Tesis: "Microfluidic processes"

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Haswell, Stephen John. "The development of microfluidic based processes". Thesis, University of Plymouth, 2015. http://hdl.handle.net/10026.1/4189.

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Kim, Jae Jung Ph D. Massachusetts Institute of Technology. "Microfluidic processes to create structured microparticle arrangements and their applications". Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/115018.

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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2017.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 136-145).
Multifunctional polymeric microparticles have shown the great potentials in a variety of fields. While the advance in particle synthesis allows for fine tuning of their physical properties and chemical functionality, particle manipulation is still appealing, but challenging issue in colloidal science. In order to expand the utility of microparticles, many particle manipulation techniques have been developed to arrange large-scale of particles at precise locations. However, current approaches cannot simultaneously fulfill desired capabilities of arrangement: scalability, precision, specificity, and versatility. This thesis explores the ability to synthesize particles with a controllability of characteristics, and development of a new microfluidic platform, porous microwell arrays, to create structured large-scale microparticle arrays using a scaling theory, which is a function of particles' characteristics. Lastly, we demonstrate the potential of generated particle arrays in various bioengineering application and material sciences. First, we synthesize anisotropic, cell-adhesive microparticles using stop flow lithography (SFL) and carbodimide coupling. Synthesized microparticles are functionalized with collagen or poly-L-lysine using streptavidin-biotin interaction, resulting in cell-adhesiveness. After functionalization, target cells are spread on the particles and spatially patterned only on the functionalized region. Thus, cells are not exposed to potentially harmful components of particle synthesis processes, photoinitiators and ultraviolet light, ensuring no physiological changes. Second, we synthesize multi-striped, upconverting nanocrystal (UCN)-laden microparticles using SFL. Distinct upconversion emission colors are combined with the ability to spatial pattern them, providing superior encoding capacities. We can fine-tune upconversion emission by controlling the dopant composition in nanocrystal, and synthesize microparticles in a highly reproducible manner by SFL, allowing for the development of predictable decoding system. Two types of particles are synthesized with this appealing encoding strategy for two distinct applications: thermally stable particles for anti-counterfeiting application; and porous hydrogels for multiplexed microRNA detection. Third, we develop a microfluidic platform, porous microwell arrays, to manipulate microparticles while fulfilling all four desired capabilities (i.e. scalability, precision, specificity, and versatility). Microwells are fabricated on top of porous membrane by a vacuum-assisted molding method. Particles are guided and assembled into wells by hydrodynamic force associated with fluid flow through pores in microwell. Iteration of assembly and washing steps ensures high-throughput, large-scale particle arrangement with high yields on filling and capturing. Scaling theory allows for the rational design of platform to specifically position microparticles depending on their physical characteristics (i.e. size, shape, and modulus), enabling to generate complex patterns. We utilize this platform in three practical applications: high-throughput, large-scale single-cell arrays; microenvironment fabrication for neutrophil chemotaxis; and UCN-laden covert 2D tags for anti-counterfeiting. Lastly, we modified the porous microwell platform to a closed system, microfluidic channels, to park and isolate particles in monodisperse droplets surrounded by fluorinated oil. Rational modification retains the platform's desired capabilities, resulting in a single particle in a droplet with high yields on both parking and isolation. Particle-in-droplet arrays enables the observation of reaction in confined volume over the time. Such arrays can be utilized to accumulate the desired product from enzymatic reaction, amplifying the signal and improving the sensitivity of bioassays. We demonstrate the highly sensitive, multiplexed miRNA detections with these particle-in-droplet arrays.
by Jae Jung Kim.
Ph. D.

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3

Tarn, Mark Duncan. "Continuous flow processes on single magnetic and diamagnetic particles in microfluidic devices". Thesis, University of Hull, 2011. http://hydra.hull.ac.uk/resources/hull:4915.

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Magnetic microparticles have seen increasing interest in (bio)chemical processes in recent years due to their various surface functionalities, high surface-to-volume ratio, small sizes, and ease of manipulation via magnetic fields. However, conventional reactions and assays that use magnetic particles as solid supports are typically performed in multi-step procedures that require consecutive reaction and washing steps. While offering high capture efficiencies, these are batch processes that, due to the consecutive steps required, are typically time-consuming and laborious. Their incorporation into microfluidic devices has brought about benefits including finer control over the movement of particles and reagent/sample solutions, as well as the ability to place a magnet closer to the area of interest. However, most instances of on-chip magnetic particle based procedures rely on trap-and-release methodology, essentially requiring the same stepwise routine as with conventional systems. A method of reducing these inefficiencies is to perform the reaction or separation in continuous flow, thereby allowing continuous sample introduction and analysis of the process in rapid times, and with minimal reagent consumption and waste production.Two methods of performing continuous flow procedures on single particles in microfluidic devices via the application of magnetic forces were investigated: 1) the use of magnetic microparticles as mobile solid supports for performing rapid separations, reactions, and immunoassays via magnetic attraction, and 2) the use of diamagnetic repulsion forces for performing similar procedures on non-magnetic particles, with a view to the label-free processing of diamagnetic species such as polymer particles and biological cells, based on their intrinsic properties.For the magnetic attraction experiments, a study into the effect of temperature on magnetic particle deflection behaviour and separations was performed, whereupon it was found that an increased temperature of the system yielded increased deflection distances and separation resolution due to the reduced viscous drag. This was followed by several investigations into the deflection of particles through laminar flow streams containing alternating reagents and washing buffers for performing multistep reactions and assays. The setup was used to demonstrate amide bond formation and polyelectrolyte deposition in continuous flow, before being used to detect clinically relevant levels (5 and 10�g mL-1) of the inflammatory biomarker, C-reactive protein. Thus, these findings show great potential for rapid, continuous processing of particles for a number of chemical and biological applications, as well as in clinical diagnostics.For the diamagnetic repulsion studies, diamagnetic polystyrene particles were suspended in paramagnetic media and deflected away from a magnetic field in continuous flow. The effect of particle size and the magnetic susceptibility of the paramagnetic media on particle deflection were investigated using high magnetic fields, where it was found that larger particles in a medium with higher susceptibility yielded the greatest deflection. This work was extended via a proof-of-principle setup in which polystyrene particles were repelled out of a reagent stream and into a buffer stream using permanent magnets, with a view to performing continuous flow reactions through laminar flow reagent and washing buffer streams, akin to those achieved via magnetic attraction. Finally, flow focussing of polystyrene particles and label-free cells was achieved via diamagnetic repulsion forces applied by permanent magnets, demonstrating the ability to manipulate cells in continuous flow by magnetic forces based on their intrinsic properties. This work could be applied to the label-free processing of particles and cells for separations, reactions, and assays.

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Sendekie, Zenamarkos Bantie. "Clogging dynamics of particles and bacteria in microfluidic systems mimicking microfiltration processes". Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30355/document.

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L'objectif de cette thèse est de progresser dans la compréhension du colmatage lors de la filtration de la matière molle (particules colloïdales et bactéries) et d'étudier l'efficacité et la faisabilité de séparateurs microfluidiques. Ces recherches sont réalisées avec des puces microfluidiques constituées de canaux dont la taille est du même ordre de grandeur que les objets filtrés. Ces puces, conçues pour représenter les processus ayant lieu en microfiltration frontale et tangentielles, permettent d'observer in-situ sous microscope les mécanismes de colmatage. Le système est instrumenté avec des capteurs de débit et de pression et permet ainsi une analyse croisée entre les observations et les variations de perméabilité. Les expériences ont été réalisées pour différentes conditions hydrodynamiques (débit, mode de filtration) et conditions d'interactions colloïdales (en changeant la force ionique). Les résultats mettent en évidence l'importance de la dynamique du blocage de pore par des agrégats de particules et du réentrainement de ces agrégats lorsqu'ils sont fragilisés par l'écoulement. La dynamique de ces évènements provoque des fluctuations de perméabilité. Les interactions particule-particule ou particule-paroi jouent également un rôle important sur la dynamique du colmatage. Trois scenarios sont discutés par analogie anthropomorphique : un scenario panique (0.01 mM) où les répulsions entre les particules induit un phénomène de poussée entre particules qui engendre la formation d'arches à l'entrée des canaux ; un scenario instinct de troupeau (10 mM) où l'attraction entre particules (dans un minimum DLVO secondaire) facilite le transport dans le canal et retarde le colmatage ; un scenario sacrificiel (100 mM) où l'efficacité de capture des particules par les parois est élevée mais les agrégats formés sont très fragiles et fréquemment réentraînés par l'écoulement. Cette analyse illustre l'importance des phénomènes collectifs lors du colmatage par des particules inter-agissantes. Le mécanisme de colmatage par des particules biologiques (bactéries) et notamment la création de panaches bactériens en aval des canaux sont ensuite analysés. Ces phénomènes sont étudiés pour différentes conditions de culture (ratio carbone-azote dans le substrat) afin d'examiner l'effet de la production de substances polymériques extracellulaires (EPS) sur le colmatage. Les résultats montrent que les EPS (et donc les conditions de cultures) jouent un rôle crucial sur le développement de panaches bactériens lors d'écoulement dans des constrictions. Il est montré également que la filtration d'un mélange entre des bactéries produisant peu d'EPS et des bactéries produisant d'EPS favorise la formation des panaches bactériens. Des filtrations de mélange de bactéries et de particules montrent que la présence de bactérie modifie la dynamique du blocage des canaux ; de façon surprenante l'ajout de bactérie permet de retarder le colmatage et de former des dépôts de particules plus fragiles. Des systèmes microfluidiques avec un design spécifique ont également été développés pour réaliser un fractionnement par taille de dispersions sous un écoulement tangentiel. Des résultats préliminaires ont permis d'optimiser leur fonctionnement en trouvant des conditions permettant de filtrer en évitant le blocage des canaux ; leur utilisation pour réaliser des fractionnements continus dans des puces microfluidiques peut être envisagée
The aim of the PhD is to progress in the understanding of the fouling phenomena during filtration of soft matter (colloidal particles and bacteria) and to examine the efficiency and feasibility of microfluidic separators. These studies are realized with microfluidic devices constituted of micrometric channels having the same size range as the materials being filtered. These devices, which mimic membrane dead-end and cross-flow microfiltration processes, allow in-situ and direct microscopic observations of the fouling mechanisms. The microfluidic system is equipped with flow rate and pressure measurement devices allowing a dynamic cross analysis of the observations with the variations of permeability. Experiments have been realized for different hydrodynamic conditions (flow rate, filtration mode) and for different colloidal interactions (by varying the ionic strength) in order to analyse their interplay in the clogging mechanism by soft matter (interacting particles). The results evidenced the importance of clogs formation, fragility and sweeping out dynamics during the fouling process. These dynamic events at bottlenecks induce important permeability fluctuations. The particle-particle and particle-wall interactions also play important roles on the clogging dynamics. Three different scenarios are discussed by analogy to crowd swarming: panic scenario (0.01 mM) where repulsion between particles induce pushing effects leading to the creation of robust arches at pore entrances; herding instinct scenario (10 mM) where the attraction (in secondary minima) between particles enhances the transport in pores and delays clogging; sacrifice scenario (100 mM) where the capture efficiency is high but the aggregates formed at the wall are fragile. These analyses illustrate the importance of collective behaviour exhibited by interacting particles during fouling. The fouling phenomena by biological particles (bacteria) are analysed in terms of the streamer formation conditions and mechanisms. The streamer formation phenomena are in turn analysed by playing with the cultivation conditions (the carbon to nitrogen ratio in the substrate) in order to study the effect of extracellular polymeric substances (EPS) on the process. The results show that EPS (and hence the bacterial cultivation conditions) play crucial role in streamer formation by microorganisms under flow in constrictions. Furthermore, the presence of non-EPS producing bacterial species along with EPS producing species in a mixed culture enhances the streamer formation. On the other hand, filtration of mixed particles and bacteria suspensions show that the presence of bacteria substantially modifies the clogging dynamics. Microfluidic devices with specific configurations have also been developed for fractionation in order to maximize performances of these processes. The preliminary results with these chips in cross-flow conditions show that it is possible to limit the clogging impact by working below a critical flux; their use for continuous microparticles fractionation could be then considered

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Xu, Jin (Jin C. ). "Fabrication and function of microfluidic devices for monitoring of in-vitro fertilization processes". Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/40930.

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Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2007.
Includes bibliographical references (leaf 36).
The process of assistive reproduction is often a headache and heartache for those who choose to go through it. The field currently relies heavily on morphological characteristics to determine embryo health and development success, a highly unreliable method. While they appear healthy at implantation, many embryos, in reality, have poor development potential and fail to survive within the womb. Therefore, to offset the high chances of miscarriage, multiple eggs are implanted in the uterus. This has occasionally lead to multi-fetal pregnancies, which have a higher maternal mortality risk, and, in general, is more physically demanding. This thesis researches a microfluidic device that aids in the crucial stages of in vitro- fertilization. The device allows for a fertilized egg to be cultured within, and provides the ability to carefully monitor its health through a series of metabolic assays, a better indication of embryo health. This microfluidic embryo health monitoring device is comprised of two layers of channel networks. It works through passing fluids along flow channels that are driven by control channels. The control layer, when pressurized with gas, operates as valves and peristaltic pumps along the flow layer to pump and transport fluids through the flow channels. As embryonic fluids are passed through the channels, the status of the fertilized egg can be monitored with metabolic assays taken of the embryo at various detection sites.
by Jin Xu.
S.B.

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Abdelhady, Ahmed Mohammed Said lutfi. "Developing novel processes in chemistry for several types of nanoparticles". Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/developing-novel-processes-in-chemistry-for-several-types-of-nanoparticles(0712d3c6-e2d5-415a-b787-c9ce457e1355).html.

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The work presented in this thesis reports the use of a series of novel thiobiuret metal complexes [M(SON(CNiPr2)2)n] (M = Cu, Ni, Fe, Zn, Cd or In; n = 2 or 3) for the first time as single source precursors for the colloidal synthesis of metal sulfide nanoparticles. Other single source precursor(s) were also used for the synthesis of CdSe, CdS, CdSe/CdS core/shell, CdSeS alloys and Cu2-xS nanoparticles in microfluidic reactors. Thermolysis experiments of [Cu(SON(CNiPr2)2)2] using only oleylamine produced Cu7S4 nanoparticles as a mixture of monoclinic and orthorhombic phases. Pure orthorhombic Cu7S4 nanoparticles were obtained when a solution of precursor in octadecene was injected into hot oleylamine whereas, Cu1.94S nanoparticles were obtained when a solution of the precursor in oleylamine was injected into hot dodecanethiol. The thermolysis of [Ni(SON(CNiPr2)2)2] gave Ni3S4 in all cases except when precursor solution in oleylamine was injected into hot octadecene which produced NiS nanoparticles. The thermolysis of [Fe(SON(CNiPr2)2)3] in oleylamine/oleylamine produced Fe7S8 nanoparticles but other combinations, in most cases, gave amorphous material. Thermolysis of [Zn(SON(CNiPr2)2)2] in oleylamine produced spherical ZnS nanoparticles. Particles with size smaller than 4.3 nm had a cubic phase, whereas the particles with size larger than 4.3 nm had a hexagonal crystal structure as suggested by the selected area electron diffraction. Powder X-Ray diffraction showed that the CdS nanoparticles obtained from the thermolysis of [Cd(SON(CNiPr2)2)2] in oleylamine were cubic under all reaction conditions except when dodecanethiol was used as an injection solvent which produced hexagonal CdS. β-In2S3 were synthesized from the thermolysis of [In(SON(CNiPr2)2)3]. Transmission electron microscopy showed that the copper, nickel and iron sulfide nanoparticles had various morphologies such as spherical, hexagonal disks, trigonal disks, rods or wires; depending on the reaction temperature, concentration of the precursor, the growth time and the solvent/capping agent combination. The zinc and cadmium sulfide nanoparticles were mostly spherical whereas the indium sulfide nanoparticles were produced in the form of ultra-thin (< 1.0 nm) nanorods or nanowires. ZnxCd1-xS and CuInS2 nanoparticles were synthesised from the 1,1,5,5-tetra-iso-propyl-4-thiobiureto complexes of Zn, Cd and Cu, In, respectively. Powder X-Ray diffraction showed that the obtained ZnxCd1-xS nanoparticles are cubic under all reaction conditions. The ZnxCd1-xS nanoparticles had an average diameter between 3.5 to 6.4 nm as shown by transmission electron microscopy. The optical properties of the ZnxCd1-xS nanoparticles were highly dependent on the ZnS to CdS precursor ratio and the solvents/capping agents. Chalcopyrite (tetragonal), wurtzite (hexagonal) or a mixture of both CuInS2 nanoparticles were obtained depending on the reaction conditions. TEM showed that the CuInS2 nanoparticles could be synthesised with different morphologies (spherical, hexagonal, trigonal or cone). Luminescent CuInS2 nanoparticles were obtained only in the absence of oleylamine. [Cd(S2CNMenHex)2], [Cd(Se2P(iPr)2)2] and [Cu(SON(CNiPr2)2)2] were used as single source precursor(s) for the synthesis of CdS, CdSe, CdSe/CdS core/shell, CdSeS alloys and Cu2-xS in microfludic reactor. The CdS nanoparticles were in size range of 5.0 to 8.0 nm whereas the CdSe nanoparticles were ultra small (ca. 2 nm) with blue luminescence. The CdSe/CdS core/shell and the CdSeS alloys were bluish green or green luminescent depending on their size. The copper sulfide nanoparticles were found to be monoclinic Cu7S4 or monoclinic Cu7S4 with minor impurities of rhombohedral Cu9S5 depending on the reaction conditions.

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Haben, Patrick. "Controlling the Synthesis of Bunte Salt Stabilized Gold Nanoparticles Using a Microreactor Platform in Concert with Small Angle X-ray Scattering Analysis". Thesis, University of Oregon, 2013. http://hdl.handle.net/1794/13429.

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Gold nanoparticles (AuNPs) have garnered considerable attention for their interesting size-dependent properties. These properties have fueled applications that span a continuum ranging from simple to sophisticated. Applications for these materials have grown more complex as syntheses for these materials have improved. For simple applications, current synthetic processes are sufficient. However, development of syntheses that generate well-defined particle sizes with specifically tailored surface functionalities is an on-going challenge for chemists. The aim of this dissertation is to improve upon current AuNP syntheses to produce sophisticated materials needed to discover new material properties, and provide efficient access to materials to develop new advanced applications. The research described in this dissertation improves upon current methods for AuNP production by using a microreactor to provide enhanced mixing and synthetic control, and small angle X-ray scattering (SAXS) as a precise, rapid, solution-based method for size distribution determination. Using four ligand-stabilized AuNP samples as reference materials, SAXS analysis was compared to traditional microscopic size determination. SAXS analysis provided similar average diameters while avoiding deposition artifacts, probing a larger number of particles, and reducing analysis time. Next, the limits of SAXS size analysis was evaluated, focusing on identifying multiple distributions in solution. Utilizing binary and ternary mixtures of well-defined AuNP reference samples, SAXS analysis was shown to be effective at identifying multiple distributions. While microscopy has limited ability to differentiate these modes, SAXS analysis is more rapid and introduces less researcher bias. Because AuNP size and ligand functionality are interdependent, accessing desired core sizes with varied functionality is challenging. To address this, a new microfluidic synthetic method was developed to produce thiolate-passivated AuNPs with targeted core sizes from 1.5 - 12 nm with tailored functionality. This ability to control size while independently varying surface functionality is unprecedented. Lastly, AuNP core formation was probed by simultaneous in situ SAXS and UV/visible spectroscopy. A coalescence mechanism for AuNP growth was observed when using Bunte salt ligands. This finding compares well to observed coalescence in other systems using weakly-passivating ligands, and supports the hypothesis that Bunte salts passivate ionically during particle growth while resulting in covalent linkages.
2015-10-10

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Janakiraman, Vijayakumar. "DESIGN, FABRICATION AND CHARACTERIZATION OF BIFURCATING MICROFLUIDIC NETWORKS FOR TISSUE-ENGINEERED PRODUCTS WITH BUILT-IN MICROVASCULATURE". Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1196457966.

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Schianti, Juliana de Novais. "Sistemas de microcanais em vidro para aplicações em microfluidica". Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/3/3140/tde-19082008-083259/.

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Neste trabalho são apresentados resultados relativos ao desenvolvimento de um processo de fabricação para a produção de sistemas de microcanais em vidro tipo borosilicato, 7059 Corning Glass. O objetivo do trabalho é implementar um processo básico, mas completo, de fabricação de sistemas microfluídicos em vidro, que possam futuramente ser aprimorados com a introdução de dispositivos ópticos e eletrônicos e de elementos microfluídicos ativos, como válvulas e microbombas, para sensoreamento e controle de fluxo. O processo de fabricação foi dividido em três grandes etapas, sendo a primeira delas, a produção dos microcanais, envolvendo processos como litografia e corrosão úmida. Nos estudos de corrosão procurou-se uma solução que permitisse a obtenção de canais com superfície uniforme e lisa, sem a produção de resíduos durante a corrosão do vidro. Os melhores resultados foram obtidos com a solução HF + HCl + H2O (1:2:3), com a possibilidade de produzir canais com até 150 µm de profundidade. A segunda etapa do processo de produção dos sistemas microfluídicos envolveu o encapsulamento dos microcanais, o que foi feito através de um processo de soldagem direta (vidro com vidro) à temperatura ambiente, com aplicação de pressão entre 0,1 a 1,0 MPa. Os melhores resultados nesta etapa envolveram pressões acima de 0,5 MPa, podendo-se obter cerca de 95 - 100% da área das lâminas soldadas. A terceira etapa do processo de fabricação engloba a interconexão com o meio externo, envolvendo a produção dos furos no vidro para entrada e saída de líquidos e a introdução dos tubos de acesso para o meio externo. Para a produção dos furos foi desenvolvido um sistema posicionador computarizado que movimenta o substrato de vidro nas direções x, y e z com precisão de alguns micrometros, garantindo o alinhamento necessário entre as duas lâminas de vidro que devem ser soldadas para encapsular os microcanais. Os furos foram feitos com broca diamantada de uso odontológico fixa em uma furadeira comum. Cateteres e scalps de uso médico foram empregados como tubos de acesso, sendo selados com resina epóxi. Os sistemas microfluídicos fabricados foram testados monitorando o fluxo de soluções aquosas de anilina, o qual foi mantido através de bomba peristáltica. Os resultados se mostraram reprodutíveis, tendo se obtido microcanais lisos e sem resíduos, sem apresentar vazamentos e exibindo regime de fluxo tipicamente laminar. Em conjunto, estes resultados mostraram-se muito promissores para desenvolvimento futuro de aplicações em áreas como Biotecnologia e Análises Químicas.
In this work, a process for the fabrication of microchannels over borlosilicate 7059 Corning Glass is presented. The main objective is to develop a simple and complete process for the fabrication of microfluidic systems over glass, that can be further improved in the future, with the integration of optical, electronic and active microfluidic devices such as valves and micropumps, for sensing and flow control. The fabrication process has three main parts. The first part is the microchannel production, which is achieved through contact-lithography and wet etching. In the etching studies, a solution that led to the fabrication of channels with uniform and smooth surfaces, without residue formation was sought. The best results were attained with a HF + HCl + H2O (1:2:3), which allow for the production of channels with depths of up to 150 µm. The second part of the fabrication process is the microchannels encapsulation, which is achieved through direct (glass-glass) bonding at room temperature, with applied pressure ranging from 0.1 to 1.0 MPa. The best results were obtained with pressure values above 0.5 MPa, which allowed for the bonding of up to 95 -100% of the glass sufaces. The third part of the fabrication process concerns the interconnection with the outside environment, which involves hole production and the introduction of tubes, to allow external access of liquids. For the hole production, a computer controlled positioning system was developed, for accurate positioning of the glass substrate in the x, y and z directions, with a precision of a few micrometers. This system guaranteed the necessary alignment of the upper and lower glass substrates, which were bonded for the encapsulation of the microchannels. The holes were made with diamond burs with a common drill. Medical catheters and scalps were used as access tubes, with epoxy resin. The characterization of the fabricated microfluidic systems was achieved by monitoring the flow of aniline aqueous solutions, which was maintained through a peristaltic pump. Reproducible results were obtained, with the production smooth and residue free microchannels, which did not present leakage and exhibited a laminar flow behavior. These results are very promising for the future application of this process in the fabrication of devices for areas such as biotechnology and chemical analysis, among others.

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Kirschbaum, Michael. "A microfluidic approach for the initiation and investigation of surface-mediated signal transduction processes on a single-cell level". Phd thesis, Universität Potsdam, 2009. http://opus.kobv.de/ubp/volltexte/2009/3957/.

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For the elucidation of the dynamics of signal transduction processes that are induced by cellular interactions, defined events along the signal transduction cascade and subsequent activation steps have to be analyzed and then also correlated with each other. This cannot be achieved by ensemble measurements because averaging biological data ignores the variability in timing and response patterns of individual cells and leads to highly blurred results. Instead, only a multi-parameter analysis at a single-cell level is able to exploit the information that is crucially needed for deducing the signaling pathways involved. The aim of this work was to develop a process line that allows the initiation of cell-cell or cell-particle interactions while at the same time the induced cellular reactions can be analyzed at various stages along the signal transduction cascade and correlated with each other. As this approach requires the gentle management of individually addressable cells, a dielectrophoresis (DEP)-based microfluidic system was employed that provides the manipulation of microscale objects with very high spatiotemporal precision and without the need of contacting the cell membrane. The system offers a high potential for automation and parallelization. This is essential for achieving a high level of robustness and reproducibility, which are key requirements in order to qualify this approach for a biomedical application. As an example process for intercellular communication, T cell activation has been chosen. The activation of the single T cells was triggered by contacting them individually with microbeads that were coated with antibodies directed against specific cell surface proteins, like the T cell receptor-associated kinase CD3 and the costimulatory molecule CD28 (CD; cluster of differentiation). The stimulation of the cells with the functionalized beads led to a rapid rise of their cytosolic Ca2+ concentration which was analyzed by a dual-wavelength ratiometric fluorescence measurement of the Ca2+-sensitive dye Fura-2. After Ca2+ imaging, the cells were isolated individually from the microfluidic system and cultivated further. Cell division and expression of the marker molecule CD69 as a late activation event of great significance were analyzed the following day and correlated with the previously recorded Ca2+ traces for each individual cell. It turned out such that the temporal profile of the Ca2+ traces between both activated and non-activated cells as well as dividing and non-dividing cells differed significantly. This shows that the pattern of Ca2+ signals in T cells can provide early information about a later reaction of the cell. As isolated cells are highly delicate objects, a precondition for these experiments was the successful adaptation of the system to maintain the vitality of single cells during and after manipulation. In this context, the influences of the microfluidic environment as well as the applied electric fields on the vitality of the cells and the cytosolic Ca2+ concentration as crucially important physiological parameters were thoroughly investigated. While a short-term DEP manipulation did not affect the vitality of the cells, they showed irregular Ca2+ transients upon exposure to the DEP field only. The rate and the strength of these Ca2+ signals depended on exposure time, electric field strength and field frequency. By minimizing their occurrence rate, experimental conditions were identified that caused the least interference with the physiology of the cell. The possibility to precisely control the exact time point of stimulus application, to simultaneously analyze short-term reactions and to correlate them with later events of the signal transduction cascade on the level of individual cells makes this approach unique among previously described applications and offers new possibilities to unravel the mechanisms underlying intercellular communication.
Zelluläre Interaktionen sind wirkungsvolle Mechanismen zur Kontrolle zellulärer Zustände in vivo. Für die Entschlüsselung der dabei beteiligten Signaltransduktionsprozesse müssen definierte Ereignisse entlang der zellulären Signalkaskade erfasst und ihre wechselseitige Beziehung zueinander aufgeklärt werden. Dies kann von Ensemble-Messungen nicht geleistet werden, da die Mittelung biologischer Daten die Variabilität des Antwortverhaltens individueller Zellen missachtet und verschwommene Resultate liefert. Nur eine Multiparameteranalyse auf Einzelzellebene kann die entscheidenden Informationen liefern, die für ein detailliertes Verständnis zellulärer Signalwege unabdingbar sind. Ziel der vorliegenden Arbeit war die Entwicklung einer Methode, welche die gezielte Kontaktierung einzelner Zellen mit anderen Zellen oder Partikeln ermöglicht und mit der die dadurch ausgelösten zellulären Reaktionen auf unterschiedlichen zeitlichen Ebenen analysiert und miteinander korreliert werden können. Da dies die schonende Handhabung einzeln adressierbarer Zellen erfordert, wurde ein auf Dielektrophorese (DEP) basierendes mikrofluidisches System eingesetzt, welches die berührungslose Manipulation mikroskaliger Objekte mit hoher zeitlicher und örtlicher Präzision erlaubt. Das System besitzt ein hohes Potential zur Automatisierung und Parallelisierung, was für eine robuste und reproduzierbare Analyse lebender Zellen essentiell, und daher eine wichtige Voraussetzung für eine Anwendung in der Biomedizin ist. Als Modellsystem für interzelluläre Kommunikation wurde die T-Zell-Aktivierung gewählt. Die Aktivierung der einzelnen T-Zellen wurde durch ihre gezielte Kontaktierung mit Mikropartikeln („beads“) induziert, welche mit Antikörpern gegen spezielle Oberflächenproteine, wie die dem T-Zell-Rezeptor assoziierte Kinase CD3 oder das kostimulatorische Protein CD28, beschichtet waren. Die Stimulation der Zellen mit den funktionalisierten beads führte zu einem raschen Anstieg der intrazellulären Ca2+-Konzentration, welche über eine ratiometrische Detektion des Ca2+-sensitiven Fluoreszenzfarbstoffs Fura-2 gemessen wurde. Anschließend wurden die einzelnen Zellen aus dem mikrofluidischen System isoliert und weiterkultiviert. Am nächsten Tag wurden Zellteilung und die CD69-Expression – ein wichtiger Marker für aktivierte T-Zellen – analysiert und auf Ebene der individuellen Zelle mit dem zuvor gemessenen Ca2+-Signal korreliert. Es stellte sich heraus, dass der zeitliche Verlauf des intrazellulären Ca2+-Signals zwischen aktivierten und nicht aktivierten, sowie zwischen geteilten und nicht geteilten Zellen signifikant verschieden war. Dies zeigt, dass Ca2+-Signale in stimulierten T-Zellen wichtige Informationen über eine spätere Reaktion der Zelle liefern können. Da Einzelzellen äußerst empfindlich auf ihre Umgebungsbedingungen reagieren, war die Anpassung der experimentellen Vorgehensweise im Hinblick auf die Zellverträglichkeit von großer Bedeutung. Vor diesem Hintergrund wurde der Einfluss sowohl der mikrofluidischen Umgebung, als auch der elektrischen Felder auf die Überlebensrate und die intrazelluläre Ca2+-Konzentration der Zellen untersucht. Während eine kurzzeitige DEP-Manipulation im mikrofluidischen System die Vitalität der Zellen nicht beeinträchtigte, zeigten diese unregelmäßige Fluktuationen ihrer intrazellulären Ca2+-Konzentration selbst bei geringer elektrischer Feldexposition. Die Ausprägung dieser Fluktuationen war abhängig von der Expositionszeit, der elektrischen Feldstärke und der Feldfrequenz. Über die Minimierung ihres Auftretens konnten experimentelle Bedingungen mit dem geringsten Einfluss auf die Physiologie der Zellen identifiziert werden. Die Möglichkeit, einzelne Zellen zeitlich definiert und präzise mit anderen Zellen oder Oberflächen zu kontaktieren, die unmittelbare Reaktion der Zellen zu messen und diese mit späteren Ereignissen der Zellantwort zu korrelieren, macht die hier vorgestellte Methode einzigartig im Vergleich mit anderen Ansätzen und eröffnet neue Wege, die der interzellulären Kommunikation zugrunde liegenden Mechanismen aufzuklären.

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11

Rao, Xi. "Développement de microréacteurs catalytiques par procédés plasma et procédés sol-gel". Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066145/document.

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Ce travail vise non seulement à la conception et la fabrication de nouvelles puces microfluidiques pour l'oxydation de l'alcool benzylique, mais aussi au développement d'une méthode utilisant le plasma. Cette dernière est consacrée à la fonctionnalisation de surface avec un liant afin d'ancrer des particules de catalyseur. Les résultats montrent que le procédé PECVD est une méthode universelle permettant de déposer un nombre élevé de fonctions amines à partir de l’APTES sur différentes surfaces. Suite à l’étude des différents paramètres, des conditions optimales ont été trouvées. En effet, par rapport à la fonctionnalisation conventionnelle par voie humide, une meilleure hydrophilicité, une épaisseur de dépôt ainsi qu’une densité de groupements amines plus élevées ont été obtenus sur les échantillons traités. De plus, les résultats avec les AuNPs immobilisés sur la zéolite indiquent que l’APTES est un meilleur précurseur que le MPTES car il offre une plus grande teneur en or. Pour la zéolite et AuNPs@zéolite, les particules sont fonctionnalisées à l'aide du CES en tant qu’agent de liaison pour les amines protonées présentes sur la surface du COC ; ce dernier étant prétraité en utilisant le procédé PECVD. Le microréacteur à base d'or présente une sélectivité élevée stable au benzaldéhyde (~94%). Cependant, il montre également une conversion faible d'alcool benzylique (~20%). Le microréacteur type AuNPs@zéolites réalise la meilleure activité catalytique dans notre étude, car une sélectivité élevée par rapport au benzaldéhyde (>99%) est obtenue avec la conversion la plus élevée de l'alcool benzylique (~40%)
This work aims not only at designing and fabricating new microfluidic chips for benzyl alcohol oxidation, but also at developing a methodology of plasma devoted to the surface functionalization with linkage reagent in order to anchor catalyst particles in the next step. Results show that the PECVD method is a universal method that can deposit high amine content of APTES polymerized film on various substrate surfaces. Optimized plasma conditions for APTES deposition were found and lead to a better hydrophilicity of the substrates, a higher coating thickness, as well as a higher amine group density than the conventional wet chemistry method. In addition, the APTES depositions lead to a further higher coverage and amount of AuNPs when the pH value is 6.2. Moreover, the results of immobilizing AuNPs on zeolite indicate that APTES is a better linker than MPTES as it provides a higher amount of gold loading. For zeolite and AuNPs@zeolite deposition, the particles were functionalized with carboxyl group using CES as a linker for bounding the protonated amines on COC surface that is pre-modified using PECVD method. The latter coating is stable in hydrodynamic flows and could be further used in microfluidics. Finally, the gold \Y zeolite \AuNPs@zeolite microreactors are respectively connected into pre-designed microfluidic system. The gold type microreactor exhibits stable high selectivity to benzaldehyde (~94%). However, it also shows relative low benzyl alcohol conversion (~20%). The AuNPs@zeolites type microreactor performs the best catalytic activity in our study as a high benzaldehyde selectivity (>99%) is obtained with the highest benzyl alcohol conversion (~40%)

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12

Zollo, Margaux. "Solvants à hydrophilie commutable au CO2 : applications en microfluidique pour les processus chimiques". Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0193.

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Un des défis dans le développement de procédés chimiques plus écologiques est de trouver des solvants à faible volatilité, facilement séparables et recyclables. Une solution prometteuse est l’utilisation de solvants à hydrophilie commutable sensibles au CO2 (CO2-SHS), offrant une alternative aux solvants volatiles aux propriétés fixes. Cette étude propose une nouvelle approche pour évaluer les performances des SHS en utilisant le 2-2-Dibutylaminoéthanol (DBAE), un SHS connu, dans un dispositif microfluidique continu en poly(diméthylsiloxane) (PDMS). Cette méthode offre une alternative rapide et flexible aux réacteurs batch traditionnels et aux plateformes millifluidiques existantes. Le système DBAE/eau/CO2 a été caractérisé par des techniques spectroscopiques (ATR-IR et Raman) pour identifier les espèces impliquées dans le mécanisme de réaction. Le changement d’hydrophilie a été testé dans un ensemble millifluidique inspiré des plateformes existantes et dans le dispositif PDMS conçu
One of the main challenges in developing greener chemical processes is finding lowvolatility solvents that are easily separable, energy-efficient, and recyclable. A promising solution is the use of reversible CO2-Switchable Hydrophilicity Solvents (CO2-SHS), which offer an energy-efficient alternative to solvents with fixed properties. In this study, we propose a novel approach to rapidly investigate SHS performance using 2-2-Dibutylaminoethanol (DBAE), a known CO2-SHS, within a continuous microfluidic device made of poly(dimethylsiloxane) (PDMS). This method provides a highly adaptable alternative to traditional batch reactors and millifluidic platforms. First, the DBAE/water/CO2 system was characterized using spectroscopic techniques (ATR-IR and Raman) to identify the species involved in the phase change mechanism. Then, the hydrophilicity switch was tested, initially in a millifluidic assembly inspired by existing platforms, and subsequently in the designed PDMS device

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13

Wang, Hanyang. "Two Examples of Ratchet Processes in Microfluidics". Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37649.

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The ratchet effect can be exploited in many types of research, yet few researchers pay attention to it. In this thesis, I investigate two examples of such effects in microfluidic devices, under the guidance of computational simulations. The first chapter provides a brief introduction to ratchet effects, electrophoresis, and swimming cells, topics directly related to the following chapters. The second chapter of this thesis studies the separation of charged spherical particles in various microfluidic devices. My work shows how to manipulate those particles with modified temporal asymmetric electric potentials. The rectification of randomly swimming bacteria in microfluidic devices has been extensively studied. However, there have been few attempts to optimize such rectification devices. Mapping such motion onto a lattice Monte Carlo model may suggest some new mathematical methods, which might be useful for optimizing the similar systems. Such a mapping process is introduced in chapter four.

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14

Shelby, James Patrick. "The application of microfluidics to the study of biological processes /". Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/8483.

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15

Cairone, Fabiana. "Models and Systems for the Control of Two-Phase Processes in Microfluidics". Doctoral thesis, Università di Catania, 2019. http://hdl.handle.net/10761/4147.

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The strong point of the microfluidics is the ability to miniaturize and integrate one or several laboratory functions on the same device, to have a portable and user-friendly instrument. Most applications require accurate measures and control within the microfluidic channels. In this thesis, the optical techniques were adopted to monitor, sensing and control the processes, leading to the research area of optofluidics that are based on the integration of fluidics and optics. To reduce the cost to develop these devices, the 3D Printing technology based on the Poly(dimethyl-siloxane) (PDMS) is proposed. All these aspects were addressed considering the two-phase flow (named slug) generated by the interaction of two immiscible fluids, a very common condition in bio-chemical applications. The methodological aspects were discussed in the first part of the thesis, starting from the extraction of parameters for the flow characterization, to their use for the flows real-time modelling and control schemes development; the second part investigates aspects faced for the realization of micro-optical flow detector by using the 3D Printing technology.

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16

Bhopte, Siddharth. "Study of transport processes from macroscale to microscale". Diss., Online access via UMI:, 2009.

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Thesis (Ph. D.)--State University of New York at Binghamton, Thomas J. Watson School of Engineeering and Applied Science, Department of Mechanical Engineering, 2009.
Includes bibliographical references.

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17

Vinner, Gurinder K. "Engineering bacteriophage encapsulation processes to improve stability and controlled release using pH responsive formulations". Thesis, Loughborough University, 2018. https://dspace.lboro.ac.uk/2134/35524.

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Enteric pathogens form a large part of infectious diseases which contribute to a bulk of the healthcare costs. Enteric infections are usually contracted via the faecal-oral route or through contact with contaminated surfaces. Treatment by antibiotics is becoming increasingly ineffective due to the growing number of antibiotic resistant strains. Anti-microbial resistance poses a serious threat to the future of healthcare worldwide and necessitates the search for alternate forms of therapy. Bacteriophages (phages), are viruses which specifically infect and lyse bacteria. To introduce phages as a viable form of therapy, route of administration needs to be considered carefully. Model phages with broad host ranges are ideal for therapy however oral delivery to the lower gastro-intestinal (GI) poses several challenges. The acidic stomach environment can be detrimental to phages, rendering them inactive during passage. To overcome this challenge and improve the stability of phage during encapsulation and storage, this PhD research has been conducted. pH responsive polymers, Eudragit and alginate were used to develop composite microparticles which protected phage from acidic pH (pH 1-3). A novel method of acidifying oil was developed for crosslinking droplets in vitro to avoid the use of harsh solvent systems that can cause phage inactivation. Platform microfluidic technology was employed for phage encapsulation for the first time. Monodispersed droplets and particles were produced, offering fine-tuning of droplet diameter to tailor the release and pH protection of encapsulated phage. Process scale-up was attempted using membrane emulsification (ME) to produce larger volumes of encapsulated phage. In vitro and in-situ models investigated the efficacy of encapsulated phage-bacterial killing. Industrial scale method of spray drying, and electrospinning were also used to demonstrate the versatility of the formulation. Tableting dry powder phage, showed an effective method for producing solid dosage forms for therapy. Additionally, electrospun phage fibres also showed the potential use of pH responsive formulations in addressing wound infections. Improvement in encapsulated phage storage stability was observed with the addition of trehalose in the formulation. This research underpins the need for testing phage encapsulation for site-specific delivery and offers insight into the potential use of commercially available technologies.

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18

Lamperti, Emanuele. "PDMS based microfluidics membrane contactors for CO2 removal applications". Master's thesis, Alma Mater Studiorum - Università di Bologna, 2018. http://amslaurea.unibo.it/15261/.

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This work proposes a gas-liquid contactor study in microfluidics field, using dense membrane working with a concentration gradient; a microfluidic gas-liquid contactor was developed for CO2 removal and the general idea is to transport CO2 through a polymer dense membrane, followed by its capture by a liquid solvent with chemical absorption. Like recent studies demonstrate, this kind of devices could solve problems related to extracorporeal lung oxygenation (Garofalo, C. Quintavalle, G. Romano, C.M. Croce, 2013) for critical surgical support and critical care medicine, it can work like a real lung because can mimic the architecture of the human vasculature better than the existing technologies. Applications in this fields are related for example to the separation of Xenon from CO2 in anaesthesia. Xe is a very expensive element perfect for anaesthesia, is hemodynamically stable, low soluble in liquid and produces high regional blood flow reducing the risk of hypoxia (Malankowska et al., 2018). The major advantage of using microfluidics devices is that they could be reach a high surface to volume ratio and thanks to miniaturization can be tested reducing the time as well as the production of waste, thus increasing the number of experimental tests can be achieved. In the present thesis in particular one alveolar design channel based of literature results (Malankowska et al., 2018) was realized with soft lithography and tested in different experimental conditions. In particular, for the present geometry the transport of CO2 through the membrane was monitored, calculating the overall mass transfer coefficient and the molar flow of the gas through the membrane in different operating conditions. In additions, the production of other two microfluidics device with different channels configurations was attempted by using a 3-D printing technique that allows the generations of complex structures with high surface to volume ratio.

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19

Aramphongphun, Chuckaphun. "In-mold coating of thermoplastic and composite parts microfluidics and rheology /". Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1141759615.

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20

Shu, Zhe [Verfasser], Andreas [Gutachter] Tünnermann, Klaus D. [Gutachter] Jandt y Romain [Gutachter] Quidant. "Solution-processed organic light surces for microfluidic lab-on-a-chip systems / Zhe Shu ; Gutachter: Andreas Tünnermann, Klaus D. Jandt, Romain Quidant". Jena : Friedrich-Schiller-Universität Jena, 2018. http://d-nb.info/1170399339/34.

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21

Terblanche, Johannes C. "Modified polysaccharide-based particles for strengthening paper". Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/5376.

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Thesis (PhD (Process Engineering))--University of Stellenbosch, 2010.
ENGLISH ABSTRACT: The ongoing trend in papermaking industries is to lower production costs by increasing the low cost filler content in the sheets. However, the disruption of inter-fibre bonding is accompanied by a deterioration of paper stiffness and mechanical properties if filler content exceeds 18 wt%. Polysaccharide solutions, such as starch, are often used as a low cost biodegradable additive to improve internal sheet strength when added to the wet-end of production. The amount of starch that can be added is however limited as only a small percentage will be retained in the paper web. A dual additive multifunctional polysaccharide system was developed to allow higher filler loading levels without detrimental deterioration in paper properties. In order to achieve a larger surface area for fibre/filler interaction and to reduce drainage losses, at least one of these additives was in particulate form. Anionic, cationic, and unsaturated derivatives were prepared using sodium monochloroacetate, 3-chloro-2-hydroxypropyltrimethylammonium chloride, and allyl bromide, respectively. The degree of substitution was determined by 1H-NMR spectroscopy and back titration methods and the interaction of the ionic modified derivatives with paper components was determined using fluorescence microscopy. Anionic modified polysaccharide particles were prepared using techniques such as macrogel ultrasonification, water-in-water emulsification, and in-situ cross-linking and carboxymethylation of granular starch. A process of adding sequential layers of oppositely charged polyelectrolyte layers onto the filler particles was also investigated. A novel approach of preparing modified particles with tailored size and distribution using microfluidics was studied and modelled using response surface methodology. Hand sheets were prepared using the dual additive system and improvements in stiffness, tear resistance, breaking length, and folding endurance were observed. The modified granular maize starch particles had a pre-eminent effect on improving stiffness at higher filler loadings (14% improvement at 30 wt% filler loading), while bulky particles prepared using microfluidics showed a more consistent improvement (between 6% and 10%) across the loading range. Overall improvements gained by the introduction of multi-layered soluble polymers onto fillers suggest that the introduction of nanotechnology to the papermaking process should be of potential benefit to the industry. Furthermore, the dual additive system developed during the course of this study should also be tested on a continuous pilot plant papermaking process.
AFRIKAANSE OPSOMMING: Die papierindustrie neig voortdurend daarna om produksiekostes te verlaag deur die persentasie lae koste vulstof wat gebruik word te verhoog. Aangesien die vulstof vesel kontak belemmer, gaan hoër vlakke (> 18 wt%) egter gepaard met ’n verlaging in papier styfheid en meganiese eienskappe. Polisakkaried oplossings, soos byvoorbeeld stysel, word dikwels gebruik as lae koste vergaanbare bymiddel om papier intern te versterk wanneer dit voor die vormingsproses bygevoeg word. Slegs ’n beperkte hoeveelheid stysel word egter behou in die papier matriks en oormatige oplossings ontsnap tydens dreinering in die afvalwater. ’n Dubbele multi-funksionele polisakkaried bymiddelsisteem was ontwikkel wat ongewensde verwakking in papiereienskappe verminder tydens vulstof verhogings. Ten minste een van die bymiddels was in partikelvorm om sodoende ’n groter oppervlak te bied vir vesel/vulstof interaksie en om dreineringsverliese te verminder. Anioniese, kationiese, sowel as onversadigde derivate was berei deur onderskeidelik gebruik te maak van natrium monochloroasetaat, 3-chloro-2-hidroksiepropieltrimetielammonium chloried, en alliel bromied. Die graad van substitutiese was bepaal met behulp van 1H-KMR spektroskopie sowel as titrasie tegnieke terwyl die ioniese interaksie van die gemodifiseerde stysels met die papierkomponente ondersoek was met behulp van fluoressensie mikroskopie. Anioniese polisakkaried partikels was berei met tegnieke soos makro-jel ultrasonifikasie, water-in-water emulsifikasie, en in-situ kruisbinding en karboksiemetielasie van stysel granulate. ’n Proses was ook ondersoek waar vulstof partikels omhul was in verskeie lae poliëlektroliet oplossings. ’n Nuwe benadering was toegepas waar gemodifiseerde partikels met voorafbepaalde grootte en verspreiding berei is deur gebruik te maak van mikrofluïdika en gemodelleer met behulp van oppervlakte ontwerp metodeleer. Papier toetse was uitgevoer met die bymiddelsisteem en algehele verbetering in styfheid, skeurweerstand, breeklengte, en voulydsaamheid is waargeneem. Die gemodifiseerde stysel granulate het die grootste verbetering in styfheid by hoë vulstofladings getoon (14% verbetering by 30 wt% vulstoflading) terwyl die groter mikrofluïdika-bereide partikels algehele verbetering (tussen 6% en 10%) getoon het oor die hele vulstoflading reeks. Die verbeteringe in styfheid sowel as meganiese eienskappe van papier voorberei met poliëlektroliet omhulde vulstof toon dat aanwending van nanotegnologie in hierdie bedryf potensieel voordelig kan wees. Opskalering van die polisakkaried bymiddels ontwikkel gedurende hierdie studie behoort uitgevoer te word vir verdere toetse op ’n kontinue papier loodsaanleg.

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22

Monteiro, Moniellen Pires 1988. "Estudo de processos de adesão bacteriana : propriedades mecânicas e efeitos do microambiente sobre adesão, crescimento e mobilidade da Xylella fastidiosa". [s.n.], 2017. http://repositorio.unicamp.br/jspui/handle/REPOSIP/325073.

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Orientador: Mônica Alonso Cotta
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin
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Resumo: Nesta tese investigamos processos de adesão da Xylella fastidiosa, bactéria gram-negativa, fitopatógena, que forma biofilmes no xilema de plantas. O trabalho teve como objetivos entender alguns aspectos do processo de adesão bacteriana e do mecanismo de transporte de células e biofilmes em sistemas que simulam os vasos do xilema. Consideramos em particular as estratégias utilizadas pela X.fastidiosa para aderir à superfície, dentre elas, a secreção de substâncias poliméricas extracelulares (EPS), a presença de adesinas fimbriais (pili) e afimbriais (XadA1) e moléculas sinalizadoras de detecção de quórum (relacionadas à formação de agregados). Como ponto de partida quantificamos as propriedades elásticas do sistema composto pelo EPS e células bacterianas, em diferentes tempos de cultivo bacteriano. Para isso utilizamos medidas de espectroscopia de força e Raman confocal durante os estágios iniciais de adesão celular e formação de agregados. Mostramos que a rigidez do sistema célula/EPS diminui progressivamente com o aumento do tempo de crescimento bacteriano. Verificamos que existe uma mudança no valor de rigidez em diferentes partes da célula, região polar e corpo bacteriano; os menores valores de rigidez encontrados no polo sugerem uma resposta mecânica mais flexível nesta região, associada com o ponto de adesão inicial da célula à superfície. No estudo de adesão e mobilidade da X.fastidiosa, utilizamos dispositivos microfluídicos modificados quimicamente, via funcionalização de superfície (em microcanais Polidimetilsiloxano/vidro) e via introdução de molécula de detecção de quórum (em microcanais impressos em poliácido láctico), para tornar o ambiente mais próximo ao do xilema da planta. Foram feitas funcionalizações de superfície com uma celulose sintética, simulando a composição química dos vasos do xilema (majoritariamente composto por celulose), e com a adesina XadA1, e observamos os efeitos sobre a adesão, crescimento e mobilidade celular. Verificamos que a adesina XadA1 aumenta a densidade bacteriana se comparada às demais superficies, além de aumentar a força de adesão bacteriana à superfície. Quanto a inserção de molécula sinalizadora, observamos que a presença destas moléculas no cultivo bacteriano aumenta a densidade celular e altera a forma de pequenos agregados
Abstract: In this thesis we investigated the adhesion processes of Xylella fastidiosa, a gram-negative, phytopathogenic bacterium that forms biofilms in the xylem of plants. The objective of this work was the understanding of several aspects of the bacterial adhesion process, as well as the mechanism of cell and biofilm transport in systems that simulate xylem vessels. In particular, we considered the strategies used by X.fastidiosa to adhere to a surface; among them, the secretion of extracellular polymeric substances (EPS), the presence of fimbrial (pili) and afimbrial (XadA1) adhesins and quorum detection molecules (related to cluster formation). As a starting point we quantified the elastic properties of the system composed of EPS and bacterial cells, at different times of bacterial culture. For this purpose, we used force spectroscopy and confocal Raman measurements during the initial stages of cell adhesion and cluster formation. We have shown that stiffness decreases progressively with increasing bacterial growth time. We observed that stiffness values varied along different parts of the cell, polar region and bacterial body. The lower stiffness values found at the pole suggest a more flexible mechanical response in this region, associated with the initial adhesion point of the cell to the surface. For the investigation on X.fastidiosa adhesion and mobility, we used chemically modified microfluidic devices via surface functionalization (in Polydimethylsiloxane / glass microchannels) and via the introduction of a quorum detection molecule (in microchannels printed on polylactic acid) to make the environment more closely resemble the plant xylem. Surface functionalizations were performed with a synthetic cellulose, simulating the chemical composition of xylem vessels (mainly composed of cellulose), and the XadA1 adhesin, and we observed the effects on cell adhesion, growth and mobility. Our results showed that immobilized XadA1 increased the bacterial density when compared to other surfaces studied; furthermore, it increased the bacterial adhesion force to the surface. Regarding the addition of the signaling molecules, we observed that their presence in the bacterial culture increases cell density and changes the shape of small clusters
Doutorado
Física
Doutora em Ciências
2010/51748-7
479486/2012-3
FAPESP
CNPQ

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23

Mark, Daniel [Verfasser] y Roland [Akademischer Betreuer] Zengerle. "Unit operations for the integration of laboratory processes in the field of nucleic acid analysis based on centrifugal microfluidics = Einheitsoperationen für die Integration von Laborprozessen im Bereich der Nukleinsaeureanalytik basierend auf zentrifugaler Mikrofluidik". Freiburg : Universität, 2013. http://d-nb.info/1123477361/34.

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24

Zhang, Fan. "Intensification du procédé antisolvant supercritique (SAS) par l'usage de microréacteur sous pression". Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0269.

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Dans le cadre de cette thèse, nous nous proposons d’étudier le comportement thermo-hydrodynamique d’un mélange solvant/antisolvant supercritique dans une puce microfluidique, pour des conditions utilisées dans le procédé SAS (Supercritical Antisolvent System). Ce travail se base sur une approche complémentaire expérience/simulation via l’utilisation de techniques de recherches avancées telles que la caractérisation in situ sur puce microfluidique (micro-PIV – micro Particle Image Velocimetry) et la simulation numérique intensive. L’objectif de la thèse est de définir les conditions favorables à un « très bon » mélange (total et rapide) des espèces en termes de vitesse, température, pression et « design » d’injecteur. Les simulations sont effectuées avec le code de calcul Notus, massivement parallèle. Après un premier chapitre détaillant l’état de l’art sur les procédés antisolvant supercritiques, puis un second concernant les méthodologies utilisées (modèle numérique, outils microfluidiques), nous comparons dans un premier temps les résultats des simulations numériques à ceux obtenus avec les expériences de micro-PIV en écoulement laminaire. La comparaison est très bonne pour l’ensemble des expériences réalisées. Le code de calcul ainsi validé, nous proposons d’utiliser l’outil numérique comme véritable outil de recherche des meilleures conditions opératoires pour favoriser le mélange. Pour cela, des simulations du mélange de deux fluides (typiquement CO2 et éthanol) sont effectuées pour différentes conditions opératoires (vitesse, température, pression) pour des conditions laminaires mais également en conditions turbulentes, régime rarement atteint à ces échelles de réacteur. En effet, nous avons montré expérimentalement que le régime turbulent pouvait être atteint dans le microcanal grâce à la technologie « microfluidique haute pression » développé au laboratoire. L’étude de la qualité du mélange se base sur deux critères communément utilisées dans la littérature. Le premier est l’index de ségrégation basé sur la variance du champ de concentration ou fraction massique dans notre cas. Celui-ci peut être estimé pour tous les cas de simulation, du laminaire au turbulent. Le deuxième critère est le temps de micromélange basé sur l’estimation du taux de dissipation de l’énergie cinétique turbulente. Celui-ci est calculé uniquement dans les cas turbulents car basé sur les fluctuations des vitesses par rapport à la valeur moyenne. Un des intérêts majeurs de l’utilisation des puces microfluidiques réside notamment dans ses faibles échelles de temps et d’espace. D’un point de vue numérique, de telles échelles permettent, dans des temps de calcul raisonnables, de proposer des simulations numériques directes (DNS), i.e., dont les plus petites mailles sont inférieures ou très proches de l’échelle de Kolmogorov. Ceci est de tout premier intérêt car nous sommes capables de capter les plus petites échelles du mélange et notamment le micromélange. Ainsi, les résultats de simulation nous ont permis de proposer une analyse fiable du mélange d’un point de vue qualitatif et quantitatif, faisant la preuve que les conditions de mélange dans ce type de dispositif sont particulièrement favorables pour l’élaboration de matériaux par antisolvant supercritique. Les conditions optimales de mélange ainsi déterminées, nous proposons dans une dernière partie de simuler la synthèse de nanoparticules organiques dans de tels dispositifs. L’approche numérique est basée sur un couplage des équations de la mécanique des fluides et d’une équation de bilan de population permettant de prendre en compte la nucléation et croissance des particules. Les résultats de simulation ont été comparés avec succès avec ceux expérimentaux obtenues au laboratoire
In the context of this thesis, we propose to study the thermo-hydrodynamic behavior of a mixture, a solvent and a supercritical antisolvent (CO2) in a microfluidic chip, for conditions used in the Supercritical Antisolvent (SAS) process. This work is based on a complementary approach of both experiments and simulations through the use of advanced research techniques, such as the in situ characterization inside the microfluidic reactor (Micro-Particle Image Velocimetry) and the High Performance Computing. The objective of the thesis is to determine the favorable conditions for a "very good" mixture (total and fast) of species in terms of velocity, temperature, pressure and injector "design". The simulations are performed with the massively parallel code Notus. After the first chapter detailing the state of the art on the supercritical antisolvent processes, then the second concerning the applied methodologies (numerical model, microfluidic tools), we first compare the results of the numerical simulations to the experimental data obtained by micro-PIV in laminar flow conditions. The simulation results are in good agreement with the experiments. After the validation of the numerical code, we propose to use the numerical tool to determine the optimal operating conditions of mixing. For this, simulations of the mixture of two fluids (typically CO2 and ethanol) are performed for different operating conditions (velocity, temperature, pressure) for laminar conditions but also for turbulent conditions, a regime rarely reached in microreactors. Indeed, we have shown experimentally that the turbulent mixing could be reached in the microchannel thanks to the "high pressure microfluidic" technology developed in the laboratory. The study of the mixing quality is based on two criteria commonly used in the literature. The first is the segregation intensity based on the variance of the ethanol concentration. This can be estimated for all simulation cases, from laminar to turbulent mixing. The second criterion is the micromixing time related to the turbulent kinetic energy dissipation rate directly estimated from the local velocity fluctuations in turbulent flow conditions. One of the major interests of the use of microfluidic reactors lies especially in its small scales of time and space. From a numerical point of view, such scales allow, within reasonable CPU time, to perform direct numerical simulations (DNS), i.e., in which the grid size is smaller or very close to the Kolmogorov scale. This is of primary interest because we are able to capture the smallest scales of the mixture including the micromixing. Thus, the simulation results allow us to propose a reliable analysis of the mixture from both qualitative and quantitative point of view, proving that the mixing conditions in this type of device are particularly favorable for the material synthesis by supercritical antisolvent. After determining the optimal mixing conditions, we propose in a final part to simulate the synthesis of organic nanoparticles in such devices. The numerical approach is based on the coupling between the CFD code and a population balance equation to take into account the nucleation and growth of particles. The simulation results are also in a good agreement with the experimental measurements performed in the laboratory

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Shu, Cheng-Gang. "Modélisation physique, simulation numérique et investigation expérimentale de l'estampage à chaud des polymères thermoplastiques amorphes". Thesis, Besançon, 2014. http://www.theses.fr/2014BESA2004/document.

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Le procédé d’estampage à chaud est considéré comme l'un des procédés les plus prometteurs de micro-Réplication pour l'élaboration des micro-Composants ou nano-Composants avec des matériaux polymériques dans différents domaines d'application . La mémoire consiste à caractériser les propriétés physiques des polymères thermoplastiques amorphes (PS, PMMA et PC) sur une large plage de température, ainsi que la modélisation physique, la simulation numérique et vérification expérimentale du procédé d’estampage à chaud.[...]Les propriétés visco élastiques des polymères retenus ont été caractérisées avec les essais décompression dynamiques. Le module de conservation, le module de perte et le facteur d'amortissement de polymère PMMA à partir de la température ambiante jusqu'à légèrement au-Dessus de Tg ont été obtenues. Le comportement visco élastique des polymères a été décrit par un modèle de Maxwell Généralisé et un bon accord a été observé. La simulation numérique des étapes du remplissage de procédé d’estampage à chaud a été réalisée enprenant compte des propriétés visco élastiques de polymère. Les effets de la température et dela pression de compression sur l'exactitude de réplication dans le procédé d’estampage à chaud ont été étudiés.[...]Un nouveau moule de compression complet, y compris le système de chauffage, le système de refroidissement et le système de vide a été développé dans notre groupe de recherche. Les dispositifs micro fluidiques avec la dimension de la cavité : environ 200 μm, 100 μm et 50 μmen PS, PMMA et PC plaque (épaisseur de 2 mm) ont été élaborés par le procédé d’estampage à chaud. Les effets des paramètres du procédé, tels que l’entrefer imposé, la température décompression, la matière compressée et la dimension de micro cavité, sur l’exactitude de réplication du procédé d’estampage à chaud ont été étudiés
Hot embossing process is considered as one of the most promising micro replication processes for the elaboration of micro or nano components with polymeric materials invarious application fields. The thesis consists to characterize the physical properties of widelyused amorphous thermoplastic polymers (PS, PMMA and PC) over a large temperature range,along with the physical modelling, numerical simulation and experimental verification of thehot embossing process.[...] The polymers’ viscoelastic properties have been characterized with the dynamical compression tests. The storage modulus, loss modulus and damping factor of PMMA polymerfrom ambient temperature to lightly above Tg have been obtained. The viscoelastic behaviourof polymer has been described by a proposed Generalized Maxwell model and a good agreement has been observed. The numerical simulation of filling stage of hot embossing process has been achieved by taking into account of polymer’s viscoelastic properties. Theeffect of compression temperature and pressure on the replication accuracy in hot embossing process has been investigated in the simulation.[...] A new complete micro compression mould tools, including heating system, cooling system and vacuum system have been developed in our research group. The microfluidic devices with the cavity dimension eq. to about 200 μm, 100 μm and 50 μm in PS, PMMA and PC plate(thickness eq. to 2 mm) have been elaborated by the hot embossing process. The effects of the processing parameters, such as the compressive gap imposed, compression temperature, embossed material and die cavity dimensions, on the replication accuracy of hot embossing process have been investigated

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26

Locatelli, Emanuele. "Dynamical and collective properties of active and passive particles in Single File". Doctoral thesis, Università degli studi di Padova, 2014. http://hdl.handle.net/11577/3423763.

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Particles motion inside complex, irregular or crowded environments is a common phenomenon ranging from microscopic to macroscopic scales. It can be involved in everyday practical problems, like traffic, in fundamental biological mechanisms, like growth and reproduction of cells, and in important industrial or chemical applications, like oil catalysis. In many cases, transport in crowded environments is guided by 'active' elements, i.e. units that consume energy in order to produce motion. Among systems belonging in this class, the diffusion of hard-core particles in a channel so narrow they cannot pass each other, known as Single File Diffusion, has assumed a particular role. Single File Diffusion is responsible for the transport of ions in membrane channels, the diffusion in nano- and micro-porous materials and has been observed in many other natural and artificial systems. Aim of this thesis is to investigate Single File system of passive (purely diffusive) or active (self propelled) particles, focusing on the effects of the activity on the Single File motion and on the Single File properties in the presence of absorbing boundaries. Most of the work has been carried out developing analytical and numerical tools within the framework of the Stochastic Processes. By using single particle techniques in a microfluidic approach, we obtained an excellent comparison between experimental data and numerical model of particles emptying a Single File channel with open ends. In this thesis, after a brief introduction in the framework of confined diffusion processes, we will review the most relevant works in the theoretical and experimental literature of Single File Diffusion, with particular attention to an analytical technique, the Reflection Principle Method, which will be extensively used in this thesis. We will investigate the properties of Single File systems of diffusing particles in presence of two absorbing boundaries, with particular interest to the survival probability, i.e. the probability to find a particle between the boundaries at time t. We will provide an analytical solution of the emptying process, i.e. we calculate the probability characterizing the progressive decrease of the number of particles in the presence of absorbing boundaries, and for the survival probability of a Tagged Particle within the file, either in the presence or in the absence of a constant external force. We also characterize the trend of the characteristic survival times (also called Mean First Passage Times) as function of the system size and of the initial number of particles. We also investigate numerically the case when only the central particle is affected by the absorbing boundaries. We find an exponential decay of the survival probability, as it happens for normal diffusive processes, even in the presence of overcrowding. We will then introduce activity in a Single File system, through a Self-Propelled Particle model, for which we will provide a detailed characterization. In particular, within this model, particles can be either runners or tumblers, if their motion is dominated by straight runs or by changes of direction, respectively. Under Single File conditions, runners tend to form dynamical aggregates: these clusters are continuously formed and disassembled due to random fluctuations of the activity. For tumblers, the survival probabilities are still well described by the analytical theory developed for passive diffusing particles. Conversely, the formation of dynamical clusters enhances anomalous behaviours in the characteristic survival times of runners and induces a remarkable capacity to overcome the action of an external force.
Il moto di particelle in mezzi irregolari, complessi o affollati è un fenomeno comune, dalla scala microscopica a quella macroscopica. Lo si può incontrare tanto in situazioni comuni, come il traffico, quanto in meccanismi biologici, come la riproduzione e la crescita delle cellule, e in importanti processi chimici e tecnologici, come la catalisi di idrocarburi. In molti casi, il trasporto in mezzi confinati o affollati è guidato da elementi 'attivi', cioè unità che consumano energia per sostenere il loro stato di moto. Fra i diversi sistemi soggetti a confinamento, particolare rilevanza è rivestita dalla diffusione di sfere impenetrabili in un canale così stretto da non permettere il passaggio di più di una particella alla volta, conosciuto come diffusione in Single File. La diffusione in Single File è il meccanismo responsabile del trasporto di ioni attraverso la membrana cellulare, della diffusione in materiali micro e nanoporosi ed è stata osservata in molti altri sistemi naturali ed artificiali. Scopo di questa tesi è lo studio su scala mesoscopica di particelle passive (diffusive) o attive (auto-propellenti) in condizioni di Single File, con particolare attenzione all'effetto dell'attività sulla dinamica e sulle proprietà delle particelle nel caso siano presenti condizioni al contorno assorbenti. Gran parte del lavoro è stato svolto nello sviluppo di risultati analitici e numerici nel contesto dei Processi Stocastici. Inoltre, mediante tecniche di manipolazione ottica di singola particella in canali microfluidici, abbiamo ottenuto una eccellente confronto fra dati sperimentali e numerici per il processo di svuotamento di un sistema di particelle in condizioni di Single File. In questa tesi, dopo una breve introduzione ai processi diffusivi fortemente confinati, passeremo in rassegna i lavori più rilevanti della letteratura teorica e sperimentale sulla Single File Diffusion, con particolare attenzione ad un formalismo matematico, il Reflection Principle Method, che sarà applicato in maniera estensiva nel corso della tesi. Studieremo poi le proprietà di un sistema di particelle diffusive in Single File in presenza di condizioni al contorno assorbenti, concentrandoci sulla survival probability, cioè la probabilità di trovare una particella fra gli estremi del sistema al tempo t. Mostreremo come, in condizioni di Single File, abbiamo ottenuto una soluzione analitica per il processo di svuotamento, cioè calcoleremo la probabilità che caratterizza la progressiva diminuzione del numero di particelle in presenza di condizioni al contorno assorbenti, e per la survival probability di una particella 'marcata' all'interno della Single File sia in presenza che in assenza di una forza esterna costante. Caratterizzeremo gli andamenti dei tempi caratteristici di sopravvivenza, chiamati Tempi Medi di Primo Passaggio, in funzione della taglia del canale e del numero iniziale di particelle. Indagheremo inoltre numericamente il caso in cui solo la particella centrale del sistema in Single File subisce l'effetto delle condizioni al contorno assorbenti. Osserviamo un decadimento esponenziale della survival probability, come accade nell'usuale moto Browniano, anche in presenza di estremo confinamento. Introdurremo l'attività nella Single File attraverso un modello di particelle Self-Propelled, di cui descriveremo le proprietà in dettaglio. In particolare in questo modello le particelle possono essere o runners o tumblers, a seconda che la loro traiettoria sia dominata da lunghi tratti rettilinei o da cambi di direzione. In condizioni di Single File, i runners tendono a formare aggregati dinamici: questi cluster vengono continuamente formati e distrutti dalle fluttuazioni casuali della forza propulsiva. Per i tumblers, le probabilità di sopravvivenza sono ben descritte dalla teoria analitica sviluppata per le particelle passive. Per contro, la formazione di cluster dinamici accresce i comportamenti anomali nei tempi caratteristici di sopravvivenza dei runners e ne induce una notevole capacità di opporsi all'azione di un campo esterno.

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27

Ziane, Nadia. "Outils microfluidiques pour l’exploration de diagrammes de phase : de la pervaporation à la microdialyse". Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0147/document.

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Ce travail de thèse porte sur le développement technologique d’outils miniaturiséspour l’exploration de diagrammes de phase de fluides complexes (dispersions colloïdales,solutions de polymères ou tensioactifs, etc). Les outils élaborés permettent dedéterminer des diagrammes de phase par une approche continue à l’aide de la microfluidique.Ils sont basés sur deux types de procédés membranaires différents : la pervaporation(mécanisme d’évaporation de solvant) et la dialyse (mécanisme d’échangesosmotiques). En s’appuyant sur le processus de pervaporation, il a été montré théoriquementet expérimentalement qu’il existe une géométrie pour laquelle le séchageconfiné est homogène. Il est donc possible de construire des diagrammes de phase demélanges à plusieurs composants de l’échelle moléculaire aux colloïdes. Une étudeconsacrée à la compréhension de la complexité du séchage des nanoparticules de silicecommerciales dans un canal microfluidique de type microévaporateur a été miseen place. La cinétique de concentration des particules est décrite jusqu’à la formationd’un état dense ainsi que les divers phénomènes liés au séchage comme l’existenced’une transition de phase dans un système colloïdal, l’apparition de fractures ou la délaminationdu matériau dense. Un nouvel outil microfluidique intégrant une membranede type dialyse offre la possibilité de contrôler les échanges osmotiques à l’échelle dunanolitre. Le protocole de fabrication ainsi que le dimensionnement de la géométriesont présentés. Grâce à cet outil, il est possible de mesurer des pressions osmotiquesde dispersions colloïdales
This work deals with the technological development of miniaturized tools for theexploration of the phase diagram of complex fluids (colloidal dispersions, solutions ofpolymers or surfactants, etc). The microfluidic tools we elaborated make it possibleto determine phase diagrams of a series of formulations of complex fluids by consumingonly minute amounts of samples. These devices exploit two types of membraneprocesses to concentrate the chemical species : pervaporation (solvent evaporationthrough a dense membrane) and dialysis (osmotic exchanges through a membrane).Concerning the case of pervaporation, we demonstrated theoretically and experimentallythat a specific microfluidic design exists for which concentration fields of chemicalspecies remain spatially homogeneous along the kinetic path followed withinthe phase diagram. Then, it enables to obtain phase diagrams of multi-componentsmixtures from molecular compounds up to colloids, at the nanolitre scale. We reporta study concerning the understanding of the drying process of commercial silica nanoparticlesusing a dedicated microfluidic experiment involving pervaporation. Wepresent the kinetics of the concentration of the particles within the channel up to theformation of a dense colloidal packed bed which invades the channel at a controlledrate. We developed an original microfluidic tool integrating a dialysis membranewhich makes it possible to control osmotic exchanges at the nanoliter scale. We reportthe protocol of microfabrication of this chip and its specific geometry.We presentpreliminary results showing that this tool can be used to measure osmotic pressures ofcolloidal suspensions

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28

Eysert, Fanny. "Etude des mécanismes impliquant le facteur de risque génétique FERMT2 dans le métabolisme de l’APP et ses conséquences dans le processus physiopathologique de la maladie d’Alzheimer". Thesis, Lille 2, 2019. http://www.theses.fr/2019LIL2S040.

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La mise en place d’études d’association pangénomiques (GWAS) a permis une avancée majeure pour l’identification de nouveaux facteurs de susceptibilité génétique de la maladie d’Alzheimer (MA). En revanche, ces analyses réalisées sans a priori ne permettent pas de déterminer le rôle de ces gènes dans le processus physiopathologique de la MA. Dans ce contexte, seule la réalisation d’analyses dites « analyses post-GWAS » peut préciser les mécanismes moléculaires impliquant ces gènes. Le laboratoire a donc entrepris d’identifier quels sont, parmi les facteurs génétiques caractérisés par les GWAS, ceux dont la variation d’expression module le métabolisme de l’APP. De plus, notre modèle nous a permis d’étudier l’implication potentielle des micro-ARNs (miRs) dans la dérégulation de ces gènes.Dans ce contexte, nous avons pu montrer que le miR-4504, qui est surexprimé dans le cerveau des patients atteints de la MA par rapport aux témoins, diminue l’expression du gène FERMT2, facteur de susceptibilité génétique de la MA. Nos résultats montrent que cette sous-expression serait dépendante de la présence d’un variant (rs7143400) localisé dans le 3’UTR de FERMT2 qui entraîne alors une modulation du métabolisme de l’APP et une augmentation de la sécrétion du peptide Aβ.Dans ce projet, j’ai pu montrer que les effets de FERMT2 sur ce métabolisme nécessitent son interaction directe avec l’APP. De plus, l’utilisation du modèle de culture primaire de neurones en chambres micro-fluidiques m’a permis d’étudier les fonctions neuronales du complexe FERMT2/APP. J’ai ainsi pu identifier que cette interaction FERMT2/APP participe à la régulation de la croissance axonale et à la synaptogenèse. Finalement, nos analyses de la potentialisation à long terme dans le cerveau de souris, pour lesquelles une sous-expression de FERMT2 a été induite, montrent une diminution de la plasticité synaptique ; mécanisme pouvant être à l’origine de l’effet délétère de la baisse d’expression de FERMT2 dans les neurones et dans le processus physiopathologique de la MA.En conclusion, l’ensemble de ces résultats suggère le rôle du facteur de risque FERMT2, régulé par la présence du variant fonctionnel rs7143400 et du miR-4504 dans le processus physiopathologique de la MA en conduisant à des altérations synaptiques de façon dépendante de l’expression d’APP. Ce travail permettrait, à terme, de mieux comprendre le processus physiopathologique conduisant à la MA et de caractériser de nouveaux mécanismes impliqués dans le fonctionnement synaptique
The establishment of genome-wide association study (GWAS) constitutes a major advance for the identification of new genetic susceptibility factors of Alzheimer’s Disease (AD). In contrast with the target gene approach, these analyses are done sans a priori and do not allow us to determine the role of the identified genes in the pathophysiological process of AD. In this context, only performing "post-GWAS analyses" can explain the molecular processes involving these genes. Our laboratory therefore aimed to identify the genetic risk factors identified by GWAS whose expression levels impact the APP metabolism. Moreover, our model allowed us to study the potential involvement of micro-RNAs (miRs) in the dysregulation of the expression of these genes.In this context, we showed that miR-4504, which is overexpressed in the brains of AD patients compared with controls, decreases the expression of FERMT2, a genetic susceptibility factor of AD. Our results show that FERMT2 under-expression is dependent on the presence of a variant (rs7143400) localized in the 3'UTR of FERMT2, which then leads to the modulation of the APP metabolism and the subsequent increase in Aβ peptide secretion.In this project, I was able to show that the effects of FERMT2 on APP metabolism require its direct inter-action with APP. In addition, using a model of primary neurons cultured in microfluidic devices enabled me to study neuronal functions of the FERMT2/APP complex. I was able to determine that FERMT2/APP interaction contributes to the regulation of axonal growth and synaptogenesis. Finally, by analyzing the long-term potentiation in the brains of mice in which FERMT2 under-expression was induced, we show a decrease in synaptic plasticity – potentially the underlying mechanism of the deleterious effect of decreased FERMT2 expression in neurons and of the pathophysiological process of AD.In conclusion, these results suggest that the genetic risk factor FERMT2, regulated by the presence of the functional variant rs7143400 and miR-4504, participates in the pathophysiological process of AD via synaptic alterations in an APP-dependent manner. This work would ultimately lead to a better understanding of the pathophysiological process leading to AD and help characterize new mechanisms involved in synaptic functions

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29

Wang, Fei. "Gas-Solid Fluidization: ECVT Imaging and Mini-/Micro-Channel Flow". The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1290390285.

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30

Agostinelli, Simone. "A compartmentalised microchip platform with charged hydrogel to study protein diffusion for Single Cell Analysis". Master's thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amslaurea.unibo.it/20333/.

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Within one tumor, cancer cells exist as different sub-populations due to the variations in expression of crucial bio-markers. The prevalence of even minor cell sub-populations can determine overall cancer progression and treatment response. Single-cell protein analysis is a way to identify these cell sub-populations; therefore we developed a microfluidic platform with ultrahigh-sensitivity for single-cell protein analysis. As the key step to develop such a platform, protein migration under the application of an electric field has to be understood. COMSOL multi-physics software is used as a tool to understand the protein migration in microfluidic channels, which contain ion-selective hydrogels as the separation matrix. The objective of this thesis work, is to minimize the protein losses to diffusion and to maximize the fluorescent signal in order to quantify the protein expression in single cells. The novelty of this work lies in the use of ion-selective hydrogels to eliminate the diffusional losses and separate the proteins based on their mass and charge. This thesis project has been performed thanks to an Erasmus fellowship at MCS Department of the University of Twente.

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31

Bindini, Elisa. "Understanding in vivo degradation of mesoporous silica therapeutic vectors through in situ ellipsometry". Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS115/document.

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Dans les dernières 15 ans, la recherche biomédicale a exploré en profondeur l’utilisation de nanoparticules pour la délivrance ciblée de médicaments. Parmi plusieurs matériaux étudiés, la silice mésoporeuse représente une plateforme exceptionnelle pour ce type d’applications puisque elle est biocompatible et capable d’être chargé avec une quantité élevée de médicament, tout en étant facile à synthétiser et à fonctionnaliser. La connaissance des interactions entre nanoparticules de silice et environnement biologique est nécessaire pour concevoir des vecteurs thérapeutiques efficaces et pas toxiques. Cet étude a développé une nouvelle méthode d’analyse in situ pour suivre les interactions entre silice mésoporeuse et fluides biologiques réels (sérum et sang), employant une cellule d’analyse microfluidique et l’ellipsométrie en réflexion totale interne. Nous avons ainsi réalisé le suivi dynamique de la dégradation de vecteurs models à base de silice poreuse structuré dans une solution tampon à pH physiologique et une solution concentré de protéines. Ces analyses ont permis d’évaluer l’influence de la structure poreuse, de l’adsorption de protéines sur la surface et de la vitesse du flux sur la dissolution de la silice mésoporeuse
Dans les dernières 15 ans, la recherche biomédicale a exploré en profondeur l’utilisation de nanoparticules pour la délivrance ciblée de médicaments. Parmi plusieurs matériaux étudiés, la silice mesoporeuse représente une plateforme exceptionnelle pour ce type d’applications puisque elle est biocompatible et capable d’être chargé avec une quantité élevée de médicament, tout en étant facile à synthétiser et à fonctionnaliser .La connaissance des interactions entre nanoparticules de silice et environnement biologique est nécessaire pour concevoir des vecteurs thérapeutiques efficaces et pas toxiques. Cet étude a développé une nouvelle méthode d’analyse in situ pour suivre les interactions entre silice mesoporeuse et fluides biologiques réels (serum et sang), employant une cellule d’analyse microfluidique et l’ellipsometrie en réflexion totale interne. Nous avons ainsi réalisé le suivi dynamique de la dégradation de vecteurs models à base de silice poreuse structuré dans une solution tampon à pH physiologique et une solution concentré de protéines. Ces analyses ont permis d’évaluer l’influence de la structure poreuse, de l’adsorption de protéines sur la surface et de la vitesse du flux sur la dissolution de la silice mesoporeuse

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32

Delhaye, Caroline. "Spectroscopie Raman et microfluidique : application à la diffusion Raman exaltée de surface". Thesis, Bordeaux 1, 2009. http://www.theses.fr/2009BOR13927/document.

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Ce mémoire porte sur la mise au point de plateforme microfluidique couplée à la microscopie Raman confocale, utilisée dans des conditions d’excitation de la diffusion Raman (diffusion Raman exaltée de surface), dans le but d’obtenir une détection de très haute sensibilité d’espèces moléculaires sous écoulement dans des canaux de dimensions micrométriques. Ce travail a pour ambition de démontrer la faisabilité d’un couplage microscopie Raman/microfluidique en vue de la caractérisation in-situ et locale, des espèces et des réactions mises en jeu dans les fluides en écoulement dans les microcanaux. Nous avons utilisé un microcanal de géométrie T, fabriqué par lithographie douce, dans lequel sont injectées, à vitesse constante, des nanoparticules métalliques d’or ou d’argent dans une des deux branches du canal et une solution de pyridine ou de péfloxacine dans l’autre branche. La laminarité et la stationnarité du processus nous ont permis de cartographier la zone de mélange et de mettre en évidence l’exaltation du signal de diffusion Raman de la pyridine et de la péfloxacine, obtenue grâce aux nanoparticules métalliques, dans cette zone d’interdiffusion. L’enregistrement successif de la bande d’absorption des nanoparticules d’argent (bande plasmon) et du signal de diffusion Raman de la péfloxacine, en écoulement dans un microcanal, nous a permis d’établir un lien entre la morphologie des nanostructures métalliques, et plus précisément l’état d’agrégation des nanoparticules d’argent, et l’exaltation du signal Raman de la péfloxacine observé. Nous avons alors modifié la géométrie du canal afin d’y introduire une solution d’électrolyte (NaCl et NaNO3) et de modifier localement la charge de surface des colloïdes d’argent en écoulement. Nous avons ainsi confirmé que la modification de l’état d’agrégation des nanoparticules d’argent, induite par l’ajout contrôlé de solutions d’électrolytes, permet d’amplifier le signal SERS de la péfloxacine et d’optimiser la détection en microfluidique. Enfin, nous avons développé une seconde approche qui consistait à mettre en place une structuration métallisée des parois d’un microcanal. Nous avons ainsi démontré que la fonctionnalisation chimique de surface via un organosilane (APTES) permettait de tapisser le canal avec des nanoparticules d’argent et d’amplifier le signal Raman des espèces en écoulement dans ce même microcanal
This thesis focuses on the development of a microfluidic platform coupled with confocal Raman microscopy, used in excitation conditions of Raman scattering (Surface enhanced Raman scattering, SERS) in order to gain in the detection sensitivity of molecular species flowing in channels of micrometer dimensions. This work aims to demonstrate the feasibility of coupling Raman microscopy / microfluidics for the in situ and local characterization of species and reactions taking place in the fluid flowing in microchannels. We used a T-shaped microchannel, made by soft lithography, in which gold or silver nanoparticles injected at constant speed, in one of the two branches of the channel and a solution of pyridine or pefloxacin in the other one. The laminar flow and the stationarity of the process allowed us to map the mixing zone and highlight the enhancement of the Raman signal of pyridine and pefloxacin, due to the metallic nanoparticles, in the interdiffusion zone. The recording of the both absorption band of the silver nanoparticles (plasmon band) and the Raman signal of pefloxacin, flowing in microchannel, allowed us to establish a link between the shape of the metallic nanostructure, and more precisely the silver nanoparticle aggregation state, and the enhancement of the Raman signal of pefloxacin observed. We then changed the channel geometry to introduce an electrolyte solution (NaCl and NaNO3) and locally modify the surface charge of the colloids. We have put in evidence that the change of the silver nanoparticle aggregation state, induced by the controlled addition of electrolyte solutions, could amplify the SERS signal of pefloxacin and thus optimizing the detection in microfluidics. At last, we established second a approach that consists in the metallic structuring of microchannel walls. This has shown that the surface chemical functionalization through organosilanes (APTES) allowed the pasting of the channel with silver nanoparticles, thus amplifying the Raman signal of the species flowing within the same microchannel

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33

Bindini, Elisa. "Understanding in vivo degradation of mesoporous silica therapeutic vectors through in situ ellipsometry". Electronic Thesis or Diss., Sorbonne université, 2018. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2018SORUS115.pdf.

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Dans les dernières 15 ans, la recherche biomédicale a exploré en profondeur l’utilisation de nanoparticules pour la délivrance ciblée de médicaments. Parmi plusieurs matériaux étudiés, la silice mésoporeuse représente une plateforme exceptionnelle pour ce type d’applications puisque elle est biocompatible et capable d’être chargé avec une quantité élevée de médicament, tout en étant facile à synthétiser et à fonctionnaliser. La connaissance des interactions entre nanoparticules de silice et environnement biologique est nécessaire pour concevoir des vecteurs thérapeutiques efficaces et pas toxiques. Cet étude a développé une nouvelle méthode d’analyse in situ pour suivre les interactions entre silice mésoporeuse et fluides biologiques réels (sérum et sang), employant une cellule d’analyse microfluidique et l’ellipsométrie en réflexion totale interne. Nous avons ainsi réalisé le suivi dynamique de la dégradation de vecteurs models à base de silice poreuse structuré dans une solution tampon à pH physiologique et une solution concentré de protéines. Ces analyses ont permis d’évaluer l’influence de la structure poreuse, de l’adsorption de protéines sur la surface et de la vitesse du flux sur la dissolution de la silice mésoporeuse
Dans les dernières 15 ans, la recherche biomédicale a exploré en profondeur l’utilisation de nanoparticules pour la délivrance ciblée de médicaments. Parmi plusieurs matériaux étudiés, la silice mesoporeuse représente une plateforme exceptionnelle pour ce type d’applications puisque elle est biocompatible et capable d’être chargé avec une quantité élevée de médicament, tout en étant facile à synthétiser et à fonctionnaliser .La connaissance des interactions entre nanoparticules de silice et environnement biologique est nécessaire pour concevoir des vecteurs thérapeutiques efficaces et pas toxiques. Cet étude a développé une nouvelle méthode d’analyse in situ pour suivre les interactions entre silice mesoporeuse et fluides biologiques réels (serum et sang), employant une cellule d’analyse microfluidique et l’ellipsometrie en réflexion totale interne. Nous avons ainsi réalisé le suivi dynamique de la dégradation de vecteurs models à base de silice poreuse structuré dans une solution tampon à pH physiologique et une solution concentré de protéines. Ces analyses ont permis d’évaluer l’influence de la structure poreuse, de l’adsorption de protéines sur la surface et de la vitesse du flux sur la dissolution de la silice mesoporeuse

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34

Coleman, Jeffrey Thomas. "Electrokinetic processes for microfluidic devices". 2005. http://hdl.handle.net/1828/859.

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35

Tumarkin, Ethan. "Microfluidic Studies of Biological and Chemical Processes". Thesis, 2012. http://hdl.handle.net/1807/35077.

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This thesis describes the development of microfluidic (MF) platforms for the study of biological and chemical processes. In particular the thesis is divided into two distinct parts: (i) development of a MF methodology to generate tunable cell-laden microenvironments for detailed studies of cell behavior, and (ii) the design and fabrication of MF reactors for studies of chemical reactions. First, this thesis presented the generation of biopolymer microenvironments for cell studies. In the first project we demonstrated a high-throughput MF system for generating cell-laden agarose microgels with a controllable ratio of two different types of cells. The MF co-encapsulation system was shown to be a robust method for identifying autocrine and/or paracrine dependence of specific cell subpopulations. In the second project we studied the effect of the mechanical properties on the behavior of acute myeloid leukemia (AML2) cancer cells. Cell-laden macroscopic agarose gels were prepared at varying agarose concentrations. A modest range of the elastic modulus of the agarose gels were achieved, ranging from 0.62 kPa to 20.21 kPa at room temperature. We observed a pronounced decrease in cell proliferation in stiffer gels when compared to the gels with lower elastic moduli. The second part of the thesis focuses on the development of MF platforms for studying chemical reactions. In the third project presented in this thesis, we exploited the temperature dependent solubility of CO2 in order to: (i) study the temperature mediated CO2 transfer between the gas and the various liquid phases on short time scales, and (ii) to generate bubbles with a dense layer of colloid particles (armoured bubbles). The fourth project involved the fabrication of a multi-modal MF device with integrated analytical probes. The MF device comprised a pH, temperature, and ATR-FTIR probes for in-situ analysis of chemical reactions in real-time. Furthermore, the MF reactor featured a temperature controlled feedback system capable of maintaining on-chip temperatures at flow rates up to 50 mL/hr.

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36

White, William Neil. "Microfluidic cell sorting techniques to study disease processes /". 2009. http://digital.library.louisville.edu/cgi-bin/showfile.exe?CISOROOT=/etd&CISOPTR=909&filename=910.pdf.

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37

Kao, Peng-Kai y 高鵬凱. "Fabrication of Microfluidic Paper-based Analytical Devices Using Plasma Processes". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/05500605933774590472.

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碩士
國立臺灣大學
化學工程學研究所
102
In this work, we first demonstrated an all-dry, top-down, and one-step rapid process to fabricate paper-based microfluidic devices using fluorocarbon plasma polymerization. This process is able to create fluorocarbon-coated hydrophobic patterns on filter paper substrates while maintaining the trench and detection regions intact and free of contamination after the fabrication process, as confirmed by ATR-FTIR and XPS. We have shown that the processing time is one critical factor that influences the device performance. For the device fabricated with a sufficiently long processing time (180 s), the sample fluid flow can be well confined in the patterned trenches. By testing the device with 800 μm channel width, a sample solution amount as small as 4.5 μL is sufficient to perform the test. NO2&;#8722; assay is also performed and shows that such a device is capable for biochemical analysis. In the second part of this master thesis, a portable microplasma generation device (MGD) operated in ambient air is introduced for making a microfluidic paper-based analytical device (μPAD) that serves as a primary healthcare platform. By utilizing a printed circuit board fabrication process, a flexible and lightweight MGD can be fabricated within 30 min with ultra low-cost. This MGD can be driven by a portable power supply (less than two pounds), which can be powered using 12V-batteries or AC-DC converters. This MGD is used to perform maskless patterning of hydrophilic patterns with sub-mm spatial resolution on hydrophobic paper substrates with good pattern transfer fidelity. Using this MGD to fabricate μPADs is demonstrated. With a proper design of the MGD electrode geometry, μPADs with 500 μm-wide flow channels can be fabricated within 1 min and with a cost of less than $USD 0.05/device. We then test the μPADs by performing quantitative colorimetric assay tests and establish calibration curve for detection of glucose and nitrite. The results show a linear response to glucose assay for 1-50 mM and nitrite assay for 0.1-5 mM. The low cost, miniaturized, and portable MGD can be used to fabricate μPADs on demand, which is suitable for in-field diagnostic tests. We believe this concept brings impact to the field of biomedical analysis, environmental monitoring, and food safety survey.

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38

Chang, Y. Z. y 張裕智. "Study of Processes Parameters of Injection-Compression Molding of Microfluidic Chips". Thesis, 2003. http://ndltd.ncl.edu.tw/handle/09725356918288582639.

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39

Ferreira, Joana Maria Pereira. "Numerical analysis of transport processes in a microfluidic device for bacteria confinement". Master's thesis, 2016. https://hdl.handle.net/10216/88513.

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Ferreira, Joana Maria Pereira. "Numerical analysis of transport processes in a microfluidic device for bacteria confinement". Dissertação, 2016. https://hdl.handle.net/10216/88513.

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41

Kirschbaum, Michael [Verfasser]. "A microfluidic approach for the initiation and investigation of surface mediated signal transduction processes on a single-cell level / von Michael Kirschbaum". 2009. http://d-nb.info/1000068676/34.

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42

Li, Wei. "Integrated Droplet-based Microfluidics for Chemical Reactions and Processes". Thesis, 2010. http://hdl.handle.net/1807/24814.

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This thesis describes a study of various aspects of chemical reactions conducted in microfluidic reactors. (i) In the first project, we proposed the application of the 'internal trigger' approach to multi-step microfluidic polymerization reactions conducted in droplets, namely, polyaddition and polycondensation. We hypothesized and experimentally established that heat generated in the exothermic free radical polymerization of an acrylate monomer triggers the polycondensation of the urethane oligomer. As a result, we synthesized monodispersed poly(acrylate/urethane) microparticles with an interpenetrating polymer network structure. (ii) In the second project, we developed a multiple modular microfluidic reactor with the purpose of increasing productivity in microfluidic synthesis. Compared to the productivity of the single microfluidic reactor < 1g/hr, we synthesized poly(N-isopropylacrylamide) particles at a productivity of approximately 50g/hr with a CV < 5%. We analyzed and addressed several challenges of this process, such as the fidelity in the fabrication of microfluidic reactors, crosstalk between individual reactors sharing a common liquid supply, and coalescence of droplets. (iii) We developed an integrated microfluidic reactor comprising four parallel individual reactors to study the effect of geometry and surface energy of the microchannels on the emulsification process. We spontaneously generated droplets with different volumes by integrating individual droplet generators in parallel with varying geometry. This approach is important in studies of the effect of droplet surface and volume on chemical reactions, and in the studies of diffusion-controlled processes. (iv) We conducted a microfluidic study of the reversible binding of CO2 to secondary amines in the process that mediates solvent polarity switch. We studied reaction rates and CO2 uptake by generating plugs of gaseous a CO2 and monitoring the change in their dimensions. We also demonstrated fast screening of reaction conditions, as well as the ability to reverse the reaction in situ.

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43

Davalos, Saucedo Cristian Aaron. "Microencapsulation for tailored food using microfluidics in industrial processes". Tesi di dottorato, 2014. http://www.fedoa.unina.it/9841/1/Tesi%20Davalos%20Saucedo%20Cristian%20Aaron_XXVI_Ciclo.pdf.

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Microfluidics technologies are of great interest on research due to their advantages and the possibility to use it on different industrial areas. For food industry could be an important innovation for the microencapsulation of aromas to improve flavors or mask disgusting flavors improving the palatability of the product or giving an added value to the product. The aim of this work was to develop a microfluidic device to encapsulate essential oil through a flow-focusing technique using mainly sodium alginate as matrix. Different devices were created to test and to compare the possibility of produce microparticles and the important parameters for the production of microparticles production using flow focusing. Due to the versatility of the devices, the diameter size of the droplets generated in different emulsion configuration such as (o-w) (w-o), is possible to reach a size of the droplets generated from 200µm (CV > 9%). A monodispersed droplets generation of proteins and pectin (P/P) using sunflower oil for their formation using an opposing focusing flows in a coaxial capillaries device and varying the flow ratio between P/P inner flow rate and oil and consequently controlling with precision the droplet diameter. Obtained droplets have dimensions from 200 µm diameter, showed good stability over time and good properties to be used as a material for active films production. Moreover, the microfluidic device was modified using 3 capillaries, by the central capillary was injected a first fluid as a core of the droplet (active principle) then, a second fluid recovers the (oily) core part of the disperse phase, a third fluid (sunflower oil) continuum phase is useful to focus the disperse phase generating the droplets. For the microparticles production using sodium alginate, different geometries configurations were tested, trying to keep the simplest design that allows the scaling up easily for the industrial application. However changing the configuration allows to produce forms of microparticles of diverse kinds such as matrix, mononuclear, or multinuclear for instance. Although for practical uses the most of the tests were conducted in a configuration of the geometry to produce microparticles in a matrix form due to its simplicity. Also there are proposed different uses that can be applied easily, using the same technique and the same devices with a minimum of modifications that can be used in the food industry. Some examples are the mixing of solutions with accurate precision, cell encapsulation and the production of complexes of protein pectin. Another modification of the device was the use of air to improve the microparticle production. In this case, the alginate solidification of microparticles was performed using gellification with direct immersion on calcium chloride at relative high speed. Finally, an industrial application into a baked-frozen bread was made to conserve the aroma and/or to mask disgusting aromas, preparing an emulsion with alginate, rosemary essential oil and surfactants such as Tween 20 and Span 80. The microparticles were prepared previously and solidified then were added to the bread and packed. Samples were analyzed using a gas chromatograph. The results did not shown any difference between the samples with alginate microparticles containing rosemary essential oil and the control samples prepared in the absence of microparticles. In conclusion, it is of great importance to know the different characteristics involved in this technique such as materials used, solution polarity, configuration of the geometry, emulsionant presence, but the most important consideration for the well functionality of the devices is the concentricity due to the nature axisymmetric of the system.

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Panwar, Jatin. "Droplet Microfluidics for Nucleic Acid Quantification and Single Cell Analysis". Thesis, 2019. https://etd.iisc.ac.in/handle/2005/5018.

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Droplet microfluidics provides controlled generation of monodispersed droplets of the order of a few picoliters in multiphase microfluidic systems. These droplets are employed as micro-reactors to conduct chemical/biochemical reactions and assays in a controlled and high-throughput manner that find applications in point-of-care and lab-on-chip platforms. While the microfluidic devices are compact, the existing solutions to control fluid flow operations have a significant footprint that effects their portability, logistic viability and economics. As an alternate to the existing instrumentation-intensive flow-rate driven control for droplet generation, we studied and standardised suction driven fluid-flow control. In multiphase and multi-channel devices with suction-based flow control, microchannel geometry and suction pressure at the outlet determine the flow rates in individual channels. It is thus critical to understand the role of geometry along with suction pressure in the dynamics of droplet generation. We propose a governing parameter, called as modified capillary number, that captures droplet generation behaviour and outlines the design requirements for a suction driven droplet generation. As droplet microfluidics allows capture and analysis of individual cells with unprecedented control and throughput, single cell studies with microdroplets are gaining popularity. However, such analysis requires microfluidic devices with multiple unit operations that become a challenge with suction driven fluid-flow due to limited pressure head and lack of independent control over dispersed and continuous phase flow rates. To demonstrate single cell analysis, we defined and developed individual unit operations integrated in a multi-operation suction microfluidic device designed to quantify the low copy number RNA from single cells. The device, droplet digital Single cell Nucleic Acid Quantifier (dd-ScNAQ), successively performs encapsulation of single cells in droplets, cell lysis and cellular lysate/RNA distribution in smaller secondary droplets followed by on-chip temperature controlled isothermal nucleic acid amplification for quantification using fluorescence microscopy in a continuous flow geometry. Finally, to bypass the optical methods for detection of cells in droplets, which limits ‘in-field’ microfluidic applications; we developed a low-cost microfluidic impedance cytometry (MIC) approach for single cell quantification. We devised a rapid micro-fabrication protocol for flow devices with integrated coplanar in-contact field’s metal (icFM) electrodes to conduct MIC. With a single-step photolithography protocol, our icFM electrodes provide a cost-effective alternate to the conventional clean-room intensive microelectrode fabrication processes. The performance of icFM electrodes, averaged over a frequency range of 0.5 to 4 MHz, is found to be comparable to the widely used platinum electrodes in the detection of single human erythrocytes in a feedback-controlled suction driven MIC setup. However, the two electrodes show frequency dependent variability during impedance measurements that is attributed to the contrast between double layer capacitance and effective charge densities at their respective surfaces. We also demonstrate quantification of single cells entrapped in water-in-oil droplets using our icFM MIC devices as a non-optical and label-free method for droplet based single cell analysis. Together, this study extends the reach of existing microfluidic technologies to address the needs of the rapidly growing lab-on-chip industry by presenting novel methods to conduct microfluidic operations for single cell studies.

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45

李其恩. "Study of Microfluidics Processed W/O/W Microspheres as Drug-Delivery Agents in Hydroxyapatite Bone Cement". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/19301112626544459948.

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碩士
逢甲大學
生醫資訊暨生醫工程碩士學程
103
This study focuses on developing new medical material combining microspheres with dual drug release function and bone cement as customized orthopedic scaffold composites. Such proposed innovative orthopedic composites enables to offer patients a better medical treatment for perfecting bone repair and wound surgery. The microfluidic technique was employed to include both hydrophilic and lipophilic drugs to form a W/O/W gelatin/sodium alginate microspheres, which can cope with suppressing osteomyelitis more effectively. Microfluidics design and surface modification process for micro-channels to produce uniform microspheres containing different kind of drugs into core-shell structure. The design of gelatin/alginate composite microspheres with of dual drug release function combined with hydroxylapatite (HA) bone cement is attempted to emulate human skeletal structure in order to perform a slow-release drug efficacy.

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Tesis sobre el tema "Microfluidic processes"

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