Hydrophilic poly(2-hydroxyethyl methacrylate), PHEMA, and hydrophobic poly(dimethyl siloxane), PDMS, segments containing copolymers have been widely used as a biomaterial. These amphiphilic copolymers also used as an emulsifying agent in polymer solutions and compatibilizer in polymer blends. In this case, solution polymerizations of HEMA by radiation, ATRP and RAFT methods were studied. The thermal degradation mechanism of PHEMA, which was prepared in aqueous solution by gamma radiation technique, was studied in detail. The DSC, TGA and Mass Spectroscopy analyses revealed that the degradation is linkage and depolymerization with a combination of monomer fragmentation. The ATRP of HEMA was performed with ethyl-2-bromoisobutyrate (EBriB) initiator and CuCl/bipyridine catalyst in MEK/1-propanol solvent mixture. Cu(II) complexes and PHEMA obtained via ATRP were characterized by UV-vis, FTIR and 1H-NMR analysis. The RAFT polymerization of HEMA with different [RAFT]/[AIBN] ratios were also investigated in three solvents (methyl ethylketone, ethyl acetate and toluene). The controlled polymerization of HEMA with the ratio of [RAFT]/ [AIBN]=18 at 80 oC in MEK and ethyl acetate, shows the first-order kinetic up to the nearly 40 % conversion Macroazoinitiator PDMS-MAI was synthesized from bifunctional PDMS and then copolymerized with MMA, EMA, HEMA and TMS-HEMA monomers Different characterization methods such as FTIR, 1H-NMR, solid state NMR, GPC, XPS, SEM, DSC, etc. have been used for the characterization of block copolymers. P(DMS-b-TMSHEMA) was converted to the P(DMS-b-HEMA) block copolymer by deprotection of TMS groups. The phase separated morphology was observed for the P(DMS-b-HEMA) copolymer, which was different from P(DMS-b-MMA) and P(DMS-b-EMA) copolymers.

Multi-domain Vertical Alignment Flexible Liquid Crystal Display based on photolithography and replica-Molding method has been demonstrated. In order to maintain a uniform cell gap between flexible substrate,the microstructures were fabricated with polydimethylsiloxane (PDMS) material by replica-molding method. The microstructures master were designed and fabricated using a photosensitive resin (SU-8) by photolithography. The microstructures of pixel-encapsulated walls enhance the mechanical strength to prevent the liquid crystal molecules flow in the bend state deformations. Besides, the elastomeric material, PDMS, provide weak surface energy and induce vertical alignment for liquid crystal spontanelusly without any surface treatment. The microstructure protrusions made by PDMS can provide multi-domain vertical alignment (MVA) effect with wide viewing angle and high contrast ratio. Therefore, this method could be implemented for achieving multi-domain vertical alignment on a flexible LCD applications. The flexible LCD have great stability reproducibility, durability and good electro-optical performances.

Strain engineering is used as a means of manufacturing micro- and nano- scale particles with the ability to reversibly alter their geometry from three dimensional tubes to two dimensional flat layers. These particles are formed from a bi-layer of two dissimilar materials, one of which is the elastomeric material polydimethylsiloxane (PDMS), deposited under stress on a sacrificial substrate. Upon the release of the bi-layer structure from the substrate, interfacial residual stress is released resulting in the formation of tubes or coils. These particles possess the ability to dramatically alter their geometry and, consequently, change some properties that are reversible and can be triggered by a stimulus. This work focuses on the material selection and manufacturing of the bi-layer structures used to create the responsive particles and methods for characterizing and controlling the responsive nature of the particles. Furthermore, the potential of using these particles for a capture/release application is explored, and a systematic approach to scale up the manufacturing process for such particles is provided. This includes addressing many of the problems associated with fabricating ultra-thin layers, tuning the size of the particles, understanding how the stress accumulated at the interface of a bi-layer structure can be used as a tool for triggering a response as well as developing methods (i.e. experiments and applications) that allow the demonstration of this response.

Compliant microelectrodes have been designed in a microcable geometry that can be used individually or in an array and either as a shank-style electrode or as a string-like electrode that can be threaded around features such as the peripheral nerve. The fabrication process, using spin-cast micromolding (SCuM), is simple and adaptable to different patterns. The microcables were fabricated using polydimethyl siloxane (PDMS) for the insulating substrate and thin-film gold for the conductive element. The thin, metal film and the low tensile modulus of the PDMS substrate created an electrode with a composite tensile modulus lower than other compliant electrodes described in the literature. The gold film increased the composite modulus approximately three-fold compared to the unaltered PDMS. The durability of the electrodes and tolerance for stretch was also tested. The microcables were found to be conductive up to 6% strain and to regain conductivity after release from multiple applications of 200% strain. The tolerance for high-strain shows that the electrodes can be deployed for use and stretched or pulled into place as needed without damaging the conductivity. The microcable electrode recording sites were electrically characterized using frequency-based impedance modeling and were tested for electrophysiological recording using a peripheral nerve preparation. A suitable insertion mechanism was designed to use the microcables as shank-style cortical electrodes. The microcables were coated on one side with fibrin, which, when dry, stiffens the microcables for insertion into cortical tissue. A 28-day implant study testing the inflammatory response to fibrin coated PDMS microcable electrodes showed a positive, but relatively low inflammatory response, as measured by glial fibrillary astrocytic protein (GFAP; indicating activated astrocytes) immediately at the tissue edge of the implant site. The response of the control, silicon shank-style electrodes, was varied, but also trended toward low levels of GFAP expression. The GFAP staining was possibly due to the clearance of the fibrin from the implant site in addition to the presence of the PDMS-based electrode. Implant studies extending beyond 28 days are necessary to determine whether and to what degree the inflammation persists at the implant site of PDMS-based electrodes.

Nous avons développé un microlaboratoire pour étudier la diffusion et son couplage<br />avec la réaction chimique. Il est constitué d'une chambre d'analyse dans laquelle on peut<br />appliquer des champs électriques en deux dimensions pour obtenir des profils de concentration<br />stationnaires ou non-stationnaires. La simplicité spatiale du flux électrophorétique<br />utilisé permet d'appliquer systématiquement une analyse dans l'espace de Fourier. Ce traitement<br />fournit le coefficient de diffusion d'un analyte pur ainsi que la constante thermodynamique<br />et les constantes cinétiques d'un mélange réactif. Dans le but de développer des<br />techniques de séparation resposant sur la cinétique, nous avons étudié la réaction d'hybridation<br />entre deux brins d'ADN et constitué une banque d'oligonucléotides avec des<br />constantes cinétiques variées. Ces études nous ont mené à developper, en collaboration<br />avec le Museum National d'Histoire Naturelle, une sonde oligonucléotidique fluorescente à<br />motif quadruplex permettant une discrimination cinétique lorsqu'elle s'hybride avec une<br />séquence parfaitement complémentaire ou mésappariée.

Les techniques d'analyses médicales nécessitent le développement, à faible coût, de capteurs chimiques fiables. Dans ce contexte, les transistors chimiques à effet de champ CHEMFETs offrent des solutions innovantes à condition d'optimiser l'interface entre microtechnologies et biotechnologies. Au cours de cette thèse, nous nous sommes attachés à développer des techniques permettant de coupler espèces biologiques et silicium. Deux approches ont été étudiées, toutes les deux basées sur l'utilisation des polymères. La première approche a été centrée sur le développement des techniques d'encapsulation et de création de micro-volumes. Pour cela, des micro-cuves d'analyse ont été réalisées d'abord en plexiglas® puis en PDMS. Après l'optimisation des caractéristiques géométriques, le suivi de lactivité bactérienne a été effectué grâce au suivi du pH de la solution à l'aide de pH-ISFETs. Nous avons ainsi démontré la possibilité de détecter l'activité bactérienne dans le cas de Lactobacillus Acidophilus et commencé à déterminer la « signature » biologique de cette bactérie. La deuxième approche a été consacrée à l'adaptation des CHEMFETs à la détection enzymatique. Pour cela, nous avons envisagé d'utiliser un polymère en tant que matrice de support d'un élément biologique. L'utilisation des techniques de photolithographie a ainsi permis la fabrication collective de couches enzymatiques en PVA en vue d'une détection biochimique. Après avoir appliqué le protocole de dépôt mis au point à l'uréase, nous avons caractérisé l'évolution de l'activité enzymatique des membranes ainsi réalisées. Ensuite, nous avons validé ce procédé par la fabrication de microcapteurs chimiques de type ENFET et nous avons détecté des taux d'urée par le suivi des variations du pH au sein de solutions de différentes concentrations.

Les techniques d'analyses chimiques et biologiques nécessitent le développement à faible coût de capteurs chimiques fiables. Dans ce contexte, les transistors chimiques à effet de champ ChemFETs et les microélectrodes offrent des solutions innovantes à condition d'optimiser l'interface entre les différents domaines que sont les microtechnologies, la biologie et la chimie. Au cours de cette thèse, nous nous sommes attachés à développer des techniques permettant de coupler des agents chimiques au silicium. Deux approches ont été étudiées, toutes les deux basées sur l'utilisation de polymère. La première approche a été centrée sur le développement des techniques d'encapsulation avec la réalisation de microcuves et micro-canaux d'analyse en PDMS. Le suivi de l'activité bactérienne à l'aide de pH-ISFETs a été optimisé dans le cadre de l'étude des lactobacillus acidophilolus. La deuxième approche s'est intéressée à l'adaptation des ChemFETs et des microélectrodes d'or à la détection d'ions tels que le potassium et le sodium. L'utilisation des techniques de photolithographie a ainsi permis la fabrication collective de couches ionosensibles en PSX (polysiloxane)

Malaria remains a serious concern for people living and traveling to warm climates in Africa, Asia, and some parts of America. Understanding the mechanism of the malaria parasite in the liver phase could lead to important discoveries for preventative and treatment therapeutics before the disease develops into the blood stage. While in vitro liver cell culture models have been explored, a device that mimics the liver cell architecture with the capability of high-resolution imaging has never been created. In this research, a cell culture microfluidic device was designed and fabricated with a membrane integrated design to mimic the architecture of a liver, cell chamber dimensions affable for high-resolution imaging, and fluidic port design for optical access to both sides of the membrane for the study of malaria parasite invasion.

Incident ions, from a Van de Graaff accelerator, in the MeV energy range, deposit their energy into the near surface of a sample. This, in turn, causes atomic, molecular, cluster and fragment ion species to be desorbed and ionized, while simultaneously emitting characteristic elemental X-rays. The multielemental X-rays provide qualitative elemental information, which may be deconvoluted and fit to a theoretical X-ray spectrum, generated by a quantitative analysis program, GUPIX, while the atomic, molecular, cluster, and fragment ion species are identified using a quadrupole mass spectrometer. This methodology directly links elemental determinations with chemical speciation.The development of this particle desorption ionization particle induced X-ray emission mass spectrometer, the PDI-PIXE-MS (or PIXE-MS) instrument, which has the ability to collect both qualitative multielemental X-rays and mass spectral data is described. This multiplexed instrument has been designed to use millimeter-sized MeV particle beams as a desorption ionization (PDI) and X-ray emission (PIXE) source. Two general methods have been employed, one simultaneous and the other sequential. Both methods make use of a novel X-ray/ion source developed for use with the quadrupole mass spectrometer used in these experiments. The first method uses a MeV heavy ion particle beam, typically oxygen, to desorb and ionize the sample, while simultaneously producing characteristic multielemental X-rays. The resulting molecular, cluster, and fragment ions are collected by the mass spectrometer, and the X-rays are collected using a Si-PIN photodiode detector in conjunction with a multichannel analyzer (MCA). Heavy ions of N+, O+, O+2, Ar+, and Kr+ have been investigated, although heavy ion X-ray and mass spectra have focused on the use of oxygen particle beams. The second method is performed by first collecting the X-ray data with a MeV ion beam of He+ ions, then desorbing and ionizing the sample species with a MeV particle beam of heavy ions, producing good ion yields, for mass spectral data collection. The potential development of a scanning microprobe instrument, that would provide micron-scale, imaged, multielemental, and molecular and fragment ion chemical information is being investigated through the development of this prototype PIXE-MS instrument.

In vertebrate nervous system, formation of myelin sheaths around axons is essential for rapid nerve impulse conduction. However, the signals that regulate myelination in CNS remain largely unknown partially due to the lack of suitable in vitro models for studying localized cellular and molecular basis of axon-glia signals. We utilize microfabrication technologies to develop series of CNS neuron culture microsystems capable of providing localized physical and biochemical manipulation for studying neuron-glia interaction and neural progenitor development. First, a circular neuron-glia co-culture platform with one soma-compartment and one axon/glia compartment has been developed. The device allows physical and fluidic isolation of axons from neuronal somata for studying localized axon-glia interactions under tightly controlled biochemical environment. Oligodendrocyte (OL) progenitor cells co-cultured on isolated axons developed into mature-OLs, demonstrating the capability of the platform. The device has been further developed into higher-throughput devices that contain six or 24 axon/glia compartments while maintaining axon isolation. Increased number of compartments allowed multiple experimental conditions to be performed simultaneously on a single device. The six-compartment device was further developed to guide axonal growth. The guiding feature greatly facilitated the measurement of axon growth/lengths and enabled quantitative analyses of the effects of localized biomolecular treatment on axonal growth and/or regeneration. We found that laminin, collagen and Matri-gel promoted greater axonal growth when applied to somata than to the isolated axons. In contrast, chondroitin sulfate proteoglycan was found to negatively regulate axon growth only when it was applied to isolated axons. Second, a microsystem for culturing neural progenitor cell aggregates under spatially controlled three-dimensional environment was developed for studies into CNS neural development/myelination. Dense axonal layer was formed and differentiated OLs formed myelin sheaths around axons. To the best to our knowledge, this was the first time to have CNS myelin expressed inside a microfluidic device. In addition, promotion of myelin formation by retinoic acid treatment was confirmed using the device. In conclusion, we have developed series of neuron culture platforms capable of providing physical and biochemical manipulation. We expect they will serve as powerful tools for future mechanistic understanding of CNS axon-glia signaling as well as myelination.