Numerical investigation of field-effect control on hybrid electrokinetics for continuous and position-tunable nanoparticle concentration in microfluidics

We introduce herein an effective way for continuous delivery and position-switchable trapping of nanoparticles via field-effect control on hybrid electrokinetics (HEK). Flow field-effect transistor exploiting HEK delicately combines horizontal linear electroosmosis and transversal nonlinear electroosmosis of a shiftable flow stagnation line (FSL) on gate terminals under DC-biased AC forcing. The microfluidic nanoparticle concentrator proposed herein makes use of a simple device geometry, in which an individual or a series of planar metal strips serving as gate electrode (GE) are subjected to a hybrid gate voltage signal and arranged in parallel between a pair of 3D driving electrodes. On the application of a DC-biased AC electric field across channel length direction, all the GE are electrochemically polarized, and the action of imposed hybrid electric field on the multiple-frequency bipolar counterions within the composite-induced double layer generates two counter-rotating induced-charge electroosmotic (ICEO) micro-vortices on top of each GE. Symmetry breaking in ICEO flow profile occurs once the gate voltage deviates from natural floating potential of corresponding GE. The gate voltage offset not only results in an additional pump motion of working fluid for enhanced electroosmotic transport but also directly changes the location of FSL where nanoparticles are preferentially collected by field-effect HEK. Our results of field-effect control on HEK are supposed to guide an elaborate design of flexible electrokinetic frameworks embedding coplanar metal strips for a high degree of freedom analyte manipulation in modern micro-total-analytical systems.     

Recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices

AC electrokinetics is a generic term that refers to an induced motion of particles and fluids under nonuniform AC electric fields. The AC electric fields are formed by application of AC voltages to microelectrodes, which can be easily integrated into microfluidic devices by standard microfabrication techniques. Moreover, the magnitude of the motion is large enough to control the mass transfer on the devices. These advantages are attractive for biomolecular analysis on the microfluidic devices, in which the characteristics of small space and microfluidics have been mainly employed. In this review, I describe recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices. The applications include fluid pumping and mixing by AC electrokinetic flow, and manipulation of biomolecules such as DNA and proteins by various AC electrokinetic techniques. Future prospects for highly functional biomolecular analysis on microfluidic devices with the aid of AC electrokinetics are also discussed.     

On hybrid electroosmotic kinetics for field‐effect‐reconfigurable nanoparticle trapping in a four‐terminal spiral microelectrode array

Induced‐charge electroosmosis (ICEO) has attracted tremendous popularity for driving fluid motion from the microfluidic community since the last decade, while less attention has been paid to ICEO‐based nanoparticle manipulation. We propose herein a unique concept of hybrid electroosmotic kinetics (HEK) in terms of bi‐phase ICEO (BICEO) actuated in a four‐terminal spiral electrode array, for effective electrokinetic enrichment of fluorescent polystyrene nanoparticles on ideally polarizable metal strips. First, by alternating the applied AC voltage waves between consecutive discrete terminals, the flow stagnation lines where the sample nanoparticles aggregate can be switched in time between two different distribution modes. Second, we innovatively introduce the idea of AC field‐effect flow control on BICEO; by altering the combination of gating voltage sequence, not only the number of circulative particle trapping lines is doubled, but the collecting locations can be flexibly reconfigured as well. Third, hydrodynamic streaming of DC‐biased BICEO is tested in our device design, wherein the global linear electroosmosis dominates BICEO contributed from both AC and DC components, resulting in a reduction of particle enrichment area, while with a sharp increase in sample transport speed inside the bulk phase. The flow field associated with HEK is predicted using a linear asymptotic analysis under Debye–Huckel limit, with the simulation results in qualitative agreement with in‐lab observations of nanoparticle trapping by exploiting a series of improved ICEO techniques. This work provides an affordable and field‐deployable platform for real‐time nanoparticle trapping in the context of dilute electrolyte.     

Electrokinetic particle entry into microchannels

The fundamental understanding of particle electrokinetics in microchannels is relevant to many applications. To date, however, the majority of previous studies have been limited to particle motion within the area of microchannels. This work presents the first experimental and numerical investigation of electrokinetic particle entry into a microchannel. We find that the particle entry motion can be significantly deviated from the fluid streamline by particle dielectrophoresis at the reservoir-microchannel junction. This negative dielectrophoretic motion is induced by the inherent non-uniform electric field at the junction and is insensitive to the microchannel length. It slows down the entering particles and pushes them toward the center of the microchannel. The consequence is the demonstrated particle deflection, focusing, and trapping phenomena at the reservoir-microchannel junction. Such rich phenomena are studied by tuning the AC component of a DC-biased AC electric field. They are also utilized to implement a selective concentration and continuous separation of particles by size inside the entry reservoir.     

Rapid concentration of deoxyribonucleic acid via Joule heating induced temperature gradient focusing in poly-dimethylsiloxane microfluidic channel

This paper reports rapid microfluidic electrokinetic concentration of deoxyribonucleic acid (DNA) with the Joule heating induced temperature gradient focusing (TGF) by using our proposed combined AC and DC electric field technique. A peak of 480-fold concentration enhancement of DNA sample is achieved within 40 s in a simple poly-dimethylsiloxane (PDMS) microfluidic channel of a sudden expansion in cross-section. Compared to a sole DC field, the introduction of an AC field can reduce DC field induced back-pressure and produce sufficient Joule heating effects, resulting in higher concentration enhancement. Within such microfluidic channel structure, negative charged DNA analytes can be concentrated at a location where the DNA electrophoretic motion is balanced with the bulk flow driven by DC electroosmosis under an appropriate temperature gradient field. A numerical model accounting for a combined AC and DC field and back-pressure driven flow effects is developed to describe the complex Joule heating induced TGF processes. The experimental observation of DNA concentration phenomena can be explained by the numerical model.     

Towards high concentration enhancement of microfluidic temperature gradient focusing of sample solutes using combined AC and DC field induced Joule heating

It is challenging to continuously concentrate sample solutes in microfluidic channels. We present an improved electrokinetic technique for enhancing microfluidic temperature gradient focusing (TGF) of sample solutes using combined AC and DC field induced Joule heating effects. The introduction of an AC electric field component services dual functions: one is to produce Joule heat for generating temperature gradient; the other is to suppress electroosmotic flow. Consequently the required DC voltages for achieving sample concentration by Joule heating induced TGF are reduced, thereby leading to smaller electroosmotic flow (EOF) and thus backpressure effects. As a demonstration, the proposed technique can lead to concentration enhancement of sample solutes of more than 2500-fold, which is much higher than the existing literature reported microfluidic concentration enhancement by utilizing the Joule heating induced TGF technique.     

Dielectrophoretic focusing of particles in a microchannel constriction using DC‐biased AC flectric fields

This paper presents a fundamental study of particle electrokinetic focusing in a single microchannel constriction. Through both experiments and simulations, we demonstrate that such dielectrophoresis‐induced particle focusing can be implemented in a much smaller magnitude of DC‐biased AC electric fields (10 kV/m in total) as compared to pure DC electric fields (up to 100 kV/m). This is attributed to the increase in the ratio of cross‐stream particle dielectrophoretic velocity to streamwise electrokinetic velocity as only the DC field component contributes to the latter. The effects of the 1 kHz frequency AC to DC electric field ratio on particle trajectories and velocity variations through the microchannel constriction are also examined, which are found to agree with the simulation results.     

DC-biased AC-electrokinetics: a conductivity gradient driven fluid flow

This paper studies the principles of fluid flow manipulation based on DC-biased AC-electrokinetics. This method makes use of planar parallel electrodes in a microfluidic channel in contact with an electrolyte solution, with a DC biased AC electrical signal applied to the electrode pair. Due to the application of DC bias, incipient Faradaic electrolytic reactions take place resulting in an increase of the ionic content of the bulk solution. The ionic content was found to be dissimilar at the cathodic and anodic sides of the channel and a conductivity difference of approximately 10% was measured for 2 V(DC). Fluid flow is generated by the action of the DC biased AC electric signal acting on the transverse conductivity gradient generated across the microchannel. The induced flow in the form of vortex was characterized experimentally and the results substantiated theoretically. The velocity of the induced flow vortex under the employed experimental conditions was ~600 to 700 μm s(-1) which is faster than those obtained in conventional AC-electroosmosis and AC-electrothermal types of flows.     

An Ohmic model for electrokinetic flows of binary asymmetric electrolytes

The transport of electrolytes in electric fields is a ubiquitous phenomenon commonly harnessed in microfluidics. A classic leaky dielectric model for flow generated by electric fields accurately predicts electrohydrodynamic transport phenomenon but is valid for millimeter-scale and larger flows and at relatively low ionic strength. Here, we derive and use a modified version of this model to sub-millimeter scales more relevant to microfluidics, where diffusive transport of charged species becomes non-negligible. We formulate a general equation set, the modified Ohmic model, applicable to the transport of binary, asymmetric electrolytes. We leverage this model to describe a variety of microfluidic electrokinetic systems, including DC electroosmosis, alternating current electrokinetics (ACEK) and induced-charge electroosmosis (ICEO), thus highlighting some unifying principles of these flows.     

Continuous and reversible mixing or demixing of nanoparticles by dielectrophoresis

Mixing and demixing (separation) are essential tasks in microfluidic devices, which seem to be contrary in nature. Accordingly, completely different strategies and devices are usually employed for their realization. We here present a microfluidic device which is capable of performing both these tasks as it can be operated in either mixing or demixing mode. The mixing and demixing processes are reversible and are accomplished by continuous operation of the device. An asymmetric S-shaped ridge extends over the full width of a microfluidic channel (200 μm) creating a constriction of 620 nm in height with an aspect ratio of 1 : 500. Appropriate AC and DC voltages generate electrodeless dielectrophoresis at the constriction as well as (linear) electrokinetic driving forces along the channel. These de/mixing parameters can be adapted in real time in such a way that continuous separation and mixing efficiencies of 85-100% can be achieved. As a proof of concept we demonstrate continuous mixing and demixing of polystyrene nanoparticles (20 and 100 nm). The experimental results are complemented by numerical simulations illustrating the particles' motion under the influence of the electrokinetic effects and thermal noise (diffusion). The monolithic one-step fabrication process by soft lithography (with PDMS in our case) will make integration and combination of several mixing and demixing functions into a more complex lab-on-a-chip device possible.     

Surfactant addition and alternating current electrophoretic oscillation during size fractionation of nanoparticles in channels with two or three different height segments

An array of parallel planar nanochannels containing two or three segments with varying inner heights was fabricated and used for size fractionation of inorganic and biological nanoparticles. A liquid suspension of the particles was simply drawn through the nanochannels via capillary action. Using fluorescently labeled 30 nm polyacrylonitrile beads, different trapping behaviors were compared using nanochannels with 200-45 nm and 208-54-30 nm height segments. Addition of sodium dodecyl sulfate (SDS) surfactant to the liquid suspension and application of an AC electric field were shown to aid in the prevention of channel clogging. After initial particle trapping at the segment interfaces, significant particle redistribution occurred when applying a sinusoidal 8V peak-to-peak oscillating voltage with a frequency of 150 Hz and DC offset of 4V. Using the 208-54-30 nm channels, 30 nm hepatitis B virus (HBV) capsids were divided into three fractions. When the AC electric field was applied to this trapped sample, all of the virus particles passed through the interfaces and accumulated at the channel ends.     

Negative dielectrophoresis-based particle separation by size in a serpentine microchannel

Dielectrophoresis has been widely used to focus, trap, concentrate, and sort particles in microfluidic devices. This work demonstrates a continuous separation of particles by size in a serpentine microchannel using negative dielectrophoresis. Depending on the magnitude of the turn-induced dielectrophoretic force, particles travelling electrokinetically through a serpentine channel either migrate toward the centerline or bounce between the two sidewalls. These distinctive focusing and bouncing phenomena are utilized to implement a dielectrophoretic separation of 1 and 3 μm polystyrene particles under a DC-biased AC electric field of 880 V/cm on average. The particle separation process in the entire microchannel is simulated by a numerical model.     

Single-cell analysis by electrochemical detection with a microfluidic device

A novel electrochemical method with a microfluidic device was developed for analysis of single cells. In this method, cell injection, loading and cell lysis, and electrokinetic transportation and detection of intracellular species were integrated in a microfluidic chip with a double-T injector coupled with an end-channel amperometric detector. A single cell was loaded at the double-T injector on the microfluidic chip by using electric field. Then, the docked cell was lysed by a direct current electric field strength of 220 V/cm. The analyte of interest inside the cell was electrokinetically transported to the detection end of separation channel and was electrochemically detected. External standardization was used to quantify the analyte of interest in individual cells. Ascorbic acid (AA) in single wheat callus cells was chosen as the model compound. AA could be directly detected at a carbon fiber disk bundle electrode. The selectivity of electrochemical detection made the electropherogram simple. The technique described here could, in principle, be applied to a variety of electroactive species within single cells.     

Dynamic analyte introduction and focusing in plastic microfluidic devices for proteomic analysis

Isoelectric focusing (IEF) separations, in general, involve the use of the entire channel filled with a solution mixture containing protein/peptide analytes and carrier ampholytes for the creation of a pH gradient. Thus, the preparative capabilities of IEF are inherently greater than most microfluidics-based electrokinetic separation techniques. To further increase sample loading and therefore the concentrations of focused analytes, a dynamic approach, which is based on electrokinetic injection of proteins/peptides from solution reservoirs, is demonstrated in this study. The proteins/peptides continuously migrate into the plastic microchannel and encounter a pH gradient established by carrier ampholytes originally present in the channel for focusing and separation. Dynamic sample introduction and analyte focusing in plastic microfluidic devices can be directly controlled by various electrokinetic conditions, including the injection time and the applied electric field strength. Differences in the sample loading are contributed by electrokinetic injection bias and are affected by the individual analyte's electrophoretic mobility. Under the influence of 30 min electrokinetic injection at constant electric field strength of 500 V/cm, the sample loading is enhanced by approximately 10-100 fold in comparison with conventional IEF.     

Magnetic force-based multiplexed immunoassay using superparamagnetic nanoparticles in microfluidic channel

This paper describes a novel microfluidic immunoassay utilizing binding of superparamagnetic nanoparticles to beads and deflection of these beads in a magnetic field as the signal for measuring the presence of analyte. The superparamagnetic 50 nm nanoparticles and fluorescent 1 microm polystyrene beads are immobilized with specific antibodies. When target analytes react with the polystyrene beads and superparamagnetic nanoparticles simultaneously, the superparamagnetic nanoparticles can be attached onto the microbeads by the antigen-antibody complex. In the poly(dimethylsiloxane)(PDMS) microfluidic channel, only the microbeads conjugated with superparamagnetic nanoparticles by analytes consequently move to the high gradient magnetic fields under the specific applied magnetic field. In this study, the magnetic force-based microfluidic immunoassay is successfully applied to detect the rabbit IgG and mouse IgG as model analytes. The lowest concentration of rabbit IgG and mouse IgG measured over the background is 244 pg mL(-1) and 15.6 ng mL(-1), respectively. The velocities of microbeads conjugated with superparamagnetic nanoparticles are demonstrated by magnetic field gradients in microfluidic channels and compared with the calculated magnetic field gradients. Moreover, dual analyte detection in a single reaction is also performed by the fluorescent encoded microbeads in the microfluidic device. Detection range and lower detection limit can be controlled by the microbeads concentration and the higher magnetic field gradient.     

Induction and suppression of cell lysis in an electrokinetic microfluidic system

The ability to strategically induce or suppress cell lysis is critical for many cellular-level diagnostic and therapeutic applications conducted within electrokinetic microfluidic platforms. The chemical and structural integrity of sub-cellular components is important when inducing cell lysis. However, metal electrodes and electrolytes participate in undesirable electrochemical reactions that alter solution composition and potentially damage protein, RNA, and DNA integrity within device microenvironments. For many biomedical applications, cell viability must be maintained even when device-imposed cell-stressing stimuli (e.g., electrochemical reaction byproducts) are present. In this work, we explored a novel and tunable method to accurately induce or suppress device-imposed artifacts on human red blood cell (RBC) lysis in non-uniform AC electric fields. For precise tunability, a dielectric hafnium oxide (HfO₂) layer was used to prevent electron transfer between the electrodes and the electric double layer and thus reduce harmful electrochemical reactions. Additionally, a low concentration of Triton X-100 surfactant was explored as a tool to stabilize cell membrane integrity. The extent of hemolysis was studied as a function of time, electrode configuration (T-shaped and star-shaped), cell position, applied non-uniform AC electric field, with uncoated and HfO₂ coated electrodes (50 nm), and absence and presence of Triton X-100 (70 µM). Tangible outcomes include a parametric analysis relying upon literature and this work to design, tune, and operate electrokinetic microdevices to intentionally induce or suppress cellular lysis without altering intracellular components. Implications are that devices can be engineered to leverage or minimize device-imposed biological artefacts extending the versatility and utility of electrokinetic diagnostics.     

Hybrid continuum-atomistic approach to model electrokinetics in nanofluidics

In this study, for the first time, a hybrid continuum-atomistic based model is proposed for electrokinetics, electroosmosis and electrophoresis, through nanochannels. Although continuum based methods are accurate enough to model fluid flow and electric potential in nanofluidics (in dimensions larger than 4 nm), ionic concentration is too low in nanochannels for the continuum assumption to be valid. On the other hand, the non-continuum based approaches are too time-consuming and therefore is limited to simple geometries, in practice. Here, to propose an efficient hybrid continuum-atomistic method of modelling the electrokinetics in nanochannels; the fluid flow and electric potential are computed based on continuum hypothesis coupled with an atomistic Lagrangian approach for the ionic transport. The results of the model are compared to and validated by the results of the molecular dynamics technique for a couple of case studies. Then, the influences of bulk ionic concentration, external electric field, size of nanochannel, and surface electric charge on the electrokinetic flow and ionic mass transfer are investigated, carefully. The hybrid continuum-atomistic method is a promising approach to model more complicated geometries and investigate more details of the electrokinetics in nanofluidics.     

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.     

Role of electric field on surface wetting of polystyrene surface

The role of surface charge in fluid flow in micro/nanofluidics systems as well as the role of electric field to create switchable hydrophobic surfaces is of interest. In this work, the contact angle (CA) and contact angle hysteresis (CAH) of a droplet of deionized (DI) water were measured with applied direct current (DC) and alternating current (AC) electric fields. The droplet was deposited on a polystyrene (PS) surface, commonly used in various nanotechnology applications, coated on a doped silicon (Si) wafer. With the DC field, CA decreased with an increase in voltage. Because of the presence of a silicon oxide layer and a space charge layer, the change of the CA was found to be lower than with a metal substrate. The CAH had no obvious change with a DC field. An AC field with a positive value was applied to the droplet to study its effect on CA and CAH. At low frequency (lower than 10 Hz), the droplet was visibly oscillating. The CA was found to increase when the frequency of the applied AC field increased from 1 Hz to 10 kHz. On the other hand, the CA decreased with an increasing peak-peak voltage at or lower than 10 kHz. The CAH in the AC field was found to be lower than in the DC field and had a similar trend to static CA with increasing frequency. A model is presented to explain the data.     

Induced-charge electrokinetic phenomena

The field of nonlinear “induced-charge” electrokinetics is rapidly advancing, motivated by potential applications in microfluidics as well as by the unique opportunities it provides for probing fundamental scientific issues in electrokinetics. Over the past few years, several surprising theoretical predictions have been observed in experiments: (i) induced-charge electrophoresis of half-metallic Janus particles, perpendicular to a uniform AC field; (ii) microfluidic mixing around metallic structures by induced-charge electro-osmosis, and (iii) fast, high-pressure AC electro-osmotic pumping by non-planar electrode arrays, and ICEK effects upon the collective behavior of polarizable particle suspensions has been studied theoretically and computationally. A new experimental system enables a clean and direct comparison between theoretical predictions and measured ICEK flows, providing a route to fundamental studies of particular surfaces and high-throughput searches for optimal ICEK systems. Systematic discrepancies between theory and experiment have engendered the search for mechanisms, including new theories that account for electrochemical surface reactions, surface contamination, roughness, and the crowding of ions at high voltage. Promising directions for further research, both fundamental and applied, are discussed.