Dielectrophoresis Manipulation Research Articles

Dielectrophoresis: Measurement technologies and auxiliary sensing applications.

Dielectrophoresis (DEP), which arises from the interaction between dielectric particles and an aqueous solution in a nonuniform electric field, contributes to the manipulation of nano and microparticles in many fields, including colloid physics, analytical chemistry, molecular biology, clinical medicine, and pharmaceutics. The measurement of the DEP force could provide a more complete solution for verifying current classical DEP theories. This review reports various imaging, fluidic, optical, and mechanical approaches for measuring the DEP forces at different amplitudes and frequencies. The integration of DEP technology into sensors enables fast response, high sensitivity, precise discrimination, and label-free detection of proteins, bacteria, colloidal particles, and cells. Therefore, this review provides an in-depth overview of DEP-based fabrication and measurements. Depending on the measurement requirements, DEP manipulation can be classified into assistance and integration approaches to improve sensor performance. To this end, an overview is dedicated to developing the concept of trapping-on-sensing, improving its structure and performance, and realizing fully DEP-assisted lab-on-a-chip systems.

Numerical Simulations of Combined Dielectrophoresis and Alternating Current Electrothermal Flow for High-Efficient Separation of (Bio)Microparticles.

High-efficient separation of (bio)microparticles has important applications in chemical analysis, environmental monitoring, drug screening, and disease diagnosis and treatment. As a label-free and high-precision separation scheme, dielectrophoresis (DEP) has become a research hotspot in microparticle separation, especially for biological cells. When processing cells with DEP, relatively high electric conductivities of suspending media are sometimes required to maintain the biological activities of the biosample, which results in high temperature rises within the system caused by Joule heating. The induced temperature gradient generates a localized alternating current electrothermal (ACET) flow disturbance, which seriously impacts the DEP manipulation of cells. Based on this, we propose a novel design of the (bio)microparticle separator by combining DEP with ACET flow to intensify the separation process. A coupling model that incorporates electric, fluid flow, and temperature fields as well as particle tracking is established to predict (bio)microparticle trajectories within the separator. Numerical simulations reveal that both ACET flow and DEP motion act in the same plane but in different directions to achieve high-precision separation between particles. This work provides new design ideas for solving the very tricky Joule heating interference in the DEP separation process, which paves the way for further improving the throughput of the DEP-based (bio)microparticle separation system.

Migration Study of Dielectrophoretically Manipulated Red Blood Cells in Tapered Aluminium Microelectrode Array: A Pilot Study.

Dielectrophoresis (DEP) is one of the microfluid-based techniques that can manipulate the red blood cells (RBC) for blood plasma separation, which is used in many medical screening/diagnosis applications. The tapered aluminium microelectrode array (TAMA) is fabricated for potential sensitivity enhancement of RBC manipulation in lateral and vertical directions. In this paper, the migration properties of dielectrophoretically manipulated RBC in TAMA platform are studied at different peak-to-peak voltage (Vpp) and duration supplied onto the microelectrodes. Positive DEP manipulation is conducted at 440 kHz with the RBC of 4.00 ± 0.2 µm average radius attracted to the higher electric field intensity regions, which are the microelectrodes. High percentage of RBC migration occurred at longer manipulation time and high electrode voltage. During DEP manipulation, the RBC are postulated to levitate upwards, experience the electro-orientation mechanism and form the pearl chains before migrating to the electrodes. The presence of external forces other than the dielectrophoretic force may also affect the migration response of RBC. The safe operating limit of 10 Vpp and manipulation duration of ≤50 s prevent RBC rupture while providing high migration percentage. It is crucial to define the safe working region for TAMA devices that manipulate small RBC volume (~10 µL).

Dynamic dielectrophoretic cell manipulation is enabled by an innovative electronics platform

We report on a portable dielectrophoresis manipulation platform, for the positioning and immobilization of small dielectric objects, such as cells or microbes, using a circular array of up to six symmetrically arranged and independently controllable micro-electrodes. The system’s micro-controller-instructed electronic drivers can be operated in three distinct modes. We demonstrate the system’s function by actuating bacterial cells to specific locations and orientations within a region of interest. Using a deep learning approach, we map voltage phase combinations of the six electrodes to geometrical trap position locations, thereby facilitating smooth trajectory planning.

Protein Albumin Manipulation and Electrical Quantification of Molecular Dielectrophoresis Responses for Biomedical Applications.

Research relating to dielectrophoresis (DEP) has been progressing rapidly through time as it is a strong and controllable technique for manipulation, separation, preconcentration, and partitioning of protein. Extensive studies have been carried out on protein DEP, especially on Bovine Serum Albumin (BSA). However, these studies involve the usage of dye and fluorescent probes to observe DEP responses as the physical properties of protein albumin molecular structure are translucent. The use of dye and the fluorescent probe could later affect the protein’s physiology. In this article, we review three methods of electrical quantification of DEP responses: electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and capacitance measurement for protein BSA DEP manipulation. The correlation of these methods with DEP responses is further discussed. Based on the observations on capacitance measurement, it can be deduced that the electrical quantifying method is reliable for identifying DEP responses. Further, the possibility of manipulating the protein and electrically quantifying DEP responses while retaining the original physiology of the protein and without the usage of dye or fluorescent probe is discussed.

Methods of Generating Dielectrophoretic Force for Microfluidic Manipulation of Bioparticles.

Manipulation of microscale bioparticles including living cells is of great significance to the broad bioengineering and biotechnology fields. Dielectrophoresis (DEP), which is defined as the interactions between dielectric particles and the electric field, is one of the most widely used techniques for the manipulation of bioparticles including cell separation, sorting, and trapping. Bioparticles experience a DEP force if they have a different polarization from the surrounding media in an electric field that is nonuniform in terms of the intensity and/or phase of the electric field. A comprehensive literature survey shows that the DEP-based microfluidic devices for manipulating bioparticles can be categorized according to the methods of creating the nonuniformity via patterned microchannels, electrodes, and media to generate the DEP force. These methods together with the theory of DEP force generation are described in this review, to provide a summary of the methods and materials that have been used to manipulate various bioparticles for various specific biological outcomes. Further developments of DEP-based technologies include identifying materials that better integrate with electrodes than current popular materials (silicone/glass) and improving the performance of DEP manipulation of bioparticles by combining it with other methods of handling bioparticles. Collectively, DEP-based microfluidic manipulation of bioparticles holds great potential for various biomedical applications.

Measurement of Electric Double Layer Capacitance Using Dielectrophoresis-Based Particle Manipulation.

An electric double layer (EDL) generally exists at the interface between a conductive electrode and its adjacent liquid electrolyte. Accurate measurement of the capacitance of EDL is requisite but a great challenge due to the complexity of its variation mechanism correlated with the magnitude and frequency of applied signals and the difficulty in measuring the inner layer potentials across the EDL. Herein, a novel dielectrophoresis (DEP)-based approach is proposed to measure the capacitance of an EDL at a microelectrode/electrolyte interface. The measurement is achieved by employing DEP manipulation to micro polystyrene (PS) spheres suspended in a liquid electrolyte and determining the capacitance of EDL on the microelectrodes from the moving velocities of spheres. This method allows measurement of the capacitances of EDL under alternating current (AC) signals with different magnitudes and frequencies, so that the capacitance change with the magnitude and frequency of the applied signal can be characterized. The method avoids the impedance interference from the liquid electrolyte, external measuring systems, and other crosstalks, enabling an accurate measurement of double layer capacitance. In addition, the inner layer potentials across EDL under different magnitudes and frequencies of applied signals are comprehensively investigated, which facilitates an understanding of the ion behavior at the interfacial boundary that governs external observations of electrochemical reactions. The accurate measurement of the capacitance of EDL is of significance to explore the mechanism of interfacial functioning of electrochemical and bioelectrical devices and systems.

Dielectrophoretic interactions of two rod-shaped deformable particles under DC electric field

Dielectrophoresis (DEP) has become one of the commonly employed technologies for manipulating bioparticles in micro/nano-devices. Based on the thin electric double layer (EDL) hypothesis and the arbitrary Lagrangian-Eulerian (ALE) method, a mathematical model including electric field, fluid flow and particle’s deformation is developed to obtain accurate DEP force, which can be used to analyze the DEP interactions of rod-shaped deformable particles under DC electric field. The numerical simulation results show that the particles with smaller elastic modulus deform sharply, and two particles undergo four sequential steps: deform, approach, rotate, and array. Under negative DEP, regardless of their initial positions, two particles eventually align to form a particle-particle chain parallel to the applied electric field. The result of this study reveals the basic principle of DEP manipulation of rod-shaped deformable particles, which can provide possible help for the design of microfluidic devices.

Parametric study on the geometrical parameters of a lab-on-a-chip platform with tilted planar electrodes for continuous dielectrophoretic manipulation of microparticles

Advances in lab-on-a-chip (LOC) devices have led to significant improvements in the on-chip manipulation, separation, sorting, and isolation of particles and cells. Among various LOC-based approaches such as inertia-based methods, acoustophoresis, and magnetophoresis, the planar-slanted-electrode dielectrophoresis (DEP) method has demonstrated great potential as a label-free, cost-effective, and user-friendly approach. However, the devices built based on this method suffer from low flow throughput compared to devices functioning based on other LOC-based manipulation approaches. In order to overcome this obstacle, the geometrical parameters of these types of DEP-based devices must be studied to increase the effectiveness of DEP manipulation. With the consideration of both numerical and experimental studies, this paper studies the geometrical factors of a LOC platform consisting of tilted planar electrodes with the goal of achieving higher throughput in continuous manipulation of polystyrene particles. COMSOL Multiphysics software was used to study the effect of the electrodes geometry on the induced electric field. The simulation results show that by increasing the electrode’s width and decreasing the electrode’s spacing, higher DEP force is generated. Furthermore, the experimental outcomes indicated that lower channel height, higher voltage, and larger particle size resulted in the most improvement to DEP manipulation. Additionally, the experimental results demonstrated that slanted electrodes with an angle of 8° with respect to the direction of flow provide a more effective configuration.

Cell patterning via optimized dielectrophoretic force within hexagonal electrodes in vitro for skin tissue engineering

Tissue reconstruction through in vitro cell seeding is a popular method for tissue engineering. In this paper, we proposed a thin-layer structure consisting of multiple hexagons for the regeneration of skin tissue. Cells could be seeded and cultured within the structure via dielectrophoresis (DEP) actively. A thin layer of the structure was fabricated with biocompatible medical-grade stainless steel via precise laser cutting. The fabricated layers were stacked together to form a 3D electrode pair, which could be used to generate a 3D electric field. Thus, the suspended cells within the structure could be patterned via DEP manipulation. The input voltage was examined and optimized to ensure cell viability and patterning efficiency during the DEP manipulation process. As soon as we applied the optimized voltage, human foreskin fibroblast (HFF) cells could be attracted along the edge of the electrodes, forming hexagonal cellular patterns. After that, a single layer of the patterned cells was further cultured in an incubator for 7 days and observed under a microscope. The obtained images showed that the seeded cells could proliferate and fill in the hexagonal wells, which could be used for further skin tissue regeneration. As shown in the experimental results, this structure could be used for active cell seeding and proliferation for the development of skin tissue engineering.

Dielectrophoretic manipulation of nanomaterials: A review.

Nanomaterials manipulation using dielectrophoresis (DEP) is one of the major research areas that could potentially benefit the micro/nano science for diverse applications, such as microfluidics, nanomachine, and biosensor. The innovation and development of basic theories, methods or applications will have a huge impact on the entire related field. Specifically, for DEP manipulation of nanomaterials, improvements in comprehensive performance of accuracy, flexibility and scale could promote broader applications in micro/nano science. Therefore, to explore the directions for future research, this paper critically provides an overview on the fundamentals, recent progress, current challenges, and potential applications of DEP manipulation of nanomaterials. This review will also act as a guide and reference for researchers to explore promising applications in relevant research.

Circular electrodes stepping manipulation platform for A549 cancer cell detection

In this paper, a novel design of an impedance sensor integrated on stepping dielectrophoresis manipulation platform for biological cells detection is presented. The platform consists of fluidic working chamber and manipulating/sensing gold electrodes. Gold electrodes are patterned on glass substrate with an insulating layer covered to avoid the direct contact between metal electrodes and electrolyte. The outer electrodes implement biological cell manipulating function while the inner electrodes construct sensing electrodes pair which are connected to an impedance analyser to detect the appearance of biological cells on the sensing area. In this work, several experiments have been implemented to investigate the performance of A549 cell line trapping ability based on aptamer immobilisation on gold surface method with different concentrations of aptamer solution. Impedance spectroscopy responses of the proposed sensor with frequency ranges from 10 kHz to 1.0 MHz are examined. The impedance spectroscopy shows an impedance change of up to approximately 2500 Ω at 200 kHz when 16 A549 cells appear in the sensing area.

Engineered bone scaffolds with Dielectrophoresis-based patterning using 3D printing.

Patterning of cells into a specific pattern is an important procedure in tissue engineering to facilitate tissue culture and ingrowth. In this paper, a new type of 3D-printed scaffold utilizing dielectrophoresis (DEP) for active cell seeding and patterning was proposed. This scaffold adopted a concentric-ring design that is similar to native bone tissues. The scaffold was fabricated with a commercial three-dimensional (3D) printer. Polylactic Acid (PLA) was selected as the material for the printer and the fabricated scaffold was coated with gold to enhance the conductivity for DEP manipulation. Simulation from COMSOL confirmed that non-uniform electric fields were successfully generated under a voltage input. The properties of the scaffold were first characterized through a series of experiments. Then, preosteoblast MC3T3-E1 cells were seeded onto the coated scaffold and multiple cellular rings were observed under the microscope. The biocompatibility of the material was also examined and mineralized bone nodules were detected using Alizarin Red S Staining after 28 days of culture. The proposed scaffold design can enable formation of multiple ring patterns via DEP and the properties of the scaffold are suitable for bone tissue culture. This new type of 3D-printed scaffold with cell seeding mechanism offers a new and rapid approach for fabricating engineered scaffolds that can arrange cells into different patterns for various tissue engineering applications.

Characterizing Esophageal Cancerous Cells at Different Stages Using the Dielectrophoretic Impedance Measurement Method in a Microchip.

Analysis of cancerous cells allows us to provide useful information for the early diagnosis of cancer and to monitor treatment progress. An approach based on electrical principles has recently become an attractive technique. This study presents a microdevice that utilizes a dielectrophoretic impedance measurement method for the identification of cancerous cells. The proposed biochip consists of circle-on-line microelectrodes that are patterned using a standard microfabrication processes. A sample of various cell concentrations was introduced in an open-top microchamber. The target cells were collectively concentrated between the microelectrodes using dielectrophoresis manipulation, and their electrical impedance properties were also measured. Different stages of human esophageal squamous cell carcinoma lines could be distinguished. This result is consistent with findings using hyperspectral imaging technology. Moreover, it was observed that the distinguishing characteristics change in response to the progression of cancer cell invasiveness by Raman spectroscopy. The device enables highly efficient cell collection and provides rapid, sensitive, and label-free electrical measurements of cancerous cells.

Portable microsystem integrates multifunctional dielectrophoresis manipulations and a surface stress biosensor to detect red blood cells for hemolytic anemia.

Hemolytic anemia intensity has been suggested as a vital factor for the growth of certain clinical complications of sickle cell disease. However, there is no effective and rapid diagnostic method. As a powerful platform for bio-particles testing, biosensors integrated with microfluidics offer great potential for a new generation of portable point of care systems. In this paper, we describe a novel portable microsystem consisting of a multifunctional dielectrophoresis manipulations (MDM) device and a surface stress biosensor to separate and detect red blood cells (RBCs) for diagnosis of hemolytic anemia. The peripheral circuit to power the interdigitated electrode array of the MDM device and the surface stress biosensor test platform were integrated into a portable signal system. The MDM includes a preparing region, a focusing region, and a sorting region. Simulation and experimental results show the RBCs trajectories when they are subjected to the positive DEP force, allowing the successful sorting of living/dead RBCs. Separated RBCs are then transported to the biosensor and the capacitance values resulting from the variation of surface stress were measured. The diagnosis of hemolytic anemia can be realized by detecting RBCs and the portable microsystem provides the assessment to the hemolytic anemia patient.

Modelling and adaptive dynamic sliding mode control of dielectrophoresis-based micromanipulation

Automated, precise single particle manipulation in the microscale is in great demand and is one of the great challenges in biomedical and biochemical engineering. Automatic micromanipulation has also become a microrobotics challenge. Following this challenge, control technology is integrated with dielectrophoresis (DEP)-based micromanipulation technology in this paper to construct automatic DEP-based micromanipulation systems. DEP micromanipulation systems with electrodes of quadrupole polynomial geometry are developed as controllable microactuators. A semianalytical modelling method is proposed to formulate the analytical models of the DEP manipulation systems, which manifests that the DEP manipulation systems are non-affine non-linear systems. Then, taking the parameter uncertainties, unmodelled dynamics and external disturbances into account, an adaptive law combined with a dynamic sliding mode controller is designed for two-dimensional trajectory tracking control of a DEP micromanipulation system. The closed-loop system is proved stable in the presence of bounded lumped uncertainty based on the Lyapunov theorem. Finally, simulation results show the validity of the proposed control design.

Protein dielectrophoresis and the link to dielectric properties.

There is a growing interest in protein dielectrophoresis (DEP) for biotechnological and pharmaceutical applications. However, the DEP behavior of proteins is still not well understood which is important for successful protein manipulation. In this paper, we elucidate the information gained in dielectric spectroscopy (DS) and electrochemical impedance spectroscopy (EIS) and how these techniques may be of importance for future protein DEP manipulation. EIS and DS can be used to determine the dielectric properties of proteins predicting their DEP behavior. Basic principles of EIS and DS are discussed and related to protein DEP through examples from previous studies. Challenges of performing DS measurements as well as potential designs to incorporate EIS and DS measurements in DEP experiments are also discussed.

Controllably moving individual living cell in an array by modulating signal phase difference based on dielectrophoresis

This paper reports a novel dielectrophoresis (DEP) based method for manipulating individual living cells by modulating phase difference of electrical signals applied on DEP electrodes. A novel microchip with an array structure is also proposed, consisting of a plurality of quadrupole-electrode units patterned into array on a glass substrate with a pair of center electrodes locating at the center of each quadrupole-electrode unit. Living cells can be trapped and positioned at the center of each quadrupole-electrode unit by using negative DEP (nDEP) manipulation and form an array. The trapped cells in the array can be controllably moved from one position to another and even from one of quadrupole-electrode units to adjacent unit by changing the phase difference of the signals applied on the two pairs of opposite electrodes in each quadrupole-electrode unit. The microchip allows an efficient and flexible manipulation of individual living cells that can be applied to study single cells. The experiments are performed to verify that different types of cells (MCF-7 cell and HeLa cell) can be effectively distinguished between each other using the method without label and fluorometric measurements. An identification of individual living cell from dead cells is also well demonstrated.

A dielectrophoresis method to manipulate and monitor the Shewanella oneidensis

Shewanella oneidensis is capable of producing electrons and transferring to the solid electrodes. To characterize the electrical properties of S. oneidensis and manufacture the miniature microbial fuel cells, cellular dielectrophoresis has been developed into a powerful and flexible tool to utilize microfabricated electrode arrays fulfilling S. oneidensis manipulation and monitoring. When S. oneidensis with green fluorescent protein were placed under the influence of an applied inhomogeneous field, the translation and enrichment of the green bacteria were observed by the fluorescence microscope. The distribution of electric field around the microelectrodes was simulated in finite element analysis software. The dielectrophoresis manipulation parameters were also optimized according to the peak value of applied alternating current signals and its frequency. In short, this study shows that dielectrophoresis can be a valuable tool to manipulate S. oneidensis to the sidewalls of microelectrode.

Effects of chip geometries on dielectrophoresis and electrorotation investigation

The electric fields employed for such work are generated using chips, such as planar linear interdigitated arrays or two parallel arrays. However, chip geometries usually affect the investigation of dielectrophoresis (DEP) and electrorotation (ER) significantly, and even may misdirect the theoretical prediction. In order to understand the electrodes geometries effect and provide a suitable range of parameters, three-dimensional simulations for the DEP and ER characterizations on the quadrupolar hyperbolical electrodes are carried out. Influences of the electrodes gaps, cell height, work region, energized voltage and frequencies for the DEP and ER manipulations are analyzed, and the analysis results show that the gaps of the electrodes and the cell height have enormous effects, but the work region is not so important. Moreover, depending on the theoretical analysis, ER experiments for polystyrene microspheres with the diameter of 20 μm are carried out on two kinds of chips. The experimental results show that the microspheres rotate in the counter-field direction and the maximum rotation speed appears in the megahertz range. In addition, the experimental results are compared with the simulation results, showing that the three-dimensional simulations considering the chip geometries are more accurate than the two-dimensional predictions. This paper provides a new understanding for the theoretical predictions of DEP and ER manipulations, which decreases the difference of the theoretical and experimental results significantly, and will be significant for the lab chip research.