Tesi: "Microfluidic method"

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Nguyen, Khanh H. (Khanh Huy). "Hot embossing as a method for rapid prototyping microfluidic devices." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/85789.

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Thesis: M. Eng. in Manufacturing, Massachusetts Institute of Technology, Department of Mechanical Engineering, 2013. Title as it appears in Degrees awarded program, September 17, 2003: Design and analysis of a hot embossing machine and the effects of toolware and accuracy of resin replication of high aspect ratio microfluidic features Cataloged from PDF version of thesis. Includes bibliographical references (pages 132-135). Hot embossing is a growing technology proven to be capable of reproducing micro-scale features on thermoplastics and can be an effective process for rapid prototyping microfluidic devices with high aspect ratio micro features. Advantages of this manufacturing process can include tooling flexibility, fast production time, low capital cost and a vast selection of production materials. A greater understanding on the micro feature transferring capabilities and use limits of tools are needed so that hot embossing may advance to becoming a practical technique for producing microfluidic parts. This work focuses on both the design and analysis of a hot embossing system and a brass tool to replicate an existing functional high aspect ratio micro feature onto Polymethyl methacrylate (PMMA). The aspect ratio of features ranged from 10:1 to 4,000:1. Optimal embossing parameters used a pressure of 3.5kN, hold time of 12 minutes, tool temperatures of 140°C and substrate temperature of 130°C to produce parts that filled shoulder heights and widths up to 97% and 90%, respectively. The wearing of features on the metal tool were also characterized for purposes of understanding the limits on tool use and was found that a maximum range of +/-3[mu]m in dimensional change existed. Gains in tool dimensions were then mainly attributed to the deposition of embossed materials onto the tool. The study further determined a method for creating usable resin tool copies that exhibited a replication accuracy of less than 2%, on average, for micron size features. by Khanh H. Nguyen. M. Eng. in Manufacturing

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Lustrino, Michelle E. (Michelle Elizabeth). "The development of an innovative bonding method for microfluidic applications." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/67622.

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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011. Cataloged from PDF version of thesis. Includes bibliographical references (p. 145-149). The field of microfluidics has powerful applications in low-cost healthcare diagnostics, DNA analysis, and fuel cells, among others. As the field moves towards commercialization, the ability to robustly manufacture these devices at low cost is becoming more important. One of the many challenges in microfluidic manufacturing is the reliable sealing of the microfluidic chips once the channels have been generated. This work was an investigation of innovative ways to robustly heat the substrate-cover plate interface of a microfluidic device for the purpose of bonding and sealing the microfluidic channels. An extensive literature review revealed the benefits of interfacial heating, and both simulations and experimental investigations were used to evaluate a few different methods. Ultimately, a unique method was established that uses light to provide both the bonding energy and the illumination for an in-process vision system for real-time viewing and control of the bonding process. The process results in the generation of a homogenous and optically clear bond, and preliminary tests show that when properly controlled, a bond with minimal microchannel deformation can be created. by Michelle E. Lustrino. S.M.

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Wu, Jun, and 吴隽. "Drug delivery devices fabricated by microfluidic method and their applications in long-term antimicrobial therapy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/198816.

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Controlled drug delivery devices provide numerous advantages such as reduced side effects, higher therapeutic efficiency and improved patient compliance. Biodegradable polymer has become the most important material for controlled drug delivery device because of the excellent biocompatibility and tunable physicochemical properties. Biodegradable polymeric drug delivery devices are usually processed into various types of micro-particles due to the ease of fabrication and administration. However, controlling the drug release kinetics of these microparticles is still a challenge. One important reason is that drug release kinetics is significantly influenced by the microstructure of drug delivery devices, which is difficult to control. 　Microfluidic method is a group of technologies involved in the manipulation of fluids using channels in the scale of micrometers. Microfluidic method is particularly useful in controlling the structure of micro-droplets and generating homogeneous droplets. Therefore, microfluidics suggests great potential in controlling microstructures of drug delivery devices and drug release kinetics. 　In this study, biodegradable polymer based controlled drug delivery devices were fabricated using microfluidic method. Various types of microstructures were developed such as microspheres, core-shell microspheres, hollow microspheres and hydrogel microspheres. The results showed that microstructures were well controlled by fluid flow rates and geometries of capillary microfluidic devices. Both hydrophobic and hydrophilic drugs could be delivered by choosing drug delivery devices with suitable microstructures. 　Drug release kinetics of biodegradable polymeric microspheres has been studies a lot, yet complete understanding is still to be achieved. The diameter is an important factor which contributes to the drug release kinetics. However, the influence of diameter has not been systemically studied because monodisperse microspheres are difficult to obtain. Using microfluidic method, monodisperse PLGA microspheres with different diameters were fabricated to study the influence of diameter on drug release kinetics. It was found that diameter only influence the duration of the first phase (lag phase) in drug release process and smaller microspheres exhibited shorter lag phase. The relatively faster expansion of smaller microspheres was found to be responsible for the size effect by monitoring physicochemical changes during drug release. 　Rifampicin, a broad-spectrum antibiotic, was encapsulated by PLGA microspheres and PLGA-alginate core-shell microspheres. The long-term antimicrobial effects of drug loaded microspheres were investigated by drug release test and antimicrobial test against Staphylococcus aureus. The results showed that drug delivery devices could provide antimicrobial effect for more than one month. These drug delivery devices show potential in applications of controlled drug delivery and long-term antimicrobial therapy. 　In conclusion, drug delivery devices with different microstructures were fabricated using microfluidic method. The diameter of PLGA microspheres only influence the first phase of drug release profile (lag phase) and smaller microspheres exhibited shorter lag phase. The size effect is due to the relatively faster expansion rate of smaller microspheres. Rifampicin loaded PLGA microspheres and PLGA-alginate core-shell microspheres could provide sustained release of rifampicin for more than one month. The released rifampicin was able to inhibit the growth of Staphylococcus aureus. The controlled drug delivery devices presented showed great potential in long-term antimicrobial applications. published_or_final_version Orthopaedics and Traumatology Doctoral Doctor of Philosophy

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PENNELLA, FRANCESCO. "Analysis of microscale flows in tissue engineering systems and microfluidic devices." Doctoral thesis, Politecnico di Torino, 2013. http://hdl.handle.net/11583/2514479.

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The doctoral research summarized in this thesis has focused on the study of microflows in Tissue Engineering (TE) scaffolds and microdevices. The thesis is organized in two parts. In the first part, the properties influencing mass transport through scaffold are investigated both experimentally and in silico. In detail: (1) an acoustic measurement system suitable for the evaluation of TE porous scaffolds and based on a single (pressure) transducer is developed; (2) realistic models of irregular porous scaffolds were reconstructed from micro-CT images and fluid transport through them is simulated by applying the Lattice Boltzmann method. In the second part, the issue of mixing of species in microdevices is investigated in depth and a novel low-cost passive microfluidic mixer design is proposed and its performance evaluated both in silico and in vitro. PART I: The performance of porous scaffold for tissue engineering (TE) applications are generally evaluated in terms of porosity, pore size and distribution, and pore tortuosity. However these descriptors are often confounding when they are applied to characterize the mass transport within porous scaffolds. On the contrary, permeability is a more effective parameter in (1) estimating mass and species transport through the scaffold and (2) describing its topological features. Therefore, this first part has focused on the study of TE porous scaffold permeability and on its dependence on the microscopic features of the scaffold. Firstly, an overview of methods applied to evaluate TE scaffold permeability is provided, with an emphasis on both experimental and computational approaches. In detail, after a discussion on the most relevant scaffolds features to be considered in the evaluation of the permeability, the presentation of the theoretical background and the introduction of semi-empirical models relating scaffolds features to permeability, the most widely applied experimental setup for the direct measurement of tissue engineered scaffold permeability are presented. Then, the focus is put on the application of computational methods, useful to verify and compare the experimental measurements of permeability, and to integrate experimental data with a more quantitative analysis which is very effective in supporting the design process of TE porous scaffolds. In conclusion, limitations of the methods and future challenges are pointed out. Successively, an acoustic permeability measurement system to quantify the inter-pore connectivity structure of tissue-engineering scaffolds by using a single (pressure) transducer is presented. The proposed method has been developed keeping in mind the limitations of the permeability measurement system in TE field. Technically, this system uses a slow alternating airflow as a fluid medium and allows at the same time a simple and accurate measurement procedure. The intrinsic permeability has been determined in the linear Darcy’s region, and deviation from linearity due to inertial losses has been also quantified. The structural parameters of a scaffold, such as effective porosity, tortuosity and effective length of cylindrical pores, have been estimated using the modified Ergun’s equation. From this relation, it is possible to achieve a well-defined range of data and associated uncertainties for characterizing the structure/architecture of tissue-engineering scaffolds. This quantitative analysis is of paramount importance in tissue engineering, where scaffold topological features are strongly related to their biological performance. In the last investigation of this part, the permeability of three bioactive glass/polymer composite scaffolds for bone tissue regeneration is evaluated. Structural features such as porosity, specific surface area and tortuosity, and lacunarity have been measured as well. Concerning lacunarity analysis, results confirmed its potential in providing insights into (i) self-similarity, (ii) random structure at some scale (i.e. heterogeneity) and (iii) Representative Elementary Volume (REV) identification. Permeability is evaluated both experimentally and computationally using the novel acoustic permeability system and Lattice Boltzmann Method (LBM), respectively. The advantage of LBM approach is due to their geometric versatility in simulating flows in irregular porous media. Results of the LBM models are in good agreement with the experimental results, even if the permeability values estimated in silico overestimate experimental data. This discrepancy is due to the influence of grid resolution and sample size on permeability calculations. In addition, the lower permeability values obtained in this study than the permeability data of different bone tissue reported in literature confirms the need to optimize the design of these scaffolds in terms of mass transport. PART II: Microfluidic deals with the control and manipulation of fluids at the microscale. A typical microfluidic platform is characterized by several components. One of the most important is the micromixer. Mixing of species is often critical to be achieved, since microfluidics is characterized mainly by very low Reynolds flows, and cannot take advantage of turbulence in order to enhance mixing. A good understanding of the dynamic of mixing becomes crucial to i) improve the effectiveness of and ii) speed up chemical reactions. In order to enhance mixing, several techniques have been developed. In general, mixing strategies can be classified as either active or passive, according to the operational mechanism. Active mixers employ external forces in order to perform mixing, so that actuation system must be embedded into the microchips. On the contrary, passive mixers avoid resorting to external electrical or mechanical sources by exploiting characteristics of specific flow fields in microchannel geometries to mix species, offering the advantage to be easy to be produced and integrated. The aim of this investigation was to develop a new low-cost passive microfluidic mixer design. First, a survey of the passive micromixing solutions currently adopted is provided. In detail, the most widely used microchannel geometries and the metrics used to quantify mixing effectiveness in microfluidic applications has been discussed. Then, a new low-cost passive microfluidic mixer design, based on a replication of identical mixing units composed of microchannels with variable curvature (clothoid) geometry, is shown. The micromixer presents a compact and modular architecture that can be easily fabricated using a simple and reliable fabrication process. The particular clothoid-based geometry enhances the mixing by inducing transversal secondary flows and recirculation effects. The role of the relevant fluid mechanics mechanisms promoting the mixing in this geometry have been analysed using computational fluid dynamics (CFD) for Reynolds numbers ranging from 1 to 110. A measure of mixing potency has been quantitatively evaluated by calculating mixing efficiency, while a measure of particle dispersion has been assessed through the lacunarity index. The results showed that the secondary flow arrangement and recirculation effects are able to provide a mixing efficiency equal to 80% at Reynolds number above 70. In addition, the analysis of particles distribution promotes the lacunarity as powerful tool to quantify the dispersion of fluid particles and, in turn, the overall mixing. On fabricated micromixer prototypes the microscopic-Laser-Induced-Fluorescence (µLIF) technique has been applied to characterize mixing. The experimental results confirmed the mixing potency of the microdevice. In conclusion, the proposed design (i) assures a good mixing efficiency (i.e. comparable, if not superior, to other passive micromixer, (ii) is easy to fabricate (i.e. single layer microfluidic devices) and (iii) is easy to integrate (i.e. high modularity).

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Jeon, Jessie Sungyun. "3D cyclic olefin copolymer (COC) microfluidic chip fabrication using hot embossing method for cell culture platform." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/61871.

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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2010. Cataloged from PDF version of thesis. Includes bibliographical references (p. 48-51). A microfluidic system has been developed for studying the factors inducing different responses of cells in vascular system using a three-dimensional microenvironment. The devices have been transferred from PDMS to a platform in cyclic olefin copolymer (COC) which has advantages in terms of hydrophobicity, production by the more commercially-viable hot embossing technique, and amenability to surface treatments. Here the fabrication process is described and the new systems are characterized. Surface wettability, bond strength between the system body and a covering plastic film, and cell viability data are presented and compared to systems fabricated in PDMS. by Jessie Sungyun Jeon. S.M.

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Winer, Michael Hubert. "A three-dimensional (3D) defocusing-based particle tracking method and applications to inertial focusing in microfluidic devices." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50194.

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Three-dimensional analysis of particles in flows within microfluidic devices is a necessary technique in the majority of current microfluidics research. One method that allows for accurate determination of particle positions in channels is defocusing-based optical detection. This thesis investigates the use of the defocusing method for particles ranging in size from 2-18 μm without the use of a three-hole aperture. Using a calibration-based analysis motivated by previous work, we were able to relate the particle position in space to its apparent size in an image. This defocusing method was then employed in several studies in order to validate its effectiveness in a wide range of particle/flow profiles. An initial study of gravitational effects on particles in low Reynolds number flows was conducted, showing that the method is accurate for particles with sizes equal to or greater than approximately 2 μm. We also found that the resolution of particle position accuracy was within 1 μm of expected theoretical results. Further studies were conducted in inertial focusing conditions, where viscous drag and inertial lift forces balance to create unique particle focusing positions in straight channels. Steady-state inertial studies in both rectangular and cylindrical channel geometries showed focusing of particles to positions similar to previous work, further verifying the defocusing method. A new regime of inertial focusing, coined transient flow, was also investigated with the use of the 3D defocusing method. This study established new regimes of particle focusing due to the effects of a transient flow on inertial forces. Within the transient study, the effects of fluid and particle density on particle focusing positions were also investigated. Finally, we provide recommendations for future work on the defocusing method and transient flows, including potential applications. Applied Science, Faculty of Graduate

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Othman, Rahimah. "Production of functional pharmaceutical nano/micro-particles by solvent displacement method using advanced micro-engineered dispersion devices." Thesis, Loughborough University, 2016. https://dspace.lboro.ac.uk/2134/22905.

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The rapid advancement of drug delivery systems (DDS) has raised the possibility of using functional engineered nano/micro-particles as drug carriers for the administration of active pharmaceutical ingredients (APIs) to the affected area. The major goals in designing these functional particles are to control the particle size, the surface properties and the pharmacologically active agents release in order to achieve the site-specification of the drug at the therapeutically optimal rate and dose regimen. Two different equipment (i.e. glass capillary microfluidic device and micro-engineered membrane dispersion cell) were utilised in this study for the formation of functional nano/micro-particles by antisolvent precipitation method. This method is based on micromixing/direct precipitation of two miscible liquids, which appear as a straightforward method, rapid and easy to perform, does not require high stirring rates, sonication, elevated temperatures, surfactants and Class 1 solvents can be avoided. Theoretical selection of a good solvent and physicochemical interaction between solvent-water-polymer with the aid of Bagley s two-dimensional graph were successfully elucidated the nature of anti-solvent precipitation method for the formation of desired properties of functional pharmaceutical nano/micro-engineered particles. For the glass capillary microfluidic experiment, the organic phase (a mixture of polymer and tetrahydrofuran/acetone) was injected through the inner glass capillary with a tapered cross section culminated in a narrow orifice. The size of nanoparticles was precisely controlled by controlling phase flow rates, orifice size and flow configuration (two- phase co-flow or counter-current flow focusing). The locations at which the nanoparticles would form were determined by using the solubility criteria of the polymer and the concentration profiles found by numerical modelling. This valuable results appeared as the first computational and experimental study dealing with the formation of polylactide (PLA) and poly(ε-caprolactone) (PCL) nanoparticles by nanoprecipitation in a co-flow glass capillary device. The optimum formulations and parameters interactions involved in the preparation of paracetamol encapsulated nanoparticles (PCM-PCL NPs) using a co-flow microfluidic device was successfully simulated using a 25-full factorial design for five different parameters (i.e. PCL concentration, orifice size, flow rate ratios, surfactant concentration and paracetamol amount) with encapsulation efficiency and drug loading percentage as the responses. PCM-loaded composite NPs composed of a biodegradable poly(D,L-lactide) (PLA) polymer matrix filled with organically modified montmorillonite (MMT) nanoparticles were also successfully formulated by antisolvent nanoprecipitation in a microfluidic co-flow glass capillary device. The incorporation of MMT in the polymer matrix improved the drug encapsulation efficiency and drug loading, and extended the rate of drug release in simulated intestinal fluid (pH 7.4). The encapsulation of MMT and PCM in the NPs were well verified using transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). PCL drug-carrier nanoparticles were also produced by rapid membrane micromixing combined with nanoprecipitation in a stirred cell employing novel membrane dispersion. The size of the NPs was precisely controlled by changing the aqueous-to-organic volumetric ratio, stirring rate, transmembrane flux, the polymer content in the organic phase, membrane type and pore morphologies. The particle size decreased by increasing the stirring rate and the aqueous-to-organic volumetric ratio, and by decreasing the polymer concentration in the aqueous phase and the transmembrane flux. The existence of the shear stress peak within a transitional radius and a rapid decline of the shear stress away from the membrane surface were revealed by numerical modelling. Further investigation on the PCL nanoparticles loaded immunosuppressive rapamycin (RAPA) drug were successfully synthesised by anti-solvent nanoprecipitation method using stainless steel (SS) ringed micro-engineered membrane. Less than 10 μm size of monohydrate piroxicam (PRX) micro-crystals also was successfully formed with the application of anti-solvent precipitation method combined with membrane dispersion cell that has been utilised in the formation of functional engineered nanoparticles. This study is believed to be a new insight into the development of integrated membrane crystallisation system.

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Murali, Divya. "A Sampling Method for the Reduction of Power Consumption in Battery Operated UHF Receivers." University of Akron / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=akron1220634056.

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Duford, David. "Instrumentation, fabrication techniques and method development for sample introduction, preparation and extraction on centrifugal microfluidic devices in motion." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110441.

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A growing number of pollutants are being shown to have a large environmental and health impact resulting in stricter legislative limits. Increased environmental monitoring is forcing analytical chemists to consider automating and miniaturizing current standard methods. Instrumentation and sample handling techniques for centrifugal microfluidic devices in motion have been developed with the objective of integrating multi-step reactions into a single device for the analysis of environmental solid samples.In order to study and optimize centrifugal microfluidic devices in motion, motorized stages integrating a camera, strobe and a variety of other peripheral components were developed. These allowed precise control of the devices throughout the methods' spin sequences and simultaneous acquisition of a series of stop action photographs of the devices.Non-contact methodologies for sample introduction, preparation and extraction on centrifugal microfluidic devices in motion are presented. To achieve this, hybrid fabrication techniques including the use of 3D printers were investigated and a World-to-Disk interface permitting the introduction of a solution gradient to a spinning device was developed. The interaction of integrated mobile magnets with a series of fixed magnets placed below the spinning devices was also investigated resulting in the development of both a magnetically actuated solid sample preparation and a magnetically actuated liquid-solid extraction technique. New automated and miniaturized methods for the analysis of environmentally important species such as polycyclic aromatic hydrocarbons and pesticides in solid samples are presented. Les polluants ont des impacts importants sur la santé et l'environnement résultant à des restrictions accrues des limites législatives. Cette surveillance environnementale accrue pousse les chimistes analytiques vers l'automatisation et la miniaturisation des méthodes de référence actuelles. L'analyse d'échantillons environnementaux solides bénéficiera de cette envolée par le développement de nouveaux instruments et techniques de manipulation d'échantillon via des dispositifs microfluidiques centrifuges qui intègrent des réactions à étapes multiples sur un dispositif unique.Afin d'étudier et d'optimiser les dispositifs microfluidiques centrifuges en mouvement, des plateformes motorisées qui incluent une caméra, une lumière stroboscopique et une variété d'autres composantes périphériques ont été développées. Celles-ci ont permis le contrôle efficace des dispositifs tout au long des séquences giratoires et l'acquisition simultanée de séries de photographies en arrêt sur image.Des méthodologies sont présentées pour l'introduction, la préparation et l'extraction d'échantillons sur des dispositifs microfluidiques centrifuges en mouvement. Ceci fut réalisé grâce à la recherche de techniques de fabrication hybrides incluant l'utilisation d'imprimantes 3D menant au développement d'une interface permettant l'introduction de solutés à concentrations variables aux dispositifs en mouvement. De plus, l'interaction d'aimants mobiles intégrés avec une série d'aimants fixes placée sous les dispositifs en mouvement a mené au développement des techniques de préparation d'échantillons solides par force magnétique et d'extraction liquide-solide d'échantillons par force magnétique. De nouvelles méthodes automatisées et miniaturisées ont été développées pour l'analyse d'espèces environnementales importantes telles que les hydrocarbures polycycliques aromatisés et les pesticides dans des échantillons solides.

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Kim, Ho Jun. "Theoretical and numerical studies of chaotic mixing." Diss., Texas A&M University, 2008. http://hdl.handle.net/1969.1/85940.

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Theoretical and numerical studies of chaotic mixing are performed to circumvent the difficulties of efficient mixing, which come from the lack of turbulence in microfluidic devices. In order to carry out efficient and accurate parametric studies and to identify a fully chaotic state, a spectral element algorithm for solution of the incompressible Navier-Stokes and species transport equations is developed. Using Taylor series expansions in time marching, the new algorithm employs an algebraic factorization scheme on multi-dimensional staggered spectral element grids, and extends classical conforming Galerkin formulations to nonconforming spectral elements. Lagrangian particle tracking methods are utilized to study particle dispersion in the mixing device using spectral element and fourth order Runge-Kutta discretizations in space and time, respectively. Comparative studies of five different techniques commonly employed to identify the chaotic strength and mixing efficiency in microfluidic systems are presented to demonstrate the competitive advantages and shortcomings of each method. These are the stirring index based on the box counting method, Poincare sections, finite time Lyapunov exponents, the probability density function of the stretching field, and mixing index inverse, based on the standard deviation of scalar species distribution. Series of numerical simulations are performed by varying the Peclet number (Pe) at fixed kinematic conditions. The mixing length (lm) is characterized as function of the Pe number, and lm ∝ ln(Pe) scaling is demonstrated for fully chaotic cases. Employing the aforementioned techniques, optimum kinematic conditions and the actuation frequency of the stirrer that result in the highest mixing/stirring efficiency are identified in a zeta potential patterned straight micro channel, where a continuous flow is generated by superposition of a steady pressure driven flow and time periodic electroosmotic flow induced by a stream-wise AC electric field. Finally, it is shown that the invariant manifold of hyperbolic periodic point determines the geometry of fast mixing zones in oscillatory flows in two-dimensional cavity.

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Lafferty, William Henry. "DEVELOPMENT OF A HIGH PRECISION QUANTUM DOT SYNTHESIS METHOD UTILIZING A MICROFLUIDIC REACTOR AND IN-LINE FLUORESCENCE FLOW CELL." DigitalCommons@CalPoly, 2014. https://digitalcommons.calpoly.edu/theses/1317.

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Quantum dots show great potential for use as spectral converters in solar cells, lighting applications, and biological imaging. These applications require precise control of quantum dot size to maximize performance. The quality, size, and fluorescence of quantum dots depend on parameters that are difficult to control using traditional batch synthesis processes. An alternative, high precision process was developed for the synthesis of cadmium-selenide quantum dots using a microfluidic reactor and fluorescence flow cell. The process required creating separate cadmium and selenium precursors that were then mixed in a nitrogen environment at 17°C. Using an NE-300® syringe pump, the solution was pumped through a microfluidic reactor submerged in a 240°C oil bath. The reactor then fed through a water quench bath at 25°C to terminate the nucleation and growth reaction. The fluorescence profiles of the quantum dot solutions were then characterized with an in-line fluorescence flow cell used in conjunction with an Ocean Optics® USB4000® spectrometer and a ThorLabs® LED UV light source. Flow rates through the reactor were varied from 0.05ml/min to 2ml/min. A central peak wavelength was registered in the fluorescence profiles for each flow rate. Monodisperse Cd-Se quantum dot solutions were synthesized across a broad spectrum of wavelengths ranging from 490nm to 620nm. An empirical relationship between flow rate and center wavelength was determined.

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Stewart-James, Samantha Ann. "Development of a microfluidic flow cytometry platform with fluorescence and light scattering detection for the rapid characterization of circulating tumor cells." Thesis, Kansas State University, 2015. http://hdl.handle.net/2097/19078.

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Master of Science Department of Chemistry Christopher T. Culbertson Circulating tumor cells (CTCs) have become a key component in the identification and treatment of cancer. Once dislodged from the main tumor, CTCs travel through the bloodstream and cause metastasis. Early detection and identification of these cells can help in the evaluation and prognosis of various types of cancer, as well as assisting in patient treatments by determining the spread of the disease. Here, a high-throughput microfluidic analysis technique is described that can efficiently detect and identify cells, with the specific identification of CTCs as a future application through fluorescent labeling in mind. As proof of principle, the device has been shown to detect and characterize individual human Jurkat (T-lymphocyte) cells at a rate of 100 cells/minute. The device employs micro-scale flow focusing to isolate individual cells. The cells are detected using both light scattering and laser-induced fluorescence to evaluate cell size and surface functionality.

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Banerjee, Ansuman. "A polarization isolation method for measurement of fluorescence assays in a microfluidic system using organic electronics for application to point-of-care diagnostics." Cincinnati, Ohio : University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view.cgi?acc_num=ucin1218238821.

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Thesis (Ph.D.)--University of Cincinnati, 2008. Advisor: David Klotzkin (Committee Chair), Ian Papautsky (Committee Member), Marc Cahay (Committee Member), Fred Beyette (Committee Member), Paul Bishop (Committee Member). Title from electronic thesis title page (viewed Jan. 18, 2009). Keywords: OLED; OPD; microfluidic; lab-on-a-chip; on-chip fluorescence detector; MEMS; thin films; organic electronics. Includes abstract. Includes bibliographical references.

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Guglielmino, Maud. "Développement d'une nouvelle méthode analytique du formaldéhyde dans l'air basée sur un dispositif microfluidique." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAF048.

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Le formaldéhyde (HCHO) est un polluant majeur de l’air intérieur. L’objectif de cette thèse est de réaliser les avancées scientifiques et technologiques nécessaires à l’obtention d’une méthode analytique basée sur un dispositif microfluidique de mesure du formaldéhyde dans l’air associant précision, sélectivité, rapidité d’analyse avec pour objectif majeur une autonomie suffisante sur de longues durées, typiquement un mois. Le principe de la méthode reposait initialement sur trois étapes clés, à savoir le piégeage du formaldéhyde gazeux en solution, la réaction du formaldéhyde avec un agent dérivatif, puis la détection du produit de dérivation par colorimétrie ou fluorimétrie. La méthode a finalement évolué vers seulement deux étapes distinctes grâce à l’utilisation d’un dispositif microfluidique innovant dans lequel le piégeage et la réaction ont lieu simultanément. L’étude des performances analytiques du dispositif a permis de valider la méthode développée pendant cette thèse Formaldehyde (HCHO) is a major pollutant in indoor air. The objective of this work is to realize the scientific and technological advances required to obtain an analytical method based on a microfluidic device to measure air formaldehyde combining precision, selectivity, analysis speed with for major objective a sufficient autonomy on a long time, typically one month. The principle of the method was initially based on three key steps, the gaseous formaldehyde uptake in solution, the formaldehyde derivatization reaction, then the detection of reaction product by colorimetry or fluorimetry. The method has finally advanced toward only two definite steps thanks to the use of an innovative microfluidic device in which uptake and reaction take place simultaneously. The study of analytical performances of the device allows to validate the method developedduring this work

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Hartmann, Michael. "Microfluidic Methods for Protein Microarrays." Doctoral thesis, KTH, Analytisk kemi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-26083.

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Protein microarray technology has an enormous potential for in vitro diagnostics (IVD)1. Miniaturized and parallelized immunoassays are powerful tools to measure dozens of parameters from minute amounts of sample, whilst only requiring small amounts of reagent. Protein microarrays have become well-established research tools in basic and applied research and the first diagnostic products are already released on the market. However, in order for protein microarrays to become broadly accepted tools in IVD, a number of criteria have to be fulfilled concerning robustness and automation. Robustness and automation are key demands to improve assay performance and reliability of multiplexed assays, and to minimize the time of analysis. These key demands are addressed in this thesis and novel methods and techniques concerning assay automation, array fabrication as well as performance and detection strategies related to protein microarrays are presented and discussed. In the first paper an automated assay format, based on planar protein microarrays is described and evaluated by the detection of several auto-antibodies from human serum and by quantification of matrix metalloproteases present in plasma. Diffusion-rate limited solid phase reactions were enhanced by microagitation, using the surface acoustic wave technology, resulting in a slightly increased signal-to-noise ratio. In the second paper of the thesis, a novel multiplexed immunoassay system was developed by combining a direct immunoassay with a competitive system. This set-up allows quantification of analytes present in widely varying concentrations within a single multiplex assay. In the third paper, a new concept for sample deposition is introduced, addressing contemporary problems of contact or non-contact microarrayers in protein microarray fabrication. In the fourth paper, a magnetic bead-based detection method for protein microarrays is described as a cost-effective alternative approach to the commonly used fluorescence-based confocal scanning systems. The magnetic bead-based detection could easily be performed by using an ordinary flatbed scanner. In addition, applying magnetic force to the magnetic bead-based detection approach enables to run the detection step more rapidly. Finally, in paper five, a microfluidic bead-based immunoassay for multiplexed detection of receptor tyrosine kinases in breast cancer tissue is presented. Since the assay is performed inside a capillary, the amounts of sample and reagent material could be reduced by a factor of 30 or more when compared with the current standard protein microarray assay. QC 20101112

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16

Zhang, Yingbo. "Microfluidic methods for biomolecular analysis." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/274931.

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Microfluidics is the science and technology of manipulating fluids at small scales ranging from microlitres (10$^{-6}$) to picolitres (10$^{-12}$). The fundamental physics is distinct from fluid behaviour on bulk scales and laminar flow is the key characteristic on this scale. Microfluidic systems have a wide range of applications in many disciplines from engineering to physics, chemistry and biotechnology. In this thesis, I explore different strategies exploiting the capabilities of microfluidic devices for manipulating and analysing biomolecules. A particular focus of the work is on the study of amyloid fibrils. These species are protein aggregates related to a wide range of human diseases and functional materials. In chapter 3 I demonstrate an efficient way to separate particles in different sizes based on a microfluidic diffusion method. This method enables us to explore the properties of amyloid fibrils, such as their growth kinetics and interaction with small molecules. Rapid binding information could be obtained with only microlitres of sample in tens of seconds time scale. A further manipulation method for charged particles is introduced in chapter 4, based on the integration of microfluidics and free flow electrophoresis. I present a very effective and simple way to overcome one of the most critical problem in this situation. High electric filed can be applied through two streams of conductive solutions, with all the electrolysis by products, e.g., gas bubbles and other deposits, removed simultaneously without interfering with the system. In addition to microfluidic devices made by soft lithography in PDMS, I also set up a hot embossing fabrication process with the Teflon material (chapter 5). Teflon has many advantages compared with PDMS, such as lower protein adsorption, higher mechanical strength and better chemical compatibility. With different materials and structures, microfluidic devices can be expanded to more applications.

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17

af, Klinteberg Ludvig. "Computational methods for microfluidics." Licentiate thesis, KTH, Numerisk analys, NA, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-116384.

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This thesis is concerned with computational methods for fluid flows on the microscale, also known as microfluidics. This is motivated by current research in biological physics and miniaturization technology, where there is a need to understand complex flows involving microscale structures. Numerical simulations are an important tool for doing this. The first paper of the thesis presents a numerical method for simulating multiphase flows involving insoluble surfactants and moving contact lines. The method is based on an explicit interface tracking method, wherein the interface between two fluids is decomposed into segments, which are represented locally on an Eulerian grid. The framework of this method provides a natural setting for solving the advection-diffusion equation governing the surfactant concentration on the interface. Open interfaces and moving contact lines are also incorporated into the method in a natural way, though we show that care must be taken when regularizing interface forces to the grid near the boundary of the computational domain. In the second paper we present a boundary integral formulation for sedimenting particles in periodic Stokes flow, using the completed double layer boundary integral formulation. The long-range nature of the particle-particle interactions lead to the formulation containing sums which are not absolutely convergent if computed directly. This is solved by applying the method of Ewald summation, which in turn is computed in a fast manner by using the FFT-based spectral Ewald method. The complexity of the resulting method is O(N log N), as the system size is scaled up with the number of discretization points N. We apply the method to systems of sedimenting spheroids, which are discretized using the Nyström method and a basic quadrature rule. The Ewald summation method used in the boundary integral method of the second paper requires a decomposition of the potential being summed. In the introductory chapters of the thesis we present an overview of the available methods for creating Ewald decompositions, and show how the methods and decompositions can be related to each other. QC 20130124

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18

Herling, Therese Windelborg. "Microfluidic methods for quantitative protein studies." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709392.

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19

Ashok, Praveen Cheriyan. "Integration methods for enhanced trapping and spectroscopy in optofluidics." Thesis, University of St Andrews, 2011. http://hdl.handle.net/10023/2546.

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“Lab on a Chip” technologies have revolutionized the field of bio-chemical analytics. The crucial role of optical techniques in this revolution resulted in the emergence of a field by itself, which is popularly termed as “optofluidics”. The miniaturization and integration of the optical parts in the majority of optofluidic devices however still remains a technical challenge. The works described in this thesis focuses on developing integration methods to combine various optical techniques with microfluidics in an alignment-free geometry, which could lead to the development of portable analytical devices, suitable for field applications. The integration approach was applied to implement an alignment-free optofluidic chip for optical chromatography; a passive optical fractionation technique fractionation for cells or colloids. This system was realized by embedding large mode area photonic crystal fiber into a microfluidic chip to achieve on-chip laser beam delivery. Another study on passive sorting envisages an optofluidic device for passive sorting of cells using an optical potential energy landscape, generated using an acousto-optic deflector based optical trapping system. On the analytical side, an optofluidic chip with fiber based microfluidic Raman spectroscopy was realized for bio-chemical analysis. A completely alignment-free optofluidic device was realized for rapid bio-chemical analysis in the first generation by embedding a novel split Raman probe into a microfluidic chip. The second generation development of this approach enabled further miniaturization into true microfluidic dimensions through a technique, termed Waveguide Confined Raman Spectroscopy (WCRS). The abilities of WCRS for online process monitoring in a microreactor and for probing microdroplets were explored. Further enhanced detection sensitivity of WCRS with the implementation of wavelength modulation based fluorescent suppression technique was demonstrated. WCRS based microfluidic devices can be an optofluidic analogue to fiber Raman probes when it comes to bio-chemical analysis. This allows faster chemical analysis with reduced required sample volume, without any special sample preparation stage which was demonstrated by analyzing and classifying various brands of Scotch whiskies using this device. The results from this study also show that, along with Raman spectroscopic information, WCRS picks up the fluorescence information as well, which might enhance the classification efficiency. A novel microfabrication method for fabricating polymer microlensed fibers is also discussed. The microlensed fiber, fabricated with this technique, was combined with a microfluidic gene delivery system to achieve an integrated system for optical transfection with localized gene delivery.

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20

Klauber, Kameron L. "Rapid prototyping method for a microfluidics device." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/74446.

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Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2012. Cataloged from PDF version of thesis. Includes bibliographical references (p. 12). The product design process can be described as a number of steps taken to turn an idea into a reality. One particular design process of creating a microfluidics device was studied and analyzed. A device containing channels for fluid flow presents a number of challenges for designers. The particular device in this study had a number of specifications, which include a small scale, a necessity to hold fluid, and a desire to control fluid flow. The overall process for developing this product can be broken into the idea, concept development, 3D CAD, simulations, 3D prototyping, assembly, and biochemistry testing. This is one process that has been completed and studied to identify certain design decisions related to this particular device. Further testing and future design iterations will be needed to prove the success of this particular device. by Kameron L. Klauber. S.B.

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21

Russom, Aman. "Microfluidic bead-based methods for DNA analysis." Doctoral thesis, KTH, Skolan för elektro- och systemteknik (EES), 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-155.

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With the completion of the human genome sequencing project, attention is currently shifting toward understanding how genetic variation, such as single nucleotide polymorphism (SNP), leads to disease. To identify, understand, and control biological mechanisms of living organisms, the enormous amounts of accumulated sequence information must be coupled to faster, cheaper, and more powerful technologies for DNA, RNA, and protein analysis. One approach is the miniaturization of analytical methods through the application of microfluidics, which involves the manipulation of fluids in micrometer-sized channels. Advances in microfluidic chip technology are expected to play a major role in the development of cost-effective and rapid DNA analysis methods. This thesis presents microfluidic approaches for different DNA genotyping assays. The overall goal is to combine the potential of the microfluidic lab-on-a-chip concept with biochemistry to develop and improve current methods for SNP genotyping. Three genotyping assays using miniaturized microfluidic approaches are addressed. The first two assays are based on primer extension by DNA polymerase. A microfluidic device consisting of a flow-through filter chamber for handling beads with nanoliter liquid volumes was used in these studies. The first assay involved an allelespecific extension strategy. The microfluidic approach took advantage of the different reaction kinetics of matched and mismatched configurations at the 3’-ends of a primer/template complex. The second assay consisted of adapting pyrosequencing technology, a bioluminometric DNA sequencing assay based on sequencing-bysynthesis, to a microfluidic flow-through platform. Base-by-base sequencing was performed in a microfluidic device to obtain accurate SNP scoring data on nanoliter volumes. This thesis also presents the applications of monolayer of beads immobilized by microcontact printing for chip-based DNA analysis. Single-base incorporation could be detected with pyrosequencing chemistry on these monolayers. The third assay developed is based on a hybridization technology termed Dynamic Allele-Specific Hybridization (DASH). In this approach, monolayered beads containing DNA duplexes were randomly immobilized on the surface of a microheater chip. DNA melting-curve analysis was performed by dynamically heating the chip while simultaneously monitoring the DNA denaturation profile to determine the genotype. Multiplexing based on single-bead analysis was achieved at heating rates more than 20 times faster than conventional DASH provides. QC 20101008

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22

Chawan, Aschvin Bhagirath. "Novel methods for microfluidic mixing and control." Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/54016.

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Microfluidics is a constantly evolving area of research. The implementation of new technologies and fabrication processes offers novel methodologies to solve existing problems. There are currently a large number of established techniques to address issues associated with microscale mixing and valving. We present mixing and valving techniques that utilize simplified and inexpensive techniques. The first technique addresses issues associated with microscale mixing. Exercising control over animal locomotion is well known in the macro world but in the micro-scale world, control requires more sophistication. We present a method to artificially magnetize microorganisms and use external permanent magnets to control their motion in a microfluidic device. This effectively tethers the microorganisms to a location in the channel and controls where mixing occurs. We use the bulk and ciliary motion of the microswimmers to generate shear flows, thus enhancing cross-stream mixing by supplementing diffusion. The device is similar to an active mixer but requires no external power sources or artificial actuators. The second technique examines a methodology involving the integration of electroactive polymers into microfluidic devices. Under the influence of high applied voltages, electroactive polymers with fixed boundary conditions undergo out-of-plane deformation. We use this finding to create a valve capable blocking flow in microchannels. Electrolytic fluid solutions are used as electrodes to carry the voltage signal to the polymer surface. Currently we have demonstrated this methodology as a proof of concept, but aim to optimize our system to develop a robust microvalve technology. Master of Science

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23

Ung, Warren Lloyd. "Microfluidic Methods for High-Throughput Biological Screening." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845504.

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Often in biology, rare individuals within a population dominate the population’s overall behavior, and we wish to extract those individuals for further analysis. We design a sorting instrument as a flexible platform for the development of novel microfluidic sorting techniques. We demonstrate a microfluidic cell sorter, which screens cells at rates approaching those of commercially-available fluorescence-activated cell sorters. This device incorporates a three-dimensional flow-focusing nozzle with a slanted ceiling groove to enhance the capabilities of a surface acoustic wave (SAW) transducer by harnessing the component of the SAW oriented normal to the plane of the substrate. The device achieves sorting at a rate of 9000 events/s with 54% purity and yields 89% purity, while operating at 1000 events/s; this level of performance approaches that of a FACS operating in its high-purity mode. We also present a rare event sorting technique, which can successfully extract desired droplets from a sample containing nearly a billion droplets. The technique yields pure samples after two rounds. The preliminary round is fast, capable of screening 10 ml of droplets at 100 ml/h, but each sort also captures many other droplets together with the droplet of interest. The second round of sorting enriches the sample to nearly 100% purity, using known designs for high purity drop-by-drop sorting. Thus, we devise a method, which can sort droplets rapidly and achieve high purity of few droplets from samples containing large numbers of droplets. The two disparate approaches to microfluidic sorting use a common platform to create new methods for sorting with biological applications. Engineering and Applied Sciences - Engineering Sciences

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Rossetto, Nicola. "Materials and methods for modular microfluidic devices." Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3422583.

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This thesis work concerns the investigation of materials and methods that can be applied to the realization of microfluidic devices (MFDs). In particular, the attention is placed on modular MFDs, as opposed to fully integrated ones. The reasons behind this choice are given in detail in Section 1.2 of this work, but they can be here summarized in the fact that while integrated MFDs offer great advantages in terms of portability, modular devices are more versatile, and so particularly well suited for research applications. The first part of the work here reported describes the microfabrication techniques employed for the realization of single-function microfluidic modules. Devices have been fabricated through PDMS replica molding from SU-8 masters. Masters have been in turn realized through masked UV-lithography or one- or two-photon direct laser writing, depending on the resolution requirements. The replica molding method is a very fast and efficient way to realize MFDs, but suffers from some limitations in the structure shapes that can be successfully replicated. In light of this, a photopolymerizable hybrid organic/inorganic sol-gel blend is proposed and tested as alternative material for MFDs fabrication. The characterization results reveal that this material is biocompatible and features better mechanical properties than PDMS, but structures with more than one dimension exceeding a few micrometers tend to crack during fabrication, making this blend unusable as bulk material. Still, this material could be efficiently employed to fabricate sub-structuration inside PDMS channels. Following this investigation on materials, a microfluidic mixing module is proposed and tested. Since laminar flow conditions dominate inside microchannels, efficient mixing in MFDs require the use of specifically designed mixers. The proposed module makes use of obstructions inside a microchannel to perturb the laminar flow and thus enhance mixing of two species. The most efficient geometries have been selected with the aid of numerical simulations, and two promising layouts have been fabricated and experimentally tested by measuring the dilution of a fluorophore (mixing between a fluorophore solution and pure solvent) through confocal fluorescence microscopy. Thirdly, the fabrication and characterization of an optofluidic light switching module is reported. This device employs a water/air segmented flow generated by a T-junction to alternatively transmit or total-reflect a laser beam. This deflection is proved to be periodical, and its frequency can be varied nonlinearly by adjusting the injection flow rates of air and water. The duty cycle of the module is also characterized, and a method to modulate it by increasing the water temperature is proposed and verified. Finally, a number of attempts to generate a nanoporous, low refractive index PDMS are described. The identification of an efficient procedure to fabricate this kind of material would lead to the possibility of using common microfluidic channels as water-core waveguides. To date, these attempts have not been totally successful, but critical points are identified, and viable strategies for future works on the subject are proposed. Questo lavoro di tesi tratta dello studio di materiali e metodi che possono essere applicati alla realizzazione di dispositivi microfluidici (DMF). In particolare l’attenzione è rivolta ai dispositivi modulari, piuttosto che a quelli altamente integrati. Le ragioni dietro questa scelta sono spiegate in dettaglio nella Sezione 1.2 di questa tesi, ma possono essere qui sintetizzate nel fatto che anche se i DMF integrati offrono grandi vantaggi in termini di dimensioni finali, i dispositivi modulari sono più versatili, e quindi particolarmente utili per applicazioni nel campo della ricerca. La prima parte del lavoro qui riportato descrive le tecniche di microfabbricazione utilizzate per la realizzazione di moduli microfluidici monofunzionali. I dispositivi sono stati realizzati per replica molding in PDMS a partire da master in SU-8. I master sono stati a loro volta fabbricati tramite litografia UV con maschera oppure per scrittura laser diretta ad uno o due fotoni, a seconda dei requisiti di risoluzione. Il replica molding è un metodo molto rapido ed efficiente per realizzare DMF, ma presenta alcuni limiti per quanto riguarda la forma delle strutture che è possibile replicare con successo. Alla luce di questo, un sol-gel fotopolimerizzabile ibrido organico/inorganico viene qui proposto e testato come materiale alternativo per la fabbricazione di DMF. I risultati della caratterizzazione rivelano che questo materiale è biocompatibile e presenta proprietà meccaniche migliori di quelle del PDMS, ma strutture con più di una dimensione eccedente i pochi micrometri tendono a sviluppare cricche, cosa che impedisce l’utilizzo di questo sol-gel come materiale massivo. Ciononostante, questo sol-gel potrebbe venir efficacemente impiegato per la realizzazione di sottostrutturazioni all’interno di canali microfluidici. Dopo questo studio sui materiali, un modulo microfluidico per il mescolamento è proposto e testato. Dato che le condizioni di flusso laminare sono dominanti all’interno dei microcanali, per ottenere un mescolamento efficiente in un DMF è necessario includere nel dispositivo un miscelatore specificatamente progettato. Il modulo proposto utilizza delle ostruzioni all’interno del microcanale per perturbare il flusso laminare e quindi favorire il mescolamento. Con l’aiuto di alcune simulazioni numeriche, le geometrie più efficienti sono state individuate, e due layout particolarmente promettenti sono stati realizzati e caratterizzati sperimentalmente misurando la diluizione di un fluoroforo (mescolamento tra una soluzione del fluoroforo e puro solvente) attraverso la microscopia confocale di fluorescenza. A seguire, viene riportata la fabbricazione e caratterizzazione di un modulo optofluidico per la deflessione della luce. Questo dispositivo utilizza un flusso segmentato acqua/aria generato da una giunzione a T per trasmettere o riflettere (per riflessione totale interna) alternativamente un fascio laser. Questa alternanza è periodica, e la sua frequenza può essere controllata variando la portata dei flussi iniettati di aria e acqua. Inoltre, il duty cycle del modulo è stato caratterizzato, e viene proposto e verificato un metodo per modularlo attraverso un aumento della temperatura dell’acqua. Infine, vengono descritti alcuni tentativi di generare un PDMS nanoporoso con basso indice di rifrazione. La messa a punto di una procedura efficiente per la fabbricazione di questo genere di materiale porterebbe alla possibilità di usare i classici canali microfluidici come guide d’onda. Al momento questi tentativi hanno avuto solo parziale successo, ma i maggiori punti di criticità sono stati identificati, e vengono proposte alcune strategie per il loro futuro superamento.

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25

Mukhitov, Nikita. "Microfluidic Methods for the Study of Biological Dynamics." Thesis, The Florida State University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10633959.

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The work in this dissertation presents microfluidic methods developed for the study of biological dynamics. The requirements for the methods development was to create approaches with the ability to perform dynamic cell stimulation, measurement, and sample preparation. The methods presented herein were initially developed for the study of pancreatic islet biology but are expected to be translatable to other applications. In another study, a method to interface transmission electron microscopy (TEM) with microfluidics methods was developed. The primary biological topic of interest investigated was the mechanisms of inter-islet synchronization. To test this, a microfluidic device fabricated from poly(dimethylsiloxane) (PDMS) was used to culture and stimulate pancreatic islets. Intracellular calcium ([Ca2+]i) imaging was performed with a fluorescent indicator, Fura-2-acetoxymethyl ester (Fura-2 AM). Under constant glucose (11 mM), islets demonstrated asynchronous and heterogeneous [Ca2+]i oscillations that drifted in period. However, when exposed to a glucose wave (11+/– 1 mM, 5 min period) islets were entrained to a common and consistent [Ca2+]i oscillation mode. The effect of islet entrainment on cellular function was investigated by measuring gene expression levels with microarray profiling. Calcium-dependent genes were found to be differentially expressed. Furthermore, it was speculated that islet entrained produced a beneficial effect on cell function and upkeep. While [Ca2+]i imaging is an acceptable proxy measurement for insulin, it is not a viable reporter for other islet peptides and direct measurement is desired. Electrophoretic affinity assays can be performed on a microfluidic device in a serial manner to measure peptide release from an on-chip cell culture in near real-time. Successful analysis of electrophoretic affinity assays depends strongly on the preservation of the affinity complex during separations. Elevated separation temperatures due to Joule heating promotes complex dissociation leading to a reduction in sensitivity. To address this limitation, a method to cool a glass microfluidic chip for performing an affinity assay for insulin was achieved by a Peltier cooler localized over the separation channel. The Peltier cooler allowed for rapid stabilization of temperatures, with 21 °C the lowest temperature that was possible to use without producing detrimental thermal gradients throughout the device. Kinetic capillary electrophoresis analysis was utilized as a diagnostic of the affinity assay and indicated that optimal conditions were at the highest attainable separation voltage, 6 kV, and the lowest separation temperature, 21 °C, leading to 3.4% dissociation of the complex peak during the separation. These optimum conditions were used to generate a calibration curve and produced 1 nM limits of detection (LOD), representing a 10-fold improvement over non-thermostated conditions. To date, most approaches for measurement of rapid changes in insulin levels rely on separations, making the assays difficult to translate to non-specialist laboratories. To enable rapid measurements of secretion dynamics from a single islet in a manner that will be more suitable for transfer to non-specialized laboratories, a microfluidic online fluorescence anisotropy immunoassay was developed. A single islet was housed inside a microfluidic chamber and stimulated with varying glucose levels from a gravity-based perfusion system. The total effluent of the islet chamber containing the islet secretions was mixed with gravity-driven solutions of insulin antibody and cyanine-5 (Cy5) labeled insulin. After mixing was complete, a linearly polarized 635 nm laser was used to excite the immunoassay mixture and the emission was split into parallel and perpendicular components for determination of anisotropy. Key factors for reproducible anisotropy measurements, including temperature homogeneity and flow rate stability were optimized, which resulted in a 4 nM LOD for insulin with < 1% RSD of anisotropy values. The capability of this system for measuring insulin secretion from single islets was shown by stimulating an islet with varying glucose levels. As the entire analysis is performed optically, this system should be readily transferable to other laboratories. To increase the number of analytes that can be simultaneously monitored by a fluorescence anisotropy immunoassay, frequency encoding was introduced. As a demonstration of the method, simultaneous competitive immunoassays for insulin and glucagon were performed by measuring the ratio of bound and free Cy5-insulin and fluorescein isothiocyanate (FITC)-glucagon in the presence of their respective antibodies. A vertically polarized 635 nm laser was pulsed at 73 Hz and used to excite Cy5-insulin, while a vertically polarized 488 nm laser pulsed at 137 Hz excited FITC-glucagon. The total emission was split into parallel and perpendicular polarizations and collected onto separate photomultiplier tubes. The signals from each channel were demodulated using a fast Fourier transform, resolving the contributions from each fluorophore. Anisotropy calculations were carried out using the magnitude of the peaks in the frequency domain. The method produced the expected shape of the calibration curves with LOD of 0.6 and 5 nM for insulin and glucagon, respectively. (Abstract shortened by ProQuest.)

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Morthomas, Julien. "Intéractions hydrodynamiques entre colloïdess confinés le long d'une paroi." Thesis, Bordeaux 1, 2009. http://www.theses.fr/2009BOR13882/document.

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Appliquer un champ électrique ou un gradient de température à une solution colloïdale implique la migration des particules (soluté) en suspension. Ce déplacement n’est pas la conséquence de forces de volume comme dans le cas de la sédimentation mais de forces interfaciales agissant sur la double couche électrique présente à la surface des particules colloïdales chargées. Ces forces induisent un écoulement de surface qui à son tour engendre un champ de vitesse du fluide en 1/r³ autour des particules dans la direction opposée à leurs déplacements, où r distance au centre des particules. Dans ce travail on considère une situation différente où la suspension est confinée dans un demi-espace infini limité par une paroi rigide. Un colloïde, sous l’action d’un champ extérieur, se dépose le long de la surface rigide. Bien qu’immobile le colloïde continue de pomper le fluide environnant. Il apparaît alors un écoulement latéral le long du mur et en direction du colloïde. D’autres colloïdes insérés dans un tel écoulement subissent une force hydrodynamique de trainée à l’origine de la formation d’agrégats. De tels agrégats ont été observés aussi bien lors de déposition électrophorétique que plus récemment lors de déposition thermophorétique pour des particules micrométriques en solution aqueuse. Le champ de vitesse confiné prend une forme plus complexe que dans le cas infini : il doit satisfaire à la fois la condition limite fixée à la surface de la particule et sur le mur. Deux méthodes perturbatives, la méthode des réflexions et la méthode d’Oseen, sont utilisées pour résoudre l’équation de Stokes et trouver une solution exacte pour l’écoulement autour du colloïde confiné en puissance de e = a/h rapport du rayon de la particule sur sa distance au mur. La solution usuelle à l’ordre zéro en e donne de pauvres résultats alors que les corrections suivantes donnent de meilleurs conclusions en accord avec les récentes mesures expérimentales de potentiel hydrodynamique de paire entre colloïdes sous champ confinés le long d’un mur Applying a steady electric field or a constant thermal gradient to a colloidal suspension induces a finite velocity of the dispersed particles. The motion of particles is not due to a net body force like in sedimentation but to interfacial forces acting on the electric double layer at their surface. These forces involve a surface flow, which, in turn, results in a velocity field of the surrounding fluid in 1/r³ in the opposite direction of the particle displacement, with r the distance from the centre of the particle. In this work we consider a somewhat different situation, where the suspension is confined to a semi-infinite half space. The particle, under the action of the applied field, is trapped against the solid interface. Still, the creep flow remains; more precisely the particle continues to pump the fluid in the opposite direction. As a consequence there arises a lateral flow along the solid surface towards the particle. Thus others particles inserting themselves in this flow undergo drag forces and form clusters. Particles aggregation has been observed in Electrophoresis deposition and more recently in Thermophoresis deposition for micron sized polystyrene beads in aqueous solution. The total velocity field takes a form significantly more complicated than in the above mentioned unbounded cases; it must satisfy boundary conditions both at the particle surface and at the confining wall. Using the perturbative method of reflections or Oseen method based on Fourier transform we resolve the Stokes equation and find an analytic solution for the drag flow along the interface in powers of the ratio e=a/h of particle radius and wall distance. The usual solution at the zero order induces poor approximation, when following corrections in e involves better results in agreement with experimental measurements of hydrodynamic pair potential between two particles along a wall

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27

White, Celesta E. "Advanced Methods, Materials, and Devices for Microfluidics." Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/5287.

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Advanced Methods, Materials, and Devices for Microfluidics Celesta E. White 217 Pages Directed by Dr. Clifford L. Henderson Microfluidics is a rapidly growing research area that has the potential to influence a variety of industries from clinical diagnostics to drug discovery. Unlike the microelectronics industry, where the current emphasis is on reducing the size of transistors, the field of microfluidics is focusing on making more complex systems of channels with more sophisticated fluid-handling capabilities, rather than reducing the size of the channels. While lab-on-a-chip devices have shown commercial success in a variety of biological applications such as electrophoretic separations and DNA sequencing, there has not been a significant amount of progress made in other potential impact areas for microfluidics such as clinical diagnostics, portable sensors, and microchemical reactors. These applications can benefit greatly from miniaturization, but advancement in these and many other areas has been limited by the inability or extreme difficulty in fabricating devices with complex fluidic networks interfaced with a variety of active and passive electrical and mechanical components. Several techniques exist for the fabrication of microfluidic devices, but these methods have significant limitations, and alternative fabrication approaches are currently desperately needed. One such method that shows promise for its ability to integrate the desired high levels of functionality utilizes thermally sacrificial materials as place holders. An encapsulating overcoat material provides structural stability and becomes the microchannel walls when the sacrificial material is removed from the channel through thermal decomposition. Disadvantages of this method, however, include numerous processing steps required for sacrificial layer patterning and elevated temperatures needed for the decomposition of initial sacrificial materials. These limitations keep this method from becoming an economical alternative for microfluidic device fabrication. The materials needed for this method to reach its full potential as a valid fabrication technology for m-TAS are not currently available, and it was a major focus of this work to develop and characterize new sacrificial materials, particularly photosensitive polycarbonate systems. In addition to the development of new sacrificial polymers, the framework for a working microfluidic device was developed to show that this concept will indeed provide significant advancements in the development of future generations of microfluidic systems. Finally, novel fabrication methods for microfluidics through combined imprinting and photopatterning of photosensitive sacrificial materials was demonstrated.

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Visitkul, Viput. "Novel method for high throughput FRET screening with microfluidics." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/novel-method-for-high-throughput-fret-screening-with-micro-uidics(f5b7a493-ff9c-42d0-889d-3f773591a97e).html.

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Functional imaging can provide a level of quantification that is not possible in what might be termed traditional high-content screening. This is due to the fact that the current state-of-the-art high-content screening systems take the approach of scaling-up single cell assays, and are therefore based on essentially pictorial measures as assay indicators. Such phenotypic analyses have become extremely sophisticated, advancing screening enormously, but this approach can still be somewhat subjective. Recent advances in high-content screening with functional read-outs such as FRET (by FLIM or anisotropy imaging) have enabled screening of compound libraries of inhibitors and siRNA against a known protein interaction readout but this is still relatively slow in comparison to true high throughput methodologies. In order to further increase the predictive and statistical power of functional FRET assays, we have developed a compact lifetime-based flow cytometer, utilising a commercial microfluidic chip, to screen large non-adherent cell population. Fluorescent signals from cells are detected using time correlated single photon counting (TCSPC) in the burst integrated fluorescence lifetime (BIFL) mode and used to determine the fluorescence lifetime of each cell. Initially, the system was tested using 2 μm and 10 μm highly fluorescent beads to determine optical throughput and detection efficiency. The system was validated with a number of cell lines transiently transfected with FRET standards, consisting of eGFP and mRFP1 fluorescent proteins linked by 7, 19, and 32 amino acid chains. Analysis software was developed to process detected signals in BIFL mode and chronologically save the transient burst data for each cell in a multidimensional image file. Furthermore, the system was validated using an EGFR phosphorylation assay in MCF7 cells to ascertain the sensitivity of the system for protein-protein interaction screening with a transfected protein and a labelled antibody.

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Kilimnik, Alexander. "Cross stream migration of compliant capsules in microfluidic channels." Thesis, Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/43669.

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An understanding of the motion of soft capsules in microchannels is useful for a number applications. This knowledge can be used to develop devices to sort biological cells based on their size and stiffness. For example, cancer cells have a different stiffness from healthy cells and thus can be readily identified. Additionally, devices can be developed to detect flaws in synthetic particles. Using a 3D hybrid lattice Boltzmann and lattice spring method, the motion of rigid and soft capsules in a pressure-driven microfluidic flow was probed. The effect of inertial drift is evaluated in channels different Reynolds numbers. Other system parameters such as capsule elasticity and channel size are also varied to determine their effect. The equilibrium position of capsules in the channel is also obtained. The equilibrium position of rigid and soft capsules depends on the relative particle size. If the capsule is small, the equilibrium position is found to be closer to the channel wall. Conversely, for larger capsules, the equilibrium position is closer to the channel centerline. The capsule stiffness affects the magnitude of the cross-stream drift velocity. For a given Reynolds number, the equilibrium position of softer capsules is closer to the channel centerline. However, It is found that the equilibrium position of soft capsules is insensitive to the magnitude of the Reynolds number.

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Coquinco, Bernard. "Alternative replica molding methods for polymer based microfluidic channels." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50190.

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Microfluidics provides an opportunity to create low cost devices that can potentially contain many elements of a diagnostics lab on a single chip. While the cost of the finished product may be low, a common method of fabricating microfluidic devices such as soft lithography can be expensive to prototype due to the use of photolithography equipment meant for the semiconductor industry. In addition, the majority of microfluidic research has been done using rectangular channels but in some cases the ability to make circular cross-section channel microfluidic devices would be very useful. For areas such as modelling cardiovascular flows, investigating micro flow cytometry and inertial particle focusing, the ability to create circular channels could provide improvement over the use of rectangular channels. To address these issues, an ultra low cost method of making silicon molds patterned with SU-8 has been developed as well as a method to create circular microfluidic channels via hot embossing and double casting techniques in both thermoplastic materials and PDMS. This hot embossing based method to create round channels allows for the rapid creation of straight and curving round channels in PMMA and other plastics as well as a method to create PDMS round channels using soft lithography. Applied Science, Faculty of Graduate

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Belotti, Yuri. "Microfluidic methods for investigating cell migration and cell mechanics." Thesis, University of Dundee, 2016. https://discovery.dundee.ac.uk/en/studentTheses/fb5ac03d-a752-45a1-8b95-37c8180dc7d9.

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In this thesis I explore how migratory properties of the model organism Dictyostelium discoideum are influenced by dimensionality and topology of the environment that surrounds the cell. Additionally, I sought to develop a microfluidic device able to measure mechanical properties of single cells with a sufficient throughput to account for the inherent heterogeneity of biological samples. Throughout this thesis I made use of microfabrication methods such as photo-lithography and soft-lithography, to develop ad hoc microstructured substrates. These tools enabled me to tackle different biological and biomedical questions related to cell migration and cell mechanics. Confining cells into channels with low dimensionality appeared to regulate the velocity of cellular locomotion, as well as the migration strategy adopted by the cell. Spatial confinement induced an altered arrangement of the acto-myosin cytoskeleton and microtubules. Moreover, the spatial constraint resulted in a simplified, mono-dimensional migration, characterised by constant average speed. Additionally, some cellular processes tended to occur in a periodic fashion, upon confinement. Interestingly, if Dictyostelium cells migrated through asymmetric bifurcating micro- channels, they appeared to be able to undergo a ’decision-making’ process leading to a directional bias. Although the biophysical mechanism underlying this response is yet to be understood, the data shown in this thesis suggest that Dictyostelium cells respond to differences in local concentrations of chemoattractants. The speed of a cell that crawls in a channel also depends on the cell’s stiffness, that in turn represents a measure of the density and structure of its cytoskeleton. To date, only a few methods have been developed to investigate cell mechanics with sufficient throughput. This motivated my interest in developing a microfluidic-based device that, exploiting the recording capabilities of a modern high speed camera, enabled me to assess the cellular mechanical properties at a rate greater than 10,000 cells per second, without the need for cell labelling. In this thesis I presented an example of how this method can be employed to detect differences between healthy and cancerous prostate cells, as well as to differentiate between prostate and bladder cancer cells based on their mechanical response. In conclusion, the work presented in this thesis highlights the interdisciplinarity required to investigate complex biological and biomedical problems. Specifically, the use of quantitative approaches that span from microtechnology, live imaging, computer vision and computational modelling enabled me to investigate novel biological processes as well as to explore new diagnostic technologies that aim to promote the improvement of the future healthcare.

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Rose, Klint A. "Microfluidic manipulation and detection methods for metal microbarcode particles /." May be available electronically:, 2007. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.

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Teo, Adrian J. "Active Droplet Control and Manipulation in Microfluidics." Thesis, Griffith University, 2020. http://hdl.handle.net/10072/392033.

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Droplet microfluidics involves the use of small volumes of fluids dispersed in an immiscible phase to perform multiple functions. Droplet microfluidics brings advantages such as the miniaturization of experiments, portability of devices, efficient use of resources and capabilities for scaling up production. These tools have been finding their use in a broad range of applications, from chemical and biological analysis to optics and information technology. Various types of controls have been developed to enable the manipulation of droplets. These techniques are categorized into passive and active methods. Passive methods only involve the device geometries and the fluid flow. Active techniques on the other hand provide another level of controllability for adjusting droplet parameters, allowing rapid change of droplet parameters within a single experiment. This flexibility enables user to select parameters and subsequent actions on the same device. Particularly, droplet-on-demand systems benefit from these techniques. The aim of this thesis is the development of different active methods for droplet manipulation. The thesis first focuses on three active control methods, pneumatic, acoustic and electric. Firstly, negative pressure is applied for the controlling droplet generation in a device. The novel application of negative pressure directly affects the flow in the microchannel to generate droplets on demand. This control approach, unlike other active approaches eliminates space constraints within the device with no need for external equipment. Next, a new fabrication approach for interdigitated transducers for generating acoustic waves was developed. This approach eliminates the use of expensive fabrication equipment and simplifies fabrication procedures. Acoustic streaming in a droplet was successfully demonstrated with these transducers. Finally, electric methods are used for controls in droplet generation and coalescence. Non-Newtonian droplets are generated through application of the electric field. On-demand coalescence of droplets is also observed using a combination of AC electric field and a micropillar. The new approaches reported in this thesis provide a greater versatility in microfluidics applications. The simpler alternatives suggested here would overcome current limitations of fabrication complexity and large device footprint, allowing microfluidics to be more accessible and easily implemented. The outcome of this thesis contributes to enhancing the uptake of microfluidics in multidisciplinary research and to broadening the user base of this technology. Thesis (PhD Doctorate) Doctor of Philosophy (PhD) School of Eng & Built Env Science, Environment, Engineering and Technology Full Text

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Carlborg, Carl Fredrik. "Development of materials, surfaces and manufacturing methods for microfluidic applications." Doctoral thesis, KTH, Mikrosystemteknik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-38605.

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This thesis presents technological advancements in microfluidics. The overall goals of the work are to develop new miniaturized tests for point-of-care diagnostics and robust super-lubricating surfaces for friction reduction. To achieve these goals, novel materials, surfaces and manufacturing methods in microfluidics have been developed. Point-of-care diagnostic tests are portable miniaturized instruments that downscale and automate medical tests previously performed in the central laboratories of hospitals. The instruments are used in the doctor’s office, in the emergency room or at home as self-tests. By bringing the analysis closer to the patient, the likelihood of an accurate diagnosis, or a quick therapy adjustment is increased. Already today, there are point-of-care tests available on the market, for example blood glucose tests, rapid streptococcus tests and pregnancy tests. However, for more advanced diagnostic tests, such as DNA-tests or antibody analysis, integration of microfluidic functions for mass transport and sample preparation is required. The problem is that the polymer materials used in academic development are not always suited for prototyping microfluidic components for sensitive biosensors. Despite the enormous work that has gone into the field, very few technical solutions have been implemented commercially. The first part of the work deals with the development of prototype point of-care tests. The research has focused on two major areas: developing new manufacturing methods to leverage the performance of existing materials and developing a novel polymer material platform, adapted for the extreme demands on surfaces and materials in miniaturized laboratories. The novel manufacturing methods allow complex 3D channel networks and the integration of materials with different surface properties. The novel material platform is based on a novel off-stoichiometry formulation of thiol-enes (OSTE) and has very attractive material and manufacturing properties from a lab-on-chip perspective, such as, chemically stable surfaces, low absorption of small molecules, facile and inexpensive manufacturing process and a biocompatible bonding method. As the OSTE-platform can mirror many of the properties of commercially used polymers, while at the same time having an inexpensive and facile manufacturing method, it has potential to bridge the gap between research and commercial production. Friction in liquid flows is a critical limiting factor in microfluidics, where friction is the dominant force, but also in marine applications where frictional losses are responsible for a large part of the total energy consumption of sea vessels. Microstructured surfaces can drastically reduce the frictional losses by trapping a layer of air bubbles on the surface that can act as an air bearing for the liquid flow. The problem is that these trapped air bubbles collapse at the liquid pressures encountered in practical applications. The last part of the thesis is devoted to the development of novel low fluidfriction surfaces with increased robustness but also with active control of the surface friction. The results show that the novel surfaces can resist up to three times higher liquid pressure than previous designs, while keeping the same friction reducing capacity. The novel designs represent the first step towards practical implementation of micro-structured surfaces for friction reduction. QC 20110907

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Salem, Mohamed Yafia Okba. "Enhanced actuation and fabrication methods for integrated digital microfluidic systems." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/60456.

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Introducing a practical digital microfluidic (DMF) platform has been always an important goal that can facilitate and broaden the use of DMF systems in various applications on a regular basis. In particular, a desired DMF platform may be the one which is fabricated easily and is also affordable, portable, battery powered, and user friendly. It should perform DMF operations reliably, accept mass-produced replaceable chips and can be readily integrated into a post processing station as well. Accordingly, the development of a practical DMF platform with these characteristics is the main target of this research. Specifically, the research has enhanced DMF systems through i) improved and novel actuation mechanisms, ii) cost-effective rapid prototyping techniques, and iii) full system integration. First, detailed experimental and numerical characterization of droplet morphology is performed to insinuate useful design and prototyping tips for enhanced DMF devices. Since droplet transport predominantly depends on the gap height, a major objective of the thesis is understanding the motion dynamics of a droplet at different gap heights. The characterization of the droplet behaviour in different regimes led to enhancing the actuation process in DMF systems. In addition, a variable gap size actuation (VGSA) mechanism is integrated into the DMF system to optimize DMF operations including droplet transport, splitting, dispensing and merging in real time. Consequently, the DMF operations can be performed reliably by adjusting the optimum operating conditions. Second, for rapid prototyping DMF chips, a new fabrication method is presented in which the electrodes are generated using screen printing. As a batch fabrication technique, the proposed screen printing approach is advantageous to the widely reported DMF electrode fabrication methods in terms of fabrication volume, time, and cost. In addition, a laser scribing technique is introduced as a low-cost, rapid and facile method for fabricating laser scribed graphene electrodes for DMF systems. Third, an ultraportable, low-cost, and modular DMF platform was successfully integrated with a smartphone that is used as a high-level controller. A colorimetric assay for pH value detection is introduced to demonstrate the performance of the device as a microscope and a post processing station. Applied Science, Faculty of Engineering, School of (Okanagan) Graduate

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Klepáčová, Ivana. "Detekce biomarkerů pomocí elektrochemických metod mikrofluidickým čipem." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2017. http://www.nusl.cz/ntk/nusl-317012.

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The thesis is focused on the development of the electrochemical system with microfluidic platform for the detection of multiple biomarkers. It analyses the use of biomarkers for the early diagnosis of cancer. The theoretical part contains basic information about voltammetric methods and microfluidic systems. The practical part provides solutions to the microfluidic chips, including the description of the used materials, designs, methodologies of preparation and conclusions from the testing of the manufactured microfluidic systems. The thesis describes the lock-in electrochemical system which measures the response of 4 electrochemical cells simultaneously. For the electrochemical system measurements, an electrochemical chip consisting of 64 electrochemical cells was used. The results of the analysis include the processing of the system tests and detected voltammetric curves of the Fe2+/Fe3+ solution and cysteine.

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Dawson, Amy. "Paper microfluidics for clinical diagnostics using colourimetric detection methods." Thesis, University of Hull, 2014. http://hydra.hull.ac.uk/resources/hull:10515.

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Microfluidics is a technology currently aiming to advance the medical devices currently available in the developing and developed world through simultaneously creating point-of-care devices which are “as good” or better than current methods at a cheaper production cost. To be able to diagnose diseases and infections quickly and affordably remains the aim of many researchers and the use microfluidics has advantages which plug this difficulty. However, one main gap in the research is to train users for these devices which give accurate results when compared to current methods. Described herein are three point-of-care devices which would not require specialist users and give no significantly different results from hospital methods. The aim of this project was to design, fabricate and use a microfluidic device made from filter paper as a cheaper alternative to current microfluidic devices already available. The creation of channels to direct the movement of fluid within the paper matrix was established by modifying a photolithography method, thereby providing hydrophilic channels surrounded by a hydrophobic barrier. A three dimensional device was constructed entirely from filter paper to incorporate the simultaneous removal, reduction and detection of iron(II) via bathophenanthroline detection for the determination of iron(II) levels in a patient, indicative of the nutritional state of the patient e.g. does the pateitn suffer from anaemia. This method was deemed accurate by comparing the results to a conventional laboratory method (spectrophotometer analysis) completed in a hospital pathology laboratory. No significant difference was observed between results received from the hospital and results found using the paper microfluidic device, 15 μM ± 0.6% SEM versus 15.5 μM ± 0.8% SEM respectively. Two paper devices were developed to allow a quick and reliable measurement assessment of a patient’s renal function. The first for urea, as a simple colour change for a high or low readout of urea levels in serum samples, e.g. ≥ 150 μg/mL then an orange/red colour would be seen on the paper device, indicative of renal failure ≤ 150 ug mL¯¹. The second device used the Jaffe reaction on filter paper as a dipstick assay. No significant difference was observed between results received from the hospital and results found using the paper device 3.92 ± 1.2% versus 3.88 mg mL¯¹ ± 0.6% respectively. These three devices fulfil the aims of the project outline by remaining simplistic to use and are cost effective in both the developing and developed world, whilst maintaining accuracy as seen in the results received from hospital pathology laboratories.

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af, Klinteberg Ludvig. "Fast and accurate integral equation methods with applications in microfluidics." Doctoral thesis, KTH, Numerisk analys, NA, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-185758.

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This thesis is concerned with computational methods for fluid flows on the microscale, also known as microfluidics. This is motivated by current research in biological physics and miniaturization technology, where there is a need to understand complex flows involving microscale structures. Numerical simulations are an important tool for doing this. The first, and smaller, part of the thesis presents a numerical method for simulating multiphase flows involving insoluble surfactants and moving contact lines. The method is based on an interface decomposition resulting in local, Eulerian grid representations. This provides a natural setting for solving the PDE governing the surfactant concentration on the interface. The second, and larger, part of the thesis is concerned with a framework for simulating large systems of rigid particles in three-dimensional, periodic viscous flow using a boundary integral formulation. This framework can solve the underlying flow equations to high accuracy, due to the accurate nature of surface quadrature. It is also fast, due to the natural coupling between boundary integral methods and fast summation methods. The development of the boundary integral framework spans several different fields of numerical analysis. For fast computations of large systems, a fast Ewald summation method known as Spectral Ewald is adapted to work with the Stokes double layer potential. For accurate numerical integration, a method known as Quadrature by Expansion is developed for this same potential, and also accelerated through a scheme based on geometrical symmetries. To better understand the errors accompanying this quadrature method, an error analysis based on contour integration and calculus of residues is carried out, resulting in highly accurate error estimates. Denna avhandling behandlar beräkningsmetoder för strömning på mikroskalan, även känt som mikrofluidik. Detta val av ämne motiveras av aktuell forskning inom biologisk fysik och miniatyrisering, där det ofta finns ett behov av att förstå komplexa flöden med strukturer på mikroskalan. Datorsimuleringar är ett viktigt verktyg för att öka den förståelsen. Avhandlingens första, och mindre, del beskriver en numerisk metod för att simulera flerfasflöden med olösliga surfaktanter och rörliga kontaktlinjer. Metoden är baserad på en uppdelning av gränsskiktet, som tillåter det att representeras med lokala, Euleriska nät. Detta skapar naturliga förutsättningar för lösning av den PDE som styr surfaktantkoncentrationen på gränsskiktets yta. Avhandlingens andra, och större, del beskriver ett ramverk för att med hjälp av en randintegralformulering simulera stora system av styva partiklar i tredimensionellt, periodiskt Stokesflöde. Detta ramverk kan lösa flödesekvationerna mycket noggrant, tack vare den inneboende höga noggrannheten hos metoder för numerisk integration på släta ytor. Metoden är också snabb, tack vare den naturliga kopplingen mellan randintegralmetoder och snabba summeringsmetoder. Utvecklingen av ramverket för partikelsimuleringar täcker ett brett spektrum av ämnet numerisk analys. För snabba beräkningar på stora system används en snabb Ewaldsummeringsmetod vid namn spektral Ewald. Denna metod har anpassats för att fungera med den randintegralformulering för Stokesflöde som används. För noggrann numerisk integration används en metod kallad expansionskvadratur (eng. Quadrature by Expansion), som också har utvecklats för att passa samma Stokesformulering. Denna metod har även gjorts snabbare genom en nyutvecklad metod baserad på geometriska symmetrier. För att bättre förstå kvadraturmetodens inneboende fel har en analys baserad på konturintegraler och residykalkyl utförts, vilket har resulterat i väldigt noggranna felestimat. QC 20160427

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Lu, Chunmeng. "Development of novel micro-embossing methods and microfluidic designs for biomedical applications." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1156820643.

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With, Sebastian [Verfasser]. "Microfluidics as a method to follow dynamic assembly of colloidal systems / Sebastian With." München : Verlag Dr. Hut, 2015. http://d-nb.info/1075409209/34.

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Sun, Xinyu. "Fault Modeling and Fault Type Distinguishing Test Methods for Digital Microfluidics Chips." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1380557053.

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Fidalgo, Luis Miguel. "Novel methods for droplet fusion, extraction and analysis in multiphase microfluidics." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611619.

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Moon, Jiyoung. "Rheological Behavior of Complex Fluid with Deformable and Rigid Particles." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17106.

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Predicting the rheological properties of particles in matrix is one of the most challenging and complicated problems in material and fluid sciences. The complication is arisen by the particles collision and interactions with the surrounding fluid. A full description of the rheology of particles requires a complete understanding of the interactions between particles, interaction between the particles and the matrix fluid, and interactions between channel and particles. Thus consideration of above factors can lead to a better understanding of the rheological behavior of suspensions with particles flow. In this thesis, fluid with deformable particle and fluid with rigid particles are considered. A combination model of the three dimensional lattice Boltzmann method (LBM) and the immersed boundary method (IBM) are used to simulate these suspension systems. For the single particle deformation in the flow, the boundary thickness and value on transit time in a microchannel was analyzed. To see the physics behind the single particle in a micro channel, the path selection (navigation) of a single moving particle in a microfluidic channel network was analyzed. To see the interaction between wall property and suspension flow, deformable particles in hydrophobic and hydrophilic surface microfluidic channels was analyzed. To see the effect of particle roughness on rheology, the results of measuring the viscometric flow of concentrated rigid-sphere suspensions with constant-viscosity matrices, both Newtonian (silicone oil) and non-Newtonian were presented. Finally, the rough particle was analyzed by lattice Boltzmann method to find the physics behind the experimental results.

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Shah, Kumar. "Quantitative Analysis of Tobacco Specific Nitrosamine in Human Urine Using Molecularly Imprinted Polymers as a Potential Tool for Cancer Risk Assessment." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1954.

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Measuring urinary tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide conjugate may provide the best biomarker of tobacco smoke lung carcinogen metabolism. Existence of differences in the extent of NNAL metabolism rates may be potentially related to an individuals’ lung cancer susceptibility. Low concentrations of NNAL in smokers urine (<1 ng/mL) require sensitive and selective methods for analysis. Traditionally, this involves extensive, time-consuming sample preparation that limits throughput and adds to measurement variability. Molecularly imprinted polymers (MIPs) have been developed for the analysis of urinary NNAL by offline cartridge extraction combined with LC-MS/MS. This method when reproduced demonstrated problems with matrix effects. In the first part of this work, investigation of matrix effects and related problems with sensitivity for the published offline extraction method has been conducted. In order to address the need to improve throughput and other analytical figures of merit for the original method, the second part of this work deals with development of a high-throughput online microfluidic method using capillary-columns packed with MIP beads for the analysis of urinary NNAL. The method was validated as per the FDA guidance, and enabled low volume, rapid analysis of urinary NNAL by direct injection on a microfluidic column packed with NNAL specific MIP beads. The method was used for analysis of urinary NNAL and NNAL-Gluc in smokers. Chemometric methods were used with this data to develop a potential cancer-risk-assessment tool based on pattern recognition in the concentrations of these compounds in urine. In the last part, method comparison approaches for the online and the offline sample extraction techniques were investigated. A ‘fixed’ range acceptance criterion based on combined considerations of method precision and accuracy, and the FDA bioanalytical guidance limits on precision and accuracy was proposed. Data simulations studies to evaluate the probabilities of successful transfers using the proposed criteria were performed. Various experimental designs were evaluated and a design comprised of 3 runs with 3 replicates each with an acceptance range of ±20% was found appropriate. The off-line and the on-line sample extraction methods for NNAL analysis were found comparable using the proposed fixed range acceptance criteria.

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Tran, Thi Thuy. "Compact-disc microfluidic methods for characterization of therapeutic antibodies : Analysis of post-translational modifications." Doctoral thesis, Stockholms universitet, Institutionen för analytisk kemi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-83355.

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Characterization of post-translational modifications (PTMs) of therapeutic proteins is very important during the bioprocess development to maintain desired product quality and during the submission process to regulatory authorities for product approval. Monitoring glycosylation in pharmacokinetic studies can be useful to evaluate the dependence of clearance rates on different glycoforms. The cost and efficiency of characterization affect the speed to market of biopharmaceutical proteins. A reduction in the number of manual processing steps, cost of reagents and consumption of sample, as well as the time required for chemical analysis, is therefore necessary. The research presented in this thesis is focused on the potential of using microfluidic discs for automated, miniaturized, parallel and rapid sample preparation for PTM characterization of therapeutic monoclonal antibodies. Paper I describes the method development for N-linked glycosylation profiling. Several sample preparation steps have been performed in an integrated process in the microfluidic compact disc (CD). Paper II demonstrates the use of the method presented in paper I in combination with multivariate statistics for discrimination of glycosylation profiles of different therapeutic antibodies and simulation of a real case of quality control. Paper III is focused on a method for monitoring changes in glycosylation profiles of therapeutic antibodies in serum over time by incubation with an exoglycosidase enzyme. Paper IV describes the method for peptide mapping of therapeutic antibodies. In addition, recent work (unpublished results) assesses the potential of this method for methionine oxidation detection. The developed methods were fast, robust with low sample/reagent consumption. Generation of glycosylation profile data for one sample was established in approximately 2 h. The amount of samples and antigens loaded into the CD platform for one replicate was less than 0.3 μg and approximately 0.06 μg, respectively. Furthermore, considering the parallel function of the CD, conducting the analysis for 54 samples can be completed within a day. At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.

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Fiabane, Joe. "A novel method of producing microbubbles for targeted drug delivery." Thesis, Robert Gordon University, 2016. http://hdl.handle.net/10059/1579.

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Microbubbles, currently employed in diagnostic ultrasound as a contrast agent, have a potential new application as vehicles for targeted drug delivery, which could revolutionise medicine by eliminating side-effects. A new device is developed which outperforms all existing devices in terms of minimum microbubble size:channel diameter ratio. A numerical model is established to describe the flow behaviour and it is determined that the flow regime and resulting microbubble size are dependent on the ratio of inner- to outer Weber number.

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Tartagni, Ottavia <1992&gt. "Advanced cell culture platforms: methods for drug testing with microfluidics and microstructured devices." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2022. http://amsdottorato.unibo.it/10234/1/Tartagni_Ottavia_Advanced%20cell%20culture%20platforms%20methods%20for%20drug%20testing.pdf.

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Advanced cell cultures are developing rapidly in biomedical research. Nowadays, various approaches and technologies are being used, however, these culturing systems present limitations from increasing complexity, requiring high costs, and not easily customization. We present two versatile and cost-effective methods for developing culturing systems that integrate 3D cell culture and microfluidic platforms. Firstly, for drug screening applications, many high-quality cell spheres of homogeneous size and shape are required. Conventional approaches usually have a dearth of control over the size and geometry of cell spheres and require sample collection and manipulation. To overcome this difficulty, in this study, hundreds of spheroids of several cell lines were generated using multi-well plates that housed our microdevices. Tumor spheroids grow at a uniform rate (in scaffolded or scaffold-free environments) and can be harvested at will. Microscopy imaging are done in real time during or after the culture. After in situ immunostaining, fluorescence imaging can be conducted while keeping the spatial distribution of spheroids in the microwells. Drug effects were successfully observed through viability, growth, and morphologic investigations. Also, we fabricated a microfluidic device suitable for directed and selective cell culture treatments. The microfluidic device was used to reproduce and confirm in vitro investigations carried out using normal culture methods, using a microglia cell line. The device layout and the syringe pump system, entirely designed in our lab, successfully allowed culture growth and medium flow regulation. Solution flows can be finely controlled, allowing treatments and immunofluorescence in one single chamber selectively. To conclude, we propose the development of two culturing platforms (microstructured well devices and in-flow microfluidic chip), which are the result of separate scientific investigations but have the primary goal of performing treatments in a reproducible manner. Our devices shall improve future studies on drug exposure testing, representing adjustable and versatile cell culture systems.

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48

Rua, Gonzalez Diego. "Synthèse de matériaux catalytiques de type oxydes mixtes pour la production de méthanol par la précipitation en flux continu en système microfluidique." Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAF001.

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Le réchauffement climatique est une préoccupation pour les générations actuelles et futures en raison de l'augmentation des émissions de gaz à effet de serre (GES) dans l'atmosphère, principalement dues à la dépendance aux combustibles fossiles. L'utilisation de carburants alternatifs tels que le méthanol durable produit à partir de H2 renouvelable et de CO2 contribuerait à réduire les émissions de GES et les effets du changement climatique. La synthèse du méthanol à partir de matières premières riches en CO2 se fait préférentiellement en utilisant un catalyseur solide composé de CuO, ZnO et ZrO2. Ce type de catalyseur peut être produit par coprécipitation des espèces métalliques à l'aide d'un dispositif microfluidique, avec des avantages qui ont été démontrés par rapport aux catalyseurs synthétisés par coprécipitation discontinue. Dans ce travail, différents catalyseurs pour l'hydrogénation du CO2 en méthanol ont été synthétisés en utilisant la technique microfluidique dans différentes conditions, afin d'explorer différents paramètres de synthèse pouvant conduire au développement de catalyseurs plus actifs. Les différences de propriétés et d'activité entre un catalyseur synthétisé par la méthode microfluidique et un autre synthétisé par la méthode batch ont été étudiées, suivies d'une exploration des effets du temps de vieillissement et de la température de coprécipitation sur les catalyseurs. Enfin, l'effet de différentes compositions de catalyseurs sur les propriétés et l'activité a été déterminé, en étudiant différentes teneurs en CuO, l'utilisation de CeO2 comme promoteur et l'utilisation de In2O3 comme promoteur et comme métal actif Global warming is a concern for the current and future generations due to the increasing greenhouse gases (GHG) emissions to the atmosphere, mainly due to the dependence on fossil fuels. The use of alternative fuels such as sustainable methanol produced from renewable H2 and from CO2 would contribute to reduce the GHG emissions and the effects of climate change. The synthesis of methanol using CO2 rich feedstock is preferentially done by using a solid catalyst composed of CuO, ZnO and ZrO2. This type of catalyst can be produced by coprecipitation of the metal species using a microfluidic device, with advantages that have been demonstrated over catalysts synthesized by batch coprecipitation. In this work, different catalysts for the hydrogenation of CO2 to methanol were synthesized using the microfluidic technique under different conditions, in order to explore different synthesis parameters that could lead to the development of more active catalysts. The differences in the properties and activity between a catalyst synthesized by the microfluidic method and another synthesized by the batch method were investigated, followed by an exploration of the effects of the aging time and the coprecipitation temperature on the catalysts. Lastly, the effect of different compositions of catalysts on the properties and activity were determined, by investigating different CuO contents, the use of CeO2 as a catalyst promoter, and the use of In2O3 as a catalyst promoter and as active metal

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49

Steiner, Thomas. "Dissipative particle dynamics simulation of microfluidic systems with fluid particle methods on high performance computers." Aachen Shaker, 2009. http://d-nb.info/995271100/04.

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50

Alabi, Oluwarotimi Ocilama. "The development of microfluidic and surface enhanced Raman methods for petroleum analysis : asphaltene and naphthenic acids." Thesis, University of Aberdeen, 2015. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=228647.

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Microfluidic H-cells and surface enhanced Raman spectroscopy are capable of analysing the asphaltene content of petroleum. An H-cell is a microfluidic device that exploits the non-turbulent flow of fluids within a micrometre-dimensioned channel. Diffusive separation in an H-cell permits a liquid that is miscible with the sample matrix to be used as an extractant. It was demonstrated that n-hexane can be used as extractant to obtain an asphaltene-free fraction of oil. The difference between the UV-Vis adsorption spectra of the asphaltene-free oil and the oil sample can then be used to estimate its asphaltene content. This has been demonstrated for a range of oils with asphaltene content between 1-30% and API gravity values between 40-10°, thus liquid petroleum and bitumen can be rapidly assayed by an H-cell; similarly, asphaltene and carboxylic acid content of oil can be determined simultaneously when methanol is used as extractant. The results were shown to be comparable to assays achieved via the ASTM D4124 and ASTM D974 methods respectively. For the first time it was demonstrated that surface enhanced Raman spectroscopy, using a gold substrate and illumination at 514 nm, can detect extremely low concentrations of asphaltene. This was shown to be achievable for asphaltene and related materials at concentrations of 0.001 ppm. In addition, data also demonstrated that the core of the Raman-responsive units within asphaltene have crystallite sizes equivalent to the Raman-responsive units in kerogen (~3 nm). Both methods provide technological advances because they make it possible to detect asphaltene in small sample volumes, using smaller footprint instrumentation. The H-cell method would be extremely useful for appraising oilfield potential, record the attenuation of oil-spills and provide frequent geochemical data that can monitor these at point of need. Similarly, the SERS technique widens the field of application into areas previously inaccessible to current techniques such as the effect of low concentrations of asphaltene-like materials in ecological and living systems.

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Tesi sul tema "Microfluidic method"

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