Colin Dalton

Continuous dielectrophoretic cell separation microfluidic device

We present a prototype microfluidic device developed for the continuous dielectrophoretic (DEP) fractionation and purification of sample suspensions of biological cells. The device integrates three fully functional and distinct units consisting of an injector, a fractionation region, and two outlets. In the sheath and sample injection ports, the cell sample are hydrodynamically focused into a stream of controlled width; in the DEP fractionation region, a specially shaped nonuniform (isomotive) electric field is synthesized and employed to facilitate the separation, and the sorted cells are then delivered to two sample collection ports. The microfluidic behavior of the injector region was simulated and then experimentally verified. The operation and performance of the device was evaluated using yeast cells as model biological particles. Issues relating to the fabrication and operation of the device are discussed in detail. Such a device takes a significant step towards an integrated lab-on-a-chip device, which could interface/integrate to a number of other on-chip components for the device to undertake the whole laboratory procedure.

A novel alternating current multiple array electrothermal micropump for lab-on-a-chip applications

The AC electrothermal technique is very promising for biofluid micropumping, due to its ability to pump high conductivity fluids. However, compared to electroosmotic micropumps, a lack of high fluid flow is a disadvantage. In this paper, a novel AC multiple array electrothermal (MAET) micropump, utilizing multiple microelectrode arrays placed on the side-walls of the fluidic channel of the micropump, is introduced. Asymmetric coplanar microelectrodes are placed on all sides of the microfluidic channel, and are actuated in different phases: one, two opposing, two adjacent, three, or all sides at the same time. Micropumps with different combinations of side electrodes and cross sections are numerically investigated in this paper. The effect of the governing parameters with respect to thermal, fluidic, and electrical properties are studied and discussed. To verify the simulations, the AC MAET concept was then fabricated and experimentally tested. The resulted fluid flow achieved by the experiments showed good agreement with the corresponding simulations. The number of side electrode arrays and the actuation patterns were also found to greatly influence the micropump performance. This study shows that the new multiple array electrothermal micropump design can be used in a wide range of applications such as drug delivery and lab-on-a-chip, where high flow rate and high precision micropumping devices for high conductivity fluids are needed.

Study on an alternating current electrothermal micropump for microneedle-based fluid delivery systems

In this paper, we report on a modeling study of an AC electrothermal (ACET) micropump with high operating pressures as well as fast flow rates. One specific application area is for fluid delivery using microneedle arrays which require higher pressures and faster flow rates than have been previously reported with ACET devices. ACET is very suitable for accurate actuation and control of fluid flow, since the technique has been shown to be very effective in high conductivity fluids and has the ability to create a pulsation free flow. However, AC electrokinetic pumps usually can only generate low operating pressures of 1 to 100 Pa, where flow reversal is likely to occur with an external load. In order to realize a high performance ACET micropump for continuous fluid delivery, applying relatively high AC operating voltages (20 to 36 Vrms) to silicon substrate ACET actuators and using long serpentine channel allows the boosting of operating pressure as well as increasing the flow rates. Fast pumping flow rates ...

Modeling of drug delivery into tissues with a microneedle array using mixture theory

In this paper, we apply mixture theory to quantitatively predict the transient behavior of drug delivery by using a microneedle array inserted into tissue. In the framework of mixture theory, biological tissue is treated as a multi-phase fluid saturated porous medium, where the mathematical behavior of the tissue is characterized by the conservation equations of multi-phase models. Drug delivery by microneedle array imposes additional requirements on the simulation procedures, including drug absorption by the blood capillaries and tissue cells, as well as a moving interface along its flowing pathway. The contribution of this paper is to combine mixture theory with the moving mesh methods in modeling the transient behavior of drug delivery into tissue. Numerical simulations are provided to obtain drug concentration distributions into tissues and capillaries.

AC electrothermal micropump for biofluidic applications using numerous microelectrode pairs

Electrokinetic phenomena are widely studied techniques used for micro-scale fluid delivery in many microfluidic application areas such as drug delivery, lab-on-a-chip, and biochemical analysis. AC electrothermal (ACET) micropumps are capable of operating at low voltages (up to 10 Vrms) and are suitable for applications involving high conductivity fluids (higher than 0.1 S/m), such as biological fluids. Electrothermal flow is induced by temperature gradients in the presence of a non-uniform electric field. ACET micropumps reported to date have low flow rates (up to 100nl/s) and relatively low back-pressures (up to 1kPa), limiting their utility. In addition, ACET arrays reported in the literature typically feature only a few electrode pairs. In this paper a long fluidic micro-channel, featuring an ACET micropump consisting of a row of 64 asymmetric coplanar microelectrodes is studied in order to investigate the effect of the number of microelectrode pairs on fluid flow. A simulation study is also performed for different numbers of microelectrode pairs. The results show that increasing the number of microelectrode pairs is an efficient way for increasing fluid flow of high conductivity fluids using ACET.

Investigation of human malignant cells by electrorotation

Dielectrophoresis (DEP), traveling wave dielectrophoresis (TWD) and electrorotation (ROT) are established electro-kinetic methods that can be usefully applied for the selective and controlled manipulation, isolation, concentration, separation and characterization of electrically polarizable particles, such as intact cells. Using a custom integrated fluidic microchip, capable of DEP, TWD and ROT measurements, the differences in the frequency dependent dielectric properties of malignant cells obtained from peripheral blood (PB) of patients with multiple myeloma (MM) were investigated. Utilizing these electro-kinetic phenomena will facilitate simultaneous isolation and characterization of different cell populations of PB from patients. Furthermore, the ability to detect and identify malignant cells based on their unique and precise dielectric properties will enable rapid and cost effective detection of impending relapse and/or progression of the disease in addition to the monitoring of response to therapy.

Effect of planar microelectrode geometry on neuron stimulation: Finite element modeling and experimental validation of the efficient electrode shape

BACKGROUND Microelectrode arrays have been used successfully for neuronal stimulation both in vivo and in vitro. However, in most instances currents required to activate the neurons have been in un-physiological ranges resulting in neuronal damage and cell death. There is a need to develop electrodes which require less stimulation current for neuronal activation with physiologically relevant efficacy and frequencies. NEW METHOD The objective of the present study was to examine and compare the stimulation efficiency of different electrode geometries at the resolution of a single neuron. We hypothesized that increasing the electrode perimeter will increase the maximum current density at the edges and enhance stimulation efficiency. To test this postulate, the neuronal stimulation efficacy of common circular electrodes (smallest perimeter) was compared with star (medium perimeter), and spiral (largest perimeter with internal boundaries) electrodes. We explored and compared using both a finite element model and in vitro stimulation of neurons isolated from Lymnaea central ganglia. RESULTS Interestingly, both the computational model and the live neuronal stimulation experiments demonstrated that the common circular microelectrode requires less stimulus to activate a cell compared to the other two electrode shapes with the same surface area. Our data further revealed that circular electrodes exhibit the largest sealing resistance, stimulus transfer, and average current density among the three types of electrodes tested. COMPARISON WITH EXISTING METHODS Average current density and not the maximum current density at the edges plays an important role in determining the electrode stimulation efficiency. CONCLUSION Circular shaped electrodes are more efficient in inducing a change in neuronal membrane potential.

An Integrated PDMS Microfluidic Device for Dielectrophoretic Separation of Malignant Cells

Dielectrophoresis (DEP) has been successfully applied and demonstrated to provide novel and non-invasive means for characterizing, manipulating, trapping, separating and isolating microscopic sized particles, including biological cells. In this article, we report on the design, fabrication and performance of a novel, low cost, integrated Poly(dimethylsiloxane) (PDMS)/DEP microfluidic device capable of controlled manipulation of microscopic sized cells and particles that can be simultaneously utilized both for DEP spectral analysis and cell sorting. We have prototyped microfluidic channels, with DEP microelectrodes incorporated within PDMS channels. Previously, we have evaluated the operation and performance of a prototype device using various dielectric and biological particles, including yeast cells and polystyrene latex beads. In this paper, we report initial experimental observations on malignant cancerous cells. Non-viable cells, due to positive DEP, were attracted to the planar electrodes at frequencies between 200–600 kHz and were clearly repelled from the electrodes, due to negative DEP, at frequencies above 10 MHz.Copyright

An Integrated Microfluidic Dielectrophoretic (DEP) Cell Fractionation System

In this article we report on a planar miniaturized dielectrophoretic (DEP) microfluidic device developed for the purpose of continuous fractionation and purification of sample suspensions of microscopic particles or biological cells, employing specially shaped nonuniform (isomotive) electric fields. The device integrates three fully functional and distinct sub-units consisting of 1) sheath and sample injection ports, arranged to achieve hydrodynamic focusing of the cell stream; 2) the DEP fractionation region and 3) two sample collection ports. In the DEP fractionation region, the magnitude of the field induced DEP force acting on the particle is essentially constant and independent of the particle’s position and furthermore only dependent on the intrinsic polarization response of the particle, for identical sized particles. The operation and performance in terms of sample throughput, separation efficiency and repeatability of the device was evaluated using test microscopic sized dielectric particles and biological particles, including cancerous cell lines.

A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording

Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro- and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with “nano-edges” that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes. This novel technology enables better understanding of brain function and offers a tremendous opportunity towards the development of future bionic hybrids and drug discovery devices.