Cell based High Throughput Screening (HTS) has become a very important method in pharmaceutical drug discovery and presently carried out using robots and well plates. A microfluidics based device for cell based HTS using traditional cell culture protocol would be a significant addition to the field. In this thesis novel microfluidic HTS devices targeted for cell based assays having traditional non-compartmentalized agar gel as cell culture medium and electric control over drug dose is being reported. The basic design of device consists of a gel layer supported by a nanoporous membrane that is bonded to microchannels underneath it. The pores of membrane are blocked everywhere except in selected regions that serve as fluidic interfaces between the microchannel below and the gel above. Upon application of electric field nanopores start to act as electrokinetic pumps. By selectively switching an array of such micropumps, a number of spots -containing drug molecules- are created simultaneously in the gel layer. By diffusion drugs reach to the top surface of gel where cells are to be grown. Based on this principle, a number of different devices are fabricated using microfabrication technology. The fabricated devices include, single drug spot forming device, multiple drug spot forming device and microarray of drug spots forming device. By controlling pumping potential and duration spots sizes ranging from 200μm to 6mm diameter and having inter-spot distances of 0.4mm-10mm have been created. Absence of diffusional transport through the nanoporous interfaces without electric field is demonstrated. A number of representative molecules, including surrogate drug molecules (trypan blue, and methylene blue) and biomolecules (DNA and protein) were selected for demonstration purpose. Dosing range of 50-3000 μg and spot density of 156 spots/cm² were achieved. The drug spot density was found to be limited by molecular diffusion in gel and hence numerical study was carried to find out ways for density increase. Based on this simulation, a method for diffusion reduction called diffusion barrier was proposed. Diffusion barrier used specially dimensioned (having shallow grooves) gel sheet to reduce the diffusion. / Thesis / Master of Applied Science (MASc)

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Microfluidic device construction uses certain critical structures throughout many different applications. The valve structure remains one of the primary structures that present a barrier to miniaturization and portability. The extensive support devices required to power common microfluidic valves remove a significant amount of freedom from microfluidic device design. Moving to electrostatic methods of actuation could reduce the overall footprint of the microfluidic valve. This thesis covers three concept prototypes. Concept I presents an attempt at inlaying gold electrodes into polydimethylsiloxane substrates. Concept II attempts to use liquid silver injected into channels as electrode materials. Concept III uses aluminum sputtering to fabricate valve electrodes. Each device encountered complications during fabrication which led to improved fabrication guidelines for future devices. Designing and fabricating these concept devices required the development of several new processes in the clean room, including RIE Plasma bonding, PDMS sputtering techniques, and multilayer PDMS thin film fabrication. The PDMS sputtering technique in particular allows profilometry measurement of PDMS surfaces without risk of damaging the profilometer tip, a development that could allow for much more control over PDMS film thicknesses in future projects.

One of the most important boron minerals, colemanite is reacted with sulfuric acid to produce boric acid. During this reaction, gypsum (calcium sulfate dihydrate) is formed as a byproduct. In this study, the boric acid production was handled both in a batch and four continuously stirred slurry reactors (4-CFSSR&rsquo / s) in series system. In this reaction system there are at least three phases, one liquid and two solid phases (colemanite and gypsum). In a batch reactor all the phases have the same operating time (residence time), whereas in a continuous reactor all the phases may have different residence time distributions. The residence time of both the reactant and the product solids are very important because they affect the dissolution conversion of colemanite and the growth of gypsum crystals. The main aim of this study was to investigate the dynamic behavior of continuous flow stirred slurry reactors. By obtaining the residence time distribution of the solid and liquid components, the non-idealities in the reactors can be found. The experiments performed in the continuous flow stirred slurry reactors showed that the reactors to be used during the boric acid production experiments approached an ideal CSTR in the range of the stirring rate (500-750 rpm) studied. The steady state performance of the continuous flow stirred slurry reactors (CFSSR&rsquo / s) in series was also studied. During the studies, two colemanites having the same origin but different compositions and particle sizes were used. The boric acid production reaction consists of two simultaneous reactions, dissolution of colemanite and crystallization of gypsum. The dissolution of colemanite and the gypsum formation was followed from the boric acid and calcium ion concentrations, respectively. The effect of initial CaO/ SO42- molar ratio (1.00, 1.37 and 2.17) on the boric acid and calcium ion concentrations were searched. Also, at these initial molar ratios the colemanite feed rate was varied (5, 7.5, 10 and 15 g/min) to change the residence time of the slurry. Purity of the boric acid solution was examined in terms of the selected impurities, which were the magnesium and sulfate ion concentrations. The concentrations of them were compared at the initial molar ratios of 1.00 and 1.37 with varying colemanite feed rates. It was seen that at high initial CaO/ SO42- molar ratios the sulfate and magnesium ion concentrations decreased but the calcium ion concentration increased. The gypsum crystals formed in the reaction are in the shape of thin needles. These crystals, mixed with the insolubles coming from the mineral, are removed from the boric acid slurry by filtration. Filtration of gypsum crystals has an important role in boric acid production reaction because it affects the efficiency, purity and crystallization of boric acid. These crystals must grow to an appropriate size in the reactor. The growth process of gypsum crystals should be synchronized with the dissolution reaction. The effect of solid hold-up (0.04&ndash / 0.09), defined as the volume of solid to the total volume, on the residence time of gypsum crystals was investigated and the change of the residence time (17-60 min) on the growth of the gypsum was searched. The residence time at each reactor was kept constant in each experiment as the volumes of the reactors were equal. The growth of gypsum was examined by a laser diffraction particle size analyzer and the volume weighted mean diameters of the gypsum crystals were obtained. The views of the crystals were taken under a light microscope. It was observed that the high residence time had a positive effect on the growth of gypsum crystals. The crystals had volume weighted mean diameters of even 240 &micro / m. The gypsum crystal growth model was obtained by using the second order crystallization reaction rate equation. The residence time of the continuous reactors are used together with the gypsum growth model to simulate the continuous boric acid reactors with macrofluid and microfluid models. The selected residence times (20-240 min) were modeled for different number of CSTR&rsquo / s (1-8) and the PFR. The simulated models were, then verified with the experimental data. The experimentally found calcium ion concentrations checked with the concentrations found from the microfluid model. It was also calculated that the experimental data fitted the microfluid model with a deviation of 4-7%.

Объектами исследования являются витамины разной гидрофильности и витаминосодержащие препараты в таблетированной форме. Цель работы: исследование антиоксидантных свойств витаминных препаратов различной гидрофильности. Исследована антиоксидантная емкость модельных растворов и смесей антиоксидантов разной гидрофильности потенциометрическим методом; подобраны оптимальные условия для проведения анализа липофильного и гидрофильного соединений в совместном присутствии; исследованы фармацевтические препараты в таблетированной форме, содержащие витамины С и Е; проведено сравнение результатов с методом Фолина-Чокальтеу. Рассмотрена возможность применения методики определения АОЕ в условиях микрофлюидного устройства. / The objects of research are vitamins of different hydrophilicity and vitamin-containing preparations in tablet form. Purpose of the work: study of the antioxidant properties of vitamin preparations of various hydrophilicity. The antioxidant capacity of model solutions and mixtures of antioxidants of different hydrophilicity was investigated by potentiometric method; the optimal conditions were selected for the analysis of lipophilic and hydrophilic compounds in their joint presence; investigated pharmaceutical preparations in tablet form containing vitamins C and E; the results are compared with the Folin-Chocalteu method. The possibility of using the method for determining AOE in a microfluidic device is considered.

Объектами исследования являются модельные растворы антиоксидантов и многокомпонентные объекты, содержащие антиоксиданты: этанольные экстракты лекарственных растений, промышленные напитки, витаминные препараты. Цель работы: разработка тест-систем для экспрессной оценки содержания антиоксидантов в продуктах питания и объектах фармации. Разработаны прототип калориметрической тест-системы, а также электрохимическая тест-система, представляющая микрофлюидную ячейку, для экспресс-оценки содержания антиоксидантов. С использованием разработанных тест-систем оценена антиоксидантная емкость модельных растворов антиоксидантов и их смесей; оценена антиоксидантная емкость пищевых объектов на примерах промышленных напитков и фармацевтических препаратов – этанольных экстрактов лекарственного растительного сырья и витаминных препаратов, содержащих аскорбиновую кислоту и α-токоферол; правильность результатов анализа оценена методом «введено-найдено» и сравнением с результатами известных оптических и электрохимических методов анализа. / The objects of study are model solutions of antioxidants and multicomponent objects containing antioxidants: ethanol extracts of medicinal plants, industrial drinks, vitamins. Purpose of the work: development of test systems for rapid assessment of the antioxidants content in food and pharmaceuticals. The prototype of a calorimetric test system, as well as an electrochemical test system, representing a microfluidic cell, for rapid assessment of the antioxidants content have been developed. Using the developed test systems, the antioxidant capacity of model solutions of antioxidants and their mixtures was evaluated. On the examples of industrial drinks and pharmaceuticals - ethanol extracts of medicinal plant materials and vitamins, containing ascorbic acid and α-tocopherol, the antioxidant capacity of food objects was estimated. The correctness of the analysis results was assessed by the "introduced-found" method and by comparison with the results of known optical and electrochemical methods of analysis.