<p>This thesis addresses mass transfer in multi-phase single particle systems. By using a novel technique based upon the micropipette, the dissolution of liquid and gas droplets in a liquid medium can be observed. Three classes of experimental systems are observed: pure liquid droplet dissolution in a pure liquid environment, miscible mixture liquid droplet dissolution in a pure liquid environment, and solute-containing liquid droplet dissolution in a pure liquid environment. Experiments on the dissolution of pure droplets of water in n-alcohols and n-alkanes showed that water droplets dissolved ten times faster in the alcohols as compared to in the alkanes. When solubility was taken into account, however, and diffusion coefficients calculated using the Epstein-Plesset equation, diffusion constants for alkanes were twenty five times higher in alkanes than for the corresponding alcohol (for example 12.5 vs 0.5 x 10-8 cm2/s for pentane and pentanol). This difference in rates of diffusion of the single molecules reflects the effect of hydrogen bonding on small solute diffusion, which is expounded upon in Chapter 2.</p><p> A model for the dissolution of a droplet containing a mixture, each component of which is soluble in the surrounding liquid medium is presented in Chapter 3. The model is based upon a reduced surface area approximation and the assumption of ideal homogenous mixing : Mass flux (dm_i)/dt=&#12310;Afrac&#12311;_i D_i (c_i-c_s){1/R+1/&#8730;(&#960;D_i t)}, where Afraci is the area fraction of component i, ci and cs are the initial and saturation concentrations of the droplet material in the surrounding medium, respectively, R is the radius of the droplet, t is time, and Di is the coefficient of diffusion of component i in the surrounding medium. This model was tested for the dissolution of ethyl acetate and butyl acetate in water and the dissolution of butyl acetate and amyl acetate in water, and was found to provide a good fit. In Chapter 4, a partial differential equation, R^2/D &#9500; &#8706;c/&#8706;t&#9508;|_&#951;=(&#8733;&#951;)/D &#8706;c/&#8706;&#951;+(&#8706;^2 c)/&#12310;&#8706;&#951;&#12311;^2 +2/&#951; &#8706;c/&#8706;&#951;, is presented for the dissolution of a solute containing droplet in a liquid medium, and shell or bead formation is predicted. In Chapter 5, an application of the solute containing droplet dissolution is presented in which suspensions of glassified protein microspehres are used to improve the injectability of protein based pharmaceuticals. Injectability is related to viscosity, and the viscosity of a suspension may be predicted to follow the Krieger Dougherty equation: (&#951;(&#934;))/&#951;_0 =(1-&#934;/&#934;_m )^(-2.5&#934;_m ) , where &#934; is the volume fraction of the suspensate, &#951; is the viscosity of the overall suspension, &#951;0 is the viscosity of the suspending fluid, and &#934;m is the maximum possible volume fraction. Finally, in Chapter 6, various experimental methods used to generate droplets are addressed.</p> / Dissertation

In vitro studies have shown that the major membrane phospholipid phosphatidylcholine (PC) can positively influence the incorporation of cholesterol in lipid membranes. The influence of PC on the cellular trafficking of LDL-derived free cholesterol was investigated. Sterol regulatory-defective (SRD)-4 cells are Chinese hamster ovary (CHO)-derived fibroblasts that display vastly elevated rates for the synthesis and catabolism of PC. SRD-4 cells harbor two known gene mutations: a mutation in the functional allele for SCAP, resulting in defective feedback suppression of cholesterol biosynthesis; and a loss-of-function mutation in the functional allele for acyl-CoA:cholesterol acyl transferase (ACAT), an endoplasmic reticulum (ER)-localized enzyme that esterifies free cholesterol. Incubation of SRD-4 cells with 50 µg/ml low density lipoprotein (LDL) for 18 h resulted in lysosomal accumulation of free cholesterol as revealed by filipin staining. This accumulation was not evident following LDL treatment of parental CHO7 cells, and was blunted in SRD-2 cells that express a constitutively-active form of SREBP-2 and overproduce cholesterol but have functional ACAT activity. Treatment of SRD-2 cells with LDL in the presence of an ACAT inhibitor 58-035 resulted in robust lysosomal cholesterol accumulation that was reversible upon drug washout, supporting that cholesterol trafficking in cholesterol-loaded cells is dependent on ACAT activity and, more specifically, ER free cholesterol levels. Lysosomal accumulation of LDL-derived cholesterol was prevented in SRD-4 cells supplemented with lyso-PC (50 µM), a substrate for PC synthesis through the reacylation pathway, and also in cells treated with bromoenol lactone (BEL), an inhibitor of phospholipase A2 implicated in bulk PC turnover. In a counter study, lysosomal LDL-derived cholesterol accumulation was induced in parental CHO-7 cells using R-propranolol, which inhibits the conversion of phosphatidic acid to diacylglycerol (DAG), a substrate in the CDP-choline pathway. This blockage was also relieved through co-treatment with lyso-PC. These studies support that PC to free cholesterol ratios in downstream organellar membranes can influence cholesterol trafficking out of lysosomal compartments in cholesterol-loaded cells.

Digital microfluidics is a new technology that permits manipulation of liquid droplets on an array of electrodes. Using this technology, nanoliter to microliter size droplets of different samples and reagents can be dispensed from reservoirs, moved, split, and merged together. Digital microfluidics is poised to become an important and useful tool for biomedical applications because of its capacity to precisely and automatically carry out sequential chemical reactions. In this thesis, a set of tools is presented to accelerate the integration of digital microfluidics into Lab-on-a-Chip platforms for a wide range of applications. An important contribution in this thesis is the development of three rapid prototyping techniques, including the use of laser printing to pattern flexible printed circuit board (PCB) substrates, to make the technology accessible and less expensive. Using these techniques, both digital and channel microfluidic devices can be produced in less than 30 minutes at a minimal cost. These rapid prototyping techniques led to a new method for manipulating liquid droplets on non-planar surfaces. The method, called All Terrain Droplet Actuation (ATDA), was used for several applications, including DNA enrichment by liquid-liquid extraction. ATDA has great potential for the integration of different physico-chemical environments on Lab-on-a-Chip devices. A second important contribution described herein is the development of a new microfluidic format, hybrid microfluidics, which combines digital and channel microfluidics on the same platform. The new hybrid device architecture was used to perform biological sample processing (e.g. enzymatic digestion and fluorescent labeling) followed by electrophoretic separation of the analytes. This new format will facilitate complete automation of Lab-on-a-Chip devices and will eliminate the need for extensive manual sample processing (e.g. pipetting) or expensive robotic stations. Finally, numerical modeling of droplet actuation on single-plate digital microfluidic devices, using electrodynamics, was used to evaluate the droplet actuation forces. Modeling results were verified experimentally using an innovative technique that estimates actuation forces based on resistive forces against droplet motion. The results suggested a list of design tips to produce better devices. It is hoped that the work presented in this thesis will help introduce digital microfluidics to many of the existing Lab-on-a-Chip applications and inspire the development of new ones.

<p>A digital microfluidic biochip (DMFB) is a device that digitizes fluidic samples into tiny droplets and operates chemical processes on a single chip. Movement control of droplets can be realized by using electrowetting-on-dielectric (EWOD) technology. DMFBs have high configurability, high sensitivity, low cost and reduced human error as well as a promising future in the applications of point-of-care medical diagnostic, and DNA sequencing. As the demands of scalability, configurability and portability increase, a new DMFB architecture called Microelectrode Dot Array (MEDA) has been introduced recently to allow configurable electrodes shape and more precise control of droplets.</p> <p>The objective of this work is to investigate a routing algorithm which can not only handle the routing problem for traditional DMFBs, but also be able to route different sizes of droplets and incorporate diagonal movements for MEDA. The proposed droplet routing algorithm is based on 3D-A* search algorithm. The simulation results show that the proposed algorithm can reduce the maximum latest arrival time, average latest arrival time and total number of used cells. By enabling channel-based routing in MEDA, the equivalent total number of used cells can be significantly reduced. Compared to all existing algorithms, the proposed algorithm can achieve so far the least average latest arrival time.</p>

Digital microfluidics is a new technology that permits manipulation of liquid droplets on an array of electrodes. Using this technology, nanoliter to microliter size droplets of different samples and reagents can be dispensed from reservoirs, moved, split, and merged together. Digital microfluidics is poised to become an important and useful tool for biomedical applications because of its capacity to precisely and automatically carry out sequential chemical reactions. In this thesis, a set of tools is presented to accelerate the integration of digital microfluidics into Lab-on-a-Chip platforms for a wide range of applications. An important contribution in this thesis is the development of three rapid prototyping techniques, including the use of laser printing to pattern flexible printed circuit board (PCB) substrates, to make the technology accessible and less expensive. Using these techniques, both digital and channel microfluidic devices can be produced in less than 30 minutes at a minimal cost. These rapid prototyping techniques led to a new method for manipulating liquid droplets on non-planar surfaces. The method, called All Terrain Droplet Actuation (ATDA), was used for several applications, including DNA enrichment by liquid-liquid extraction. ATDA has great potential for the integration of different physico-chemical environments on Lab-on-a-Chip devices. A second important contribution described herein is the development of a new microfluidic format, hybrid microfluidics, which combines digital and channel microfluidics on the same platform. The new hybrid device architecture was used to perform biological sample processing (e.g. enzymatic digestion and fluorescent labeling) followed by electrophoretic separation of the analytes. This new format will facilitate complete automation of Lab-on-a-Chip devices and will eliminate the need for extensive manual sample processing (e.g. pipetting) or expensive robotic stations. Finally, numerical modeling of droplet actuation on single-plate digital microfluidic devices, using electrodynamics, was used to evaluate the droplet actuation forces. Modeling results were verified experimentally using an innovative technique that estimates actuation forces based on resistive forces against droplet motion. The results suggested a list of design tips to produce better devices. It is hoped that the work presented in this thesis will help introduce digital microfluidics to many of the existing Lab-on-a-Chip applications and inspire the development of new ones.

No description available.

<p>A digital microfluidic biochip (DMFB) is a device that digitizes fluidic samples into tiny droplets and operates chemical processes on a single chip. Movement control of droplets can be realized by using electrowetting-on-dielectric (EWOD) technology. DMFBs have high configurability, high sensitivity, low cost and reduced human error as well as a promising future in the applications of point-of-care medical diagnostic, and DNA sequencing. As the demands of scalability, configurability and portability increase, a new DMFB architecture called Microelectrode Dot Array (MEDA) has been introduced recently to allow configurable electrodes shape and more precise control of droplets.</p> <p>The objective of this work is to investigate a routing algorithm which can not only handle the routing problem for traditional DMFBs, but also be able to route different sizes of droplets and incorporate diagonal movements for MEDA. The proposed droplet routing algorithm is based on 3D-A* search algorithm. The simulation results show that the proposed algorithm can reduce the maximum latest arrival time, average latest arrival time and total number of used cells. By enabling channel-based routing in MEDA, the equivalent total number of used cells can be significantly reduced. Compared to all existing algorithms, the proposed algorithm can achieve so far the least average latest arrival time.</p>

The aim of this study was to observe the properties of a spray field, with micro particle image velocimetry (£gPIV) and holographic interferometric particle imaging (IPI) employed for the imaging and analysis of the global spray field. The experiment adopted different nozzle diameters (dj = 200 £gm, and dj = 500 £gm) and different values of gauge pressure (£GP = 300 kPa, £GP = 500 kPa, and £GP = 700 kPa) as the main parameters, and DI (distilled) Water as the working medium. The study was divided into two parts. The first part used the £gPIV system to observe the two-dimensional global visualization of spray field distribution and spray angle from each nozzle under different values of gauge pressure (£GP). The flow velocity distribution and variations (axial velocity, and impact velocity) of the global spray frame were also measured. As the nozzle diameter would determine the distribution of spray droplets, the second part adopted the IPI system to measure and explore the atomized droplet sizes from each nozzle under different values of gauge pressure (£GP), whereby drop size histograms were created through statistical analysis.

Water and R-134a sprays as they impinge on the flat endplate of a circle are studied experimentally. In order to optimize water and R-134a sprays cooling efficiency, a detailed characterization and understanding of the spray formation is essentially needed. The effects of the jet exit velocity and Weber number on spray segregation are investigated. An optical image system was used to quantify the droplet size and distribution. LDV measurements were used to characterize the local velocity and velocity fluctuation distribution from a commercial available nozzle in both axial and radial directions. It is found in the water spray that local mean droplet diameter (SMD) decreases as jet exit velocity increases and as jet proceeds further downstream as well. Furthermore, the SMD and radial velocity are found to be the largest at the outer edges of the water spray. In contrast, the radial velocity is found to be the smallest at the outer edges of the R-134a spray. The SMD and radial velocity continuously decrease across both the water spray and R-134a spray toward the jet axis; while the corresponding axial velocity is the maximum there. Moreover, the R-134a spray jet heat transfer in non-boiling regime was shown to be dependent on the velocity of the impinging jets in terms of Weber number and other related parameters which are in good agreement with those of previous studies.

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