Multi-Functional System for Biomedical Application Using AC Electrokinetics

Manipulation of fluids in a small volume is often a challenge in the field of Microfluidics. While many research groups have addressed this issue with robust methodologies, manipulating fluids remains a scope of study due to the ever-changing technology (Processing Tools) and increase in the demand for “Lab-On-a-Chip” devices in biological applications. This thesis peruses the flow pattern of the orthogonal electrode pattern and circular electrode providing, examples of the flow patterns and the process micromixing. Characteristics of a multifunctional system were demonstrated using orthogonal electrode and circular electrode patterned device. Conductivity of the fluids were chosen such they reflect perfect biological conditions to determine the working conditions of the proposed devices under different AC voltage and frequency levels. Experimental results were then compared with simulated results which were obtained using COMSOL simulation software

MICROFLUIDIC PARTICLE AND CELL MANIPULATION USING RESERVOIR-BASED DIELECTROPHORESIS

Controlled manipulation of synthetic particles and biological cells from a complex mixture is important to a wide range of applications in biology, environmental monitoring, and pharmaceutical industry. In the past two decades microfluidics has evolved to be a very useful tool for particle and cell manipulations in miniaturized devices. A variety of force fields have been demonstrated to control particle and cell motions in microfluidic devices, among which electrokinetic techniques are most often used. However, to date, studies of electrokinetic transport phenomena have been primarily confined within the area of microchannels. Very few works have addressed the electrokinetic particle motion at the reservoir-microchannel junction which acts as the interface between the macro (i.e., reservoir) and the micro (i.e., microchannel) worlds in real microfluidic devices. This Dissertation is dedicated to the study of electrokinetic transport and manipulation of particles and cells at the reservoir-microchannel junction of a microfluidic device using a combined experimental, theoretical, and numerical analysis. First, we performed a fundamental study of particles undergoing electrokinetic motion at the reservoir-microchannel junction. The effects of AC electric field, DC electric field, and particle size on the electrokinetic motion of particles passing through the junction were studied. A two-dimensional numerical model using COMSOL 3.5a was developed to investigate and understand the particle motion through the junction. It was found that particles can be continuously focused and even trapped at the reservoir-microchannel junction due to the effect of reservoir-based dielectrophoresis (rDEP). The electrokinetic particle focusing increases with the increase in AC electric field and particle size but decreases with the increase in DC electric field. It was also found that larger particles can be trapped at lower electric fields compared to smaller counterparts. Next, we utilized rDEP to continuously separate particles with different sizes at the reservoir-microchannel junction. The separation process utilized the inherent electric field gradients formed at the junction due to the size difference between the reservoir and the microchannel. It was observed, that the separation efficiency was reduced by inter-particle interactions when particles with small size differences were separated. The effect of enhanced electrokinetic flow on the separation efficiency was investigated experimentally and was observed to have a favorable effect. We also utilized rDEP approach to separate particles based on surface charge. Same sized particles with difference in surface charge were separated inside the microfluidic reservoir. The streaming particles interacted with the trapped particles and reduced the separation efficiency. The influences from the undesired particle trapping have been found through experiments to decrease with a reduced AC field frequency. Then, we demonstrated a continuous microfluidic separation of live yeast cells from dead cells using rDEP. Because the membrane of a cell gets distorted when it loses its viability, a higher exchange of ions results from such viability loss. The increased membrane conductivity of dead cells leads to a different Claussius-Mossoti factor from that of live cells, which enables their selective trapping and continuous separation based on cell viability. A two-shell numerical model was developed to account for the varying conductivities of different cell layers, the results of which agree reasonably with the experimental observations. We also used rDEP to implement a continuous concentration and separation of particles/cells in a stacked microfluidics device. This device has multiple layers and multiple microchannels on each layer so that the throughput can be significantly increased as compared to a single channel/single layer device. Finally, we compared the two-dimensional and three-dimensional particle focusing and trapping at the reservoir-microchannel junction using rDEP. We observed that the inherent electric field gradients in both the horizontal and vertical planes of the junction can be utilized if the reservoir is created right at the reservoir-microchannel junction. Three-dimensional rDEP utilizes the additional electric field gradient in the depth wise direction and thus can produce three-dimensional focusing. The electric field required to trap particles is also considerably lower in three-dimensional rDEP as compared to the two-dimensional rDEP, which thus considerably reduces the non-desired effects of Joule heating. A three-dimensional numerical model which accounted for the entire microfluidic device was also developed to predict particle trajectories

Microelectromechanical Systems and Devices

The advances of microelectromechanical systems (MEMS) and devices have been instrumental in the demonstration of new devices and applications, and even in the creation of new fields of research and development: bioMEMS, actuators, microfluidic devices, RF and optical MEMS. Experience indicates a need for MEMS book covering these materials as well as the most important process steps in bulk micro-machining and modeling. We are very pleased to present this book that contains 18 chapters, written by the experts in the field of MEMS. These chapters are groups into four broad sections of BioMEMS Devices, MEMS characterization and micromachining, RF and Optical MEMS, and MEMS based Actuators. The book starts with the emerging field of bioMEMS, including MEMS coil for retinal prostheses, DNA extraction by micro/bio-fluidics devices and acoustic biosensors. MEMS characterization, micromachining, macromodels, RF and Optical MEMS switches are discussed in next sections. The book concludes with the emphasis on MEMS based actuators

DESIGN AND EVALUATION OF A CONTINUOUS-FLOW DIELECTROPHORESIS DEVICE TO ELIMINATE PATHOGENS FROM TAP WATER

M.S. Thesis. University of Hawaiʻi at Mānoa 2018

Microscale solution manipulation using photopolymerized hydrogel membranes and induced charge electroosmosis micropumps

Microfluidic technology is playing an ever-expanding role in advanced chemical and biological devices, with diverse applications including medical diagnostics, high throughput research tools, chemical or biological detection, separations, and controlled particle fabrication. Even so, local (microscale) modification of solution properties within microchannels, such as pressure, solute concentration, and voltage remains a challenge, and improved spatiotemporal control would greatly enhance the capabilities of microfluidics. This thesis demonstrates and characterizes two microfluidic tools to enhance local solution control. I first describe a microfluidic pump that uses an electrokinetic effect, Induced-Charge Electroosmosis (ICEO), to generate pressure on-chip. In ICEO, steady flows are driven by AC fields along metal-electrolyte interfaces. I design and microfabricate a pump that exploits this effect to generate on-chip pressures. The ICEO pump is used to drive flow along a microchannel, and the pressure is measured as a function of voltage, frequency, and electrolyte composition. This is the first demonstration of chip-scale flows driven by ICEO, which opens the possibility for ICEO pumping in self-contained microfluidic devices.Next, I demonstrate a method to create thin local membranes between microchannels, which enables local diffusive delivery of solute. These ``Hydrogel Membrane Microwindows'' are made by photopolymerizing a hydrogel which serves as a local ``window'' for solute diffusion and electromigration between channels, but remains a barrier to flow. I demonstrate three novel experimental capabilities enabled by the hydrogel membranes: local concentration gradients, local electric currents, and rapid diffusive composition changes. I conclude by applying the hydrogel membranes to study solvophoresis, the migration of particles in solvent gradients. Solvent gradients are present in many chemical processes, but migration of particles within these gradients is not well understood. An improved understanding would allow solvophoresis to be engineered (\emph{e.g.} for coatings and thin film deposition) or reduced (\emph{e.g.} in fouling processes during reactions and separations). Toward this end, I perform velocity measurements of colloidal particles at various ethanol-water concentrations and gradient strengths. The velocity was found to depend on the mole fraction via the equation $u=D_{SP}\nabla \ln{X}$, where $u$ is the velocity, $D_{SP}$ is the mobility, and $X$ is the ethanol mole fraction

PROBLEMS IN THE STUDY AND USE OF AC DIELECTROPHORESIS AND THEIR CONSEQUENCES: A STUDY BASED ON COMSOL MULTIPHYSICS MODELING

Dielectrophoresis (or DEP) is an important phenomenon which is induced when a dielectric particle is placed in a non-uniform electric field. The force generated by DEP has been exploited for various micro and nano fluidics applications like positioning, sorting and separation of particles involved in medical diagnostics, drug discovery, cell therapeutics, biosensors, microfluidics, nanoassembly, particle filtration etc. The integration of DEP systems into the microfluidics enables inexpensive, fast, highly sensitive, highly selective, label-free detection and also the analysis of target bioparticles. This work aims to provide a complete compilation of the factors affecting the DEP force. It elucidates the underlying mechanisms using COMSOL Multiphysics and sheds new insight into the mechanisms for the separation and sorting of different types of particles. This research identifies the problems in the literature and uses COMSOL to analyze the impact of these problems on the end results. It examines four factors that affect the DEP force: physical conditions, electrode setup, properties of the particles and suspension medium. Moreover, it analyzes the influence of the Clausius-Mossotti factor (CM factor) and its cross-over upon the magnitude and direction of the DEP force. From the analysis, it becomes clear that particle size not only affects the magnitude of the DEP force but also the conductivity of the particle. This factor, which is largely ignored, could lead to a shift in the crossover frequency. Shell model plays an important role in determining the dielectric properties of particles that are not homogenous. In such a situation assuming uniform dielectric properties may lead to inconclusive results. The presence of an electric double layer surrounding a particle affects the conductivity of the particle. Also, assuming DEP force to be the only force acting on a particle suspended in a non-uniform electric field leads to errors in the end results. This research provides knowledge on the basic characteristics of the DEP force and its mechanism. It provides a better understanding by examining numerous works carried out in the past and brings out the problems and their consequences

Micromachines for Dielectrophoresis

An outstanding compilation that reflects the state-of-the art on Dielectrophoresis (DEP) in 2020. Contributions include: - A novel mathematical framework to analyze particle dynamics inside a circular arc microchannel using computational modeling. - A fundamental study of the passive focusing of particles in ratchet microchannels using direct-current DEP. - A novel molecular version of the Clausius-Mossotti factor that bridges the gap between theory and experiments in DEP of proteins. - The use of titanium electrodes to rapidly enrich T. brucei parasites towards a diagnostic assay. - Leveraging induced-charge electrophoresis (ICEP) to control the direction and speed of Janus particles. - An integrated device for the isolation, retrieval, and off-chip recovery of single cells. - Feasibility of using well-established CMOS processes to fabricate DEP devices. - The use of an exponential function to drive electrowetting displays to reduce flicker and improve the static display performance. - A novel waveform to drive electrophoretic displays with improved display quality and reduced flicker intensity. - Review of how combining electrode structures, single or multiple field magnitudes and/or frequencies, as well as variations in the media suspending the particles can improve the sensitivity of DEP-based particle separations. - Improvement of dielectrophoretic particle chromatography (DPC) of latex particles by exploiting differences in both their DEP mobility and their crossover frequencies

Exploring Gradients in Electrophoretic Separation and Preconcentration on Miniaturized Devices

abstract: Over the last two decades, miniaturization, integration, and automation have made microfluidic systems popular. Core to advances in microfluidics are numerous electrophoretic separation and preconcentration strategies, some finding their origins on bench-top systems. Among them, gradient-based strategies are especially effective in addressing sensitivity challenges. This review introduces several gradient-based techniques according to a broad definition, including conductivity, field, and concentration, organized by the method of gradient generation. Each technique is introduced and described, and recent seminal advances explored

Analysis, Design and Fabrication of Micromixers, Volume II

Micromixers are an important component in micrototal analysis systems and lab-on-a-chip platforms which are widely used for sample preparation and analysis, drug delivery, and biological and chemical synthesis. The Special Issue "Analysis, Design and Fabrication of Micromixers II" published in Micromachines covers new mechanisms, numerical and/or experimental mixing analysis, design, and fabrication of various micromixers. This reprint includes an editorial, two review papers, and eleven research papers reporting on five active and six passive micromixers. Three of the active micromixers have electrokinetic driving force, but the other two are activated by mechanical mechanism and acoustic streaming. Three studies employs non-Newtonian working fluids, one of which deals with nano-non-Newtonian fluids. Most of the cases investigated micromixer design

Nanotechnology enabled microfluidics/Raman spectroscopy systems for bio applications

The vision for this PhD research project was born out of a desire to study the in situ behaviour of suspended nano-materials; specifically, implementing a Raman microscopy system for investigating suspended materials in the microfluidic environment. The author developed a set of innovative research goals to achieve this vision, which include: (1) forming a suitable microfluidic system which can apply controlled forces onto the suspended materials on demand, (2) implementing Raman microscopy to study the behaviour of particles under the influence of such forces while inside the microfluidic system and (3) incorporating the developed microfluidic system for investigating suspended materials of low concentration, including biological cells and surface-enhanced Raman scattering studies. The author implemented the research in three distinct stages such that the work in earlier stages could provide the platform for the future work. In the first stage, the author designed a microfluidic dielectrophoresis platform consisting of curved microelectrodes. This platform was integrated with a Raman microscopy system for creating a novel system capable of detecting suspended particles of various types and spatial concentrations. The system was benchmarked using polystyrene and tungsten trioxide suspended particles, and the outcomes of this novel integrated system showed its strong potential for the determination of suspended particles types and their direct mapping, with several unique advantages over conventional optical systems. In the second stage of this research, the author developed a novel microfluidic-DEP system that could manipulate suspended silver nanoparticles’ spacing in three dimensions. Silver nanoparticles are capable of producing strong surface enhanced Raman scattering (SERS) signals, allowing the Raman system to detect very low concentrations of suspended analytes. DEP provided facile control of the positions and spacings of the suspended silver nanoparticles, and allowed for the creation of SERS hot-spots. The system was studied to determine the optimum DEP and microfluidic flow parameters for generating SERS, and the author was able to demonstrate this as a reversible process. This stage of the research used dipicolinic acid as the target analyte, and the system was demonstrated to have detection limits as small as ~1 ppm concentration levels. In the third stage, the microfluidic-DEP platform was used for trapping and isolating yeast cells. Silver nanoparticles were again used for SERS applications. The trapped cells were interrogated by the Raman system in order to obtain deeper understandings of cells functionalities and their communications under various physical conditions: live vs. dead and isolated vs. grouped. Live vs. dead experiments were conducted as a benchmark, to observe whether SERS is capable of differentiating cells based on the life condition. The research was expanded to study cells that were isolated from one another, and compared those Raman signatures to those from cells in grouped clusters. The author was able to extract unique information from such studies, including the importance of glycine, or proteins with glycine subunits, in the proliferation of yeast cells. The developed system showed great potential as a universal platform for the in situ study of cells, their communications and functionalities