Molecular dynamics simulation of potentiometric sensor response: the effect of biomolecules, surface morphology and surface charge.

The silica-water interface is critical to many modern technologies in chemical engineering and biosensing. One technology used commonly in biosensors, the potentiometric sensor, operates by measuring the changes in electric potential due to changes in the interfacial electric field. Predictive modelling of this response caused by surface binding of biomolecules remains highly challenging. In this work, through the most extensive molecular dynamics simulation of the silica-water interfacial potential and electric field to date, we report a novel prediction and explanation of the effects of nano-morphology on sensor response. Amorphous silica demonstrated a larger potentiometric response than an equivalent crystalline silica model due to increased sodium adsorption, in agreement with experiments showing improved sensor response with nano-texturing. We provide proof-of-concept that molecular dynamics can be used as a complementary tool for potentiometric biosensor response prediction. Effects that are conventionally neglected, such as surface morphology, water polarisation, biomolecule dynamics and finite-size effects, are explicitly modelled.

Dynamic behaviour of the silica-water-bio electrical double layer in the presence of a divalent electrolyte.

Electronic devices are becoming increasingly used in chemical- and bio-sensing applications and therefore understanding the silica-electrolyte interface at the atomic scale is becoming increasingly important. For example, field-effect biosensors (BioFETs) operate by measuring perturbations in the electric field produced by the electrical double layer due to biomolecules binding on the surface. In this paper, explicit-solvent atomistic calculations of this electric field are presented and the structure and dynamics of the interface are investigated in different ionic strengths using molecular dynamics simulations. Novel results from simulation of the addition of DNA molecules and divalent ions are also presented, the latter of particular importance in both physiological solutions and biosensing experiments. The simulations demonstrated evidence of charge inversion, which is known to occur experimentally for divalent electrolyte systems. A strong interaction between ions and DNA phosphate groups was demonstrated in mixed electrolyte solutions, which are relevant to experimental observations of device sensitivity in the literature. The bound DNA resulted in local changes to the electric field at the surface; however, the spatial- and temporal-mean electric field showed no significant change. This result is explained by strong screening resulting from a combination of strongly polarised water and a compact layer of counterions around the DNA and silica surface. This work suggests that the saturation of the Stern layer is an important factor in determining BioFET response to increased salt concentration and provides novel insight into the interplay between ions and the EDL.

Flow reversal in traveling-wave electrokinetics: an analysis of forces due to ionic concentration gradients.

Pumping of electrolytes using ac electric fields from arrays of microelectrodes is a subject of current research. The behavior of fluids at low signal amplitudes (<2-3 V(pp)) is in qualitative agreement with the prediction of the ac electroosmosis theory. At higher voltages, this theory cannot account for the experimental observations. In some cases, net pumping is generated in the direction opposite to that predicted by the theory (flow reversal). In this work, we use fluorescent dyes to study the effect of ionic concentration gradients generated by Faradaic currents. We also evaluate the influence of factors such as the channel height and microelectrode array shape in the pumping of electrolytes with traveling-wave potentials. Induced charge beyond the Debye length is postulated to be responsible for the forces generating the observed flows at higher voltages. Numerical calculations are performed in order to illustrate the mechanisms that might be responsible for generating the flow.

Traveling-wave electrokinetic micropumps: velocity, electrical current, and impedance measurements.

An array of microelectrodes covered in an electrolyte and energized by a traveling-wave potential produces net movement of the fluid. Arrays of platinum microelectrodes of two different characteristic sizes have been studied. For both sizes of arrays, at low voltages (<2 V pp) the electrolyte flow is in qualitative agreement with the linear theory of ac electroosmosis. At voltages above a threshold, the direction of fluid flow is reversed. The electrical impedance of the electrode-electrolyte system was measured after the experiments, and changes in the electrical properties of the electrolyte were observed. Measurements of the electrical current during pumping of the electrolyte are also reported. Transient behaviors in both electrical current and fluid velocity were observed. The Faradaic currents probably generate conductivity gradients in the liquid bulk, which in turn give rise to electrical forces. These effects are discussed in relation to the fluid flow observations.

Analytical electric field and sensitivity analysis for two microfluidic impedance cytometer designs.

Microfabricated impedance cytometers have been developed to measure the electrical impedance of single biological particles at high speed. A general approach to analytically solve the electric field distributions for two different designs of cytometers: parallel facing electrodes and coplanar electrodes, using the Schwarz-Christoffel Mapping method is presented. Compared to previous analytical solutions, our derivations are more systematic and solutions are more straightforward. The solutions have been validated by comparison with numerical simulations performed using the finite element method. The influences on the electric field distribution due to the variations in the geometry of the devices have been discussed. A simple method is used to determine the impedance sensitivity of the system and to compare the two electrode designs. For identical geometrical parameters, we conclude that the parallel electrodes design is more sensitive than the coplanar electrodes.

On-chip high-speed sorting of micron-sized particles for high-throughput analysis.

A new design of particle sorting chip is presented. The device employs a dielectrophoretic gate that deflects particles into one of two microfluidic channels at high speed. The device operates by focussing particles into the central streamline of the main flow channel using dielectrophoretic focussing. At the sorting junction (T- or Y-junction) two sets of electrodes produce a small dielectrophoretic force that pushes the particle into one or other of the outlet channels, where they are carried under the pressure-driven fluid flow to the outlet. For a 40 microm wide and high channel, it is shown that 6 microm diameter particles can be deflected at a rate of 300/s. The principle of a fully automated sorting device is demonstrated by separating fluorescent from non-fluorescent latex beads.

Pumping of liquids with ac voltages applied to asymmetric pairs of microelectrodes.

The net flow of electrolyte induced by an ac electric potential applied to an array of asymmetric pairs of microelectrodes has recently been reported. The interaction between the oscillating electric field and the oscillating induced charge at the diffuse double layer on the electrodes results in a steady electro-osmotic velocity distribution on top of the electrodes. This slip velocity distribution is anisotropic and produces a net flow of fluid. This paper presents a theoretical analysis of the pumping phenomena based upon an electro-osmotic model in ac fields. The electrical equations are solved numerically using the charge simulation method. The bulk flow generated by the electro-osmotic slip velocity is calculated. The dependence of the fluid flow on voltage and frequency is described and compared to experiments.

Dielectric spectroscopy of Tobacco Mosaic Virus.

The dielectric properties of the Tobacco Mosaic Virus (TMV) have been measured using time domain dielectric spectroscopy (TDDS) in the temperature range from 1 to 40 degrees C. A single dielectric dispersion is observed in the MHz range. The activation energy of the process is found to be in the range 1-2 kcal/mol. The experimental data could not be completely accounted for by current theoretical models, but evidence indicates that the dielectric loss arises from polarisation of charge on and around the virus.

3D focusing of nanoparticles in microfluidic channels.

Dynamic focusing of particles can be used to centre particles in a fluid stream, ensuring the passage of the particles through a specified detection volume. This paper describes a method for focusing nanoparticles using dielectrophoresis. The method differs from other focusing methods in that it manipulates the particles and not the fluid. Experimental focusing is demonstrated for a range of different particle types, and discussed in terms of the operational limits of the device. Dynamic numerical simulations of the particle motion in the device are presented and compared with the experimental results. The potential of the device for nanoparticle control and manipulation in microfluidic chips is discussed.

Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes. III. Observation of streamlines and numerical simulation.

The application of a nonuniform ac electric field to an electrolyte using coplanar microelectrodes results in steady fluid flow. The flow has its origin in the interaction of the tangential component of the nonuniform field with the induced charge in the electrical double layer on the electrode surfaces. Termed ac electro-osmosis, the flow has been studied experimentally and theoretically using linear analysis. This paper presents experimental observations of the fluid flow profile obtained by superimposing images of particle movement in a plane normal to the electrode surface. These experimental streamlines demonstrate that the fluid flow is driven at the surface of the electrodes. Experimental measurements of the impedance of the electrical double layer on the electrodes are also presented. The potential drop across the double layer at the surface of the electrodes is calculated numerically using a linear double layer model, and also using the impedance of the double layer obtained from experimental data. The ac electro-osmotic flow at the surface of the electrodes is then calculated using the Helmholtz-Smoluchowski formula. The bulk fluid flow driven by this surface velocity is numerically calculated as a function of frequency and good agreement is found between the numerical and experimental streamlines.

Separation of submicron bioparticles by dielectrophoresis.

Submicron particles such as latex spheres and viruses can be manipulated and characterized using dielectrophoresis. By the use of appropriate microelectrode arrays, particles can be trapped or moved between regions of high or low electric fields. The magnitude and direction of the dielectrophoretic force on the particle depends on its dielectric properties, so that a heterogeneous mixture of particles can be separated to produce a more homogeneous population. In this paper the controlled separation of submicron bioparticles is demonstrated. With electrode arrays fabricated using direct write electron beam lithography, it is shown that different types of submicron latex spheres can be spatially separated. The separation occurs as a result of differences in magnitude and/or direction of the dielectrophoretic force on different populations of particles. These differences arise mainly because the surface properties of submicron particles dominate their dielectrophoretic behavior. It is also demonstrated that tobacco mosaic virus and herpes simplex virus can be manipulated and spatially separated in a microelectrode array.

Manipulation and trapping of sub-micron bioparticles using dielectrophoresis.

A non-uniform alternating electric field induces motion in polarisable particles called dielectrophoresis. The effect is governed by the relative magnitudes of the dielectric properties of the medium and the particles. The technology has been used to manipulate particles for biotechnological applications, including purification, fractionation and concentration of cells and microorganisms. However, the lower size limit for the dielectrophoretic manipulation of particles was believed to be about 1 micron, but recent work has proved otherwise. The dielectrophoretic movement and properties of latex beads and a simple rod-shaped virus, tobacco mosaic virus (TMV), have been measured using microfabricated electrode structures. Measurements have been made over a range of suspending medium conductivities, applied frequencies and electric field strengths. It is shown that under appropriate conditions both latex beads and tobacco mosaic virus particles can be selectively attracted to regions of high electric field strength located at the tips of microfabricated electrode structures. The ability to selectively trap and separate bio-particles has many potential applications in the area of biotechnology.