A Polymer Microfluidic Chip With Interdigitated Electrodes Arrays for Simultaneous Dielectrophoretic Manipulation and Impedimetric Detection of Microparticles

This paper presents the design, fabrication, and characterization of a polymer microfluidic biochip with integrated interdigitated electrodes arrays (IDAs) used to simultaneously separate, manipulate, and detect microparticles using dielectrophoresis (DEP) and electrochemical impedance spectroscopy (EIS) methods. The DEP response of silica microspheres has been characterized, and microspheres of different sizes (1.8 and 3.5 in diameter) have been DEP flow separated and individually trapped in different microchambers by IDAs in a single run. Simultaneously, the impedance change caused by microspheres captured on IDAs has been analyzed for quantification. High-throughput polymer microfabrication techniques such as micro injection molding were used in this work, so that the polymer microfluidic chip can be produced in a low-cost, disposable platform. This low-cost microfluidic chip provides a generic platform for developing multifunctional lab-on-a-chip devices that require the ability to handle and sense microparticles.     

Application of direct electrospray probe to analyze biological compounds and to couple to solid-phase microextraction to detect trace surfactants in aqueous solution

This work presents two novel direct electrospray probes (DEP) to generate an electrospray without using a capillary and/or syringe pump. One of the DEPs is simply a copper coil connecting to a high-voltage power supply. The sample solution is deposited on the coil by a micropipet and the electrospray is subsequently generated at the tip of the copper coil after high voltage is applied to it. Another DEP is constructed by inserting two parallel optical fibers through the copper coil. The two fibers extend one end of the copper coil by 1 cm. Electrospray is generated at the tip of the fibers through the solution predeposited on the copper coil as the high voltage is applied on the copper coil. The ES mass spectra of myoglobin in liquid or solid phases can be obtained using this DEP-MS. Coupling the DEP to a solid-phase microextraction fiber is extremely easy, and a trace amount (in ppb range) of surfactants (Triton X-100) in the aqueous solution are selectively concentrated and detected.     

Inexpensive, universal serial bus-powered and fully portable lab-on-a-chip-based capillary electrophoresis instrument

Capillary electrophoresis is a cornerstone of lab-on-a-chip (LOC) implementations for medical diagnostics. However, the infrastructure needed to operate electrophoretic LOC implementations tends to be large and expensive, hindering the development of portable or low-cost systems. A custom-designed and highly integrated microelectronic chip for high-voltage generation switching and interfacing is recently developed. Here, the authors integrate the microelectronic chip with a microfluidic chip, a solid-state laser, filter, lens and several dollars worth of electronic components to form an inexpensive and portable platform, which is the size of a mobile telephone. This compact system has such reduced power requirements that the complete platform can be operated using a universal serial bus link to a computer. It is believed that this system represents a significant advancement in practical LOC implementations for point-of-care medical diagnostics.     

Dielectrophoresis in microchips containing arrays of insulating posts: theoretical and experimental results

Dielectrophoresis (DEP), a nonlinear electrokinetic transport mechanism, can be used to concentrate and sort cells, viruses, and particles. To date, microfabricated DEP-based devices have typically used embedded metal electrodes to apply spatially nonuniform, time-varying (AC) electric fields. We have developed an alternative method in which arrays of insulating posts in a channel of a microchip produce the spatially nonuniform fields needed for DEP. Electrodes may be located remotely, allowing operation of the device down to zero frequency (DC) without excessive problems of electrolysis. Applying a sufficiently large electric field across an insulating-post array produces two flow regimes through a competition between electrokinetic flow (combined electrophoresis and electroosmosis) and dielectrophoresis. "Streaming DEP" is observed when DEP dominates diffusion but is overcome by electrokinetic flow. Particles concentrated by DEP forces in areas of electric field extrema travel electrokinetically down the array in flowing streams. In an array of posts, dielectrophoretic forcing within repeated rows adds coherently to produce flowing streams of highly concentrated and rarefied particles. We demonstrate that this reinforcement is a strong function of alignment of the array with respect to the applied electric field and that the particle concentrations can be "enhanced" or "depleted" along columns of posts, enabling a novel class of continuous-flow, selective particle filter/concentrator devices. To our knowledge, this is the first observation of streaming dielectrophoresis. The second regime is "trapping DEP," in which DEP forces dominate over both diffusion and electrokinetic flow, reversibly immobilizing particles on the insulating posts, enabling inexpensive and embedded batch filter/concentrator devices. Devices can be biased electrically to manipulate particles selectively by varying the field strength to vary the relative magnitudes of electrokinetic flow and DEP. Post shapes are contoured easily to control electric field gradients and, hence, DEP behavior. Simple simulations based on similitude of fluid flow and electric field that solve the Laplace equation to obtain fluid velocity have also been developed to predict the dielectrophoretic behavior in an array of posts. These simulations are in excellent agreement with the experimental observations and provide insight into electrokinetic behavior to enable design of dielectrophoretic concentrators and sorters.     

Magnetic particles as markers and carriers of biomolecules

The detection and manipulation of biomolecules on a common platform is of considerable interest not only for application in devices such as diagnostic tools but also for basic research in biological and medical systems. A promising approach is the utilisation of magnetic particles as markers and carriers for biomolecules. The principle functionality of this approach is demonstrated by the authors. Magnetic particles used as markers can be detected by highly sensitive magnetoresistive sensors resulting in a purely electronic signal. A direct comparison with the standard fluorescence method reveals the advantages of using the magnetic particles. In addition, magnetic particles used as carriers can be manipulated on-chip via currents running through especially designed line patterns. Some current drawbacks and future aspects are discussed. The combination of sensing and manipulating magnetic particles is a promising choice for future integrated lab-on-a-chip systems.     

Microfluidic characterization and continuous separation of cells and particles using conducting poly(dimethyl siloxane) electrode induced alternating current-dielectrophoresis

This paper presents a poly(dimethyl siloxane) (PDMS) polymer microfluidic device using alternating current (ac) dielectrophoresis (DEP) for separating live cells from interfering particles of similar sizes by their polarizabilities under continuous flow and for characterizing DEP behaviors of cells in stagnant flow. The ac-DEP force is generated by three-dimensional (3D) conducting PDMS composite electrodes fabricated on a sidewall of the device main channel. Such 3D PDMS composite electrodes are made by dispersing microsized silver (Ag) fillers into PDMS gel. The sidewall AgPDMS electrodes can generate a 3D electric field that uniformly distributes throughout the channel height and varies along the channel lateral direction, thereby producing stronger lateral DEP effects over the entire channel. This allows not only easy observation of cell/particle lateral motion but also using the lateral DEP force for manipulation of cells/particles. The former feature is used to characterize the frequency-dependent DEP behaviors of Saccharomyces cerevisiae (yeast) and Escherichia coli (bacteria). The latter is utilized for continuous separation of live yeast and bacterial cells from similar-size latex particles as well as live yeast cells from dead yeast cells. The separation efficiency of 97% is achieved in all cases. The demonstration of these functions shows promising applications of the microfluidic device.     

Effect of polyethylenimine on electrophoretic deposition of TiO2 nanoparticles in alternating current electric field

In this work, AC electric field was applied to deposit TiO₂ nanoparticles dispersed in Acetone on coplanar electrodes. The experiments were performed in presence and absence of an additive, polyethylenimine (PEI), at frequencies of 1 Hz and 10 kHz. It was revealed that deposition pattern changed dramatically by addition of PEI which makes particles to fill the inter electrode gap at both frequencies. When PEI is added, particles show different behavior. While they tend to fill the gap randomly at 1 Hz, they form chainlike pattern at 10 kHz. Chain formation of particles in the gap indicates presence of dielectrophoretic (DEP) forces. The ability of particles to polarize in both suspensions at 10 kHz are calculated by a multi-shell model in order to find DEP force. According to this model, the polarizability for particles in the suspension with PEI is more than the other, so DEP forces applied more strongly on them and promotes chain formation.     

Microchip separations in reduced-gravity and hypergravity environments

Microfabricated fluidics technology, e.g., lab-on-a-chip devices, offers many attractive features for performing chemistry and biochemistry on space-based platforms. We have constructed a portable, battery-operated microfluidic platform that was tested under reduced gravity and hypergravity conditions that would be experienced in space flight and launch. This device consisted of a microchip, microchip holder, two 0-8-kV high-voltage power supplies, a high-voltage switch, a solid-state diode-pumped green laser, an optical train, a channel photomultiplier, and an inertial mass measurement unit all under the control of a laptop computer and powered by 10 D-cell alkaline batteries. The unit was tested on NASA's reduced gravity research aircraft at gravity levels that are relevant to NASA's intended use of bioreporter-based microchips for environmental monitoring of space and planetary environments on manned and unmanned spacecraft. Over the course of two flights, 834 fast electrophoretic separations of four amino acids were performed under a variety of gravitational environments including zero-g, Martian-g, lunar-g, and approximately 1.8-g. All separations were performed in less than 12 s and automatically analyzed. After correction with an internal migration standard, the migration time reproducibilities were all <1% relative standard deviation.     

Non-vanishing ponderomotive AC electrophoretic effect for particle trapping

We present here a study on overlooked aspects of alternating current (AC) electrokinetics-AC electrophoretic (ACEP) phenomena. The dynamics of a particle with both polarizability and net charges in a non-uniform AC electric trapping field is investigated. It is found that either electrophoretic (EP) or dielectrophoretic (DEP) effects can dominate the trapping dynamics, depending on experimental conditions. A dimensionless parameter γ is developed to predict the relative strength of EP and DEP effects in a quadrupole AC field. An ACEP trap is feasible for charged particles in 'salt-free' or low salt concentration solutions. In contrast to DEP traps, an ACEP trap favors the downscaling of the particle size.     

Positioning living cells on a high-density electrode array by negative dielectrophoresis

We present in this paper a large-scale microelectrode array, which allows a dielectrophoretic positioning of cells in a matrix form. The electrode structure was chosen to produce regularly spaced field minima, toward which particles are directed and concentrated, under conditions of negative DEP. The need to power thousands of electrodes at the same time guided the choice of a multilayer structure. Cells can also be directed toward small wells formed in silicon, where they remain when the field is removed.     

State-of-the-art technologies and devices for high-voltage integrated circuits

The current status of high-voltage power semiconductor devices and technologies for high-voltage integrated circuits is reviewed and the new trends in this field are discussed. The paper focuses on the concepts of the novel reduced surface field and state-of-the-art silicon technologies such as high-voltage silicon on insulator, which are expected to play an increasingly important role in power system on-chip manufacturing. Lateral devices such as LDMOSFETs, superjunctions and lateral insulated gate bipolar transistors are discussed. The paper also touches on emerging technologies such as unified MEMS-IC for enhanced breakdown capability and isolation. Finally, an overview of the fierce fight of technology survival in terms of specific on-state resistance against breakdown voltage is given.     

Fabrication of Schottky barrier carbon nanotube field effect transistors using dielectrophoretic-based manipulation

Nanoscale electronic devices made from carbon nanotubes (CNTs) such as transistors and sensors are much smaller and potentially more versatile than those built using conventional IC technology. In this paper, we present a method that uses dielectrophoretic (DEP) manipulation process for the fabrication of single-channel and multi-channel carbon nanotube field effect transistors (CNT-FETs). For a typical fabrication process, single-walled carbon nanotubes (SWCNTs) are first pre-aligned to micron-precision range between two microelectrodes using DEP technique. The typically applied alternating current (AC) voltage to generate the DEP force for manipulation has a frequency of 1 MHz and amplitude of 10 V. We first demonstrated single-channel or multi-channel structures of CNT-FETs. An AFM is then used to "clean" or "sweep away" unwanted particles or CNTs around the electrodes. Lastly, the fabricated FETs were covered in a polymethylmethacrylate (PMMA) thin film and treated with an annealing process. The PMMA covered devices show improved performances over the non-covered devices.     

Portable high-voltage power supply and electrochemical detection circuits for microchip capillary electrophoresis

Miniaturized, battery-powered, high-voltage power supply, electrochemical (EC) detection, and interface circuits designed for microchip capillary electrophoresis (CE) are described. The dual source CE power supply provides +/- 1 kVDC at 380 microA and can operate continuously for 15 h without recharging. The amperometric EC detection circuit provides electrode potentials of +/-2 VDC and gains of 1, 10, and 100 nA/V. The CE power supply power is connected to the microchip through an interface circuit consisting of two miniature relays, diodes, and resistors. The microchip has equal length buffer and separation channels. This geometry allows the microchip to be controlled from only two reservoirs using fixed dc sources while providing a consistent and stable sample injection volume. The interface circuit also maintains the detection reservoir at ground potential and allows channel currents to be measured likewise. Data are recorded, and the circuits are controlled by a National Instruments signal interface card and software installed in a notebook computer. The combined size (4 in. x 6 in. x 1 in.) and weight (0.35 kg) of the circuits make them ideal for lab-on-a-chip applications. The circuits were tested electrically, by performing separations of dopamine and catechol EC and by laser-induced fluorescence visualization.     

Design and numerical investigation of a circular microchannel for particle/cell separation using dielectrophoresis

Precisely separating particles/cells with different sizes and physical properties has been an interest for point-of-care diagnostics and personalized treatment. Dielectrophoresis (DEP) is widely known as a powerful and non-invasive technique to separate particles and cells. This paper presents a comprehensive numerical investigation of particle/cell separation in circular microchannels using DEP. First, the geometrical parameters of the circular microchannel affecting DEP force are determined by performing an analytical solution. Then, by developing a solver in OpenFOAM, the effect of these parameters on particles deflection is investigated. According to the results, two different circular microchannels are presented to investigate the continuous separation of bio-particles (based on their physical properties) and polystyrene particles (based on their size). The results showed that a minimum voltage of 7, 9, and 12 V is required to achieve 100 % purity and separation efficiency for separating red blood cells from MDA-MB-231 cancer cells at the flow rate of 0.5, 1.0, and 1.5 µl/min, respectively. Also, the efficient separation of 5 and 10 µm polystyrene particles at the flow rate of 0.1 µl/min is possible only at the voltage of 9 V. The results of this numerical study can be useful for the fabrication of an optimal microdevice for the continuous DEP separation of particles and cells.     

Continuous dielectrophoretic size-based particle sorting

Continuous-flow dielectrophoretic (DEP) particle separation based on size is demonstrated in a microfluidic device. Polystyrene microspheres suspended in a neutrally buoyant aqueous solution are used as model particles to study DEP induced by an array of slanted, planar, interdigitated electrodes inside of a soft-lithography microchannel. The E-field gradients from the slanted electrodes impart a net transverse force component on the particles that causes them to "ratchet" across the channel. Over the length of the device, larger particles are deflected more than smaller particles according to the balance of hydrodynamic drag and DEP forces. Consequently, a flow-focused particle suspension containing different-sized particles is fractionated as the beads flow and separate down the length of the device. The flow behavior of spherical particles is modeled, and the total transverse particle displacement in the microfluidic device predicts fourth-order size and voltage and second-order inverse flow rate dependences. The model is verified experimentally for a range of flow rates, particle sizes, and E-field strengths.     

Review of the theory of generalised dielectrophoresis

Generalised dielectrophoresis (gDEP), including conventional dielectrophoresis (cDEP), electrorotation (ER) and travelling wave dielectrophoresis (twDEP), is an effective tool for particle (cell) manipulation and characterisation, even down to the level of nano-sized objects such as DNA, proteins and viruses. All the disciplines of gDEP are originated from the interaction of an applied electric field with its polarisation effect on the particle and can be studied systematically in a unified approach under electrostatics. In this review, the authors discuss both the quasi-static and transient theory of gDEP in an unbounded medium for both spherical and ellipsoidal particles. Then the quasi-static theory of wall effect is discussed on gDEP for a spherical particle. The wall effect is minor for ER, twDEP and cDEP parallel to wall(s), but could be significant for cDEP normal to wall(s). Force and torque expressions in terms of electric potential and its derivatives are provided and suggested for a robust calculation of the twDEP force and DEP torque. Discussions are provided for the application of the theory to nano-sized particles. The authors also illustrate some features of the Clausius-Mossotti factor using erythrocyte as an example, including both the crossover (DEP) and peak frequencies (ER) at low and high-frequency limits.     

Continuous sorting of microparticles using dielectrophoresis

Sorting of particles such as cells is a critical process for many biomedical applications, and it is challenging to integrate it into an analytical microdevice. We report an effective and flexible dielectrophoresis (DEP)-based microfluidic device for continuous sorting of multiple particles in a microchannel. The particle sorter is composed of two components-a DEP focusing unit and a Movable DEP Trap (MDT). The trap is formed by an array of microelectrodes at the bottom of the channel and a transparent electrode plate placed at the top. The location of the trap is dependent on the configuration of voltages on the array and therefore is addressable. Flowing particles are first directed and focused into a single particle stream by the focusing unit. The streamed particles are then sorted into different fractions using the movable trap by rapidly switching the applied voltage. The performance of the sorter is demonstrated by successfully sorting microparticles in a continuous flow. The proposed DEP-based microfluidic sorter can be implemented in applications such as sample preparation and cell sorting for subsequent analytical processing, where sorting of particles is needed.     

Dynamic analysis of drug-induced cytotoxicity using chip-based dielectrophoretic cell immobilization technology

Quantification of programmed and accidental cell death provides useful end-points for the anticancer drug efficacy assessment. Cell death is, however, a stochastic process. Therefore, the opportunity to dynamically quantify individual cellular states is advantageous over the commonly employed static, end-point assays. In this work, we describe the development and application of a microfabricated, dielectrophoretic (DEP) cell immobilization platform for the real-time analysis of cancer drug-induced cytotoxicity. Microelectrode arrays were designed to generate weak electro-thermal vortices that support efficient drug mixing and rapid cell immobilization at the delta-shape regions of strong electric field formed between the opposite microelectrodes. We applied this technology to the dynamic analysis of hematopoietic tumor cells that represent a particular challenge for real-time imaging due to their dislodgement during image acquisition. The present study was designed to provide a comprehensive mechanistic rationale for accelerated cell-based assays on DEP chips using real-time labeling with cell permeability markers. In this context, we provide data on the complex behavior of viable vs dying cells in the DEP fields and probe the effects of DEP fields upon cell responses to anticancer drugs and overall bioassay performance. Results indicate that simple DEP cell immobilization technology can be readily applied for the dynamic analysis of investigational drugs in hematopoietic cancer cells. This ability is of particular importance in studying the outcome of patient derived cancer cells, when exposed to therapeutic drugs, as these cells are often rare and difficult to collect, purify and immobilize.     

Sorting ZnO particles of different shapes with low frequency AC electric fields

Separation of nanoparticles from a mixture of particles with different geometries by applying non-uniform AC electric field is investigated. For this propose, two morphologies of ZnO, rod and cubic shape, were synthesized in two separate processes. Then, they were mixed and dispersed in acetone and exposed to the electric field for being separated. It was found that combination of AC-electroosmosis which is present at low frequencies, and dielectrophoretic (DEP) force exerted on particles in non-uniform AC electric fields may yield to separation of particles based on their shape difference. This paper introduces an effective method for sorting and purification of nanoparticles after chemical synthesis based on their geometrical shape.     

Effect of particle-particle interaction on dielectrophoretic single particle trap in a sudden contraction flow

Dielectrophoretic(DEP) force is significant in manipulating tiny objects in micro/nano scale. To study the effect of electric interaction force on particle manipulation, a microstructure consisting of a pair of strip electrodes and a sudden contraction micro-channel was constructed. Besides DEP force and hydrodynamic force acting on single particle, the numerical model also involved electric interaction force and force moment on two particles. The analyses revealed that the particle-particle interaction force was in the same order as that of DEP force on single trapped particle. The interaction force resulted in trapping single particle failure under continuous DEP force.Thus, pulsed DEP force, turning on/off DEP force at a given time interval, was suggested. During the "off" period,the velocity difference of the two particles located at sudden contraction micro-channel enlarged the gap between them and further weakened the particle-particle interaction. By a proof-of-concept experiment, both the trapping behavior of single particle and that of two particles were in good agreement with the model.With carefully controlled parameters, the reliable function of retaining single particle was realized by pulsed DEP.