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Fallahi, Hedieh. "Flexible and Stretchable Microfluidics." Thesis, Griffith University, 2022. http://hdl.handle.net/10072/415361.
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Microfluidics is the science and technology of manipulating and analysing small amounts of liquid. Microfluidics has several advantages including small sample volume, small footprint, being cheap, portable, and precise. Microfluidics has applications in a wide range of areas such as in chemistry, electronics, and most importantly in biological sciences.
Microfluidic functions are greatly influenced by the geometry and dimensions of the microchannels. The main challenge facing microfluidics is that once the conventional rigid microfluidic device is fabricated, its dimensions cannot be changed or modified.
To overcome this problem, we proposed the concept of flexible and stretchable microfluidics. Stretchable microfluidics allows flexible devices to change their dimensions and thus enabling new functionalities. This thesis aims to (i) understand the fundamentals of flexible microfluidics, (ii) design and fabricate a new generation of stretchable microfluidic devices with tuneable dimensions, and (iii) apply stretchable microfluidics to three main handling tasks of separation mixing and trapping. Our main goal is to evaluate how the dimensions of different types of microfluidic devices alter under elongation and how these dimensional changes influence its functions.
In this thesis, following a comprehensive introduction in chapter 1, a thorough literature review over flexible microfluidics is provided in chapter 2. The review covers three main areas of flexible microfluidics including materials, effect of flexibility on microfluidic functions, and the current applications and future perspectives of flexible microfluidics.
Chapter 3 and 4 investigate the effect of stretchability on inertial microfluidics. Inertial microfluidics is a promising approach for particle separation. The current obstacle of inertial microfluidics in biological applications is the broad size distribution of biological microparticles. Rigid microfluidic devices work well for a narrow range of particle sizes. For focusing and separating a new set of particles, troublesome and time-consuming design, fabrication, testing, and optimization procedures are needed. Thus, a stretchable a microfluidic device with tuneable dimensions was fabricated and studied in chapter 3. By changing the channel dimensions under elongation, the device could be adapted to different particle sizes and flow rate ratios. Stretching the device significantly improved the focusing and separation efficiency of the specific particle sizes. In chapter 4, we focused on the application of stretchable inertial microfluidics for cancer detection. The performance of the stretchable device was verified by isolating cancer cells from WBCs and from whole blood with high recovery rates and purities.
Chapter 5 studies the effect of stretchability on micromixing. A micromixer is an indispensable component in miniaturised platforms for chemical, biochemical, and biomedical applications. Mixing in microscale is challenging due to the laminar flow associated with low Reynolds numbers. This chapter reports a stretchable micromixer with dynamically tuneable channel dimensions. Periodic elongation of the stretchable micromixer results in mixing disturbance in intermediate Reynolds numbers. Periodically stretching the device changes the channel geometry and dimensions leading to dynamically evolving secondary and main flows. We evaluated the performance of this stretchable micromixer both experimentally and numerically.
Chapter 6 reports a stretchable microtrapper. Microfluidic technologies have been widely used for single-cell trapping. However, there are no robust methods for the facile release of the captured cells for subsequent studies. Therefore, we developed a stretchable microfluidic cell trapper for easy on-demand release of cells in a deterministic manner. By tunning the horizontal elongation of the device, the gap at the bottom of the traps widened and provided ample space for releasing particle/cell with sizes of interest. The proposed stretchable micro trapper demonstrated a deterministic recovery of the captured cells by adjusting the elongation length of the device.
Flexible and stretchable microfluidic devices with tuneable dimensions were introduced and studied extensively in this thesis. We showed that by applying stretchability to microfluidic functions including inertial microfluidics, micromixing, and single cell studies, several drawbacks associated with fixed dimensions were addressed and recovered. We believe that flexible and stretchable microfluidics is a new research direction of microfluidics.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
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Fiorini, Gina S. "Polymeric microfluidic devices : development of thermoset polyester microfluidic devices and use of poly(dimethylsiloxane) devices for droplet applications /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/8627.
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Gallagher, Sarah. "Microfluidic confinement of responsive systems." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648567.
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Chen, Tian Lan. "Thermal digital microfluidic devices for rapid DNA analysis." Thesis, University of Macau, 2017. http://umaclib3.umac.mo/record=b3691869.
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Sun, Han. "Novel microfluidic platform for bioassays." HKBU Institutional Repository, 2019. https://repository.hkbu.edu.hk/etd_oa/699.
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Microfluidics have been created to acquire, operate, and process complex fluids in extremely tiny volumes with high efficiency and high speed, and without the requirement for an experienced operator. In addition, microfluidic systems also enable miniaturization and incorporation of different complex functions, which can help bring intricate diagnostic tools out of the laboratories. Ideally, these systems should be inexpensive, precise, reliable, robust, and well-suited to the medical diagnostic systems. Most of the microfluidic devices reported previously were based on devices made of polydimethylsiloxane (PDMS). PDMS is a material that dissolves in many common organic solvents. Meanwhile, it is also prone to absorb small molecules like the proteins, which is detrimental to a stable and reliable result. Current work focuses on bioassays that are badly needed in our life and these bioassays are addressed based on microfluidic platform with different materials. The translation of microfluidic technology into large scale implementations highly relies on new materials that address the limitations of PDMS. Firstly, we fabricated two different microfluidic platforms for rapid antimicrobial susceptibility testing (AST). One was made of hydrogel, and the bacterial cells were cultured on the top of the device; the other was of polypropylene (PP), and bacterial cells were cultured inside the microchannels. Meanwhile, we developed a novel "barcode" sensor, a microscope-free method for cell accumulation and cell counting, as the downstream of the PP-based chips. As a result, AST can be accomplished simply through an application on a mobile phone rather than using an expensive and sophisticated microscope. Secondly, we presented a self-contained paper-based system for lead(II) ion detection based on G-quadruplex-based luminescence switch-on assay, comprising a novel type of paper-based chip and a matching portable device. Different from the reported paper-based devices, the paper substrate we chose was art paper, which is used for printing magazines. This type of paper could prevent the absorption of liquid into the paper matrix and hold the liquid in place for a period of time; and it could also be used for temporary liquid containing like a plastic substrate (such as polypropylene (PP) and polystyrene (PS)), but the surface of the paper is inherently hydrophilic. In such a design, liquid drops are suspended on the surface of the device in designed reservoirs, rather than absorbed into the paper; when the chip is tilted, the liquid drops will move to other reservoirs according to the guidance of channels defined on the surface. To differentiate it from reported μPAD devices that are fabricated with water-permeable paper, we name this new type of paper-based devices suspending-droplet mode paper-based microfluidic devices (SD-μPAD). Different from the conventional μPADs that use capillary force to drive liquid, our SD-μPADs uses wetting and gravity as driving force. To fabricate the superhydrophobic pattern on the paper device, we developed a new microcontact printing-based method to produce inexpensive and precisely patterned superhydrophobic coating on paper. The coating material is poly(dimethylsiloxane) (PDMS), a hydrophobic and transparent silicone that has long been used for fabricating microfluidic devices. Importantly, the negative-relief stamp we used is made of Teflon, a non-stick polymer, so that the PDMS-coated paper could be peeled from the stamp flawlessly. After such fabrication process, the stamped area of the paper is coated with a textured PDMS layer that is decorated with arrays of micropillars, which could provide superhydrophobic effect and most effectively hold the droplets in place; the remaining area of the paper is still hydrophilic. As a demonstration of this new design, we developed a method using the reaction characteristics of iridium(III) complex for rapid, onsite detection of lead(II) ions in liquid samples. As the reagents have already been loaded onto the paper device during fabrication, the only reagent the users need to add is water. Because of the large Stokes shift of the iridium(III) complex probe, inexpensive optical filters can be employed, and we were able to make an inexpensive, battery-powered compact device for routine portable detection using a smartphone as a detector, allowing the rapid analysis and interpretation of results on site as well as the automatic dissemination of data to professional institutes, including tests even in poor rural areas in developing countries. Thirdly, we upgraded our suspending-droplet mode paper-based microfluidic device (SD-μPAD), which is used for the detection of lead(II) ions in liquid solution. The reason is that our paper-based SD chips are not suitable for long reaction process (> 20 min) detection of biomolecules due to the potential permeation and contaminating problems of art papers. Hence, we chose polypropylene (PP), a hydrophobic, cheap, and thermal stable material (< 110°C), as the material for the fabrication of the SD microfluidic chip. We established a convenient, low-cost, portable and reliable platform for monitoring VEGF165 accurately, which can be applied for point-of-care (POC) testing. In this project, we also employed the label-free oligonucleotide-based luminescence switch-on assay on the microfluidic platform, which possesses the advantages of high sensitivity and high selectivity. Based on the detection of VEGF165 in a three-step reaction process, we adopted a new design for the droplet transfer throughout the channels. This design could migrate the droplet through the chambers via controlling the orientation of the chip, which systematically combined the superhydrophobic force of the coating, the gravity of the droplet and the surface tension between PP and droplet. Therefore, traditional micro pump could be avoided and the total cost for the device could be substantially reduced. In addition, we developed an automatic, matched and portable device for the detection of VEGF165, which assembled by a rotatable chip holder, a UV lamp, a filter, and a camera. Finally, we developed a new whole Teflon membrane-based chip for the aptamer screening. Our article "Whole-Teflon microfluidic chips" introduced the fabrication of a microfluidic device entirely using Teflon materials, one group of the most inert materials in the world. It was a successful and representative introduction of new materials into the fabrication of microfluidic devices, which show dramatically greater anti-fouling performance. However, even such device was inadequate for current purpose, as it is rigid and lacks convenient valve control functions for particle suspensions used in systematic evolution of ligands by exponential enrichment (SELEX). For this project, we propose a SMART screening strategy based on a highly integrated microfluidic chip. This new type of whole-Teflon devices, which are made of flexible Teflon membranes, offering convenient valving control for the whole SELEX process to be performed on chip and fulfilling the anti-fouling requirement in the meantime. The SELEX cycles including positive and negative selections could be automatically performed inside tiny-size microchambers on a microchip, and the enrichment is real-time monitored. The selection cycles would be ended after the resulted signal of the aptamers with high specificity reached a plateau, or no target aptamer is captured after a number of cycles of enrichment. Owning to the antifouling property of the chip materials, the loss of the sample is tremendously reduced. The SMART platform therefore is not only free of complicated manual operations, but also high-yield and well reproducible over conventional methods
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Weinert, Franz Michael. "Optothermal microfluidics." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-110908.
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Stenestam, Björn. "Acoustic trapping of sub-micrometreparticles within microfluidics particles within microfluidics." Thesis, Uppsala universitet, Mikrosystemteknik, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-432446.
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The aim of this project was to prove that a pre-existing standardmethod for bacterial-DNA extraction can be reduced down to the microscale and in doing so be used in an on-chip setting.The first phase in this project was to identify an appropriate methodand material for droplet generation. The first material to beassessed was poly ethylene glycol (PEG), which proved unstable andtherefore unsuitable. In contrast agarose, with its low gellingtemperature, proved to be a suitable material for droplet generationfor the purpose of this project.The second phase of this project was to design and fabricate anacoustic trapping chip using Si- and glass-wafers. When the agarosedroplets were evaluated inside of the trapping chip, they proved tohave a negative contrast factor, resulting in the droplets beingpushed out along the walls of the trapping chamber. This was solvedby mixing plastic beads in to the agarose solution used for dropletfabrication.The diffusion of particles into the agarose droplets was thenevaluated both inside and outside of the chip in order to prove thatthe chemicals intended to be used during DNA extraction would be ableto diffuse into the droplets.The end conclusion is that the experiments performed in this projecthave proved that the methods, chip designs and materials would workfor bacterial-DNA extraction on-chip.
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Ribeiro, Luiz Eduardo Bento. "Sensor químico baseado em microponte de impedância = Chemical sensor based on impedance microbridge." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/259031.
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Orientador: Fabiano FruettDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação
Made available in DSpace on 2018-08-21T04:02:00Z (GMT). No. of bitstreams: 1 Ribeiro_LuizEduardoBento_M.pdf: 4022818 bytes, checksum: d2a40b9cee4f59bc80ec0b09a97c31a8 (MD5) Previous issue date: 2012
Resumo: A integração de sistemas microeletrônicos em lab-on-a-chip está sendo cada vez mais necessária para concretizar novas aplicações dentro do emergente campo da microfluídica. Tanto na química quanto na bioquímica e até mesmo na medicina e bioengenharia, a microfluídica evolui conquistando um espaço crescente. Entretanto, desafios tecnológicos residem na sua complexa fabricação e integração com sistemas eletrônicos. Neste trabalho, foi desenvolvido um sistema sensor que emprega métodos de fabricação compatíveis tanto com a microeletrônica quanto com a microfluídica. Este sistema sensor é baseado em uma microponte de impedância composta por quatro capacitores interdigitados. Neste sistema, o fluido, guiado por um canal ou armazenado em um reservatório fabricado em polidimetilsiloxano (PDMS), passa sobre a microponte enquanto um termistor, fabricado no mesmo substrato, permite monitorar a temperatura do sistema durante a medida. A microponte é formada de eletrodos interdigitados arranjados de forma a permitir a utilização de um circuito eletrônico de condicionamento que pode ser construído bem próximo do elemento sensor. O trabalho foi validado comparando-se a função de transferência experimental do sensor, usando como analito a mistura etanol-água, com a função de transferência teórica obtida através de simulação baseada em elementos finitos. Identificamos a importância da deposição de um filme fino de boa qualidade para a proteção dos eletrodos de referência e sua influência na função de transferência experimental. Ainda, devido à utilização de materiais inertes como ouro, vidro e PDMS, o sistema sensor, com alguns ajustes, pode ser empregado para outras aplicações: desde o monitoramento da pureza e concentração de líquidos até a caracterização de filmes finos sensíveis a patógenos e fármacos
Abstract: The integration of microelectronic systems in lab-on-a-chip is being increasingly required to implement new applications on the emerging field of microfluidics. Both in chemistry and biochemistry, and even in medicine and bioengineering, microfluidics evolves gaining a growing space. However, technological challenges lie in its complex manufacturing and integration with electronic systems. In this work, we developed a sensor system that employs both fabrication methods compatible with microelectronics and with microfluidics. This sensor system is based on an impedance microbridge composed of four interdigitated capacitors. In this system, the fluid which is guided by a channel or is stored in a reservoir made of polydimethylsiloxane (PDMS), passes over the microbridge while a thermistor fabricated on the same substrate allows monitoring of the system temperature during the measurement. The microbridge is made of interdigitated electrodes arranged so as to allow the use of an electronic conditioning circuit that can be built very close to the sensor element. The study was validated by comparing experimental transfer function of the sensor, using the ethanol-water mixture as analyte, with the theoretical transfer function obtained by simulation based on finite element method. We identified the importance of depositing a good quality thin film for the protection of reference electrodes and its influence on experimental transfer function. Also, due to the use of inert materials such as gold, glass and PDMS, the sensor system, with some adjustments, can be used for other applications: from monitoring of the concentration and purity of liquid to the characterization of thin films sensitive to drugs and pathogenic agents
Mestrado
Eletrônica, Microeletrônica e Optoeletrônica
Mestre em Engenharia Elétrica
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Hardy, Brian Sauer. "Thermally-actuated microfluidics." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1998391971&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Chaurasia, Ankur Shubhlal. "Buoyancy-assisted microfluidics." Thesis, King's College London (University of London), 2016. https://kclpure.kcl.ac.uk/portal/en/theses/buoyancyassisted-microfluidics(cf325bbd-9de2-4934-a811-2cf904c246ee).html.
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A buoyancy-assisted microfluidic approach is introduced for facile production and collection of uniform drops within a wide range of sizes, particularly on a millimetre scale, which is not easily achievable via conventional microfluidic approach. The proposed methodology, characterised by vertical orientation and non-confined quiescent outer phase of the device used, was also applied to droplet-in-droplet and droplet-in-fibre encapsulation using a co-axial glass microcapillary arrangement, to obtain millimetric capsules and multi-compartmental fibres. The shell thickness of double emulsions was tuned, via altering flow rates and formulations, to produce millimetric ultrathin shelled capsules. Alginate fibres with different oil-encapsulate geometries were fabricated, via simultaneous oil-droplet formation and encapsulation, and characterised and analysed for their encapsulation volume, surface roughness, spillage ratio and mechanical strength. Furthermore, the size and locations of oil encapsulates were manipulated to obtain asymmetric fibres with parallel oil streams. An asymmetric encapsulation approach was designed and used to fabricate dehydration-responsive fibres, which demonstrated a benign and facile dehydration-triggered core-release mechanism. This core-release response was also demonstrated for fibres with parallel oil-encapsulates with multiple cargos. The fibre morphology was also tuned to provide an enhanced response to its mechanical failure, marked by a simultaneous release of potentially reactive components at the point of fracture. Such fibres, can behave as fibres with self-repairing properties. The buoyancy-assisted microfluidics was also used to produce microfibres containing gas encapsulates with tuneable morphology. The buoyancy force, driven by the trapped microbubbles, was utilised for stretching the gelling alginate fibres to fabricate ultrathin alginate microfibres, a feature not possible via conventional horizontally-oriented microfluidic techniques. The collected bubble-filled fibres were also morphed to produce new varieties of fibres, such as beaded fibres and fibres with segmented aqueous cores.
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Ogden, Sam. "High-Pressure Microfluidics." Doctoral thesis, Uppsala universitet, Mikrosystemteknik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-208915.
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In this thesis, some fundamentals and possible applications of high-pressure microfluidics have been explored. Furthermore, handling fluids at high pressures has been addressed, specifically by creating and characterizing strong microvalves and pumps. A variety of microstructuring techniques was used to realize these microfluidic devices, e.g., etching, lithography, and bonding. To be able to handle high pressures, the valves and pumps need to be strong. This necessitates a strong actuator material. In this thesis, the material of choice is paraffin wax. A new way of latching paraffin-actuated microvalves into either closed or open position has been developed, using the low thermal conductivity of paraffin to create large thermal gradients within a microactuator. This allows for long open and closed times without power consumption. In addition, three types of paraffin-actuated pumps are presented: A peristaltic high-pressure pump with integrated temperature control, a microdispensing pump with high repeatability, and a pump system with two pumps working with an offset to reduce flow irregularities. Furthermore, the fundamental behavior of paraffin as a microactuator material has been explored by finite element modeling. One possibility that arises with high-pressure microfluidics, is the utilization of supercritical fluids for different applications. The unique combination of material properties found in supercritical fluids yields them interesting applications in, e.g., extraction and cleaning. In an attempt to understand the microfluidic behavior of supercritical carbon dioxide, the two-phase flow, with liquid water as the second phase, in a microchannel has been studied and mapped with respect to both flow regime and droplet behavior at a bi-furcating outlet.
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Neale, Steven Leonard. "Optically controlled microfluidics." Thesis, University of St Andrews, 2007. http://hdl.handle.net/10023/147.
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Three projects are described in this thesis that combine microfabrication techniques with optical micromanipulation. The aim of these projects is to use expertise in microlithography and optical tweezing to create new tools for Lab-on-Chip devices. The first project looks at the creation of microgears that can be moved using an optical force. The microgears include one dimensional photonic crystal that creates birefringence. This allows the transfer of angular momentum from a circularly polarised light beam to the microgear, making them spin. The microgears are simulated, fabricated and tested. Possible biological applications are suggested. The second project looks at creating microchannels to perform micromanipulation experiments in. Different methods of fabricating the microfluidic channels are compared, and the resulting chambers are used to find the maximum flow rate an optical sorting experiment can be performed at. The third project involves using a thin photoconductive layer to allow the optical control of an electrical force called dielectrophoresis. This light induced dielectrophoresis (LIDEP) allows similar control to optical tweezing but requires less irradiance than optical tweezing, allowing control over a larger area with the same input optical power. A LIDEP device is created and experiments to measure the electrical trap size that is created with a given optical spot size are performed. These three projects show different microfabrication techniques, and highlight how well suited they are for use in optical manipulation and microfluidic experiments. As the size of objects that can be optically manipulated matches well with the size of objects that can be created with microfabrication, it seems likely that many more interesting applications will develop.
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Barrett, Louise M. "Polymers in microfluidics." Thesis, Loughborough University, 2004. https://dspace.lboro.ac.uk/2134/16615.
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There is great interest in miniaturized analytical systems for life science research, the clinical environment, drug discovery, biotechnology, quality control, and environmental monitoring and numerous articles have been written which predict the success of microfluidic based systems. It was demonstrated in this work that a microfluidic flow system could be quickly and easily manufactured in a research lab environment without the need for clean room facilities. The microfluidic device was created using polymethylmethacrylate, a CO2 laser and a standard oven. The device was designed, manufactured and ready for use within three hours. This work also investigated a chemiluminescent system which was intended for use in protease assays in the microfluidic device. This work also focused on the use of photoinitiated polymer monoliths, with immobilized tannic acid, as protein preconcentrators. The function of the monolithic devices was demonstrated by pumping low concentration solutions of BSA BODIPY® FL through the monolith. Both loading and elution were done using pressure. It was shown that BSA could be concentrated on and successfully eluted from the monolith. The elution volume for a 125 nl monolith was found to be 4 μl. Therefore an injection of a 60 μl sample of 1 x 10⁻⁹M BSA BODIPY ® FL gave rise to a concentration factor of 15. The pH optimum for the binding of BSA BODIPY ® FL was found to be pH 8.0 and the loading capacity of the tannic acid monolith was found to be 0.6 mg.ml⁻¹.
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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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Owens, Crystal (Crystal E. ). "Modular LEGO brick microfluidics." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/117456.
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Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2017.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 93-96).
Wider use and adaptation of microfluidic systems is hindered by the infrastructure, knowledge, and time required to build prototype devices, especially when multiple fluid operations and measurements are required. As a result, rapid prototyping methods based on planar and three-dimensional printing are attracting interest; however, these techniques cannot produce structures with the resolution, smoothness, and feature size needed for standard microfluidic devices. Herein I present a new approach to rapidly construct modular microfluidic systems by modification and assembly of interlocking injection-molded blocks. I demonstrate this principle using micromilling of store-bought LEGO® bricks to create surface fluidic pathways on bricks, and develop procedures for sealing and interconnecting bricks to form modular, reconfigurable microfluidic systems. Micromilling using a desktop machine achieves channel dimensions of 50 pm in depth and 150 pm in width, or greater, etched into the sidewalls of blocks. Sealing these channels with adhesive films allows internal fluid pressure of at least 400 kPa. The intrinsic tolerances of injection molded bricks and their elastically averaged connections gives mechanical locating repeatability of 1 pm, which enables fluid to pass between bricks via an O-ring with >99.9% sealing reliability. Using the LEGO-based approach, I build systems made of assembled brick units for generating droplets, sensing light, sorting with inertial and magnetic forces, and repeatably positioning a smartphone camera, and characterize their performance. Then, I fabricate and measure LEGO-like bricks made by FDM and SLA three-dimensional printing, showing that they can integrate with injection-molded bricks to add useful function, although their surface quality, resolution, and material limit performance. In addition, I adapt these components for two educational activities for high school students: a colorimetric titration device and a modular designable boat. The standard interface among all bricks enables a wide variety of brick units to be incorporated onto a common platform, making this "lab on a brick" a new and viable platform for advancing research and education in microfluidics.
by Crystal Owens.
S.M.
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Ahmed, Tanvir Ph D. Massachusetts Institute of Technology. "Microfluidics for bacterial chemotaxis." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/66851.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2011.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 136-151).
Bacterial chemotaxis, a remarkable behavioral trait which allows bacteria to sense and respond to chemical gradients in the environment, has implications in a broad range of fields including but not limited to disease pathogenesis, in-situ bioremediation and marine biogeochemistry. And therefore, studying bacterial chemotaxis is of significant importance to scientists and engineers alike. Microfluidics has revolutionized the way we study the motile behavior of cells by enabling observations at high spatial and temporal resolution in carefully controlled microenvironments. This thesis aims to explore the potential of microfluidic technology in studying bacterial behavior by investigating different aspects of bacterial chemotaxis on a microfluidic platform. We quantified population-scale transport parameters of bacteria using videomicroscopy and cell tracking in controlled chemoattractant gradients. Previously, transport parameters have been derived theoretically from single-cell swimming behavior using probabilistic models, but the mechanistic foundations of this up-scaling process have not been proven experimentally. The parameter estimates computed directly from single-cell swimming information showed good agreement with literature values providing the experimental verification of the upscaling from single cells to population-scale models. Furthermore, we also developed a diffusion-based microfluidic device to generate steady, arbitrarily shaped chemical gradients. Steady gradients, linear or nonlinear, are often a useful model of the bacterial microenvironment to study chemotaxis in the limit of slow patch diffusion or fast motility of free swimming bacterial cells. Observed cell distribution along the gradients showed good agreement with predictions from the bacterial transport equation, providing the first quantification of chemotaxis in steady nonlinear gradients. Also, by observing the time series of the bacterial distributions in different scaled gradients (both steady and unsteady) generated using microfluidic devices, the bacterial response was found to be invariant up to an 87-fold change in ambient chemoattractant concentration. These observations provide an explanation for the ability of bacteria to cope with a broad range of chemical concentrations and gradients in the environment, by means of a flexible sensing network that allows them to rescale their response to take maximum advantage of signals, while discounting less-informative background information. Finally, a microfluidic lattice habitat was developed to study the fate of a chemotactic bacterial population under the pressure of predation. It was observed that the demographic and spatial organization of the bacterial prey population depended on the predator-to-prey ratio as well as on the degree of heterogeneity of the habitat structure. These results represent a first step towards predator-prey microcosms and pave the way for future predator-prey metapopulation studies.
by Tanvir Ahmed.
Ph.D.
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Ge, Zhifei Ph D. Massachusetts Institute of Technology. "Microbial instrumentation utilizing microfluidics." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/108948.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2017.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 126-150).
Reconstruction of phylogenetic trees based on 16S rRNA gene sequencing reveals abundant microbial diversity in nature. However, studies of microbiology have been limited by the capabilities to replicate the natural environment or artificially manipulate cells. Advances in microbial instrumentation with microfluidics can break through these challenges. In nature, bacteria live in communities with abundant inter-species chemical communication. To replicate such environments in laboratory conditions, nanoporous microscale microfluidic incubators (NMMIs) for co-culture of multiple species have been developed. The NMMIs enable high-throughput screening and real-time observation of multiple species co-cultured simultaneously. The key innovation in the NMMIs is that they facilitate inter-species communication while maintaining physical isolation between species. NMMIs are a useful tool for the discovery of previously uncultivated organisms and for the study of inter-species microbial interactions. The land and seas are teeming with microbes but one region of the environment often neglected is the air. Large numbers of microbes are present in air yet little is known about the mechanisms that lead to their dispersion. We have elucidated one such dispersion mechanisms involving rain and soil bacteria. The experimental system replicates the process of raindrops impinging on soil surfaces that contain bacteria. It is demonstrated that up to 0.01% of soil bacteria can be dispersed by aerosolization and survive for more than an hour after the aerosolization process. This mechanism can be relevant for the investigation of climate change, pathogenic disease transmission, and geographic migration of bacteria. In spite of the challenges outlined above there are thousands of known species of bacteria that have been catalogued and genetically sequenced. However, few of these organisms are amenable to modem genetic manipulation tools. Thus there is a great benefit for a tool that accelerates the development of efficient genetic transformation protocols. We have developed a microfluidic electroporation device to address this challenge. The key novelty is the microchannel geometry which applies a linear electric field gradient to each sample. This design enables rapid determination of the electric field that leads to quantifiable bacterial electroporation. Bacterial strains with both industrial and medical relevance have been successfully characterized using this assay.
by Zhifei Ge.
Ph. D.
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Gong, Hua. "3D Printing for Microfluidics." BYU ScholarsArchive, 2018. https://scholarsarchive.byu.edu/etd/7690.
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This dissertation focuses on developing 3D printing as a fabrication method for microfluidic devices. Specifically, I concentrate on the 3D printing approach known as Digital Light Processing stereolithography (DLP-SLA) in which serially projected images are used to sequentially photopolymerize layers to build a microfluidic device. The motivation for this work is to explore a much faster alternative to cleanroom-based microfabrication that additionally offers the opportunity to densely integrate microfluidic elements in compact 3D layouts for dramatic device volume reduction. In the course of my research, an optical approach was used to guide custom resin formulation to help create the interconnected hollow regions that form a microfluidic device. This was based on a new a mathematical model to calculate the optical dose delivered throughout a 3D printed part, which also explains the effect of voids. The model was verified by a series of 3D printed chips fabricated with a commercial 3D printer and a custom resin. Channels as small as 108 µm x 60 µm were repeatably fabricated. Next, highly compact active fluidic components, including valves, pumps, and multiplexers, were fabricated with the same 3D printer and resin. The valves achieved a 10x size reduction compared with previous results, and were the smallest 3D printed valves at the time. Moreover, by adding thermal initiator to thermally cure devices after 3D printing, the durability of 3D printed valves was improved and up to 1 million actuations were demonstrated.To further decrease the 3D printed feature size, I built a custom 3D printer with a 385 nm LED light source and a 7.56 µm pixel pitch in the plane of the projected image. A custom resin was also developed to take advantage of the new 3D printer's features, which necessitated developing a UV absorber screening process which I applied to 20 candidate absorbers. In addition, a new mathematical model was developed to use only the absorber's molar absorptivity measurement to predict the resin optical penetration depth, which is important for determining the z-resolution that can be achieved with a given resin. The final resin formulation uses 2-nitrophenyl phenyl sulfide (NPS) as the UV absorber. With this resin, along with a new channel narrowing technique, I successfully created flow channel cross sections as small as 18 µm x 20 µm.With the custom 3D printer, smaller valves and pumps become possible, which led to the invention of a new method of creating large numbers of high density chip-to-chip microfluidic interconnects based on either simple integrated microgaskets (SIMs) or controlled-compression integrated microgaskets (CCIMs). Since these structures are directly 3D printed as part of a device, they require no additional materials or fabrication steps. As a demonstration of the efficacy of this approach, 121 chip-to-chip interconnects in an 11 x 11 array for both SIMs and CCIMs with an areal density of 53 interconnects per square mm were demonstrated, and tested up to 50 psi without leaking. Finally, these interconnects were used in the development of 3D printed chips with valves having 30x smaller volume than the valves we previously demonstrated. These valves served as a building block for demonstrating the miniaturization potential of an active fluid mixer using our 3D printing tools, materials, and methods. The mixer provided a set of selectable mixing ratios, and was designed in 2 configurations, a linear dilution mixer-pump (LDMP) and a parallelized dilution mixer-pump (PDMP), which occupy volumes of only 1.5 cubic mm and 2.6 cubic mm, respectively.
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Kang, Kai. "Microfluidics of complex fluids." The Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1064325460.
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Cortright, Emily Celia. "Microfluidics of DNA Suspensions." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1242236618.
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Luo, Yiqi. "Chemical applications of microfluidics /." May be available electronically:, 2008. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
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Kang, Kai. "Microfluidics of complex liquids." Connect to this title online, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1064325460.
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Thesis (Ph. D.)--Ohio State University, 2003.Title from first page of PDF file. Document formatted into pages; contains xiv, 212 p.; also includes graphics. Includes bibliographical references (p. 195-202).
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Yunus, Kamran. "Electrochemical approach to microfluidics." Thesis, University of Bath, 2003. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426200.
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Hinojosa, Christopher David. "Silk Cryogels for Microfluidics." PDXScholar, 2012. https://pdxscholar.library.pdx.edu/open_access_etds/513.
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Silk fibroin from silkworm cocoons is found in numerous applications ranging from textiles to medical implants. Its recent adoption as a biomaterial is due to the material's strength, biocompatibility, self-assembling behavior, programmable degradability, optical clarity, and its ability to be functionalized with antibodies and proteins. In the field of bioengineering it has been utilized as a tissue scaffolding, drug delivery system, biosensor, and implantable electrode. This work suggests a new application for porous silk in a microscale chromatography column. We demonstrate in situ cryotropic polymerization of highly porous structures in microscale geometries by freezing aqueous silk with a solvent. The resulting cryogels are experimentally characterized using flow parameters common in chromatography design; tortuosity, global pressure drop, pore diameter, and porosity. These empirical parameters are put into porous flow models to calculate an order-of-magnitude increase in functional surface area over the blank capillaries and packed-sphere columns used in traditional designs. Additionally, the pressure requirements to produce relevant flow rates in these structures are found not to threaten the integrity of microfluidic seals or connectors.
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Balbino, Tiago Albertini 1987. "Desenvolvimento de processo microfluídico para incorporação de DNA em lipossomas catiônicos destinados a terapia e vacinação gênica = Development of microfluidic process for DNA incorporation into cationic liposomes for gene therapy and vaccination." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/266739.
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Orientadores: Lucimara Gaziola de La Torre, Adriano Rodrigues AzzoniDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química
Made available in DSpace on 2018-08-20T20:39:39Z (GMT). No. of bitstreams: 1 Balbino_TiagoAlbertini_M.pdf: 2581790 bytes, checksum: 674a2d22b439ef811cbfb642774f6d4d (MD5) Previous issue date: 2012
Resumo: Esta pesquisa teve como objetivo o desenvolvimento tecnológico de processo microfluídico para a obtenção de vetores não virais, baseados na complexação eletrostática entre lipossomas catiônicos (LC) e DNA plasmideal (pDNA) destinados à terapia e vacinação gênica. O desenvolvimento desse processo foi comparado ao processo convencional "bulk", que, a partir da simples mistura manual entre as soluções ou em sistema de vórtice, gera dificuldade no controle do tamanho destas estruturas e pode produzir variações nos resultados biológicos e na estabilidade coloidal. Já o processo microfluídico, que utiliza dispositivos que processam pequenas quantidades de fluidos (10-9 a 10-18 litros), permite a complexação eletrostática em regime contínuo, com o controle das condições difusionais, o que também permite melhor controle do tamanho destes complexos. Metodologicamente, o trabalho foi dividido em três principais etapas: na primeira parte, foi realizado o estudo físico-químico, estrutural e biológico dos complexos pDNA/LC obtidos por processo "bulk". Nessa etapa, verificou-se a correlação das propriedades físico-químicas e estruturais dos complexos com o processo de transfecção in vitro em células HeLa. A segunda parte do trabalho visou à otimização da produção de lipossomas catiônicos em dois dispositivos microfluídicos, com uma única e com dupla focalização hidrodinâmica, de modo a se obter lipossomas similares aos estudados na primeira parte do trabalho. Na utilização do segundo dispositivo, foi possível operar em vazões volumétricas mais altas quando comparadas ao primeiro. Por fim, na terceira parte, foi realizado o estudo da complexação entre LC e pDNA por processo microfluídico também em dois diferentes dispositivos, um similar ao utilizado na segunda parte do trabalho, com focalização hidrodinâmica única, e outro com blocos regulares nas paredes do microcanal, o que aumenta a área de contato entre os fluidos. Os complexos formados no primeiro dispositivo apresentaram melhores respostas biológicas in vitro, as quais foram similares às do processo "bulk". No segundo dispositivo, ensaios de acessibilidade de sonda de fluorescencência ao DNA indicaram alteração na associação entre LC e DNA. Dessa forma, a partir dos resultados, conclui-se que os dispositivos microfluídicos estudados são uma alternativa promissora para a formação de LC e também sua complexão com pDNA em modo contínuo, tanto pela potencialidade tecnológica quanto biológica, o que contribui para o desenvolvimento de produtos farmacêuticos que veiculam DNA e que são destinados à terapia e vacinação gênica
Abstract: This research aimed at the technological development of microfluidic process for nonviral carriers production based on the electrostatic complexation between cationic liposomes (CL) and plasmidal DNA (pDNA) for gene and vaccine therapy applications. The development of this process was compared to the conventional bulk process, in which the solutions are mixed followed by the simple hand shaking or brief vortexing, what generates difficulties on the particles sizes control and can affect the biological functionality and colloidal stability of the formulations. In contrast, microfluidic process, which uses devices that manipulate small amounts of fluids (10-9 to 10-18 liters), allows the electrostatic complexation in continuous mode, controlling diffusion conditions, which also allows the colloidal control of the obtained formulations. Furthermore, microfluidic devices have minimum dimensions and operate with low energy consumption. Methodologically, the present work was carried out in three mean steps: in the first step, the physicochemical, structural and biological characteristics of the pDNA/CL complexes obtained by the bulk process were studied. In this step, it was possible to verify the correlation of physicochemical and structural properties with the transfection phenomenon in vitro of HeLa cells. The second part of this work focused the optimization of the production of CL through two microfluidic devices, with single and double hydrodynamic focusing, to obtain similar CL to those of the first step of this work. By employing the second device, it was possible to operate at higher volumetric flow rates than the first one. Finally, in the third step, it was explored the complexation between CL and pDNA via microfluidic process also in two different microfluidic devices; the first was similar to that employed in the second part of this work, with a single hydrodynamic focusing, and a second one with patterned microchannel walls, which increase the surface contact area between the fluids. The complexes formed in the first device showed better biological results in vitro, which were similar to the complexes formed in the bulk complexation method. In the patterned device, the experiments of the DNA accessibility to fluorescent probe pointed out modifications between the pDNA and CL association in the complexes. In conclusion, we showed that the studied microfluidic devices are a promising alternative for the production of CL and the complexation with pDNA in continuous mode, because of the technological and biological potentialities, which contributes to the development of feasible processes, for the production of new pharmaceutical products for gene and vaccine therapies
Mestrado
Desenvolvimento de Processos Biotecnologicos
Mestre em Engenharia Química
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Zhou, Yi. "Microfluidics interfacing to mass spectrometry." College Park, Md. : University of Maryland, 2007. http://hdl.handle.net/1903/7402.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2007.Thesis research directed by: Mechanical Engineering. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Bell, Laurence Livingstone. "Optically interrogated biosensors in microfluidics." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610215.
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Wright, Maya. "Investigating protein polydispersity using microfluidics." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/275422.
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Gibb, Thomas. "Nanopore sensing using multiphase microfluidics." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/30836.
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This thesis describes a new approach to the investigation of the contents of microfluidic droplets at the single molecule level. Glass nanopores with diameters below 25nm, formed by pipette pulling, are inserted into a microfluidic channel with a height and width of 100 μm. Subsequently, a segmented flow of buffered KCl droplets in an FC-40 carrier oil is flowed through the device and analysed via changes in the measured electrical signal upon application of a voltage between the nanopipettes. Initially, the thesis focuses on the optimisation of droplet generation and pipette performance. A T-junction geometry and a novel method of droplet generation using an integrated pipette are both trialled as methods for droplet production in the device. In addition, atomic layer deposition (ALD) is investigated as an approach to optimise the size of the glass nanopore for the detection of single molecules. Subsequently, droplets in the segmented flow are examined with the device. Optical studies are undertaken to study the viability of droplets in the device and the preservation of their 'isolated microreactor' status. The length and frequency of droplets is then measured electrically and compared to an optical control, the excellent agreement between the two methods confirming the validity of the electrical approach. Attention then turns to the measurement of the bulk properties of the droplet with the determination of the KCl concentration within individual droplets. Finally, single molecules of 10 kbp double stranded DNA are translocated from within the droplet into the nanopipette, illustrating the device's potential for the analysis of droplet contents and the control of their contents at the single molecule level.
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Kamalalayam, Rajan Sreejith. "Liquid Marble Based Digital Microfluidics." Thesis, Griffith University, 2020. http://hdl.handle.net/10072/394318.
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Sample handling with liquid marbles is a recent advancement in digital microfluidics. Liquid marbles are liquid droplets coated with fine hydrophobic/oleophobic particles. The external particle coating isolates the liquid droplet from the surrounding ensuring a contamination-free environment for the droplet. Mobility manipulation of the liquid marble is easier and well developed compared to the droplet counterpart. These advantages have promoted the usage of liquid marbles as a microreactor for a range of biological applications. Liquid marbles may help in reducing the non-reusable contaminated plastic waste generated in conventional biochemical reaction chambers such as plastic vials and microfluidic chips. However, the use of liquid marble as a microreactor is limited to room-temperature applications as they are susceptible to the problems of evaporation at elevated temperatures. The development of a liquid marble based digital platform for biochemical applications at elevated temperature would broaden the scope of liquid marbles, reducing the generation of contaminated plastic waste. Polymerase Chain Reaction (PCR), a DNA amplification technique is a high-temperature process, which finds application in medical diagnosis, agriculture and forensics. Millions of PCRs are carried out in plastic vials and conventional microfluidic chips annually, contributing to the increasing problem of plastic waste. So developing a liquid marble based digital microfluidic platform tailored for PCR has an immense significance. This Ph.D. thesis focusses on the development of a liquid marble-based digital microfluidic platform particularly for carrying out PCR. A basic PCR process consists of three different phases namely sample dispersion, thermal cycling, and output monitoring. Sample dispersion process should be precise and contamination-free. Manual intervention in sample dispersion should be minimised to avoid the contamination of the sample and to achieve the precise volume. We designed, developed and tested an automated on-demand liquid marble generator. The instrument demonstrated a high precision over the volume of the marble and was highly repeatable. Evaporation of the sample liquid is a major problem faced by liquid marbles operating at elevated temperature. Detailed knowledge of the evaporation dynamics of the liquid marble is essential for designing and developing a liquid-marble-based platform for PCR. We carried out experiments to study the evaporation dynamics of liquid marbles at elevated temperatures. Studies revealed that the evaporation of liquid marble also obeys the “d-square law” at higher temperature. The lifetime of the liquid marbles is a function of its volume, temperature, the relative humidity of the surrounding environment, the number of liquid marbles and the distribution of liquid marbles. We demonstrated that the lifetime of a liquid marble can be increased by providing a vapour saturated ambient. Next, we designed an experiment to demonstrate the use of a liquid marble as a microreactor for PCR. With the knowledge acquired from the previous study, a humidity-controlled environment was developed. Custom-built thermal cycler was integrated with the humidity-controlled chamber. Thermal cycling of the PCR mixture inside the liquid marble was carried out. Successful DNA amplification was observed, and the results were comparable with those obtained from the PCR in a conventional commercial machine. However, the sample volume used in this experiment was high and the marble was able to undergo only 9 thermal cycles. Furthermore, we tested the synthesis of core-shell beads using composite liquid marble technology. A volume of 2 μL PCR sample was used as a core liquid where a photopolymer was used as the shell material. We successfully achieved the synthesis of core-shell beads. Thirty thermal cycles were carried out without evaporation. Successful DNA amplification was verified. We achieved twenty-five times reduction in sample volume and 86.1% reduction in plastic waste. The present thesis explains in details the various stages of developing a liquid marble based digital microfluidic platform for PCR. A little research on characterisation and optimisation of the methods proposed in this thesis might result in a commercially viable liquid marble-based platform for PCR.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Eng & Built Env
Science, Environment, Engineering and Technology
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Meissner, Max Frederik. "Microfluidics on the colloidal scale." Thesis, University of Bristol, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.738536.
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Lilliehorn, Tobias. "Piezoactuators for Microfluidics : Towards Dynamic Arraying." Doctoral thesis, Uppsala University, Department of Engineering Sciences, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3784.
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Microfluidics can be used to increase performance, reduce reagent consumption and increase throughput in chemical analysis. With the forthcoming development of more advanced microfluidic systems, the integration of actuating elements becomes essential, giving the ability to control and manipulate fluid flow as well as sample or other components. This thesis addresses miniaturisation of piezoceramic actuators, in particular important technological issues when actuators are integrated in microfluidic systems. Thick film multilayer fabrication technology for piezoceramics has been further developed, e.g. by introducing techniques for integration of microfabricated channel structures and via interconnects in multilayer components. New building techniques have been incorporated to allow miniaturisation of devices. A rapid prototyping technique for advanced multilayer actuators based on mechanical machining has also been developed and used in subsequent work.
When interfacing the macro and the micro world in miniaturised chemical analysis systems, non-contact sample dispensing methods such as ink-jet technology are needed. Thus a piezoactuated flow-through microdispenser, suitable for high-speed on-line chemical sample handling has been investigated. A new miniaturised actuator has been developed and integrated in the microdispenser, simplifying assembly and demonstrating an improved performance of the device.
With the prospect of performing automated and highly parallel analysis in reusable microarray devices, a new concept for dynamic arraying is presented. Non-contact trapping of particle or bead clusters in a microfluidic system is demonstrated utilising acoustic radiation forces in standing ultrasonic waves. The integration of piezoceramic microtransducers has been shown to render possible localised and spatially controlled trapping of individually addressable particle clusters in microfluidics. The importance of the acoustic near field in miniaturised devices has been identified and utilised to give strong trapping forces. By making use of disposable chemically activated microbead arrays within a flow-through device, a flexible system is emerging with e.g. applications in proteomics.
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Mohammadi, Kimia. "Synthetic biology in droplet-based microfluidics." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7596/.
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Droplet microfluidics is an active multidisciplinary area of research that evolved out of the larger field of microfluidics. It enables the user to handle, process and manipulate micrometer-sized emulsion droplets on a micro- fabricated platform. The capability to carry out a large number of individual experiments per unit time makes the droplet microfluidic technology an ideal high-throughput platform for analysis of biological and biochemical samples. The objective of this thesis was to use such a technology for designing systems with novel implications in the newly emerging field of synthetic biology. Chapter 4, the first results chapter, introduces a novel method of droplet coalescence using a flow-focusing capillary device. In Chapter 5, the development of a microfluidic platform for the fabrication of a cell-free micro-environment for site-specific gene manipulation and protein expression is described. Furthermore, a novel fluorescent reporter system which functions both in vivo and in vitro is introduced in this chapter. Chapter 6 covers the microfluidic fabrication of polymeric vesicles from poly(2-methyloxazoline-b-dimethylsiloxane-b-2-methyloxazoline) tri-block copolymer. The polymersome made from this polymer was used in the next Chapter for the study of a chimeric membrane protein called mRFP1-EstA∗. In Chapter 7, the application of microfluidics for the fabrication of synthetic biological membranes to recreate artificial cell- like chassis structures for reconstitution of a membrane-anchored protein is described.
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Häberle, Stefan. "Multiphase microfluidics on a centrifugal platform /." Aachen : Shaker, 2008. http://d-nb.info/988194627/04.
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Coquinco, Ainsley. "Activity dependent synaptic plasticity and microfluidics." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/40663.
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The visual cortex of the brain is one of the fundamental preparations to study critical periods and
activity dependent changes in the brain. During development, when sensory input from one eye
is prevented, visual acuity and brain connectivity is lost in favour of inputs from the active eye.
Because of the brain’s complexity, it is difficult to perform thorough analyses of synaptic
mechanisms that exist during development. Therefore, the development of simpler in vitro
models would be advantageous. In our studies, we used a 3-compartment microfluidic device
and created a new model for dual input in vitro activity dependent synaptic plasticity.
Microfluidics offered the advantage of being able to physically and chemically isolate neurons in
distinct environments.
In chapter 2, we optimized previously developed microfluidic devices for use in our cell culture
experiments and demonstrated that their application can create a dual input activity dependent
system. Using a 3-compartment microfluidic device, the activity of one neuronal group was
reduced by application of tetrodotoxin or the GABA agonist, muscimol. Treatment caused the
formation of a greater number of synaptic contacts between the target ‘postsynaptic’ neurons and
the ‘presynaptic’ inputs at normal working activity levels compared to the opposing
‘presynaptic’ inputs with reduced activity.
In chapter 3, we established that ‘critical periods’ exist in our in vitro model by varying the ages
at which we reduced neuronal input activity. Muscimol treatment had an earlier time window to
induce activity dependent synaptic changes compared to inhibition by tetrodotoxin. By the
fourth week in culture, neither treatment induced any synaptic difference between inputs.
In chapter 4, we examined the mechanisms involved in our model. We manipulated NMDAR
activity, CamKII activity, or GluR2 internalization postynaptically under the same conditions
that we previously established. In our model, both treatments were NMDAR activity dependent
while the requirement for CamKII activity and GluR2 internalization was dependent on the
application of either muscimol or tetrodotoxin respectively.
Taken together, we showed the ability to create a new in vitro model for activity dependent
synaptic plasticity and that even in a simple system multiple mechanisms can exist.
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Lekholm, Ville. "High-Temperature Microfluidics for Space Propulsion." Doctoral thesis, Uppsala universitet, Mikrosystemteknik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-246057.
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In this thesis, microfabrication methods and tools for analysis of heated cold-gas microthrusters are presented, with the aim of improving their reliability and performance. Cold-gas thrusters operate by accelerating pressurized gas through a nozzle. These thruster systems are very straightforward in both design and operation, relying on little more than a pressurized tank, a valve, and a nozzle. This makes them suitable for miniaturization, enabling their use on very small spacecraft. However, an inherent drawback with cold-gas thrusters is their low propellant efficiency – in thrusters known as specific impulse, or Isp. This is compounded by the fact that when reducing length, the volume, e.g., that of the propellant tank, reduces with the cube of the length, meaning that the maximum amount of storable fuel reduces quickly. Hence, maximizing fuel efficiency is even more important in miniaturized systems. Still, because of their other advantages, they remain suitable for many missions. Schlieren imaging – a method of visualizing differences in refractive index – was used thrughout this thesis to visualize exhaust jets from microthrusters, and to find leaks in the components. It was found that effects of the processing of conventionally fabricated silicon nozzles, resulted in a misalignment of up to 3° from the intended thrust vector, increasing propellant consumption by up to 5%, and potentially causing unintended off-axis acceleration of the spacecraft. Schlieren imaging was also used to verify that the exhaust from thrusters fabricated with close to circular cross-sections was well behaved. These nozzles did not suffer from the previous misalignment issue, and the shape of the cross-section decreased viscous losses. For applications requiring higher temperatures, a microthruster nozzle with an integrated flow sensor was fabricated from tape cast yttria stabilized zirconia. The ceramic substrate enabled heater temperatures of the nozzle exceeding 1000 °C, resulting in an increase in Isp of 7.5%. Integration of a flow sensor allowed the elimination of couplings and reduced the number of interfaces, thereby reducing the overall risk of failure. Close integration of the sensor allowed moving the point of measurement closer to the nozzle, enabling improved reliability of the measurements of the propellant consumption. The temperature of the heater, in combination with the ion conductive properties of the substrate proved to be a limiting factor in this design. Two routes were explored to overcome these problems. One was to use the temperature dependence of the ion conductivity as a sensing principle, thereby demonstrating a completely new flow sensor principle, which results in better calibration, tighter integration, and 9 orders of magnitude stronger signal. The other was using hafnium oxide, or hafnia, as a structural material for high-temperature micro-electromechanical systems. This involved developing a recipe for casting hafnia ceramic powder, and determining the Young's modulus and thermal shock resistance of the cast samples, as well as studying the minimum feature size and maximum aspect ratio of cast microstructures.
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Zhang, Yuxiang, and 张玉相. "Microfluidics: fabrication, droplets, bubblesand nanofluids synthesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44903935.
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Perima, Angga. "Combinatorial antibiotic screening using droplet microfluidics." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066741.
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De nos jours, nous vivons à l'époque où la résistance aux antibiotiques est devenue une grave menace mondiale. L'une des solutions pour découvrir de nouveaux antibiotiques est de combiner des médicaments existants qui ont été approuvés par la FDA. Cependant, cette via les méthodes conventionnelles est très coûteuse et lente. Le but de ce projet est de combiner les antibiotiques à l'aide de la microfluidique en gouttelettes pour surmonter ces limites. Tout d'abord, nous avons caractérisé la croissance bactérienne dans les gouttelettes et calibrons un dosage de croissance de fluorescence à haut débit en utilisant Syto-9. Ensuite, nous avons sélectionné un ensemble de 11 antibiotiques qui ne fuient pas des gouttelettes aux gouttelettes. Nous présentons une technique pour émulsifier en parallèle jusqu'à 96 puits contenant des antibiotiques à différentes doses. Nous avons montré ensuite comment le couplage et la fusion microfluidiques permettent de combiner différentes bibliothèques de médicaments. Enfin, nous avons présenté une preuve de concept d'une mesure des interactions médicamenteuses dans les gouttelettes. Dans la dernière partie de ce travail, nous avons élaboré une stratégie de codage par l'ADN pour identifier les interactions médicamenteuses par séquençage après une étape de tri basée sur le test de croissance. Pour conclure, nous avons conçu et optimisé les différents modules microfluidiques au niveau suffisant pour pouvoir être combinés de manière robuste. Ils peuvent fournir une plate-forme technologique capable de réduire les coûts et le temps de dosage pour les combinaisons de médicaments à l'échelle du laboratoire avant l'essai cliniqueNowadays, we are living in the era where antibiotic resistance has become a serious worldwide threat. One of the solution to discover novel antibiotics is to combine existing drugs that have been approved by FDA. However, drug combination using conventional method is highly expensive and has low throughput. The aim of this project is to combine antibiotics using droplet microfluidics to overcome these limitations. First, we show how to control the encapsulation of bacteria E. coli MG1655 by correlating Poisson distribution and OD (Optical Density) for different volume of droplets. We then characterize bacterial growth inside droplets and calibrate a high-throughput fluorescence growth assay using Syto-9. Then, we select a set of 11 antibiotics that do not leak from droplets to droplets and represent major classes of mechanisms. We present a technique to emulsify in parallel up to 96 wells containing antibiotics at different doses. We then show how microfluidic pairing and fusion allow to combine different drug-dose libraries. Finally, we present a proof of concept of a measurement of drug interactions in droplets. In the last part of this work, we elaborate a DNA barcoding strategy to identify drug interactions by sequencing after a sorting step based on the growth assay. To conclude, we have designed and optimized the different microfluidic modules to level sufficient so that they can be combined robustly. It can provide a technological platform that is able to reduce cost and assay time for drug combinations at a laboratory scale, before clinical trial
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Monaco, Ernesto. "Multiphase lattice Boltzmann simulation of microfluidics." Thesis, University of Southampton, 2011. https://eprints.soton.ac.uk/181511/.
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Mazutis, Linas. "Droplet-based microfluidics for protein evolution." Strasbourg, 2009. http://www.theses.fr/2009STRA6178.
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La compartimentalisation de la "soupe primordiale" dans des vésicules est considérée comme l'un des principaux facteurs ayant permis l'émergence de la vie. Ces gouttelettes de quelques micromètres créent un lien entre génotype et phénotype, et grâce à la division, un mécanisme pour l’hérédité et l’évolution, qui a conduit à l'émergence des cellules actuelles. De tels microcompartiments, peuvent être créés au laboratoire sous la forme d’une émulsion composée de millions de gouttelettes contenant des gènes et tous les ingrédients nécessaires pour leur expression in vitro. Ces émulsions miment ainsi des populations de cellules artificielles qui peuvent être sélectionnées pour un phénotype donné sous des conditions strictement contrôlées non réalisables dans des systèmes in vivo. Cette thèse de doctorat présente le développement de systèmes microfluidiques pour l’évolution dirigée. Les résultats obtenus montrent qu’il est possible de produire des gouttelettes hautement monodisperses pouvant être manipulées de manière précise et contrôlable, ce qui était jusqu’à présent impossible pour des émulsions réalisées par des méthodes classiques. En utilisant un ensemble de nouveaux dispositifs microfluidiques et une composition adéquate d’huile porteuse, des gènes uniques ont été amplifiés et leur expression in vitro mesurée en microgouttelettes. Ces dispositifs ont ensuite été utilisés pour réaliser et analyser des réactions biologiques complexes et multi-étapes. Une technique originale de fusion passive de paires de gouttelettes a également été développée. Ces travaux constituent les premiers pas vers la création de plate-formes microfluidiques intégrées et totalement in vitroThe compartmentalization of the primordial soup into vesicles is thought to be one of the key features in the early emergence of life. These tiny micrometer-sized droplets provided a linkage between phenotype and genotype, and through division, a mechanism for heredity and evolution, which gave rise to modern cells. Man-made compartments, in the form of an emulsion, can also provide a tool of linking genotype to phenotype. Composed of millions of droplets containing genes with all ingredients necessary for in vitro expression, emulsions mimic populations of artificial cells that can be selected for a particular phenotype under strictly controlled conditions not feasible in living systems. The research described in this doctoral thesis focuses on the development of droplet-based microfluidics for protein evolution and presents the first steps toward an integrated and completely in vitro microfluidics platform. The results obtained in this work show that it is possible to produce highly monodisperse picoliter volume droplets (CV<1%) that can be manipulated in a precise and controllable manner, previously impossible in bulk emulsions. Using a set of novel microfluidic devices and an adequate composition of carrier oil single genes in droplets were amplified and their in vitro expression measured. The same microfluidic system was also used to perform multiple operations in order to analyze complex and sequential biological reactions in droplets. Moreover, a new passive droplet fusion technique has been developed, which can be used for preparation of monodisperse emulsions composed of pairwise fused droplets
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Loufakis, Despina Nelie. "Microfluidics for Cell Manipulation and Analysis." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/50586.
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Microfluidic devices are ideal for analysis of biological systems. The small dimensions result to controlled handling of the flow profile and the cells in suspension. Implementation of additional forces in the system, such as an electric field, promote further manipulation of the cells. In this dissertation, I show novel, unique microfluidic approaches for manipulation and analysis of mammalian cells by the aid of electrical methods or the architecture of the device. Specifically, for the first time, it is shown, that adoption of electrical methods, using surface electrodes, promotes cell concentration in a microchamber due to isoelectric focusing (IEF). In contrast to conventional IEF techniques for protein separation, a matrix is not required in our system, the presence of which would even block the movement of the bulky cells. Electric field is, also, used to breach the cell membrane and gain access to the cell interior by electroporation (irreversible and reversible). Irreversible electroporation is used in a unique, integrated microfluidic device for cell lysis and reagentless extraction of DNA. The genomic material is subsequently analyzed by on-chip PCR, demonstrating the possible elimination of the purification step. On the other hand, reversible electroporation is used for the delivery of exogenous molecules to cells. For the first time, the effect of shear stress on the electroporation efficiency of both attached and suspended cells is examined. On the second part of my dissertation, I explore the capabilities of the architecture of microfluidic devices for cell analysis. A simple, unique method for compartmentalization of a microchamber in an array of picochambers is presented. The main idea of the device lies on the fabrication of solid supports on the main layer of the device. These features may even hold a dual nature (e.g. for cell trapping, and chamber support), in which case, single cell analysis is possible (such as single cell PCR). On the final chapter of my dissertation, a computational analysis of the flow and concentration profiles of a device with hydrodynamic focusing is conducted. I anticipate, that all these novel techniques will be used on integrated microfluidic systems for cell analysis, towards point-of-care diagnostics.Ph. D.
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Ma, Sai. "Microfluidics for Genetic and Epigenetic Analysis." Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/78187.
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Microfluidics has revolutionized how molecular biology studies are conducted. It permits profiling of genomic and epigenomic features for a wide range of applications. Microfluidics has been proven to be highly complementary to NGS technology with its unique capabilities for handling small volumes of samples and providing platforms for automation, integration, and multiplexing. In this thesis, we focus on three projects (diffusion-based PCR, MID-RRBS, and SurfaceChIP-seq), which improved the sensitivities of conventional assays by coupling with microfluidic technology. MID-RRBS and SurfaceChIP-seq projects were designed to profiling genome-wide DNA methylation and histone modifications, respectively. These assays dramatically improved the sensitivities of conventional approaches over 1000 times without compromising genomic coverages. We applied these assays to examine the neuronal/glial nuclei isolated from mouse brain tissues. We successfully identified the distinctive epigenomic signatures from neurons and glia. Another focus of this thesis is applying electrical field to investigate the intracellular contents. We report two projects, drug delivery to encapsulated bacteria and mRNA extraction under ultra-high electrical field intensity. We envision rapid growth in these directions, driven by the needs for testing scarce primary cells samples from patients in the context of precision medicine.Ph. D.
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Yan, Xie. "CHEMICAL SIGNAL ANALYSIS WITH FOURIER MICROFLUIDICS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1216058414.
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Zhang, Yizhe. "Drop-Based Microfluidics for Biological Applications." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467232.
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Drop-based microfluidic technology has been attracting great attention since the prevalence of soft-lithography techniques in poly-dimethylsiloxane (PDMS) microfluidic device fabrication a decade ago. The miniaturized isolated confinement of the droplet provides an ideal environment to study single cell behaviors in vitro that might otherwise be buried in the ensemble measurements. The effective confinement of the target and its secretion, together with the high-throughput processing capability, holds the promise for efficient target search through large-scale library screening. In fact, in the past seven years, considerable efforts have been made in developing this platform towards the applications in biology and great advances in drops have been reported in areas such as directed evolution, DNA sequencing, drug screening, etc.
This thesis systematically describes our work that has been done in advancing the biological application of drop-based microfluidics through three major projects that are of significance in both fundamental research and clinical applications. Encapsulating in vitro transcription and translation reactions in the 0.5 pL drops enables us to synthesize a variety of functional RNAs and proteins from the single DNA templates in a drop environment, which not only provides a novel approach for single DNA molecule detection, but also paves the way for the high-throughput screening of the artificial proteins with drop-based microfluidics. Through successful enrichment of the restriction enzyme genes from a library consisting its truncated mutants, we demonstrated the high-throughput sorting capability of microfluidics for target gene screening that is beneficial for gene therapy applications. Finally, a non-invasive hydrogel synthesis method with microfluidic drop-maker and pico-injector is described, as a demonstration of microfluidic platform in the application of controllable synthesis of micro-sized gel particles as the 3D scaffold of, for example, mesenchymal stem cells, for the in vitro study of cell behaviors induced by cell-cell interactions and cell-environment interactions.Chemical Physics
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Cookson, Scott Warren. "Microfluidics for investigating single-cell biodynamics." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3331377.
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Thesis (Ph. D.)--University of California, San Diego, 2008.Title from first page of PDF file (viewed December 16, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 115-124).
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Anderson, Megan J. Quake Stephen R. Quake Stephen R. "Microfluidics-based strategies for protein crystallography /." Diss., Pasadena, Calif. : California Institute of Technology, 2009. http://resolver.caltech.edu/CaltechETD:etd-10172008-222221.
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Torkkeli, Altti. "Droplet microfluidics on a planar surface /." Espoo : Technical Research Centre of Finland, 2003. http://www.vtt.fi/inf/pdf/publications/2003/P504.pdf.
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Gong, Xiuqing. "PDMS based microfluidic chips and their application in material synthesis /." View abstract or full-text, 2009. http://library.ust.hk/cgi/db/thesis.pl?NSNT%202009%20GONG.
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Campos, Richard Piffer Soares de 1984. "Modificação de poli(dimetilsiloxano) para aplicações em micro sistemas de análise total." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/250597.
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Orientador: José Alberto Fracassi da SilvaDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química
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Resumo: Os micro sistemas de análise total consistem de dispositivos da ordem de centímetros que tem como objetivo a integração de várias etapas analíticas em um único chip, tais como etapas de tratamento de amostra, separação por eletroforese capilar, ou mesmo a integração de sensores em canais microfluídicos. O poli(dimetilsiloxano), PDMS, é um dos polímeros mais adotados para a fabricação destes microdispositivos, devido a suas propriedades elastoméricas, transparência óptica, permeabilidade gasosa, biocompatibilidade, fácil moldagem, relativa alta resistência química e baixo custo de fabricação, além de poder ser facilmente moldado e selado, resultando em microcanais com boa resolução. Além disso, é possível a fabricação de canais por ablação a laser sobre o polímero curado. Entretanto, a característica altamente hidrofóbica do PDMS faz com que sua aplicação para soluções aquosas seja problemática e analitos pouco polares possam sofrer forte adsorção nas paredes do canal, tornando pobre a reprodutibilidade do processo. Neste sentido, estratégias para modificar o material nativo ou mesmo a superfície dos canais vêm sendo estudadas. Neste trabalho, foi inicialmente estudada a modificação estrutural do PDMS, que consiste na utilização de um reticulante (contendo função orgânica polar metacrilato ou amina) na formação do substrato. Também foi realizada a modificação da superfície do substrato de PDMS por reação topológica, com a introdução de polietileno glicol, além da modificação do processo convencional de reticulação do PDMS Sylgard 184, pela adição do surfactante Silwet-L77 a este processo. O PDMS modificado foi avaliado quanto a sua hidrofobicidade, por medida do ângulo de contato com a água, em relação às propriedades do fluxo eletrosmótico gerado no microcanal e as modificações foram estudadas por métodos espectroscópicos. A reação de modificação de superfície do PDMS com divinil éter de polietileno glicol apresentou as melhores características hidrofílicas dentre as modificações estudadas e mobilidade do fluxo eletrosmótico com valor de 3,6x10 cm V s. Em adição, as modificações puderam ser caracterizadas por métodos de espectroscopia (IR e Raman), que se mostraram eficientes na avaliação tanto da rota de modificação quanto do produto final
Abstract: The micro total analysis systems consist of devices in the order of centimeters that aim to integrate several analytical steps on a single substrate, such as sample treatment, injection, or even integrated sensors on microfluidic channels. Poly(dimethylsiloxane), PDMS, is one of the most used polymers for microfabrication due to its elastomeric properties, optical transparency, gas permeability, biocompatility, relatively high chemical resistance and low fabrication costs. PDMS can also be easily cast and sealed, resulting in microchannels with good resolution. On top of that, it is possible to fabricate the microchannels using the lase ablation technique on the cured PDMS. However, the highly hydrophobic characteristic of PDMS makes its aqueous applications problematic. Moreover, non-polar analytes can adsorb on the channel walls, leading to poor reproducibility. In this sense, strategies to modify the raw material or channel surface have been proposed. In this work, the structural modification of PDMS, involving the use of a crosslinking agent (containing the methacrylate or amine polar functions) was studied. In addition, the surface modification of PDMS by topologic reaction with polyethylene glycol and the modification of the conventional PDMS Sylgard 184 crosslinking by the addition of Silwet-L77 surfactant were also performed. The hydrophobicity of modified PDMS was evaluated by water contact angle measurements and the modifications were studied by spectroscopic methods. The electroosmotic flow (EOF) generated in the microchannels was also evaluated. The best hydrophilic characteristic among the studied modifications were obtained with the polyethylene glycol divinyl ether PDMS modification. This device presented an EOF of 3,6x10 cm V s. In addition, the modifications could be characterized by spectroscopic methods (Raman and IR) and those techniques were efficient in the evaluation of the reaction routes as well as the final products
Mestrado
Quimica Analitica
Mestre em Química
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Oliveira, Aline Furtado 1989. "Desenvolvimento de sistema microfluídico baseado em gradiente de concentração difusivo para bioprocessos = Development of microfluidic system based on diffusive concentration gradient for bioprocess." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/266097.
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Orientadores: Lucimara Gaziola de La Torre, Reinaldo Gaspar BastosDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química
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Resumo: A microfluídica é uma ciência que opera em pequenos volumes de fluídos dentro de canais em dimensões de micrômetros (10-6 m). Estes sistemas permitem controlar moléculas no espaço e no tempo, gerando resultados rápidos e confiáveis num sistema precisamente controlado e capaz de mimetizar ambientes celulares. Os dispositivos microfluídicos apresentam uma diversidade de geometrias aplicáveis para diversas áreas de pesquisas, sendo que a capacidade de formar gradientes permite avaliar as condições e o desempenho celular microbiano. Assim, este trabalho teve como objetivo desenvolver dispositivos microfluídicos capazes de formar gradiente de concentração difusivo e investigar sua aplicabilidade em bioprocessos. Diante disso, foram propostos três modelos de dispositivos usando materiais biocompatíveis: (i) dispositivo em base de vidro, denominado de Vidro-vidro; (ii) em base de vidro e poli dimetilsiloxano (PDMS), chamado de Vidro-PDMS e (iii) vidro e PDMS modificado quimicamente para tornar a superfície hidrofílica, Vidro-mPDMS. Os três dispositivos foram avaliados quanto à capacidade de formação de gradiente de concentração difusivo, os quais apresentaram um perfil linear. Além disso, validou-se o estudo do comportamento de Saccharomyces cerevisiae ATCC 7754 num gradiente de concentração de glicose de 0 a 40 g/L de glicose, sendo usado o dispositivo vidro-vidro. Foi observado que houve crescimento de células ao longo das câmaras microfluídicas, e isso possibilitou na determinação de parâmetros cinéticos, os quais não apresentaram diferença estatisticamente significativa com o cultivo em batelada convencional. As condições da microfluídica possibilitaram também a determinação da cinética de Monod, usando menores intervalos de gradiente. Portanto, este dispositivo microfluídico mostrou-se uma ferramenta com potencial para investigar comportamento celular frente à diferença de concentração e contribuirá para a otimização de bioprocessos através da determinação de parâmetros cinéticos
Abstract: Microfluidic is a science that operates in small amounts of fluids inside channels in dimensions of micrometers (10-6 m). These systems allow the precise control of molecules in space and time, generating fast and reliable results and it can also be used to mimics environment cellular . Microfluidic devices can be produced in diversity of geometries, it can be applied in several scientific areas and especially the formation of concentration gradients can be used to evaluate conditions and performance of microbial cell. Therefore, this work had the objective to develop microfluidic devices that are able to generate diffusive concentration gradients and investigate their applicability in bioprocesses. In this context, we propose three models of microfluidics devices using biocompatible materials: (i) Glass-based device, named glass-glass; (ii) glass and poli dimetilsiloxane (PDMS) based device, Glass-PDMS and (iii) glass and chemically modified PDMS (hydrophilic surface), Glass-mPDMS. The three devices were evaluated by their capacity of generating difusive concentration gradient, demonstrating linear concentration profile. Furthermore, the behavior of Saccharomyces cerevisiae ATCC 7754 inside of glucose concentration gradient ranging from 0 to 40 g/L were validated, using the glass-glass device . It was observed that cell growth along the microfluidic chambers, having determined the kinetic parameters, which was considered statistically similar to conventional batch cultivation. Conditions of microfluidics also allowed determination of the Monod kinetic, using smaller intervals gradient Therefore, the use of concentration gradient in microfluidic device is a potential tool for investigate of microbial cell behavior against the concentration difference and it can contribute to the optimization of bioprocesses through the determination of kinetic parameters
Mestrado
Desenvolvimento de Processos Biotecnologicos
Mestra em Engenharia Química