useful in characterizing a heterogeneous collection of particles having a distribution over a range of values of the zeta potential.     

A numerical study of an electrothermal vortex enhanced micromixer

Temperature gradients aroused from the Joule heating in a non-uniform electrical field can induce inhomogeneities of electric conductivity and permittivity of the electrolyte, thus causing an electrothermal force that generates flow motion. A 2D numerical investigation of a micromixer, utilizing electrothermal effect to enhance its mixing efficiency, is proposed in this paper. Results for temperature and velocity distributions, as well as sample concentration distribution are obtained for an electrolyte solution in a microchannel with different pairs of electrodes under AC potentials with various frequencies. Numerical solutions were first carried out for one pair of electrodes, with a length of 10 μm separated by a gap of 10 μm, on one side wall of a microchannel having a length of 200 μm and a height of 50 μm. It is found that the electrothermal flow effect, in the frequency range for which Coulomb force is predominant, induces vortex motion near the electrodes, thus stirring the flow streams and enhancing its mixing efficiency. If more than one pair of electrodes is located on the opposite walls of the microchannel, the mixing efficiency depends on the AC potential applied pattern and the electrodes arrangement pattern. The distance between two pairs of electrodes on two opposite walls is then optimized numerically. Sample mixing efficiencies, using KCl solutions as the working fluid in microchannels with different number of electrodes pairs at optimal electrodes arrangement pattern, are also investigated. If root mean squared voltages of 10 V in an AC frequency range of 0.1–10 MHz are imposed on 16 pairs of electrodes separated at an optimal distance, the numerical results show that a mixing efficiency of 98% can be achieved at the end of the microchannel having a length of 700 μm and a height of 50 μm at Re = 0.01 Pe _C = 100, and Pe _T = 0.07. However, the mixing efficiency decreases sharply at a frequency higher than 10 MHz owing to the drastically decrease in the Coulomb force.     

Particle streaming and separation using dielectrophoresis through discrete periodic microelectrode array

This study presents a particle manipulation and separation technique based on dielectrophoresis principle by employing an array of isosceles triangular microelectrodes on the bottom plate and a continuous electrode on the top plate. These electrodes generate non-uniform electric fields transversely across the microchannel. The particles within the flowing fluid experience a dielectrophoretic force perpendicular to the fluid flow direction due to the non-uniform electric fields. The isosceles triangular microelectrodes were designed to continuously exert a small dielectrophoretic force on the particles. Particles experiencing a larger dielectrophoretic force would move further in the perpendicular direction to the fluid flow as they traveled past each microelectrode. Polystyrene microspheres were used as the model particles, with particles of ∅20 μm employed for studying the basic characteristics of this technique. Particle separation was subsequently demonstrated on ∅10 and ∅15 μm microspheres. Using an applied sinusoidal voltage of 20 V_pp and frequency of 1 MHz, a mean separation distance of 0.765 mm between them was achieved at a flow rate of 3 μl/min (~1 mm/s), an important consideration for high throughput separation capability in a micro-scale technology device. This unique isosceles triangular microelectrodes design allows heterogeneous particle populations to be separated into multiple streams in a single continuous operation.     

Controlled counter-flow motion of magnetic bead chains rolling along microchannels

We demonstrate controlled transport of superparamagnetic beads in the opposite direction of a laminar flow. A permanent magnet assembles 200 nm magnetic particles into about 200 μm long bead chains that are aligned in parallel to the magnetic field lines. Due to a magnetic field gradient, the bead chains are attracted towards the wall of a microfluidic channel. A rotation of the permanent magnet results in a rotation of the bead chains in the opposite direction to the magnet. Due to friction on the surface, the bead chains roll along the channel wall, even in counter-flow direction, up to at a maximum counter-flow velocity of 8 mm s⁻¹. Based on this approach, magnetic beads can be accurately manoeuvred within microfluidic channels. This counter-flow motion can be efficiently be used in Lab-on-a-Chip systems, e.g. for implementing washing steps in DNA purification.     

AC electroosmotic flow in a DNA concentrator

Experimental velocity measurements are conducted in an AC electrokinetic DNA concentrator. The DNA concentrator is based upon Wong et al. (Transducers 2003, Boston, pp 20–23, 2003a; Anal Chem 76(23):6908–6914, 2004)and consists of two concentric electrodes that generate AC electroosmotic flow to stir the fluid, and dielectrophoretic and electrophoretic force fields that trap DNA near the centre of the inside electrode. A two-colour micro-PIV technique is used to measure the fluid velocity without a priori knowledge of the electric field in the device or the electrical properties of the particles. The device is also simulated computationally. The results indicate that the numerical simulations agree with experimental data in predicting the velocity field structure, except that the velocity scale is an order of magnitude higher for the simulations. Simulation of the dielectrophoretic forces allows the motion of the DNA within the device to be studied. It is suggested that the simulations can be used to study the phenomena occurring in the device, but that experimental data is required to determine the practical conditions under which these phenomena occur.     

Induced-charge electro-osmosis of polymer-containing fluid around a metallic rod

Induced-charge electro-osmotic (ICEO) flow of polymer-containing electrolyte solution around a cylindrical gold-coated stainless steel rod under AC electric field is measured by micro-particle image velocimetry (micro-PIV) for the first time. The ICEO flows as functions of the amount of non-ionic PEG (polyethylene glycol), cationic PDADMA (polydiallyldimethylammonium chloride), and anionic PVSASS (polyvinylsulfonic acid sodium salt) polymers added into the salt solution, frequency, and strength of the AC electric field are measured. The ICEO flow of polymer-containing fluid around the rod is quadrupolar with four vortices and is proportional to the square of imposed electric field. The ICEO flow velocity exponentially decreases with an increased concentration of neutral PEG. Ionic polyelectrolytes significantly increase ICEO velocities due to the enriched net charge within the induced electric double layer arising from the electrostatic interaction between the polarized rod’s surface and the charged polyelectrolytes in ionic polymer solution. In addition, polymer concentration affects the dependence of the ICEO flow on the frequency of AC electric field.     

Mixing and hydrodynamic analysis of a droplet in a planar serpentine micromixer

In this work we combined numerical simulation with molecular-diffusion effect, high-tempo micro-particle image velocimetry (μ-PIV), and probability distribution function (PDF) analysis to investigate the chaotic mixing and hydrodynamics inside a droplet moving through a planar serpentine micromixer (PSM). Robust solutions for the distributions of interface and concentration of the droplets were obtained via computational fluid dynamics. The simulated fluid patterns are consistent with those measured with μ-PIV, which serves as a powerful nonintrusive diagnostic approach to observe the droplets. Two mechanisms are proposed to enhance the performance of mixing in a PSM—the deformation of droplets and the asymmetric recirculation within the droplets. On introducing alternating cross sections into a winding channel, this specific design of PSM is found to amplify the fluid disturbance and maximum vorticity difference. Data show that the PDF of the vorticity fields is modified and the fraction with larger vorticity is increased. Accordingly, the PSM is capable of achieving a mixing index 90% within 700 μm (Re = 2), which is eight times better than for a straight microchannel. The results not only demonstrate explicitly the fluid patterns within the droplets but also provide significant insight into the factors dominating the mixing efficiency.     

Simulation of Stokes flow over microelectrodes with least-squares meshfree method

Microelectrode structures in alternating current (AC) electrokinetics can generate high electric field strength to manipulate, characterize and separate particles in suspending medium. It has been widely used in biological, pharmaceutical and medical fields. In this paper, a least-squares meshfree method (LSMFM) based on the first-order velocity–pressure–vorticity formulation for the Stokes flow, electric potential–electric field strength expression for electric field and temperature–heat flux equations for heat transfer problem is presented to study two-dimensional electrothermally induced fluid flow over microelectrodes. Joule heat generated from electric field acts as heat source and gives rise to electric force and buoyancy force acting on the fluid. The discretization of all system of equations is completed by the least-squares method. The equal-order moving least-squares (MLS) approximation is used with Gaussian quadrature in the background cells constructed by the quadtree algorithm. A matrix-free element-by-element Jacobi preconditioned conjugate gradient method is applied to solve the resulting systems. Finally, an example of steady heat transfer problem with analytical solution is devised to analyze the error estimates of the LSMFM, and the examples of electric field of shielded microstrip line and Stokes flow over microelectrode are also solved to investigate the features of the LSMFM.     

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.     

Rapid quantification of bio-particles based on image visualisation in a dielectrophoretic microfluidic chip

We studied an imaging-based technique for the rapid quantification of bio-particles in a dielectrophoretic (DEP) microfluidic chip. Label-free particles could be successively sorted and trapped in a continuous flow manner under the applied alternating current (AC) conditions. Both 2 and 3 μm polystyrene beads at a concentration of 1.0 × 10⁷ particles ml⁻¹ could be rapidly quantified within 5 min in our DEP system. Capturing efficiencies higher than 95% could be 2 μm polystyrene beads with a linear flow speed, applied voltage and frequency of 0.89 mm s⁻¹, 20 V_p-p and 5 MHz. Yeast cells (Candida glabrata and Candida albicans) could also be captured even at a lower concentration of 2.5 × 10⁵ cells ml⁻¹. Images of aggregative particles taken from the designed trapping area were further processed based on the intensity of relative greyscale followed by correction of the particle numbers. The imaging-based quantification method showed higher agreement than that of the conventional counting chamber method and proved the stability and feasibility of our AC DEP system.     

集成惯性聚焦结构的介电泳微流控芯片的粒子连续分离

设计并制造了一种带有惯性聚焦结构的介电泳微流控芯片,以实现不同介电性质的粒子连续分离.采用MEMS工艺制作了介电泳微流控芯片:通道入口侧壁设置一对梯形结构使经过的粒子受惯性升力的作用聚焦到通道两侧;通道底部光刻一组夹角为90°的倾斜叉指电极产生非均匀电场,利用介电泳力和流体曳力的合力使通道两侧不同的粒子发生角度不同的偏转进入不同通道,从而实现分离.将酵母菌细胞和聚苯乙烯小球作为实验样本,分析了流速和交流电压对分离的影响,确定了二者分离的最优条件并进行分离.实验结果表明,将电导率为20μS/cm的样本溶液以5μL/min的流速注入到通道中,施加6 Vp-p、10 kHz的正弦信号,酵母菌细胞沿电极运动至夹角处后沿通道中心排出,聚苯乙烯小球沿通道两侧排出,成功实现分离,平均分离效率达92.8％、平均分离纯度达90.7％.     

A liquid film motor

It is well known that electro-hydrodynamical effects in freely suspended liquid films can force liquids to flow. Here, we report a purely electrically driven rotation in water and some other liquid suspended films with full control on the velocity and the chirality of the rotating vortices. The device, which is called “film motor”, consists of a quasi two-dimensional electrolysis cell in an external in-plane electric field, crossing the mean electrolysis current density. If either the external field or the electrolysis voltage exceeds some threshold (while the other does not vanish), the liquid film begins to rotate. The device works perfectly with both DC and AC fields.     

Inertial microfluidics for continuous particle filtration and extraction

In this paper, we describe a simple passive microfluidic device with rectangular microchannel geometry for continuous particle filtration. The design takes advantage of preferential migration of particles in rectangular microchannels based on shear-induced inertial lift forces. These dominant inertial forces cause particles to move laterally and occupy equilibrium positions along the longer vertical microchannel walls. Using this principle, we demonstrate extraction of 590 nm particles from a mixture of 1.9 μm and 590 nm particles in a straight microfluidic channel with rectangular cross-section. Based on the theoretical analysis and experimental data, we describe conditions required for predicting the onset of particle equilibration in square and rectangular microchannels. The microfluidic channel design has a simple planar structure and can be easily integrated with on-chip microfluidic components for filtration and extraction of wide range of particle sizes. The ability to continuously and differentially equilibrate particles of different size without external forces in microchannels is expected to have numerous applications in filtration, cytometry, and bioseparations.