The use of mass spectrometry in the biosciences has undergone huge growth in re- cent years due to sustained effort in the development of new ionisation techniques, more powerful mass analysers and better bioinformatic tools. These developments mean that it is now possible to introduce complex crude biological-mixtures into a mass spectrometric platform and to obtain detailed information about the sample. The front-end sample handling techniques used for sample preparation have, for the most part, not changed despite the recent advances in hyphenation of liquid- chromatography and mass spectrometry required to tackle the issue of increased sample complexity. In this thesis the possibility of using Digital Microfluidics (DMF) for front-end sample preparation prior to mass-spectrometric analysis of protein samples has been investigated. DMF is a micro-electromechanical system (MEMS) technology used for manipulation of sub-microlitre droplets. The movement of discrete droplets of liquid is exploited using the Coulombic forces arising due to free charge polarisation. Droplets can be split, joined, dispensed and moved over a sub-surface electrode array. In this thesis a range of DMF devices have been designed, manufactured and coupled with mass spectrometric platforms for protein analysis. A variety of techniques for mass spectrometry- based analysis of biological samples from the fluidic chips have been investigated. A robotic system has been developed to automate sample introduction, manipulation and removal. Finally the application of on-chip sample purification and enzymatic digestion have been demonstrated, providing proof of concept for digital microfluidic sample preparation in mass spectrometry-based proteomics.

<div>Single phase immiscible fluid flow in porous media is often described by Darcy’s law. However, in two-phase or multi-phase conditions, the properties of porous medium rely on the saturation of each phase. One of the constitutive equations, the relationship between capillary pressure and saturation, exhibits hysteresis property. To accurately describe two-phase immiscible fluid in porous media, some researchers used interfacial area per volume (IAV) as an additional variable. Previous experiments were done by other experimenters to support the uniqueness of IAV in capillary pressure – saturation hysteresis relationship by externally changing the capillary pressure. </div><div>A technique called Electro-Wetting On Dielectric (EWOD) was developed for sealed micro-models to examine the saturation-pressure relationship by internally manipulating the saturation which in turns affects IAV. Single-plate EWOD samples were used to select material properties and experimental parameters. These experiments found that Poly-Di-Methyl-Siloxane (PDMS) is a good dielectric material that enabled changes in the contact angle between a droplet and PDMS from ~120° (non-wetting) to ~50° (wetting). Double-plate EWOD was used to demonstrate that discrete electrodes (with PDMS as dieletric on both plates) enabled the transportation and merging of droplet(s).</div><div>A novel method was developed to incorporate EWOD into a wedge-shaped PDMS micro-model. Imbibition and drainage scans of the capillary pressure – saturation relationship (Pc-S) were performed in the channel with and without voltage. The drainage curves differed significantly between the two conditions, while the imbibition curves were similar with and without voltage. The total energy for Pc-S decreased by 70 nJ with the application of EWOD with most of difference arising from a 20 Pa decrease in pressure for the same saturation condition during drainage.</div><div>Studies were also performed to examine the amount of energy associated with depiing of fluid interfaces. A 5-step wedge-shaped micro-model with EWOD was fabricated to increase the probability of pinning during an experiment. The amount of energy released as a fluid depinned was observed to be a function of capillary pressure. More energy was released at the 1st step for higher the pressures than lower pressures. The energy released from depinning at the first step in the channel ranged from 30 – 100 nJ for pressures from 70 to 100 Pa. The occurrence and magnitude of additional depinnings along the step-shaped channel also depended on the pressure. Each successive depining released less energy.</div><div>Finally, experiments were performed to examine the range of EWOD in a sealed micro-model with discrete electrodes. When voltage was not applied directly on the fluid-fluid interface but on the solution, the voltage could still actuate the interface causing it to move and advance farther into a channel. The ability of the application of EWOD to drive fluid-fluid interfaces decreases with active electrode distance from the interface.</div>

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Electrowetting on dielectric (EWOD) is a technique for reducing the apparent contact angle of a fluid droplet, which has many promising applications in the fields of optics, digital displays, and lab-on-a-chip research. In this thesis, a design is presented for a novel single circuit device for achieving continuous droplet motion, by using the current-rectifying properties of valve metals to create diode-like behavior. This contrasts with existing designs, which require an array of individual electrodes to achieve motion in discrete steps. We are able to demonstrate continuous droplet motion across a 28mm-long test strip with an applied voltage of 303 V and a velocity of 5.59 mm/s (at 370 V) using an ionic-fluid electrolyte (BMIM-PF6), and have achieved actuation at as low as 185 V, with a maximum observed velocity (at 300 V) of 13.8 mm/s using a 1M sodium sulfate solution.

Digital microfluidics (DMF) is an emerging liquid-handling technique that facilitates manipulation of discrete droplets across an array of electrodes. Although the working principle of droplet movement is still under debate, it has gained significant interest as the technique has been applied to various applications in biology, chemistry and medicine. With recent advances in rapid prototyping and multilayer fabrication techniques using printed circuit boards, DMF has become an attractive and alternative solution to conventional macroscale fluidics techniques with additional capability of sample size reduction, faster analysis time, full automation, and multiplexing. In this thesis, we explore the use of DMF for human plasma protein depletion due to its multiple advantages. The high abundance of human serum albumin (HSA) and immunoglobulins (Igs), which constitute 80% of total plasma proteins, is a major challenge in proteome studies. Unfortunately, conventional methods to deplete high abundant proteins (e.g. macro LC-columns) are labour-intensive, require dilution of sample, and run the risk of sample loss. Furthermore, most techniques lack the ability to process multiple samples simultaneously. Hence, we developed a new method of protein depletion using anti-HSA and Protein A/G immobilized paramagnetic beads manipulated by DMF to deplete HSA and IgG from human plasma. Toward this goal, prototype DMF devices and electronic controller were designed, built and characterized (Chapter 2). Preliminary depletion experiments were first optimized in-tubes and then adapted for DMF manually (Chapter 3). At last, the entire depletion process was performed on DMF using an automated controller system (Chapter 4). Results showed that the protein depletion efficiency for immunoglobulin G (IgG) and HSA in 10 minutes for four samples simultaneously was as high as 98%, and an approximately 3-fold increase in signal-to-noise ratio after depletion was demonstrated by MALDI-MS analysis. The depletion process is sufficient for a tryptic digest to be performed on a model protein, cytochrome C, where 89% sequence coverage was obtained for a depleted sample. Although some improvements such as on-chip sample processing (e.g. digestion) need to be carried out as future work, we anticipate that the new technique is a significant alternative for applications involving protein depletion steps. / Thesis (Master, Chemistry) -- Queen's University, 2014-05-29 02:38:50.176

The goal of this work is to quantify the key design parameters such as the load capacity, actuation force, positioning repeatability, and reliability for droplet-based electrowetting actuators. Due to the fact that surface tension dominates gravity at both the mesoscale and microscale, droplet-based actuators can provide adequate force in manipulation tasks at those scales. Electrowetting, which uses an electric field to modulate the apparent surface tension of the liquid-ambient, provides a method to actuate droplets, which in turn transports the object carried by the droplet. Most previous electrowetting actuation efforts have concentrated on manipulating droplets in a closed two-plate configuration. In these configurations, a voltage potential is applied between a series of electrodes. The droplets can merge, split, and mix with only a voltage input, and without any external machinery. While some mechanical actuation demonstrations have been done, limited studies have been performed to investigate the key actuation performance characteristics of droplet-based actuators carrying solid objects. Design criteria for using droplets to carry solid components are still not well defined. The first part of this work provides fundamental understanding of the forces in electrowetting-based droplet actuation. The actuation force during electrowetting was experimentally validated according to the governing relation (Young–Lippmann equation) on a custom-designed testing apparatus. The results from the experiments show that the electrowetting actuation force is independent of surface tension below saturation, but the peak force is proportional to surface tension. Higher surface/interfacial tension would increase the actuation force in the horizontal direction, as well as the speed of the actuator. The second part of the dissertation demonstrates two actuation configurations based on electrowetting. The first actuator uses a droplet to carry a solid object and can be actuated in discrete steps to function as a micro-stepping linear motor. By implementing a leaky dielectric coating, the droplet/substrate contact area acts as an electrical diode. By varying the duty cycle of a square waveform, a range of droplet/part equilibrium position combinations are established. The underlying actuation mechanism was investigated and the position versus duty cycle relation was shown to be symmetrical but non–linear around the center of the electrodes. In contrast to the conventional electrowetting control scheme, the proposed actuation method required no feedback control loop while achieving a repeatability of less than 0.8% of the droplet diameter. Positioning matched a theoretical model based on idealized electrical elements to within 2.5% of the droplet diameter. The second type of electrowetting actuation uses metal-semiconductor diodes (Schottky diodes) in place of electrochemical diodes. This configuration uses only one pair of electrodes to actuate the droplet over a large distance (5X or more the droplet diameter). While the actuation concept had been previously demonstrated, the reliability of the diodes were shown to be insufficient. The new diodes actuated without degradation under repeated actuation (2000 cycles). Comparing this to electrochemical diodes, a 50% reduction in actuation voltage was also accomplished by Schottky diodes. The measured maximum speed also increased from 32 mm/s (electrochemical diodes) to 240 mm/s (Schottky), a 7.5 fold improvement. The last part of this dissertation used numerical simulations to investigate the load bearing capability and the stiffness variation of droplet-based actuators. The vertical force and stiffness - which are the primary figure of merit in designing droplet-based actuators are quantified. Three types of loading conditions were analyzed using simulation software and a simple analytical equation is shown to provide a useful approximation of the droplet force and stiffness. The results were further used in various case studies to demonstrate the optimal design strategy when using an electrowetting driven droplet as a fluidic bearing.

This dissertation work concentrates on novel reconfiguration technologies, including design, microfabrication, and characterization aspects with an emphasis on their applications to multifunctional recon-figurable antennas. In the literature, reconfigurable antennas have made use of various reconfiguration techniques. The most common techniques utilized revolved around switching mechanisms. Other techniques such as the incorporation of variable capacitors, varactors, and physical structure manipulation surfaced recently to overcome many problems faced in using switches and their biasing. Usage of fluids (micro-fluidic or otherwise) in antennas provides a conceptually easy reconfiguration mechanism in the aspect of physical alteration. However, a requirement of pumps, valves, etc. for liquid transportation makes the antenna implementations rather impractical for the real-life scenarios. This work reports on design and experiments conducted to evaluate the electrowetting on dielectric (EWOD) driven digital microfluidics as a reconguration mechanism for antennas.

Today the medical field is struggling to decrease bacteria biofilm formation which leads to infection. Also, biomedical devices sterilization has not changed over a long period of time which has resulted in high costs for hospitals healthcare managements. The objective of this project is to investigate electro-dynamic effects by surface energy manipulation as potential methods for preventing bacteria biofilm growing on medical devices. Based on electrokinetic environments two different methods were tested: rejection bacteria dielectrophoretic forces feasibility by numerical simulations; and electrowetting-on -dielectric by the fabrication of golden interdigitated electrodes on silicon glass substrates covered by a Teflon layer. In the first experiment, numerical simulations of gold electrodes in buffer solution and frequencies were carried out to determine the forces required to reject bacteria. In the second experiment, interdigitated gold electrodes coated with a dielectric Teflon layer, were characterized in terms of breakdown voltage, dielectric adhesion and contact angle in terms of applied voltage. Finally the effect of EWOD on bacterial adhesion was tested. The project resulted in promising simulation results for bacteria rejection using dielectrophoresis due to the wide range of frequency that rejects the modelled bacteria. However, practical experiments such as electrowetting-on-dielectric must verify this at incubation times larger than 24 hours in spite of the Teflon non-adhesive properties. / <p>opponent Alex Grossm ann Colin</p> / VRI

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