Experimental study of dielectrophoresis and liquid dielectrophoresis mechanisms for particle capture in a droplet

This work presents a microfluidic system that can transport, concentrate, and capture particles in a controllable droplet. Dielectrophoresis (DEP), a phenomenon in which a force is exerted on a dielectric particle when it is subjected to a non-uniform electric field, is used to manipulate particles. Liquid dielectrophoresis (LDEP), a phenomenon in which a liquid moves toward regions of high electric field strength under a non-uniform electric field, is used to manipulate the fluid. In this study, a mechanism of droplet creation presented in a previous work that uses DEP and LDEP is improved. A driving electrode with a DEP gap is used to prevent beads from getting stuck at the interface between air and liquid, which is actuated with an AC signal of 200 V(pp) at a frequency of 100 kHz. DEP theory is used to calculate the DEP force in the liquid, and LDEP theory is used to analyze the influence of the DEP gap. The increment of the actuation voltage due to the electrode with a DEP gap is calculated. A set of microwell electrodes is used to capture a bead using DEP force, which is actuated with an AC signal of 20 V(pp) at a frequency of 5 MHz. A simulation is carried out to investigate the dimensions of the DEP gap and microwell electrodes. Experiments are performed to demonstrate the creation of a 100-nL droplet and the capture of individual 10-μm polystyrene latex beads in the droplet.     

Front Cover: Enhancement of dielectrophoresis-based particle collection from high conducting fluids due to partial electrode insulation

Dielectrophoresis (DEP) is a successful method to recover nanoparticles from different types of fluid. The DEP force acting on these particles is created by an electrode microarray that produces a nonuniform electric field. To apply DEP to a highly conducting biological fluid, a protective hydrogel coating over the metal electrodes is required to create a barrier between the electrode and the fluid. This protects the electrodes, reduces the electrolysis of water, and allows the electric field to penetrate into the fluid sample. We observed that the protective hydrogel layer can separate from the electrode and form a closed domed structure and that collection of 100 nm polystyrene beads increased when this occurred. To better understand this collection increase, we used COMSOL Multiphysics software to model the electric field in the presence of the dome filled with different materials ranging from low-conducting gas to high conducting phosphate-buffered saline fluids. The results suggest that as the electrical conductivity of the material inside the dome is reduced, the whole dome acts as an insulator which increases electric field intensity at the electrode edge. This increased intensity widens the high-intensity electric field factor zone resulting in increased collection. This informs how dome formation results in increased particle collection and provides insight into how the electric field can be intensified to the increase collection of particles. These results have important applications for increasing the recovery of biologically-derived nanoparticles from undiluted physiological fluids that have high conductance, including the collection of cancer-derived extracellular vesicles from plasma for liquid biopsy applications.     

Bacteria capture, concentration and detection by alternating current dielectrophoresis and self-assembly of dispersed single-wall carbon nanotubes

The high polarizability and dielectrophoretic mobility of single-walled carbon nanotubes (SWNT) are utilized to capture and detect low numbers of bacteria and submicron particles in milliliter-sized samples. Concentrated SWNT solutions are mixed with the sample and a high-frequency (>100 kHz) alternating current (AC) field is applied by a microelectrode array to enhance bulk absorption of the particles (bacteria and nanoparticle substitutes) by the SWNTs via dipole-dipole interaction. The same AC field then drives the SWNT-bacteria aggregates to the microelectrode array by positive-AC dielectrophoresis (DEP), with enhanced and reversed bacteria DEP mobility due to the attached SWNTs. Since the field frequency exceeds the inverse RC time of the electrode double layer, the AC field penetrates deeply into the bulk and across the electrode gap. Consequently, the SWNTs and absorbed bacteria assemble rapidly (<5 min) into conducting linear aggregates between the electrodes. Measured AC impedance spectra by the same trapping electrodes and fields show a detection threshold of 10(4) bacteria/mL with this pathogen trapping and concentration technique.     

Manipulation and characterization of red blood cells with alternating current fields in microdevices

The motion of a suspension of erythrocytes (red blood cells, RBCs) in response to a high-frequency alternating current (AC) field in a microfluidic device is examined with parallel and orthogonal electrode configurations to delineate the various fundamental driving forces. Cell repulsion from the platinum electrodes due to electrode polarization interacting with cell membrane polarizations is observed to be the strongest force acting on the particles in the first few seconds of field application. We exploit this strong repulsion to concentrate the bioparticles between the microelectrodes to amplify multiparticle aggregation phenomenon and dielectrophoretic (DEP) manipulation in a small and well-characterized region within the microfluidic device. Secondary motions include RBC pearl chain formation along field lines due to particle polarization followed by classical dielectrophoretic motion of the chains across field lines to regions of weaker field. These are driven by far weaker dipole-dipole and field-dipole interactions than the preliminary electrode repulsions. RBC chain length and total aggregated cells are presented for a variety of AC frequencies and are significantly amplified by the electrode repulsion. Motion of particles away from the polarized electrode is found to be species- and age-sensitive and can stand by itself as a promising identification and separation mechanism. In a 0.1 S/m isotonic phosphate buffer saline medium, we observe the largest cell mobilities at an optimal frequency of approximately 1 MHz, corresponding to the inverse diffusion time across the double layer of the cell and across the electrode's polarized layer. This suggests that the dielectric responses of both particles and electrodes in the low MHz frequency range are mostly determined by normal electromigration of ions from the bulk to their interfaces. Sensitivity to RBC age and species suggests that the surface proteins and membrane ion channels can affect the capacitance of the interface to accommodate the ions from the bulk. Such surface ion accumulation and polarization mechanisms are different from the classical dielectric theories. The resonant frequency of electrode polarization at around 1 MHz falls between positive and negative dielectrophoretic resonant frequency peaks - suggesting that the double-layer polarization mechanism is a distinct and potentially important bioparticle manipulation tool.     

Dielectrophoretic separation of micron and submicron particles: A review

This paper provides an overview on separation of micron and submicron sized biological (cells, yeast, virus, bacteria, etc.) and nonbiological particles (latex, polystyrene, CNTs, metals, etc.) by dielectrophoresis (DEP), which finds wide applications in the field of medical and environmental science. Mathematical models to predict the electric field, flow profile, and concentration profiles of the particles under the influence of DEP force have also been covered in this review. In addition, advancements made primarily in the last decade, in the area of electrode design (shape and arrangement), new materials for electrode (carbon, silicon, polymers), and geometry of the microdevice, for efficient DEP separation of particles have been highlighted.     

High-throughput dielectrophoretic manipulation of bioparticles within fluids through biocompatible three-dimensional microelectrode array

Dielectrophoresis (DEP) has been deemed as a potential and ideal solution for bioparticle manipulation. A 3-D carbon micro-electro-mechanical system (MEMS) fabricated from the latest developed carbon-MEMS approach has advantages of offering low-cost, biocompatible and high-throughput DEP manipulation for bioparticles. In this paper, a typical process for fabrication of various 3-D microelectrode configurations was demonstrated; accurate numerical analysis was presented on electric field gradient distribution and DEP force based on various microelectrode array configurations. The effects of electrode edge angle, electrode edge-to-edge spacing and electrode height on the electric field distributions were investigated, and optimal design considerations and rules were concluded through analysis of results. The outcomes demonstrate that the sharp edge electrode is more effective in DEP manipulation and both electrode edge-to-edge spacing and electrode height are critical design parameters for seeking optimal DEP manipulation. The gradient magnitude increases exponentially as the electrode spacing is reduced and the electric field extends significantly as the electrode height increases, both of which contribute to a higher throughput for DEP manipulation. These findings are consistent with experimental observations in the literature and will provide critical guidelines for optimal design of DEP devices with 3-D carbon-MEMS.     

AC dielectrophoretic deformable particle-particle interactions and their relative motions

This paper develops a numerical simulation model to research the deformable particle-particle interactions caused by dielectrophoresis (DEP) under AC electric fields. The DEP force is calculated by using Maxwell stress tensor method, and the hydrodynamic force is obtained by calculating the hydrodynamic stress tensor. Simulation results show that the DEP interactive motion will facilitate the particles forming particle chains that are parallel to the electric field, and the particles with low shear modulus present a lower x-component velocity. Also, the electric field intensity and particles radius have some effects on the DEP motions, and for different particles, smaller particles with larger electric field intensity easily reach a larger velocity. The numerical research may provide universal guidance for biological cells manipulation and assembly.     

Multistep manipulations of poly(methyl‐methacrylate) submicron particles using dielectrophoresis

A microfluidic chip for multistep manipulations of PMMA submicron particles (PMMA‐SMPs) based on dielectrophoresis (DEP) has been developed that includes four main functions of focusing, guiding, trapping, and releasing the SMPs. The structure of the DEP chip consists of a top electrode made of indium tin oxide, a flow chamber formed by optically clear adhesive tape and bottom electrodes with different patterns for different purposes. The bottom electrodes can be divided into three parts: a fish‐bone‐type electrode array that provides the positive DEP force for focusing the suspended nanoparticles (NPs) near the inlet in the flow chamber; the second is for switching and guiding the focused NPs along the electrode surface to the target area, like a flow passing along a virtual channel; and a trapping electrode in the downstream for trapping and releasing the guided NPs. According to the simulation and experimental results, NPs can be aligned along the electrode of the focusing electrode and guided toward the target electrode by means of a positive DEP force between the top and bottom electrodes, with the effects of Brownian motion and Stokes force. In order to demonstrate the sequence of DEP manipulations, a PMMA‐NP suspension is introduced to the DEP chip; the size of the PMMA‐SMPs is about 300 nm. Furthermore, a LabVIEW program developed for sequence control of the AC signals for the multistep manipulations. Consequently, the DEP chip provides an excellent platform technology for the multistep manipulation of SMPs.     

Assembly of long carbon nanotube bridges across transparent electrodes using novel thickness-controlled dielectrophoresis

The assembly of carbon nanotubes (CNTs) across planner electrodes using dielectrophoresis (DEP) is one of the standard methods used to fabricate CNT-based devices such as sensors. The medium drag velocity caused by electrokinetic phenomena such as electrothermal and electroosmotic might drive CNTs away from the deposition area. This problem becomes critical at large-scale electrode structures due to the high attenuation of the DEP force. Herein, we simulated and experimentally validated a novel DEP setup that uses a top glass cover to minimize the medium drag velocity. The simulation results showed that the drag velocity can be reduced by 2–3 orders of magnitude compared with the basic DEP setup. The simulation also showed that the optimum channel height to result in a significant drag velocity reduction was between 100 μm and 240 μm. We experimentally report, for the first time, the assembly and alignment of CNT bridges across indium tin oxide (ITO) electrodes with spacing up to 125 μm. We also derived an equation to optimize the CNT's concentration in suspensions based on the electrode gap width and channel height. The deposition of long CNTs across ITO electrodes has potential use in transparent electronics and microfluidic systems.     

Dielectrophoretic tweezers as a platform for molecular force spectroscopy in a highly parallel format

We demonstrated the application of a simple electrode geometry for dielectrophoresis (DEP) on colloidal probes as a form of molecular force spectroscopy in a highly parallel format. The electric field between parallel plates is perturbed with dielectric microstructures, generating uniform DEP forces on colloidal probes in the range of several hundred piconewtons across a macroscopic sample area. We determined the approximate crossover frequency between negative and positive DEP using electrodes without dielectric microstructures-a simplification over standard experimental methods involving quadrupoles or optical trapping. 2D and 3D simulations of the electric field distributions validated the experimental behavior of several of our DEP tweezers geometries and provided insight into potential improvements. We applied the DEP tweezers to the stretching of a short DNA oligomer and detected its extension using total-internal reflection fluorescence microscopy. The combination of a simple cell fabrication, a uniform distribution of high axial forces, and a facile optical detection of our DEP tweezers makes this form of molecular force spectroscopy ideal for highly parallel detection of stretching or unbinding kinetics of biomolecules.     

Dielectrophoretic manipulation and separation of microparticles using curved microelectrodes

This paper presents the development and experimental analysis of a dielectrophoresis (DEP) system, which is used for the manipulation and separation of microparticles in liquid flow. The system is composed of arrays of microelectrodes integrated to a microchannel. Novel curved microelectrodes are symmetrically placed with respect to the centre of the microchannel with a minimum gap of 40 μm. Computational fluid dynamics method is utilised to characterise the DEP field and predict the dynamics of particles. The performance of the system is assessed with microspheres of 1, 5 and 12 μm diameters. When a high‐frequency potential is applied to microelectrodes a spatially varying electric field is induced in the microchannel, which creates the DEP force. Negative‐DEP behaviour is observed with particles being repelled from the microelectrodes. The particles of different dimensions experience different DEP forces and thus settle to separate equilibrium zones across the microchannel. Experiments demonstrate the capability of the system as a field flow fraction tool for sorting microparticles according to their dimensions and dielectric properties.     

Development of a new contactless dielectrophoresis system for active particle manipulation using movable liquid electrodes

This study presents a new DEP manipulation technique using a movable liquid electrode, which allows manipulation of particles by actively controlling the locations of electrodes and applying on–off electric input signals. This DEP system consists of mercury as a movable liquid electrode, indium tin oxide (ITO)‐coated glass, SU‐8‐based microchannels for electrode passages, and a PDMS medium chamber. A simple squeezing method was introduced to build a thin PDMS layer at the bottom of the medium chamber to create a contactless DEP system. To determine the operating conditions, the DEP force and the friction force were analytically compared for a single cell. In addition, an appropriate frequency range for effective DEP manipulation was chosen based on an estimation of the Clausius–Mossotti factor and the effective complex permittivity of the yeast cell using the concentric shell model. With this system, we demonstrated the active manipulation of yeast cells, and measured the collection efficiency and the dielectrophoretic velocity of cells for different AC electric field strengths and applied frequencies. The experimental results showed that the maximum collection efficiency reached was approximately 90%, and the dielectrophoretic velocity increased with increasing frequency and attained the maximum value of 10.85 ± 0.95 μm/s at 100 kHz, above which it decreased.     

Dielectrophoretic force on a sphere near a planar boundary

The small gap distance separating a spherical colloidal particle in electrophoretic motion from a planar nonconducting surface is a required parameter for calculating its electrophoretic mobility. In the presence of an externally applied electric field, this gap distance is determined by balancing the van der Waals, electrical double layer interaction, and gravitational forces with a dielectrophoretic (DEP) force. Here, the DEP force was determined analytically by integration of the Maxwell stress over the surface of the particle. The account of this force showed that its previous omission from the analysis always resulted in underpredicted gap distances. Furthermore, the DEP force dominated under conditions of low particle density or high electric field strength and led to much higher gap distances on the order of a few microns. In one particular case, a combination of low particle density and small particle size produced two possible equilibrium gap distances for the particle. However, the particle was unstable in the second equilibrium position when subjected to small perturbations. In general, larger particles had smaller gap sizes. The effects of four other parameters on gap distance were studied, and gap distances were found to increase with lower particle density, higher electric field strength, higher particle and wall zeta potentials, and lower Hamaker constants. Retardation effects on van der Waals attraction were considered.     

Size and medium conductivity dependence on dielectrophoretic behaviors of gas core poly‐l‐lysine shell nanoparticles

Dynamic (dis)assembly of biocompatible nanoparticles into 3D, packed structures would benefit drug delivery, films, and diagnostics. Dielectrophoretic (DEP) microdevices can rapidly assemble and manipulate polarizable particles within nonuniform electric fields. DEP has primarily discerned micrometer particles since nanoparticles experience smaller forces. This work examines conductivity and size DEP dependencies of previously unexplored spherical core‐shell nanoparticle (CSnp) into 3D particle assemblies. Poly‐l ‐lysine shell material was custom synthesized around a gas core to form CSnps. DEP frequencies from 1 kHz to 80 MHz at fixed 5 volts peak‐to‐peak and medium conductivities of 10^?5 and 10^?3 S/m were tested. DEP responses of ～220 and ～400 nm poly‐l ‐lysine CSnps were quantified via video intensity densitometry at the microdevice's quadrapole electrode center for negative DEP (nDEP) and adjacent to electrodes for positive DEP. Intensity densitometry was then translated into a relative DEP response curve. An unusual nDEP peak occurred at ～57 MHz with 25–80 times greater apparent nDEP force. All electrical circuit components were then impedance matched, which changed the observed response to weak positive DEP at low frequencies and consistently weak nDEP from ～100 kHz to 80 MHz. This impedance‐matched behavior agrees with conventional Clausius–Mossotti DEP signatures taking into account the gas core's contributions to the polarization mechanisms. This work describes a potential pitfall when conducting DEP at higher frequencies in microdevices and concurrently demonstrates nDEP behavior for a chemically and structurally distinct particle system. This work provides insight into organic shell material properties in nanostructures and strategies to facilitate dynamic nanoparticle assemblies.     

Microfluidic system for dielectrophoretic separation based on a trapezoidal electrode array

This paper presents a novel microfluidic device for dielectrophoretic separation based on a trapezoidal electrode array (TEA). In this method, particles with different dielectric properties are separated by the device composed of the TEA for the dielectrophoretic deflection of particles under negative dielectrophoresis (DEP) and poly(dimethylsiloxane)(PDMS) microfluidic channel with a sinuous and expanded region. Polystyrene microparticles are exposed to an electric field generated from the TEA in the microfluidic channel and are dielectrophoretically focused to make all of them line up to one sidewall. When these particles arrive at the region of another TEA for dielectrophoretic separation, they are separated having different positions along the perpendicular direction to the fluid flow due to their different dielectrophoretic velocities. To evaluate the separation process and performance, both the effect of the flow rate on dielectrophoretic focusing and the influence of the number of trapezoidal electrodes on dielectrophoretic separation are investigated. Now that this method utilizes the TEA as a source of negative DEP, non-specific particle adhering to the electrode surface can be prevented; conventional separation approaches depending on the positive DEP force suffer from this problem. In addition, since various particle types are continuously separated, this method can be easily applicable to the separation and analysis of various dielectric particles with high particle recovery and selectivity.     

Rapid microparticle patterning by enhanced dielectrophoresis effect on a double-layer electrode substrate

We present a feasible dielectrophoresis (DEP) approach for rapid patterning of microparticles on a reusable double-layer electrode substrate in microfluidics. Simulation analysis demonstrated that the DEP force was dramatically enhanced by the induced electric field on top interdigitated electrodes. By adjusting electric field intensity through the bottom electrodes on thin glass substrate (100 μm), polystyrene particles (10 μm) were effectively patterned by top electrodes within several seconds (<5 s). The particle average velocity can reach a maximum value of about 20.0±3.0 μm/s at 1 MHz with the strongest DEP force of 1.68 pN. This approach implements integration of functional electrodes into one substrate and avoids direct electrical connection to biological objects, providing a potential lab-on-chip system for biological applications.     

Response of Bi-disperse Polyelectrolyte Brushes to External Electric Fields——A Numerical Self-consistent Field Theory Study

The self-consistent field theory has been employed to numerically study the response of bi-disperse flexible polyelectrolyte (PE) brushes grafted on an electrode to electric fields generated by opposite surface charges on the PE-grafted electrode and a second parallel electrode. The numerical study reveals that, under a positive external electric field, the shorter and negatively charged PE chains are more responsive than the longer PE chains in terms of the relative changes in their respective brush heights. Whereas under a negative external electric field, the opposite was observed. The total electric force on the grafted PE chains was calculated and it was found that, under a positive external electric field, the magnitude of the total electric force acting on one shorter PE chain is larger than that on one longer PE chain, or vice versa. The underlying mechanism was unraveled through analyzing the total electric field across the two oppositely charged electrodes.     

Dielectrophoretic levitation in the presence of shear flow: implications for colloidal fouling of filtration membranes

The ability of dielectrophoretic (DEP) forces created using a microelectrode array to levitate particles in a colloidal suspension is studied experimentally and theoretically. The experimental system employs microfabricated electrode arrays on a glass substrate to apply repulsive DEP forces on polystyrene latex particles suspended in an aqueous medium. A numerical model based on the convection-diffusion-migration equation is presented to calculate the concentration distribution of colloidal particles in shear flow under the influence of a repulsive DEP force field. The results obtained from the numerical simulations are compared against trajectory analysis results and experimental data. The results indicate that by incorporating ac electric field-induced DEP forces in a shear flow, particle accumulation and deposition on the flow channel surfaces can be significantly reduced or even completely averted. The mathematical model is then used to indicate how the deposition behavior is modified in the presence of a permeable substrate, representative of tangential flow membrane filtration operations. The results indicate that the repulsive dielectrophoretic (DEP) forces imparted to the particles suspended in the feed can be employed to mitigate membrane fouling in a cross-flow filtration process.     

Dielectrophoresis applications in biomedical field and future perspectives in biomedical technology

Dielectrophoresis (DEP) is a technique to manipulate trajectories of polarisable particles in nonuniform electric fields by utilizing unique dielectric properties. The manipulation of a cell using DEP has been demonstrated in various modes, thereby indicating potential applications in the biomedical field. In this review, recent DEP applications in the biomedical field are discussed. This review is intended to highlight research work that shows significant approach related to DEP application in biomedical field reported between 2016 and 2020. First, single-shell model and multiple-shell model of cells are introduced. Current device structures and recently introduced electrode patterns for DEP applications are discussed. Second, the biomedical uses of DEP in liquid biopsies, stem cell-based therapies, and diagnosis of infectious diseases due to bacteria and viruses are presented. Finally, the challenges in DEP research are discussed, and the reported solutions are explained. DEP's potential research directions are mentioned.     

Dielectrophoretic assembly of nanowires

Nanowire (NW) assembly is currently of great interest, partly because NWs are considered as a fundamental component in the fabrication of a variety of devices. A powerful method has been developed to model the assembly of NWs. The three-dimensional dielectrophoretic (DEP) assembly of NWs across opposing electrodes is, for the first time, comprehensively studied using this new method. It is found that the DEP force reaches a maximum when the ratio of gap size to NW length is in the range 0.85-1.0. Both the magnitude and sign of the DEP torque on each NW varies with this ratio, and also with the orientation angle and the geometry and configuration of the electrode. The simulation of the dynamic assembly of individual and bundled NWs agrees with experiment. This method is of sufficient power that it will be of direct use in modeling DEP-based assembly and thus the manufacturing of nanoelectronic devices.