During the last decade, large and costly instruments are being replaced by system based on microfluidic devices. Microfluidic devices hold the promise of combining a small analytical laboratory onto a chip-sized substrate to identify, immobilize, separate, and purify cells, bio-molecules, toxins, and other chemical and biological materials. Compared to conventional instruments, microfluidic devices would perform these tasks faster with higher sensitivity and efficiency, and greater affordability. Dielectrophoresis is one of the enabling technologies for these devices. It exploits the differences in particle dielectric properties to allow manipulation and characterization of particles suspended in a fluidic medium. Particles can be trapped or moved between regions of high or low electric fields due to the polarization effects in non-uniform electric fields. By varying the applied electric field frequency, the magnitude and direction of the dielectrophoretic force on the particle can be controlled. Dielectrophoresis has been successfully demonstrated in the separation, transportation, trapping, and sorting of various biological particles. / Singapore-MIT Alliance (SMA)

In this thesis, three specific research contributions to the use of non-uniform electric field driven colloidal assembly are described. The first relates to experimental work using dielectrophoretic and electrohydrodynamic forces (electroosmosis) to shape three-dimensional colloidal structures. Formation and stabilization of close-packed three-dimensional structures from colloidal silica was demonstrated, using gelation of pluronic F-127 to preserve medium structure against suspension evaporation. Stabilization of ordered structures was shown to be a significant challenge, with many of the conventional techniques for immobilizing colloidal crystals being ineffective. Secondly, the significance of electrohydrodynamic flows resulting from electric and particle concentration (entropic) gradients during the assembly process was demonstrated using numerical simulations based on a thermodynamic framework. These simulations, as well as experimental validation of assembly and the presence of fluid flows, showed that assuming equilibrium behavior (stationary fluid flow), a common assumption for most modelling work to date in these systems, is inappropriate at all but the most dilute concentration cases. Finally, the relevance of multiparticle effects on electric-field induced phase transitions of dielectric colloids was demonstrated. The effect of multiparticle/multiscattering effects on the suspension permittivity were accounted for using semi-empirical continuum permittivity formulations which have been previously shown to describe a wide variety of solid packing structures, including face-centered cubic and other colloidal crystal structures. It was shown that multiparticle effects have a significant impact on both the coexistence (slow phase separation) and spinodal (fast phase separation) behavior of dielectric suspensions, which has not been demonstrated to date using a continuum framework. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2012-01-30 14:17:23.747

Molecular analysis of free circulating (fc)DNA has the potential to change the face of medicine, specifically in cancer diagnostics and in monitoring the efficacy of cancer treatments. In this study, a microfluidic device using AC electrokinetics is developed for rapid concentration and detection of fcDNA from blood. The device concentrates fcDNA using a combination of AC electrothermal flow and dielectrophoresis. The electrothermal fluid motion drives fcDNA towards the center of the electrode where dielectrophoretic trapping occurs. Once fcDNA is collected at the center, the concentration in the sample can be determined by fluorescent analysis using an intercalating dye binding to the double-stranded DNA. Effects of operating parameters are investigated to optimize the device's design. The electrokinetic device isolates high molecular weight DNA and can distinguish from low molecular weight DNA. Quantitative detection of fcDNA in physiologically relevant concentrations is demonstrated toward rapid diagnostics of cancer and monitoring of treatment efficacy.

Established techniques for the detection of pathogens, such as bacteria and viruses, require long timeframes for culturing. State of the art biosensors rely on the diffusion of the target analyte to the sensor surface. AC electric fields can be exploited to enhance the sampling of pathogens and concentrate them at specific locations on the sensor surface, thus overcoming these bottlenecks. AC electrokinetic effects like the dielectrophoretic force and electrothermal flows apply forces on the particle and the bulk fluid, respectively. While dielectrophoresis forces pathogens towards a target location, electrothermal flows circulates the fluid, thus replenishing the local concentration. Numerical simulations and experimental proof of principle demonstrate how AC electrokinetics can be used to collect model bioparticles on an antibody functionalized selective surface from a heterogeneous solution having physiologically relevant conductivity. The presence of parallel channels in a quadrupolar microelectrode design is identified as detrimental during the negative dielectrophoretic collection of bioparticles at the centre of the design while simultaneously providing secondary concentration points. These microelectrodes were incorporated onto the surface of a novel cantilever design for the rapid positive dielectrophoretic collection of Escherichia coli bacteria and enabled the subsequent detection of the bacteria by measuring the shift in the resonance frequency of the cantilever. Finally, a proof of principle setup for a Raman coupled, AC electrokinetically enhanced sampling and detection of viruses is shown where the presence of M13 phages are identified on a selective antibody functionalized surface using Raman spectroscopy. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2012-01-30 19:23:48.958

Reducing cost and time is a major concern in clinical diagnostics. Current molecular diagnostics are multi-step processes that usually take at least several hours or even days to complete multiple reagents delivery, incubations and several washing processes. This highly labor-intensive work and lack of automation could result in reduced reliability and low efficiency. The Laboratory-on-a-chip (LOC), taking advantage of the merger and development of microfluidics and biosensor technology, has shown promise towards a solution for performing analytical tests in a self-contained and compact unit, enabling earlier and decentralized testing. However, challenges are to integrate the fluid regulatory elements on a single platform and to detect target analytes with high sensitivity and selectivity. The goal of this research work is to develop an AC electrokinetic (ACEK) flow through concentrator for in-situ concentration of biomolecules and develop a comprehensive understanding of effects of ACEK flow on the biomolecule transport (in-situ concentration) and their impact on electronic biosensing mechanism and performance, achieving automation and miniaturization. ACEK is a new and promising technique to manipulate micro/bio-fluids and particles. It has many advantages over other techniques for its low applied voltage, portability and compatibility for integration into lab-on-a-chip devices. Numerical study on preconcentration system design in this work has provided an optimization rule for various biosensor designs using ACEK technique. And the microfluidic immunoassay lab-chip designed based on ACET effect has showed promising prospect for accelerated diagnostics. With optimized design of channel geometry, electrode patterns, and properly selected operation condition (ac frequency and voltage), the preconcentration system greatly reduced the reaction time to several minutes instead of several hours, and improved sensitivity of the assay. With the design of immunoassay lab-chip, one can quantitatively study the effect of ACET micropumping and mixing on molecular level binding. Improved sensors with single-chip form factor as a general platform could have a significant impact on a wide-range of biochemical detection and disease diagnostics including pathogen/virus detection, whole blood analysis, immune-screening, gene expression, as well as home land security.