Dielectrophoretic Trapping Research Articles

Hydrodynamic and direct-current insulator-based dielectrophoresis (H-DC-iDEP) microfluidic blood plasma separation.

Evaluation and diagnosis of blood alterations is a common request for clinical laboratories, requiring a complex technological approach and dedication of health resources. In this paper, we present a microfluidic device that owing to a novel combination of hydrodynamic and dielectrophoretic techniques can separate plasma from fresh blood in a microfluidic channel and for the first time allows optical real-time monitoring of the components of plasma without pre- or post-processing. The microchannel is based on a set of dead-end branches at each side and is initially filled using capillary forces with a 2-μL droplet of fresh blood. During this process, stagnation zones are generated at the dead-end branches and some red blood cells (RBCs) are trapped there. An electric field is then applied and dielectrophoretic trapping of RBCs is used to prevent more RBCs entering into the channel, which works like a sieve. Besides, an electroosmotic flow is generated to sweep the rest of the RBCs from the central part of the channel. Consequently, an RBC-free zone of plasma is formed in the middle of the channel, allowing real-time monitoring of the platelet behavior. To study the generation of stagnation zones and to ensure RBC trapping in the initial constrictions, two numerical models were solved. The proposed experimental design separates up to 0.1 μL blood plasma from a 2-μL fresh human blood droplet. In this study, a plasma purity of 99 % was achieved after 7 min, according to the measurements taken by image analysis. Graphical Abstract Schematics of a real-time plasma monitoring system based on a Hydrodynamic and direct-current insulator-based dielectrophoresis microfluidic channel.

Efficient photo-induced dielectrophoretic particle trapping on Fe:LiNbO_3 for arbitrary two dimensional patterning

1D and 2D patterning of uncharged micro- and nanoparticles via dielectrophoretic forces on photovoltaic z-cut Fe:LiNbO3 have been investigated for the first time. The technique has been successfully applied with dielectric micro-particles of CaCO3 (diameter d = 1-3 μm) and metal nanoparticles of Al (d = 70 nm). At difference with previous experiments in x- and y-cut, the obtained patterns locally reproduce the light distribution with high fidelity. A simple model is provided to analyse the trapping process. The results show the remarkably good capabilities of this geometry for high quality 2D light-induced dielectrophoretic patterning overcoming the important limitations presented by previous configurations.

Inexpensive three-dimensional dielectrophoretic microfluidic devices using milled copperclad substrates

Abstract This manuscript demonstrates an inexpensive method of fabricating 3D dielectrophoretic microfluidic devices using a milling machine equipped with a sub-millimeter end mill. Features were milled into a copperclad substrate, otherwise typically used for printed circuit boards. Milled electrodes themselves serve as walls of the microfluidic channel therefore delivering a stronger electric field throughout the depth of the microchannel compared to traditional, coplanar electrode designs. Dielectrophoretic particle trapping and concentration were demonstrated with 8 μm polystyrene beads at voltages no greater than 10 V. The method of fabrication will be discussed as well as advantages and challenges associated with this technique.

Experimental and theoretical study of dielectrophoretic particle trapping in arrays of insulating structures: Effect of particle size and shape.

Insulator-based dielectrophoresis (iDEP) employs insulating structures embedded in a microchannel to produce electric field gradients. This contribution presents a detailed analysis of the regions within an iDEP system where particles are likely to be retained due to dielectrophoretic trapping in a microchannel with an array of cylindrical insulating structures. The effects of particle size and shape on dielectrophoretic trapping were analyzed by employing 1 and 2 μm polystyrene particles and Escherichia coli cells. This research aims to study the mechanism behind dielectrophoretic trapping and develop a deeper understanding of iDEP systems. Mathematical modeling with COMSOL Multiphysics was employed to assess electrokinetic and dielectrophoretic particle velocities. Experiments were carried out to determine the location of dielectrophoretic barriers that block particle motion within an iDEP microchannel; this supported the estimation of a correction factor to match experiments and simulations. Particle velocities were predicted with the model, demonstrating how the different forces acting on the particles are in equilibrium when particle trapping occurs. The results showed that particle size and shape have a significant effect on the magnitude, location, and shape of the regions of dielectrophoretic trapping of particles, which are defined by DEP isovelocity lines and EK isovelocity lines.

Raman-activated cell sorting based on dielectrophoretic single-cell trap and release.

Raman-activated cell sorting (RACS) is a promising single-cell technology that holds several significant advantages, as RACS is label-free, information-rich, and potentially in situ. To date, the ability of the technique to identify single cells in a high-speed flow has been limited by inherent weakness of the spontaneous Raman signal. Here we present an alternative pause-and-sort RACS microfluidic system that combines positive dielectrophoresis (pDEP) for single-cell trap and release with a solenoid-valve-suction-based switch for cell separation. This has allowed the integration of trapping, Raman identification, and automatic separation of individual cells in a high-speed flow. By exerting a periodical pDEP field, single cells were trapped, ordered, and positioned individually to the detection point for Raman measurement. As a proof-of-concept demonstration, a mixture of two cell strains containing carotenoid-producing yeast (9%) and non-carotenoid-producing Saccharomyces cerevisiae (91%) was sorted, which enriched the former to 73% on average and showed a fast Raman-activated cell sorting at the subsecond level.

Highly efficient single cell arraying by integrating acoustophoretic cell pre-concentration and dielectrophoretic cell trapping.

To array rare cells at the single-cell level, the volumetric throughput may become a bottleneck in the cell trapping and the subsequent single-cell analysis, since the target cells per definition commonly exist in a large sample volume after purification from the original sample. Here, we present a novel approach for high throughput single cell arraying by integrating two original microfluidic devices: an acoustofluidic chip and an electroactive microwell array. The velocity of the cells is geared down in the acoustofluidic chip while maintaining a high volume flow rate at the inlet of the microsystem, and the cells are subsequently trapped one by one into the microwell array using dielectrophoresis. The integrated system exhibited a 10 times improved sample throughput compared to trapping with the electroactive microwell array chip alone, while maintaining a highly efficient cell recovery above 90%. The results indicate that the serial integration of the acoustophoretic pre-concentration with the dielectrophoretic cell trapping drastically improves the performance of the electroactive microwell array for highly efficient single cell analysis. This simple and effective system for high throughput single cell arraying with further possible integration of additional functions, including cell sorting and downstream analysis after cell trapping, has potential for development to a highly integrated and automated platform for single-cell analysis of rare cells.

Dielectrophoretic isolation of cells using 3D microelectrodes featuring castellated blocks.

We present 3D microelectrodes featuring castellated blocks for dielectrophoretically isolating cells. These electrodes provide a more effective dielectrophoretic force field than thin-film surface electrodes and yet immobilize cells near stagnation points across a parabolic flow profile for enhanced cell viability and separation efficiency. Unlike known volumetric electrodes with linear profiles, the electrodes with structural variations introduced along their depth scale are versatile for constructing monolithic structures with readily integrated fluidic paths. This is exemplified here in the design of an interdigitated comb array wherein electrodes with castellated surfaces serve as building blocks and form digits with an array of fluidic pores. Activation of the design with low-voltage oscillations (±5 Vp, 400 kHz) is found adequate for retaining most viable cells (90.2% ± 3.5%) while removing nonviable cells (88.5% ± 5%) at an increased throughput (5 × 10(5) cells h(-1)). The electrodes, despite their intricate profile, are structured into single-crystal silicon through a self-aligned etching process without a precision layer-by-layer assembly.

The influence of flow intensity and field frequency on continuous-flow dielectrophoretic trapping

We examine the combined influence of the intensity of pressure driven background flow and the frequency of the applied field on the continuous-flow dielectrophoretic trapping behavior of micro-particles within a micro-channel. Using an embedded interdigitated electrode array, we find that the measured trapping percentage over a continuous frequency range exhibits several curious effects which are strongly dependent on the flow intensity, including an apparent shift of the cross-over frequency and low-frequency dispersion. A numerical and theoretical model accounting for the combined effects of pressure-driven flow, dielectrophoresis and alternating-current electro-osmosis on the equation of motion for the particle is used to qualitatively describe the main experimental results.

Capillary-driven microfluidic chips with evaporation-induced flow control and dielectrophoretic microbead trapping

This work reports our efforts on developing simple-to-use microfluidic devices for point-of-care diagnostic applications with recent extensions that include the trapping of microbeads using dielectrophoresis (DEP) and the modulation of the liquid flow using integrated microheaters. DEP serves the purpose of trapping microbeads coated with receptors and analytes for detection of a fluorescent signal. The microheater is actuated once the chip is filled by capillarity, creating an evaporation-induced flow tuned according to assay conditions. The chips are composed of a glass substrate patterned with 50-nm-thick Pd electrodes and microfluidic structures made using a 20-μm-thick dry-film resist (DFR). Chips are covered/sealed by low temperature (50°C) lamination of a 50-μm-thick DFR layer having excellent optical and mechanical properties. To separate cleaned and sealed chips from the wafer, we used an effective chip singulation technique which we informally call the “chip-olate” process. In the experimental section, we first studied dielectrophoretic trapping of 10-μm beads for flow rates ranging from 80 pL s−1 to 2.5 nL s−1 that are generated by an external syringe pump. Then, we characterized the embedded microheater in DFR-covered chips. Flow rates as high as 8 nL s−1 were generated by evaporation-induced flow when the heater was biased by 10 V, corresponding to 270-mW power. Finally, DEP-based trapping and fluorescent detection of functionalized beads were demonstrated as the flow was generated by evaporation-induced flow after the microfluidic structures were filled by capillarity.

Optimization of particle trapping and patterning via photovoltaic tweezers: role of light modulation and particle size

The role of light modulation m and particle size on the morphology and spatial resolution of nano-particle patterns obtained by photovoltaic tweezers on Fe : LiNbO3 has been investigated. The impact of m when using spherical as well as non-spherical (anisotropic) nano-particles deposited on the sample surface has been elucidated. Light modulation is a key parameter determining the particle profile contrast that is optimum for spherical particles and high-m values (m ∼ 1). The minimum particle periodicities reachable are also investigated obtaining periodic patterns up to 3.5 µm. This is a value at least one order of magnitude shorter than those obtained in previous reported experiments. Results are successfully explained and discussed in light of the previous reported models for photorefraction including nonlinear carrier transport and dielectrophoretic trapping. From the results, a number of rules for particle patterning optimization are derived.

Utilization of graphene electrode in transparent microwell arrays for high throughput cell trapping and lysis

Here we present a high-throughput, transparent microfluidic device with embedded microwell arrays sandwiched between transparent electrodes made from graphene (at the bottom) and indium tin oxide (at the top) for dielectrophoretic cell trapping and electrical lysis. Graphene suppresses unwanted faradaic reaction effects on the cells and the medium that is typically observed in ITO based electrodes from application of DC field for electrical lysis. This is because graphene is more electrochemically inert than indium tin oxide (ITO) where ITO undergoes reduction–oxidation (redox) reaction in the presence of electrolyte in most standard cell media. This redox process also compromises ITO's electrical properties and optical transparency over multiple use. The presented microfluidic device shows high efficiency for cell trapping and lysis and an electrochemically stable behavior for long operational life.

Continuous-flow dielectrophoretic trapping and patterning of colloidal particles in a ratchet microchannel

Trapping and concentrating particles in a continuous flow is critical for their detection and analysis as well as removal in many fields. A variety of electrical and non-electrical forces have been demonstrated to continuously capture and enrich particles in microfluidic devices. This work presents an experimental study of the development of particle trapping in an asymmetric ratchet microchannel under dc-biased ac electric fields. The dc/ac dielectrophoretic accumulation of particles in the first pair of ratchets and the dc electrokinetic shifting of particles into the second and subsequent ratchets are studied, which are found to depend on the particle moving direction with respect to the asymmetric ratchets. The dielectrophoretically trapped particles are eventually patterned into triangular zones in all but the first pair of ratchets for both the forward and backward motions. This developing process of particle trapping can be qualitatively simulated by modifying the channel geometry in the computational domain to mimic the particle chains/clusters formed in the ratchets.

Individual Template-Stripped Conductive Gold Pyramids for Tip-Enhanced Dielectrophoresis.

Gradient fields of optical, magnetic, or electrical origin are widely used for the manipulation of micro- and nanoscale objects. Among various device geometries to generate gradient forces, sharp metallic tips are one of the most effective. Surface roughness and asperities present on traditionally produced tips reduce trapping efficiencies and limit plasmonic applications. Template-stripped, noble metal surfaces and structures have sub-nm roughness and can overcome these limits. We have developed a process using a mix of conductive and dielectric epoxies to mount template-stripped gold pyramids on tungsten wires that can be integrated with a movable stage. When coupled with a transparent indium tin oxide (ITO) electrode, the conductive pyramidal tip functions as a movable three-dimensional dielectrophoretic trap which can be used to manipulate submicrometer-scale particles. We experimentally demonstrate the electrically conductive functionality of the pyramidal tip by dielectrophoretic manipulation of fluorescent beads and concentration of single-walled carbon nanotubes, detected with fluorescent microscopy and Raman spectroscopy.

Low-Copy Number Protein Detection by Electrode Nanogap-Enabled Dielectrophoretic Trapping for Surface-Enhanced Raman Spectroscopy and Electronic Measurements

We report a versatile analysis platform, based on a set of nanogap electrodes, for the manipulation and sensing of biomolecules, as demonstrated here for low-copy number protein detection. An array of Ti nanogap electrode with sub-10 nm gap size function as templates for alternating current dielectrophoresis-based molecular trapping, hot spots for surface-enhanced Raman spectroscopy as well as electronic measurements, and fluorescence imaging. During molecular trapping, recorded Raman spectra, conductance measurements across the nanogaps, and fluorescence imaging show unambiguously the presence and characteristics of the trapped proteins. Our platform opens up a simple way for multifunctional low-concentration heterogeneous sample analysis without the need for target preconcentration.

Electrical Characterization of 4-Mercaptophenylamine-Capped Nanoparticles in a Heterometallic Nanoelectrode Gap

One concept to build up hybrid electronic devices based on molecules or nanoparticles with rectifying properties is based on nanoscale objects that are immobilized between two electrodes composed of different metals forming asymmetric contacts. Following this concept, we introduce an optimized procedure to fabricate heterometallic nanoelectrodes with a separation of only 5 nm. Gold nanoparticles (AuNPs) with a diameter of 15 nm, stabilized with 4-mercaptophenylamine, were used to form electrode1-molecule/AuNP/molecule-electrode2 devices comprising at most a small number of AuNPs. Immobilization was performed by dielectrophoretic trapping. The molecular properties of 4-mercaptophenylamine are reflected in transition voltage spectroscopy features of the device. Cyclic current–voltage measurements on 20 functional devices revealed distinct differences in conductivities based on minor differences in device geometry. Analysis of the electron transport characteristics discloses that under these experimental conditions an asymmetric contact configuration alone is not sufficient for building up a molecule-based rectifier.

Dielectrophoretic trapping of selenium nanorods for use in device applications

Dielectrophoretic alignment of the Selenium (Se) nanorods is reported for electrical characterization and possible applications as micro/nano devices. Selenium nanorods were successfully synthesized using a reverse microemulsion process. The produced material was investigated structurally using X-ray diffraction and transmission electron microscope. Suspensions of the Se powder in the concentration of 0.1 (g/l) were prepared in pure ethanol. Interdigitated platinum electrodes were employed for manipulation of suspended materials in the fluid. When Se particles were exposed to the platinum electrodes in two frequencies of 10 and 100 kHz, dielectrophoretic force captured suspended particles onto the interdigitated micro-electrode array. The trapped Se nanorods were aligned along the electric field lines and bridged the electrode gaps. Dielectrophoretic entrapment of Se nanorods on microelectrode was also detected by impedance measurements. The device was characterized and can potentially be used as a nanodevice.

Quantifying continuous-flow dielectrophoretic trapping of cells and micro-particles on micro-electrode array

An interdigitated electrode array embedded within a micro-channel with forced flow is shown to enable dielectrophoretic (DEP) characterization of particles and/or cells based on measurements of their trapping percentage over a continuous frequency range. A simplified model of the trapping percentage, using spatial averaging of the convective and DEP force, linearly correlated it to the effective DEP force (in its positive mode). Thus, the Clausius-Mossotti factor was fitted to the experimental data, yielding effective electrical characteristics of the particles and/or cells. Also, the generated trapping percentage curve response over a continuous range of frequencies facilitates sorting and detection based on differences other than just the cross-over frequencies.

Highly reduced iron-doped lithium niobate for optoelectronic tweezers

We investigate the applicability of highly reduced lithium niobate samples doped with iron for the use as optoelectronic tweezers. Increasing the reduction degree of Fe-doped lithium niobate is well known to increase the photoconductivity and reduce the writing time of internal space-charge fields. Based on our measurements of the photorefractive properties, we determine the optimal conditions for dielectrophoretic trapping and present the application of Fe-doped lithium niobate as optoelectronic tweezers. For higher reduction degrees, an unexpected decrease in the photovoltaic current density and the saturation space-charge field is reported.

Process development for cell aggregate arrays encapsulated in a synthetic hydrogel using negative dielectrophoresis

Spatial patterning of cells is of great importance in tissue engineering and biotechnology, enabling, for example the creation of bottom-up histoarchitectures of heterogeneous cells, or cell aggregates for in vitro high-throughput toxicological and therapeutic studies within 3D microenvironments. In this paper, a single-step process for creating peelable and resilient hydrogels, encapsulating arrays of biological cell aggregates formed by negative DEP has been devised. The dielectrophoretic trapping within low-energy regions of the DEP-dot array reduces cell exposure to high field stresses while creating distinguishable, evenly spaced arrays of aggregates. In addition to using an optimal combination of PEG diacrylate pre-polymer solution concentration and a novel UV exposure mechanism, total processing time was reduced. With a continuous phase medium of PEG diacrylate at 15% v/v concentration, effective dielectrophoretic cell patterned arrays and photo-polymerisation of the mixture was achieved within a 4 min period. This unique single-step process was achieved using a 30 s UV exposure time frame within a dedicated, wide exposure area DEP light box system. To demonstrate the developed process, aggregates of yeast, human leukemic (K562) and HeLa cells were immobilised in an array format within the hydrogel. Relative cell viability for both cells within the hydrogels, after maintaining them in appropriate iso-osmotic media, over a week period was greater than 90%.

Scaling down constriction‐based (electrodeless) dielectrophoresis devices for trapping nanoscale bioparticles in physiological media of high‐conductivity

Selective trapping of nanoscale bioparticles (size <100 nm) is significant for the separation and high-sensitivity detection of biomarkers. Dielectrophoresis is capable of highly selective trapping of bioparticles based on their characteristic frequency response. However, the trapping forces fall steeply with particle size, especially within physiological media of high-conductivity where the trapping can be dissipated by electrothermal (ET) flow due to localized Joule heating. Herein, we investigate the influence of device scaling within the electrodeless insulator dielectrophoresis geometry through the application of highly constricted channels of successively smaller channel depth, on the net balance of dielectrophoretic trapping force versus ET drag force on bioparticles. While higher degrees of constriction enable dielectrophoretic trapping of successively smaller bioparticles within a short time, the ETflow due to enhanced Joule heating within media of high conductivity can cause a significant dissipation of bioparticle trapping. This dissipative drag force can be reduced through lowering the depth of the highly constricted channels to submicron sizes, which substantially reduces the degree of Joule heating, thereby enhancing the range of voltages and media conductivities that can be applied toward rapid dielectrophoretic concentration enrichment of silica nanoparticles (∼50 nm) and streptavidin protein biomolecules (∼5 nm). We envision the application of these methodologies toward nanofabrication, optofluidics, biomarker discovery, and early disease diagnostics.