Insulator-based Dielectrophoresis Research Articles

Design and Evaluation of a Millifluidic Insulator-Based Dielectrophoresis (DEP) Retention Device to Separate Bacteria from Tap Water

Water is a basic necessity critical to the survival of all living beings. However, many people around the world do not have consistent access to uncontaminated drinking water. Traditional water treatment methods, such as filtration and disinfection, require physical or chemical disinfectants and are prone to fouling. Dielectrophoresis (DEP) enables a system whereby polarized bioparticles exhibit lateral movement under the influence of applied, non-uniform electric fields. A single-stage, continuous flow, millimeter-sized DEP device was designed and fabricated to remove Escherichia coli K12 from contaminated tap water. Glass beads were used to alter the electric field distribution and create zones of high electric field to trap bacterial cells. The effect of varied voltages, flow rates and bead sizes on the removal efficiency was studied. The highest removal efficiency of E. coli K12 was 99.9%, with the device set at 60 V, a flow rate of 1.0 mL/min and a 200 µm bead size. Higher applied voltages, slower flow rates, and smaller bead sizes led to an increased reduction in bacteria. An optimized macro-scale system—with multiple stages of DEP—could be suitable for commercial use and would be an effective method of removing pathogens from polluted tap water.

Particle trapping in electrically driven insulator-based microfluidics: Dielectrophoresis and induced-charge electrokinetics.

Electrokinetically driven insulator‐based microfluidic devices represent an attractive option to manipulate particle suspensions. These devices can filtrate, concentrate, separate, or characterize micro and nanoparticles of interest. Two decades ago, inspired by electrode‐based dielectrophoresis, the concept of insulator‐based dielectrophoresis (iDEP) was born. In these microfluidic devices, insulating structures (i.e., posts, membranes, obstacles, or constrictions) built within the channel are used to deform the spatial distribution of an externally generated electric field. As a result, particles suspended in solution experience dielectrophoresis (DEP). Since then, it has been assumed that DEP is responsible for particle trapping in these devices, regardless of the type of voltage being applied to generate the electric field—direct current (DC) or alternating current. Recent findings challenge this assumption by demonstrating particle trapping and even particle flow reversal in devices that prevent DEP from occurring (i.e., unobstructed long straight channels stimulated with a DC voltage and featuring a uniform electric field). The theory introduced to explain those unexpected observations was then applied to conventional “DC‐iDEP” devices, demonstrating better prediction accuracy than that achieved with the conventional DEP‐centered theory. This contribution summarizes contributions made during the last two decades, comparing both theories to explain particle trapping and highlighting challenges to address in the near future.

Review of nonlinear electrokinetic flows in insulator-based dielectrophoresis: From induced charge to Joule heating effects.

Insulator-based dielectrophoresis (iDEP) has been increasingly used for particle manipulation in various microfluidic applications. It exploits insulating structures to constrict and/or curve electric field lines to generate field gradients for particle dielectrophoresis. However, the presence of these insulators, especially those with sharp edges, causes two nonlinear electrokinetic flows, which, if sufficiently strong, may disturb the otherwise linear electrokinetic motion of particles and affect the iDEP performance. One is induced charge electroosmotic (ICEO) flow because of the polarization of the insulators, and the other is electrothermal flow because of the amplified Joule heating in the fluid around the insulators. Both flows vary nonlinearly with the applied electric field (either DC or AC) and exhibit in the form of fluid vortices, which have been utilized to promote some applications while being suppressed in others. The effectiveness of iDEP benefits from a comprehensive understanding of the nonlinear electrokinetic flows, which is complicated by the involvement of the entire iDEP device into electric polarization and thermal diffusion. This article is aimed to review the works on both the fundamentals and applications of ICEO and electrothermal flows in iDEP microdevices. A personal perspective of some future research directions in the field is also given.

An Electrokinetically-Driven Microchip for Rapid Entrapment and Detection of Nanovesicles.

Electrical Impedance Spectroscopy (EIS) has been widely used as a label-free and rapid characterization method for the analysis of cells in clinical research. However, the related work on exosomes (40–150 nm) and the particles of similar size has not yet been reported. In this study, we developed a new Lab-on-a-Chip (LOC) device to rapidly entrap a cluster of sub-micron particles, including polystyrene beads, liposomes, and small extracellular vesicles (exosomes), utilizing an insulator-based dielectrophoresis (iDEP) scheme followed by measuring their impedance utilizing an integrated electrical impedance sensor. This technique provides a label-free, fast, and non-invasive tool for the detection of bionanoparticles based on their unique dielectric properties. In the future, this device could potentially be applied to the characterization of pathogenic exosomes and viruses of similar size, and thus, be evolved as a powerful tool for early disease diagnosis and prognosis.

Toward low-voltage dielectrophoresis-based microfluidic systems: A review.

Dielectrophoretically driven microfluidic devices have demonstrated great applicability in biomedical engineering, diagnostic medicine, and biological research. One of the potential fields of application for this technology is in point-of-care (POC) devices, ideally allowing for portable, fully integrated, easy to use, low-cost diagnostic platforms. Two main approaches exist to induce dielectrophoresis (DEP) on suspended particles, that is, electrode-based DEP and insulator-based DEP, each featuring different advantages and disadvantages. However, a shared concern lies in the input voltage used to generate the electric field necessary for DEP to take place. Therefore, input voltage can determine portability of a microfluidic device. This review outlines the recent advances in reducing stimulation voltage requirements in DEP-driven microfluidics.

Joule heating-enabled electrothermal enrichment of nanoparticles in insulator-based dielectrophoretic microdevices.

Insulator-based dielectrophoresis (iDEP) exploits the electric field gradients formed around insulating structures to manipulate particles for diverse microfluidic applications. Compared to the traditional electrode-based dielectrophoresis, iDEP microdevices have the advantages of easy fabrication, free of water electrolysis, and robust structure, etc. However, the presence of in-channel insulators may cause thermal effects because of the locally amplified Joule heating of the fluid. The resulting electrothermal flow circulations are exploited in this work to trap and concentrate nanoscale particles (of 100nm diameter and less) in a ratchet-based iDEP microdevice. Such Joule heating-enabled electrothermal enrichment of nanoparticles are found to grow with the increase of alternating current or direct current electric field. It also becomes more effective for larger particles and in a microchannel with symmetric ratchets. Moreover, a depth-averaged numerical model is developed to understand and simulate the various parametric effects, which is found to predict the experimental observations with a good agreement.

Direct Current Electrokinetic Particle Trapping in Insulator-Based Microfluidics: Theory and Experiments

The classic theory of direct-current (DC) insulator-based dielectrophoresis (iDEP) considers that, in order to elicit particle trapping, dielectrophoretic (DEP) velocity counterbalances electrokinetic (EK) motion, that is, electrophoresis (EP) and electro-osmotic flow (EOF). However, the particle velocity DEP component requires empirical correction factors (sometimes as high as 600) to account for experimental observations, suggesting the need for a refined model. Here, we show that, when applied to particle suspensions, a high-magnitude DC uniform electric field induces nonlinear particle velocities, leading to particle flow reversal beyond a critical field magnitude, referred to as the EK equilibrium condition. We further demonstrate that this particle motion can be described through an exploratory induced-charge EP nonlinear model. The model predictions were validated under an insulator-based microfluidic platform demonstrating predictive particle trapping for three different particle sizes (with an estimation error < 10%, not using correction factors). Our findings suggest that particle motion and trapping in "DC-iDEP" devices are dominated by EP and EOF, rather than by DEP effects.

Detection of cell-free DNA nanoparticles in insulator based dielectrophoresis systems.

In this paper, a semi-analytical investigation was performed to study the effect of the geometrical parameters of insulator-based dielectrophoresis (iDEP) systems for cell free DNA (cfDNA) trapping. For this purpose, first electrical potential and fluid flow fields were calculated by solving the governing equations including Poisson and Navier-stokes equations with appropriate boundary conditions (BCs) and then a Lagrangian approach was utilized to analyze the motion of cfDNA under the most important forces affected on it including Brownian, Drag, electrophoresis and dielectrophoresis (DEP) forces. The effect of the different parameters such as the electrical conductivity of the medium, shape and geometrical parameters of the insulators on the dielectrophoretic behavior of cfDNA was studied and the optimal value of these parameters was presented. Finally, in order to predict the minimum voltage required for cfDNA trapping, artificial neural network (ANN) was utilized and a relation between input and output parameters was introduced.

Length-Selective Dielectrophoretic Manipulation of Single-Walled Carbon Nanotubes.

Single-walled carbon nanotubes (SWNTs) possess unique physical, optical, and electrical properties with great potential for future nanoscale device applications. Common synthesis procedures yield SWNTs with large length polydispersity and varying chirality. Electrical and optical applications of SWNTs often require specific lengths, but the preparation of SWNTs with the desired length is still challenging. Insulator-based dielectrophoresis (iDEP) integrated into a microfluidic device has the potential to separate SWNTs by length. Semiconducting SWNTs of varying length suspended with sodium deoxycholate (NaDOC) show unique dielectrophoretic properties at low frequencies (<1 kHz) that were exploited here using an iDEP-based microfluidic constriction sorter device for length-based sorting. Specific migration directions in the constriction sorter were induced for long SWNTs (≥1000 nm) with negative dielectrophoretic properties compared to short (≤300 nm) SWNTs with positive dielectrophoretic properties. We report continuous fractionation conditions for length-based iDEP migration of SWNTs, and we characterize the dynamics of migration of SWNTs in the microdevice using a finite element model. Based on the length and dielectrophoretic characteristics, sorting efficiencies for long and short SWNTs recovered from separate channels of the constriction sorter amounted to >90% and were in excellent agreement with a numerical model for the sorting process.

Insulator-based dielectrophoretic antifouling of nanoporous membrane for high conductive water desalination

Nanoporous membrane (NPM) based water desalination plays an essential role in remedying the global water scarcity crisis. However, the NPM always suffers from fouling issue because of various nanoparticles existed in sea/waste water. Based on the electrical insulation property of NPM and its ultra-small pore size, insulator-based dielectrophoresis (iDEP) is promising for manipulating the nanoparticle behavior in NPM and serves as an effective antifouling technique. Besides, the alternating current electrothermal (ACET) flow occurs due to the temperature dependent variation of water dielectric property, and it also affects the nanoparticle behavior via electrohydrodynamic (EHD) force. In this paper, the AC electrokinetic antifouling mechanism of NPM for water desalination is numerically investigated under several parametric conditions. The results indicate that iDEP force is effective for nanoparticle antifouling in NPM while ACET EHD force has a suppressing influence. Fortunately, due to its dominant magnitude, iDEP force makes the AC electrokinetic based NPM antifouling technique successful. Furthermore, the NPM with circular cone nanopore is highly recommended instead of that with circular cylinder nanopore in order to eliminate the nanoparticle “trapping zone” during antifouling process. The current investigation demonstrates the potential of handling NPM fouling issue using AC electrokinetics for membrane based water desalination technologies.

Passivated-electrode insulator-based dielectrophoretic separation of heterogeneous cell mixtures.

Rapid and accurate purification of various heterogeneous mixtures is a critical step for a multitude of molecular, chemical, and biological applications. Dielectrophoresis has shown to be a promising technique for particle separation due to its exploitation of the intrinsic electrical properties, simple fabrication, and low cost. Here, we present a geometrically novel dielectrophoretic channel design which utilizes an array of localized electric fields to separate a variety of unique particle mixtures into distinct populations. This label-free device incorporates multiple winding rows with several nonuniform structures on to sidewalls to produce high electric field gradients, enabling high locally generated dielectrophoretic forces. A balance between dielectrophoretic forces and Stokes' drag is used to effectively isolate each particle population. Mixtures of polystyrene beads (500nm and 2μm), breast cancer cells spiked in whole blood, and for the first time, neuron and satellite glial cells were used to study the separation capabilities of the design. We found that our device was able to rapidly separate unique particle populations with over 90% separation yields for each investigated mixture. The unique architecture of the device uses passivated-electrode insulator-based dielectrophoresis in an innovative microfluidic device to separate a variety of heterogeneous mixture without particle saturation in the channel.

Continuous flow separation of particles with insulator-based dielectrophoresis chromatography.

The development of insulator-based dielectrophoresis chromatography is proposed here as a novel hybrid technique that capitalizes on the simplicity of insulator-based dielectrophoresis (iDEP) and the well-known chromatographic theory. Chromatographic parameters are employed to characterize dielectrophoretic separation of particles with particles being eluted from the system as enriched particle peaks. By varying the characteristics of the insulating posts, it was possible to manipulate the interactions of the particles with the insulating post array which acted as the stationary phase. The present work studied how the characteristics of the particles affected the particle retention. Different types of particles have distinct interactions with the post array; these interactions depend on particle properties (size, electrical charge, and polarizability). This work includes mathematical modeling with COMSOL and extensive experimentation. Particles ranging from 1 to 10μm in diameter were tested for retention time and eluted as peaks in the iDEP chromatography devices. Separation results were reported in the form of dielectropherograms including the estimation of retention time (tR), separation efficiency (N/meter), and separation resolution (Rs). Two full separations were demonstrated: a separation by charge between two types of particles of similar size (~ 10μm) with different electrical surface charges and a separation by size between 2- and 5-μm particles with similar surface charge (difference in ζP of 4mV). The achieved separation resolutions were Rs = 1.8 and Rs = 3.5, respectively. This is the first study on DEP chromatography to assess performance in terms of resolution and separation efficiency, demonstrating the unique potential of iDEP chromatography.

Material-selective separation of mixed microparticles via insulator-based dielectrophoresis.

Insulator-based dielectrophoresis (iDEP) has become a powerful tool for biomicrofluidic separation and analysis because it is capable to selectively separate biological particle systems according to properties like size, material, and shape. However, it has rarely been used to solve challenging separation problems involving nonbiological particles, namely, for systems that are prone to particle agglomeration. Here, we demonstrate material-selective separation of nonbiological systems, i.e., polystyrene and gold-coated polystyrene particles of two different sizes, using iDEP at high accuracy. For this purpose, we present a method to generate fluorescent gold-coated particles. We further introduce a method to reduce the static backpressure that builds up between in- and outlet reservoir due to electroosmotic flow. Moreover, we found that particle agglomeration makes their separation impossible when conventional iDEP routines are applied. Therefore, two solutions to reduce particle agglomeration are presented: A combination of AC and DC potentials and adjustment of pH and conductivity of the suspending medium. Both approaches allow separating particles under challenging conditions such as initially low absolute particle zeta potentials and high particle concentrations. Since those conditions can also be present in biological iDEP separation processes, the results are of general value for biological and nonbiological iDEP operations.

Analysis of Bacteriophages with Insulator-Based Dielectrophoresis.

Bacterial viruses or phages have great potential in the medical and agricultural fields as alternatives to antibiotics to control nuisance populations of pathogenic bacteria. However, current analysis and purification protocols for phages tend to be resource intensive and have numbers of limitations, such as impacting phage viability. The present study explores the potential of employing the electrokinetic technique of insulator-based dielectrophoresis (iDEP) for virus assessment, separation and enrichment. In particular, the application of the parameter “trapping value” (Tv) is explored as a standardized iDEP signature for each phage species. The present study includes mathematical modeling with COMSOL Multiphysics and extensive experimentation. Three related, but genetically and structurally distinct, phages were studied: Salmonella enterica phage SPN3US, Pseudomonas aeruginosa phage ϕKZ and P. chlororaphis phage 201ϕ2-1. This is the first iDEP study on bacteriophages with large and complex virions and the results illustrate their virions can be successfully enriched with iDEP systems and still retain infectivity. In addition, our results indicate that characterization of the negative dielectrophoretic response of a phage in terms of Tv could be used for predicting individual virus behavior in iDEP systems. The findings reported here can contribute to the establishment of protocols to analyze, purify and/or enrich samples of known and unknown phages.

On the use of correction factors for the mathematical modeling of insulator based dielectrophoretic devices

Mathematical modeling is a fundamental component in the development of new microfluidics techniques and devices. Modeling allows for the rapid testing of new system configurations while saving resources. Microscale electrokinetic (EK) techniques have significantly benefited by the advances in modeling programs and software packages. However, EK phenomena are complex to model, as they dynamically affect system characteristics, including the physical properties of the particles and fluid within the system. Insulator-based dielectrophoresis (iDEP) is an EK technique that has received important attention during the last two decades. In particular, numerous research groups that study iDEP systems employ a combination of modeling and experimentation for developing new iDEP systems. An important fraction of these research groups has adopted the practice of employing "correction factors" to account for EK phenomena that cannot be accurately predicted in their models due to model complexity and limitations in computing resources. The present review article aims to provide the reader with an overview of the most common approaches in the use of correction factors for the modeling of iDEP systems.

Low frequency cyclical potentials for fine tuning insulator-based dielectrophoretic separations.

In this study, we demonstrate the use of cyclical low frequency signals with insulator-based dielectrophoresis (iDEP) devices for the separation of particles of similar characteristics and an experimental method for estimating particle DEP mobilities. A custom signal designer program was created using Matlab® and COMSOL Multiphysics® for the identification of specific low frequency signals aimed at separating particle mixtures by exploiting slight differences in surface charge (particle zeta potential) or particle size. For the separation by surface charge, a mixture of two types of 10 μm particles was analyzed and effectively separated employing both a custom step signal and a sawtooth left signal. Notably, these particles had the same shape, size, and surface functionalization as well as were made from the same substrate material. For the separation by size, a sample containing 2 μm and 5 μm particles was successfully separated using a custom step signal; these particles had the same shape, surface functionalization, were made from the same substrate materials, and had only a small difference in zeta potential (10 mV). Additionally, an experimental technique was developed to estimate the dielectrophoretic mobility of each particle type; this information was then utilized by the signal designer program. The technique developed in this study is readily applicable for designing signals capable of separating micron-sized particles of similar characteristics, such as microorganisms, where slight differences in cell size and the shape of surface charge could be effectively exploited. These findings open the possibility for applications in microbial screening using iDEP devices.

Joule heating effects in optimized insulator-based dielectrophoretic devices: An interplay between post geometry and temperature rise.

Insulator-based dielectrophoresis (iDEP) is the electrokinetic migration of polarized particles when subjected to a non-uniform electric field generated by the inclusion of insulating structures between two remote electrodes. Electrode spacing is considerable in iDEP systems when compared to electrode-based DEP systems, therefore, iDEP systems require high voltages to achieve efficient particle manipulation. A consequence of this is the temperature increase within the channel due to Joule heating effects, which, in some cases, can be detrimental when manipulating biological samples. This work presents an experimental and modeling study on the increase in temperature inside iDEP devices. For this, we studied seven distinct channel designs that mainly differ from each other in their post array characteristics: post shape, post size and spacing between posts. Experimental results obtained using a custom-built copper Resistance Temperature Detector, based on resistance changes, show that the influence of the insulators produces a difference in temperature rise of approximately 4°C between the designs studied. Furthermore, a 3D COMSOL model is also introduced to evaluate heat generation and dissipation, which is in good agreement with the experiments. The model allowed relating the difference in average temperature for the geometries under study to the electric resistance posed by the post array in each design.

Isolation and identification of Listeria monocytogenes utilizing DC insulator-based dielectrophoresis

Foodborne pathogens pose one of the greatest challenges facing public health in the modern day. One important pathogen, Listeria monocytogenes, is known to be challenging to detect and identify. Three serovars cause most of the Listeria related food-borne illnesses, which the Centers for Disease Control currently utilizes a combination of pulsed-field gel electrophoresis and whole genome sequencing for identification and the determination of clusters and outbreaks. There is a potential method for rapid collection of epidemiological information by exploiting the electrokinetic and dielectrophoretic properties of the L. monocytogenes serovars. Using dielectrophoresis, the three most commonly identified serovars of L. monocytogenes can be distinguished from each other. The electrokinetic and dielectrophoretic mobilities of each serovar was determined through a combination of electrokinetic velocity and dielectrophoretic trapping assessments, in conjunction with finite element multi-physics modeling. A mathematical model of the data, which defines the various factors of dielectrophoretic trapping, is utilized and verified based on the behavior of L. monocytogenes in the microchannel. The trapping condition for the serovars were evaluated as 2.8±0.2×109, 2.2±0.2×109, and 2.2±0.3×109Vm−2 and the electrokinetic mobility was assessed to be 19±0.7, 17±0.7, and 9.2±0.3×10−9m2V−1s−1 for the L. monocytogenes serovars 1/2a, 1/2b, and 4b, respectively.

On the design of deterministic dielectrophoresis for continuous separation of circulating tumor cells from peripheral blood cells.

Detection and analysis of circulating tumor cells (CTCs) have emerged as a promising way to diagnose cancer, study its cellular mechanism, and test or develop potential treatments. However, the rarity of CTCs among peripheral blood cells is a big challenge toward CTC detection. In addition, in cases where there is similar size range between certain types of CTCs (e.g. breast cancer cells) and white blood cells (WBCs), high-resolution techniques are needed. In the present work, we propose a deterministic dielectrophoresis (DEP) method that combines the concept of deterministic lateral displacement (DLD) and insulator-based dielectrophoresis (iDEP) techniques that rely on physical markers such as size and dielectric properties to differentiate different type of cells. The proposed deterministic DEP technology takes advantage of frequency-controlled AC electric field for continuous separation of CTCs from peripheral blood cells. Utilizing numerical modeling, different aspects of coupled DLD-DEP design such as the required applied voltages, velocities, and geometrical parameters of DLD arrays of microposts are investigated. Regarding the inevitable difference and uncertainty ranges for the reported crossover frequencies of cells, a comprehensive analysis is conducted on applied electric field frequency as design's determinant factor. Deterministic DEP design provides continuous sorting of CTCs from WBCs even with similar size and has the future potential for high throughput and efficiency.

Numerical study of insulation structure characteristics and arrangement effects on cell trapping using alternative current insulating based dielectrophoresis

Insulator-based dielectrophoresis is a recently developed technique in which insulating posts are used to produce non-uniformity in the electric field in a microchannel. This study presents the effects of insulating posts geometry and arrangement on the trapping efficiency of red blood cells in an alternating current- Insulator-based dielectrophoresis system. Microchannels containing square, circular and diamond-shaped posts with particles under the influence of positive dielectrophoresis force and fluid flow were considered. Finite element method was used to compute the velocity of the flow and electric field. The numerical method was verified by comparing the numerical results with experimental data. Two distinct criteria for examining particle trapping for distinct shapes and arrangements of insulating posts were introduced. Particle tracing simulation was implemented to observe particle trapping and compare the trapping performance of systems with distinct posts. As shown in the results for the system with circular and square posts, insulators should be narrowed to improve particle trapping, while diamond post should be widened to increase the trapping efficiency. In addition, the particle tracing results showed that microchannel with square posts is more efficient in particle trapping.