Dissertationen zum Thema „Microfluidic circuit“

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2010.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 54-57).
In this thesis, a new microfluidic device is presented for sorting of deformable particles based on the hydrodynamic resistance induced in a microchannel. Hydrodynamic resistance can be related to physical properties, including size and deformability of the particle, and can also be influenced by particle-wall interactions, hence allowing sorting based on any of these characteristics. This device could find application in cell sorting and bioseparation for therapeutics, research, and point-of-care diagnostics, as well as in sorting of droplets and emulsions for research and industrial applications (e.g., pharmaceutics, food industry, etc.). The device design is carried out using an equivalent resistance model, and numerical simulations are used to validate the design. The device is fabricated in PDMS, flow velocities are characterized using particle streak velocimetry, and sorting experiments are conducted to sort deformable gelatin particles according to size, and droplets of water and glycerol according to deformability. A sorting resolution of approximately 1 pm was obtained when sorting based on size, and droplets of water and glycerol were sorted into separate streams when sorting based on deformability. The main strength of the device over existing technology lies in its simplicity: sorting is carried out passively in the microfluidic circuit, eliminating the need for additional detection or sorting modules. Moreover, the device could be easily customized to change the sorting parameter or the sorting threshold, and multiple devices can be combined in parallel (to increase throughput) or in series (to increase resolution).
by Mohamed Salem Raafat.
S.M.

In this thesis, conventional and unconventional technologies have been studied and combined in order to make heterogeneous microfluidics with potential advantages, especially in biological applications. Many conventional materials, like silicon, glass, thermoplastic polymers, polyimide and polydimethylsiloxane (PDMS) have been combined in building heterogeneous microfluidic devices or demonstrators. Aside from these materials, unconventional materials for microfluidics such as stainless steel and the fluoroelastomer Viton have been explored. The advantages of the heterogeneous technologies presented were demonstrated in several examples: (1) For instance, in cell biology, surface properties play an important role. Different functions were achieved by combining microengineering and surface modification. Two examples were made by depositing a Teflon-like film: a) a non-textured surface was made hydrophobic to allow higher pressures for cell migration studies and b) a surface textured by ion track technology was even made super-hydrophobic. (2) In microfluidics, microactuators used for fluid handling are important, e.g. in valves and pumps. Here, microactuators that can handle high-pressures were presented, which may allow miniaturization of high performance bioanalyses that until now have been restricted to larger instruments. (3) In some applications the elastomer PDMS cannot be used due to its high permeability and poor solvent resistivity. Viton can be a good replacement when elasticity is needed, like in the demonstrated paraffin actuated membrane.(4) Sensing of bio-molecules in aquatic solutions has potential in diagnostics on-site. A proof-of-principle demonstration of a potentially highly sensitive biosensor was made by integrating a robust solidly mounted resonator in a PDMS based microfluidic system. It is concluded that heterogeneous technologies are important for microfluidic systems like micro total analysis systems (µTAS) and lab-on-chip (LOC) devices.

This diploma thesis deals with cavitation flow in the microscale, which remains an area with a lack of sufficient description of this phenomenon. At the same time, microfluidics is a field experiencing a dramatic rise in numerous biochemical applications, which underlines the relevance of researches of this type. In theoretical part of the thesis, cavitation was described in detail. In the practical part, a microfluidic device with a cavitation orifice was designed and manufactured. The ANSYS program was used for this design. An experiment was performed with the designed microchip, the aim of which was to observe a cavitating flow on the orifice. This measurement took place at the microfluidic laboratory at Victor Kaplan Department of Fluid Engineering. Due to the failure of the experiment, a CFD model of two-phase cavitation flow was built. The conclusions of the thesis were compiled from the findings of measurement and the results of modeling.

Metamaterials are artificially designed composite materials which can exhibit unique and unusual properties such as the negative refractive index, negative phase velocity, etc. The concept of metamaterials becomes prevalent in the electromagnetic society since the first experimental implementation in the early 2000s. Many fascinated potential applications, e.g. super lens, invisibility cloaking, and novel antennas that are electrically small, have been proposed based on metamaterials. However, most of the applications still remain in theory and are not suitable for practical applications mainly due to the intrinsic loss and narrow bandwidth (large dispersion) determined by the fundamental physics of metamaterials .In this dissertation, we incorporate active gain devices into conventional passive metamaterials to overcome loss and even provide gain. Two types of active gain negative refractive index metamaterials are proposed, designed and experimentally demonstrated, including an active composite left-/right-handed transmission line and an active volumetric metamaterial. In addition, we investigate the non-Foster circuits for broadband matching of electrically small antennas. A rigorous way of analyzing the stability of non-Foster circuits by normalized determinant function is proposed. We study the practical factors that may affect the stability of non-Foster circuits, including the device parasitics, DC biasing, layouts and load impedance. A stable floating negative capacitor is designed, fabricated and tested. Moreover, it is important to resolve the sign of refractive index for active gain media which can be quite challenging. We investigate the analytical solution of a gain slab system, and apply the Nyquist criterion to analyze the stability of a causal gain medium. We then emphasize that the result of frequency domain simulation has to be treated with care. Lastly, this dissertation discusses another interesting topic about THz spectroscopy of live cells. THz spectroscopy becomes an emerging technique for studying the dynamics and interactions of cells and biomolecules, but many practical challenges still remain in experimental studies. We present a prototype of simple and inexpensive cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells are transported, trapped and concentrated into the THz exposure region by applying an AC bias signal while the chip maintains a steady temperature at 37°C by resistive heating. We conduct some preliminary experiments on E. coli and T cell solution and compare the transmission spectra of empty channels, channels filled with aqueous media only, and channels filled with aqueous medium with un-concentrated and concentrated cells.

In realizing a portable chemical analysis system, adequate partitioning of a reusable component and a disposable is required. For successful implementation of micromachined sensors in an instrument, reliable methods for interconnection and interface are in great demand between these two major parts. This thesis work investigates interconnection methods of micromachined chip devices, a hybrid fluidic interface system, and measurement circuitry for completing instrumentation. The interconnection method based on micromachining and injection molding techniques was developed and an interconnecting microfluidic package was designed, fabricated and tested. Alternatively, a plug-in type design for a large amount of sample flow was designed and demonstrated. For the hybrid interface, sequencing of the chemical analysis was examined and accordingly, syringe containers, a peristaltic pump and pinch valves were assembled to compose a reliable meso-scale fluidic control unit. A potentiostat circuit was modeled using a simulation tool. The simulated output showed its usability toward three-electrode electrochemical microsensors. Using separately fabricated microsensors, the final instrument with two different designs--flow-through and plug-in type was tested for chlorine detection in water samples. The chemical concentration of chlorine ions could be determined from linearly dependent current signals from the instrument.
M.S.E.E.
Department of Electrical and Computer Engineering
Engineering and Computer Science
Electrical Engineering

Ce travail de thèse s'inscrit dans le cas d'un projet européen nommé " microfluiD ". Ce projet vise principalement la détection des polluants organiques par voie microfluidique (les micotoxines dans les aliments de bétail, les bactéries et les métaux lourds). Devant les dangers écologiques des ions Pb2+, Hg2+ et Cd2+ dans l'environnement, il est important de multiplier le nombre d'analyses dans les eaux du robinet. L'utilisation de la fluorescence et des microlasers organiques présente de nombreux avantages. Outre leur faible coût, leur sensibilité ainsi que leur sélectivité, il est possible de concevoir à partir de ces techniques des dispositifs transportables sur le terrain. Deux approches sont principalement développées : Une première est basée sur la fluorescence ; elle a consisté à synthétiser des ligands fluorescents de type DPPS-PEG et CalixDANS-3-OH pour la détection du mercure et du plomb. Les études de la complexation des ions Hg2+, Pb2+ ont d'abord été effectuées en solution. La complexation de Cd2+ en circuit microfluidique à partir du composé commercial Rhod-5N a aussi été étudiée. Des résultats très prometteurs ont été obtenus pour la détection de Hg2+ par DPPS-PEG. Nous avons aussi étudié la possibilité de détecter Pb2+ à partir du CalixDANS-3-OH greffé sur les parois du circuit microfluidique. Malgré une dégradation de la sonde, nous avons réussi à détecter une faible concentration de plomb. Une très bonne sélectivité vis-à-vis des cations interférents testés a été obtenue. La seconde approche est basée sur la détection par microlasers. Nous avons synthétisé deux copolymères blocs pour la détection du plomb et du mercure. Des problèmes de solubilité nous empêchant de fabriquer des microcavités organiques à partir de ces polymères, une deuxième stratégie consistant à greffer les ligands spécifiques de Pb2+ et de Hg2+ sur les microcavités laser PMMA a été développée. Cette dernière nous a permis d'apporter une preuve de principe pour de la détection du mercure en fonctionnalisant le mercaptopropyltriéthoxysilane à la surface du PMMA. Ce travail nous a aussi amené à synthétiser des colorants laser à base de Bodipy pour la fabrication des microcavités lasers par polymérisation à deux photons (2PP).

The continuous miniaturization of electronic systems using the three-dimensional (3D) integration technique has brought in new challenges for the computer-aided design and modeling of 3D integrated circuits (ICs) and systems. The major challenges for the modeling and analysis of 3D integrated systems mainly stem from four aspects: (a) the interaction between the electrical and thermal domains in an integrated system, (b) the increasing modeling complexity arising from 3D systems requires the development of multiscale techniques for the modeling and analysis of DC voltage drop, thermal gradients, and electromagnetic behaviors, (c) efficient modeling of microfluidic cooling, and (d) the demand of performing fast thermal simulation with varying design parameters. Addressing these challenges for the electrical/thermal modeling and analysis of 3D systems necessitates the development of novel numerical modeling methods. This dissertation mainly focuses on developing efficient electrical and thermal numerical modeling and co-simulation methods for 3D integrated systems. The developed numerical methods can be classified into three categories. The first category aims to investigate the interaction between electrical and thermal characteristics for power delivery networks (PDNs) in steady state and the thermal effect on characteristics of through-silicon via (TSV) arrays at high frequencies. The steady-state electrical-thermal interaction for PDNs is addressed by developing a voltage drop-thermal co-simulation method while the thermal effect on TSV characteristics is studied by proposing a thermal-electrical analysis approach for TSV arrays. The second category of numerical methods focuses on developing multiscale modeling approaches for the voltage drop and thermal analysis. A multiscale modeling method based on the finite-element non-conformal domain decomposition technique has been developed for the voltage drop and thermal analysis of 3D systems. The proposed method allows the modeling of a 3D multiscale system using independent mesh grids in sub-domains. As a result, the system unknowns can be greatly reduced. In addition, to improve the simulation efficiency, the cascadic multigrid solving approach has been adopted for the voltage drop-thermal co-simulation with a large number of unknowns. The focus of the last category is to develop fast thermal simulation methods using compact models and model order reduction (MOR). To overcome the computational cost using the computational fluid dynamics simulation, a finite-volume compact thermal model has been developed for the microchannel-based fluidic cooling. This compact thermal model enables the fast thermal simulation of 3D ICs with a large number of microchannels for early-stage design. In addition, a system-level thermal modeling method using domain decomposition and model order reduction is developed for both the steady-state and transient thermal analysis. The proposed approach can efficiently support thermal modeling with varying design parameters without using parameterized MOR techniques.

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 vitro
The 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

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2013.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Sorting of microparticles has numerous applications in science and technology, from cell analysis to sample purification for biomaterials, photonics, and drug delivery. Methods used for particle separation relied only on procedures that involved sedimentation, filtration through porous material or other physical procedures that could be performed macroscopically and in bulk; only recently has miniaturization of fluid systems enabled individual particle separation at the macroscopic level. In the 1980's, as new fabrication techniques originally used to miniaturize circuits became available, they were used to miniaturize structures used for filtration, creating new membranes for filtration with sub millimeter thickness and new fluidic devices that enabled completely new functionalities. Hydrodynamic resistance, the extra resistance induced by a particle as it flows through a microfluidic channel, has been recently proposed as a viable property for particle characterization. Particle-induced hydrodynamic resistance can be linked to relevant biological properties, e.g. deformability, which is an important parameter in diseases like sickle cell anemia, malaria, sepsis and some kinds of cancers. In this work we propose the concept of 'hydrodynamic resistance sorting', which adds to the repertoire of current sorting technologies. We propose a microfluidic circuit capable of sorting particles according to the hydrodynamic resistance they induce in micro channel as they flow through. The circuit has two flow modes: rejection and sorting modes. The microfluidic circuit switches from rejection to sorting mode automatically when a particle induces an increment in hydrodynamic resistance larger than a designed threshold value. The circuit uses the concept of microfluidic logic, in which a microfluidic system has multiple discrete output modes, (sorting and rejecting particle modes), which are activated by an input variable, in this case the hydrodynamic resistance. As opposed to previous logic microfluidic circuits based on droplets, the sorting circuit uses particle self-interactions and does not require particle synchronization to enable microfluidic logic; hence the circuit is asynchronous. Further, we showed the circuit's ability to work with cells by sorting red blood cells and tested the circuit's capacity to sort particles based on mechanical properties by sorting cured and uncured droplets made of a UV-curable solution. Finally, in addition to development of circuits to sort particles based on hydrodynamic resistance, we investigated the link between hydrodynamic resistance and the change in mechanical properties experienced by cells. From first principles it is unclear exactly how and to what extent cell mechanical properties affect cell passage through constrained channels. The force opposing cell passage could be proportional to the cell velocity, as it occurs during lubrication of rigid objects, or proportional to normal forces, as it occurs in the case of many macroscopic objects sliding on surfaces. We used a microfluidic differential manometer, particle image velocimetry, high-speed imaging, confocal microscopy and non-dimensional analysis to investigate the relationship between cell mechanical properties, friction forces and hydrodynamic resistance. The results revealed that the transport of cells through constrained channels is a soft lubrication flow, where the driving force depends primarily on viscous dissipation and secondarily on the compressive forces acting on the cell. This work advances our understanding of the flow of deformable particles through constrained channels and provides a method to sort single particles based on their hydrodynamic resistance. The devices developed here have potential applications in biomechanical analysis of cells, bioseparation, point-of-care diagnostics, as well as in two-phase microfluidics.
by Marco Aurelio Cartas Ayala.
Ph.D.

Thesis (Ph. D.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2006.
Michaels, Thomas E., Committee Member ; LaPlaca, Michelle, Committee Member ; Frazier, A. Bruno, Committee Member ; DeWeerth, Stephen P., Committee Member ; Allen, Mark G., Committee Chair.

The objective of this PhD research was to design and implement novel microfluidic radio-frequency (RF) structures on multilayer organic substrates for cooling and tuning purposes. The different designs were implemented to target applications up to C-band (4 GHz – 8 GHz) frequencies. The system-on-package (SoP) solution adopted throughout this work is well adapted for such designs where there is a need to integrate the functionality of different sub-components into a single hybrid fully packaged system. The first part of the thesis is dedicated to the study of a specific liquid cooling scheme using integrated microchannels on organics placed beneath different types of heat sources. A 1 W gallium nitride (GaN) die was cooled using this method and an analysis is presented regarding the cases where the coolant is static or dynamic inside the microchannel. The second part of the thesis deals with microfluidically reconfigurable microstrip RF circuits, mainly bandpass filters and power amplifiers (PAs). The microfluidic tuning technique is based on the change in the effective dielectric constant that the RF signal “sees” when traveling above two microchannels with different fluids. This technique was used to shift the frequency response of an L-band microstrip bandpass filter by replacing DI water with acetone inside a 60 mil micro-machined cavity. This technique was also used to design reconfigurable matching networks which constitute the main part of the proposed tunable GaN-based PA for S- and C-band applications. The final part of the thesis expands the previous results by combining both cooling and tuning in a single RF design. To prove the concept, cooling and tuning microchannels were integrated into a single package to cool a GaN-based PA and tune its frequency response at the same time from 2.4 GHz to 5.8 GHz and vice versa.

A primeira etapa do projeto foi realizar testes para usinagem controlada e otimizada de vidro ótico de borosilicato (BK7) por laser de femtossegundos. Parâmetros como energia, pulsos sobrepostos e a variação da posição focal foram investigados para controle da taxa de remoção do material e extensão da cratera ablacionada. Especial atenção foi dada à condição física e topográfica da superfície resultante da usinagem para torná-la menos rugosa e evitar a retenção de reagentes que possam contaminar e alterar as reações pretendidas. Microcanais, microválvulas, microbombas, misturadores, microrreatores, aquecedores e outros componentes foram desenvolvidos para compor sistemas microfluídicos. Os microcanais construídos sobre a superfície de vidro BK7 vedados por uma lâmina de polidimetilsiloxano (PDMS) são a base dos sistemas microfluídicos. O controle de fluxo de reagentes é feito por miniválvulas pneumáticas controladas por um microcontrolador Arduino através de uma plataforma Labview. Este trabalho mostra os componentes desenvolvidos e dois sistemas microfluídicos criados. O primeiro contém um circuito capaz de replicar ensaios imunoenzimáticos (ELISA) com um custo muito menor de insumos. O segundo é um sistema para a produção de nanocristais fluorescentes de NaYF4 especialmente utilizados como marcadores em imagens de sistemas biológicos.
The first stage of the project was to perform tests for controlled and optimized machining of borosilicate optical glass (BK7) by femtosecond laser. Parameters such as energy, number of overlapped pulses, and the focal position variation were investigated for a better extraction of material. Microchannels, microvalves, micropumps, mixers, reactors, heaters and other components were developed to compose applied microfluidic systems. Microchannels built on the surface of BK7 glass sealed by a polydimethylsiloxane (PDMS) sheet form the basis of the microfluidic circuits. The reagents flow control is done by pneumatic mini-valves controlled by an Arduino microcontroller through a Labview platform. This work shows the components developed and two microfluidic systems created. The first contains a microfluidic circuit capable of replicating enzyme-linked immunosorbent assays (ELISA) with a much lower cost of materials. The second has a microfluidic circuit for the production of NaYF4 fluorescent nanocrystals specially used as markers in images of biologic systems.

This thesis employs computational and experimental methods to explore hotspot cooling and high heat flux removal from a 3-D stacked chip using thermoelectric and microfluidic devices. Stacked chips are expected to improve microelectronics performance, but present severe thermal management challenges. The thesis provides an assessment of both thermoelectric and microfluidic technologies and provides guidance for their implementation in the 3-D stacked chips. A detailed 3-D thermal model of a stacked electronic package with two dies and four ultrathin integrated TECs is developed to investigate the efficacy of TECs in hotspot cooling for 3-D technology. The numerical analysis suggests that TECs can be used for on demand cooling of hotspots in 3-D stacked chip architecture. A strong vertical coupling is observed between the top and bottom TECs and it is found that the bottom TECs can detrimentally heat the top hotspots. As a result, TECs need to be carefully placed inside the package to avoid such undesired heating. Thermal contact resistances between dies, inside the TEC module, and between the TEC and heat spreader are shown to significantly affect TEC performance. TECs are most effective for cooling localized hotspots, but microchannels are advantageous for cooling large background heat fluxes. In the present work, the results of heat transfer and pressure drop experiments in the microchannels with water as the working fluid are presented and compared to the previous microchannel experiments and CFD simulations. Heat removal rates of greater than 100 W/cm2 are demonstrated with these microchannels, with a pressure drop of 75 kPa or less. A novel empirical correlation modeling method is proposed, which uses finite element modeling to model conduction in the channel walls and substrate, coupled with an empirical correlation to determine the convection coefficient. This empirical correlation modeling method is compared to resistor network and CFD modeling. The proposed modeling method produced more accurate results than resistor network modeling, while solving 60% faster than a conjugate heat transfer model using CFD. The results of this work demonstrate that microchannels have the ability to remove high heat fluxes from microelectronic packages using water as a working fluid. Additionally, TECs can locally cool hotspots, but must be carefully placed to avoid undesired heating. Future work should focus on overcoming practical challenges including fabrication, cost, and reliability which are preventing these technologies from being fully leveraged.

The field of neuroscience has recently seen optogenetics emerge as a highly utilized and powerful method of non-invasive neural activation and inhibition. This thesis seeks to enhance the optogenetic toolbox through the design, construction, and evaluation of a number of hardware and software modules for research in Caenorhabditis elegans neuroscience. In the first aim, we combine optogenetics, microfluidics, and automated image processing, to create a system capable of high-throughput analysis of synaptic function. In the second aim, we develop a multi-modal illumination system for the manipulation of optogenetic reagents. The system is capable of multi-spectral illumination in definable patterns, with the ability to dynamically alter the intensity, color, and shape of the illumination. The illumination system is controlled by a set of software programs introduced in aim three, and is demonstrated through a set of experiments in aim four where we selectively activate and inhibit specific neural nodes expressing optogenetic reagents in freely moving C. elegans. With the ability to target specific nodes in a freely moving animal, we can correlate specific neural states to behaviors allowing for the dissection of neural circuits. Taken together, the developed technologies for optogenetic researchers will allow for experimentation with previously unattainable speed, precision and flexibility.

According to the European Brain Council, the annual total cost of brain disorders such as Huntington’s disease (HD) and Parkinson’s disease (PD) in Europe is approximately €386 billion. In order to develop therapies for neurodegenerative diseases, model systems that accurately reproduce the complex circuitry of the adult brain are needed. Neuron circuits developed in vitro could be used for studying pathogenesis of disorders and for high-throughput screening of potential therapies. In vitro models may offer the potential for highly reproducible and controllable cell circuitry, mimicking to some extent the complex neural connectivity required for function. Nano- and micro-scale substrates could be fabricated using techniques such as electrospinning, lithography and microfluidics to direct neurite orientation in order to build in vitro models that mimic in vivo circuitry. Poly-lactic acid (PLA) nano-fibres and polydimethylsiloxane (PDMS) micro-groove constructs were either pre-coated with poly-D-lysine (PDL) and laminin (LN) or pre-aligned astrocytes to study attachment and orientation of striatal neurites. Neurites were more responsive to substrates made up of combined topography and chemical cues; PDL and LN coated PDMS micro-grooves yielded the best neurite alignment. Excitability of striatal and cortical neurons was verified via an electrophysiology technique of patch clamp. PDMS microfluidic devices fabricated via lithographic techniques, were developed for co-culturing basal ganglia (BG) cells to model BG in vivo circuitry. Cell populations in the microfluidic device displayed electrical activity monitored using a calcium imaging technique. Connectivity was determined by eliminating activity of one cell population using tetrodotoxin (TTX) and studying response of remaining cell populations. Micro-contact printing was further explored as a technique for patterning BG cell circuitry instead of microfluidic devices. The microfluidic-based functional and complex model developed herein provides platform technology that can be useful for pharmaceutical and regenerative therapy and evaluation, therefore massively reducing costs currently associated with neurodegenerative diseases.

Este trabalho apresenta a síntese de nanopartículas (NPs) de NaYF4 dopadas com íons terras raras a partir de sistemas microfluídicos projetados e desenvolvidos em parceria entre o Laboratório de Crescimento de Cristais e a Central de Processamento de Materiais a Laser no Centro de Laser e Aplicações IPEN. O objetivo foi o estudo de diferentes circuitos microfluídicos usinados a laser para síntese de NPs de fluoretos em geral. Como material teste foi escolhido o NaYF4:Yb3+:Er3+, visando sua obtenção na fase hexagonal com dimensões definidas. Experiências de síntese deste material por co-precipitação, sem uso de surfactantes, foram realizadas para comparação com as sínteses obtidas via microfluídica. Por co-precipitação foram obtidas partículas esféricas, na fase cubica do NaYF4. Foram projetados e fabricados, via usinagem a laser de pulsos ultracurtos em substrato de vidro ótico BK7, três circuitos microfluídicos. Nas experiências de sínteses realizadas nestes chips foram obtidas NPs de NaYF4:Yb3+:Er3+ tanto na fase cubica quanto na fase hexagonal, em diferentes proporções, dependendo dos fluxos de injeção dos precursores no micro reator, da temperatura e da taxa de residência. As NPs obtidas neste trabalho foram caracterizadas através de DRX e analise pelo método de Rietveld, para a identificação das fases do material, MET para definição de forma e tamanho da nanopartículas e MEV para estudo dos microcanais dos chips usinados a lasers. Os melhores resultados foram observados em chips com microcanais da ordem de 400-600μm, pois minimizam o problema de obstrução. Contudo, o controle da temperatura precisa ser otimizado para evitar trincas nos microcircuitos. As NPs obtidas via microfluídica apresentaram distribuição de tamanho na faixa de 5 a 200nm e fases com estrutura hexagonal e cubica. Foi possível obter NPs de fase única cubica, mas o mesmo não ocorreu para fase hexagonal do NaYF4. O presente estudo permitiu definir vários fatores para a obtenção das NPs de NaYF4 via microfluídica e também referente a fabricação, montagem e uso dos chips, porém para obter NPs desse material com controle da dimensão e fases serão necessários estudos complementares.
This work presents the synthesis of NaYF4 nanoparticles (NPs), doped with rare earth ions, using microfluidic systems designed and fabricated at IPEN through Crystal Growth Lab and Materials Laser Processing Lab partnership. The aim of this work was the study of different microfluidic chips laser machined for use in fluoride NPs synthesis. The compound NaYF4:Yb3+:Er3+ (Yb 10 mole%; Er 0.5 mole %) was chosen to test the fabricated microfluidic chips aiming the production of NPs with hexagonal structure with defined dimensions. Synthesis experiments by co-precipitation method of this material without any surfactant were performed to compare with microfluidics synthesis. By this method spherical particles, were obtained with the cubic NaYF4 crystalline structure. Three different chips were designed and fabricated, using a femtosecond laser to machine BK7 optical glass substrate. The synthesis experiments with these chips resulted in NaYF4:Yb3+:Er3+ NPs with both cubic and hexagonal crystalline structure, in different proportions, depending of precursors flux rates, temperature and resident time. The obtained materials of all experiments were characterized by X-ray diffraction and Rietveld analysis, to define crystalline structures parameters; transmission microscopy to define shape and size of NPs and scanning electron microscopy to characterize the chips micro channels machined by laser. The best results were observed for chips with channels of 400-600μm, in view of the obstruction decrease in the chips. The NPs obtained with microfluidics presented sizes from 5nm up to 200nm and hexagonal and cubic crystallographic structures. Cubic single phase NPs were obtained, but the same did not happened with the NaYF4 hexagonal phase. The present study allowed establishing many different parameters for NaYF4 NPs synthesis through microfluidics and concerning fabrication, assembly and experimental use of microfluidic chips, however, additional experiments will be necessary to obtain the fluoride NPs with controlled size and shape.

The addition of powered components for active assays into paper-based analytical devices opens new opportunities for medical and environmental analysis in resource-limited applications. Current battery designs within such devices have yet to adopt a ubiquitous circuitry material, necessitating investigation into printed circuitry for scalable platforms. In this study, a microfluidic battery was mated with silver-nanoparticle conductive ink to prototype an all-printed sensing platform. A multi-layer, two-cell device was fabricated, generating 200 μA of direct electrical current at 2.5 V sustained for 16 minutes with a power loss of less than 0.1% through the printed circuitry. Printed circuitry traces exhibited resistivity of 75 to 211 10-5 Ω m. Resistance of the printed traces increased upwards of 200% depending on fold angle and directionality. X-ray diffraction confirmed the presence of face-centered cubic silver after sintering printed traces for 30 minutes at 150°C in air. A conductivity threshold was mapped and an ink concentration of 0.636 μL mm-3 was identified as the lower limit for optimal electrical performance.

In modern microprocessors, thermal management has become one of the main hurdles in continued performance enhancement. Cooling schemes utilizing single phase microfluidics have been investigated extensively for enhanced heat dissipation from microprocessors. However, two-phase fluidic cooling devices are becoming a promising approach, and are less understood. This study aims to examine two-phase flow and heat transfer within a pin-fin enhanced micro-gap. The pin-fin array covered an area of 1cm x 1cm and had a pin diameter, height and pitch of 150μm, 200μm and 225μm, respectively, (aspect ratio of 1.33). This study covers both uniformly and partially heated scenarios. The working fluid used was R245fa. The average heat transfer coefficient and high speed flow visualization results indicated a rapid transition to the annular flow regime with a strong dependence on heat flux. Also, unique, conically-shaped two-phase wakes were observed, demonstrating the lateral spreading capability of the pin-fin array geometry.

Lab-on-a-chip (LOC) technology has blossomed into a major new technology fundamentally influencing the sciences of life and nature. From a systemic point of view however, microfluidics is still in its infancy. Here, we present the concept of a microfluidic central processing unit (CPU) which shows remarkable similarities to early electronic Von Neumann microprocessors. It combines both control and execution units and, moreover, the complete power supply on a single chip and introduces the decision-making ability regarding chemical information into fluidic integrated circuits (ICs). As a consequence of this system concept, the ICs process chemical information completely in a self-controlled manner and energetically self-sustaining. The ICs are fabricated by layer-by-layer deposition of several overlapping layers based on different intrinsically active polymers. As examples we present two microchips carrying out long-term monitoring of critical parameters by around-the-clock sampling
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Lab-on-a-chip (LOC) technology has blossomed into a major new technology fundamentally influencing the sciences of life and nature. From a systemic point of view however, microfluidics is still in its infancy. Here, we present the concept of a microfluidic central processing unit (CPU) which shows remarkable similarities to early electronic Von Neumann microprocessors. It combines both control and execution units and, moreover, the complete power supply on a single chip and introduces the decision-making ability regarding chemical information into fluidic integrated circuits (ICs). As a consequence of this system concept, the ICs process chemical information completely in a self-controlled manner and energetically self-sustaining. The ICs are fabricated by layer-by-layer deposition of several overlapping layers based on different intrinsically active polymers. As examples we present two microchips carrying out long-term monitoring of critical parameters by around-the-clock sampling.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Inkjet-printing is a technology which has for the last decade been exploited to fabricate flexible RF components such as antennas and planar circuit elements. However, the limitations of feature size and single layer fabrication prevented the demonstration of compact, and high efficiency RF components operating above 10 GHz into the mm-Wave regime which is critical to silicon integration and fully-printed modules. To overcome these limitations, a novel vertically-integrated fully inkjet-printed process has been developed and characterized up to the mm-Wave regime which incorporates up to five highly conductive metal layers, variable thickness dielectric layers ranging from 200 nm to 200 um, and low resistance through-layer via interconnects. This vertically-integrated inkjet printed electronics process, tagged VIPRE, is a first of its kind, and is utilized to demonstrate fully additive RF capacitors, inductors, antennas, and RF sensors operating up to 40 GHz. In this work, the first-ever fully inkjet printed multi-layer RF devices operating up to 40 GHz with high-performance are demonstrated, along with a demonstration of the processing techniques which have enabled the printing of multi-layer RF structures with multiple metal layers, and dielectric layers which are orders of magnitude thicker than previoulsy demonstrated inkjet-printed structures. The results of this work show the new possibilities in utilizing inkjet printing for the post-processing of high-efficiency RF inductors, capacitors, and antennas and antenna arrays on top of silicon to reduce chip area requirements, and for the production of entirely printed wireless modules.

Linvention du concept de µTAS (micro total chemical analysis system) au début des années quatre vingt dix a ouvert aux fluides la porte du monde des microsystèmes. Un laboratoire sur puce intègre toutes les fonctions dun laboratoire macroscopique (déplacer, mélanger, chauffer des liquides, filtrer, séparer, détecter des molécules, etc.) sur une petite surface (typiquement quelques centimètres carrés). Le challenge technologique repose sur le couplage entre un microsystème conventionnel et un réseau microfluidique. Si les procédés silicium et verre ont été largement utilisés durant les années quatre vingt dix, ils présentent plusieurs inconvénients rédhibitoires : incompatibilité des technologies silicium avec les forts champs électriques nécessaires pour les séparations électrophorétiques et/ou le pompage électroosmotique, technologies non adaptées pour des grandes surfaces, difficultés dintégration dans un système complet, prix élevé des matériaux et des procédés associés, etc. La solution explorée dans cette thèse consiste à construire directement le réseau microfluidique sur un microsystème conventionnel dans des résines photosensibles (SU-8), ce qui facilite lintégration et autorise la fabrication de structures 3D avec un excellent alignement niveau à niveau. Les outils de caractérisation microfluidique développées et utilisés dans le cadre de ce travail sont présentés. Les effets de surface étant fondamentaux à cette échelle, une stratégie générique de modification des propriétés physicochimiques de la SU-8 est proposée et caractérisée.

En microélectronique, plusieurs tendances telles que l'empilement 3D et l'amincissement de puces amènent des défis thermiques grandissants. Ces défis sont exacerbés lorsqu'appliqués aux appareils mobiles où l'espace et la puissance disponibles pour le refroidissement sont limités. Le but de cette thèse est de développer des outils de conception et méthodes d'implémentation de microcanaux pour le refroidissement microfluidique de puces 2D et 3D avec points chauds destinés aux appareils mobiles.Une méthode de conception pour optimiser la configuration des microcanaux refroidissant une puce est développée utilisant un plan d'expériences numériques. La configuration optimisée propose le refroidissement à une température maximale de 89 °C d'un point chaud de 2 W par un écoulement où la perte de charge est plus petit que 1 kPa. Des prototypes avec différents empilements et distributions de microcanaux sont fabriqués par gravure profonde et apposés par pick-and-place. Un banc de caractérisation et une puce thermique test sont fabriqués pour caractériser expérimentalement les prototypes de refroidissement avec différentes configurations. Un prototype avec microcanaux limités aux alentours des points chauds et reportés sur la face arrière de la puce test atteint une résistance thermique de 2.8 °C/W. Cela est réalisé avec un débit de 9.4 ml/min et des pertes de charges de 19.2 kPa, soit une puissance hydraulique de 3 mW. Ce refroidissement extrait 7.3 W générés sur un seul serpentin à un flux thermique de 1 185 W/cm² pour un coefficient de performance de 2 430. Les résultats de l'optimisation suggèrent que la dissipation thermique soit exploitée en ajoutant des microcanaux en parallèle, plutôt qu'en allongeant les microcanaux. On observe expérimentalement comme numériquement que la résistance liée à la hausse de température du fluide domine la résistance totale. Enfin, il apparaît que les différents empilements ont un effet plus important sur la résistance thermique que les distributions de microcanaux dans les plages observées
In microelectronics, trends such as 3D stacking and die thinning bring major thermal challenges. Those challenges are exacerbated when applied to mobile devices where the available space and power for cooling are limited. This thesis aims at developing design tools and implementation techniques for microchannels cooling on 2D and 3D chips with hot spots for mobile devices. A design technique to optimize the microchannel configuration for chip cooling is developed using numerical experimentation plans. The optimized configuration suggests a cooling configuration reaching a maximum temperature of 89 °C on a 2 W hot spot, using a flow at a pressure drop plus petit que 1 kPa. Prototypes with different stacking and microchannel distributions are fabricated using deep reactive ion etching process and stacked using pick-and-place technique. A characterization bench and a thermal test chip are fabricated for experimental characterization of the cooling prototypes from various configurations. A prototype with microchannel zones limited to the hot spot vicinity and installed on the backside of the test chip reached a thermal resistance of 2.8 °C/W. This performance is achieved using a flow rate of 9.4 ml/min with a pressure drop of 19.2 kPa, representing a hydraulic power of 3 mW. Such cooling removes 7.3 W generated on a single heat source, representing a heat flux of 1 185 W/cm² for a coefficient of performance of 2 430. The optimization results suggest that the heat spreading is better exploited using parallel microchannels, rather than lengthen microchannels. It is both observed experimentally and numerically that the thermal resistance related to the fluid temperature rise is the major contribution to the total thermal resistance. Finally, it appears that the different stacking effects on thermal resistance are more important than the microchannels distributions in the observed ranges

In this thesis, I have used microfluidics--the science and technology of systems that manipulate small amounts of fluids (10^-9 to 10^-18 liters) in microsized channels--to invent and implement a miniaturized continuous culture device or microchemostat. It relies on a novel in silicone sterilization approach to circumventing biofilm formation. The microchemostat system has inbuilt automation, which allows it to run, unattended, indefinitely (for up to months at a time). With a working volume of ~10 nL, the microchemostat is capable of culturing extremely small populations of bacteria (100 to ~10^4 cells vs ~10^9 in macroscale cultures). The microsized population reduces the number of cell-division events per unit time and hence slows down microbial evolution. This aspect facilitates long-term monitoring of the behavior of genetically engineered microbes while preserving their genetic homogeneity. Unlike its conventional continuous-culture counterparts, the microchemostat allows simultaneous operation of fourteen (or more) independent microreactors which enjoy ultralow consumption of medium and biological reagents, allowing high-throughput research at low cost. It also facilitates automated, noninvasive monitoring of bacterial behavior in terms of bacterial count, cell morphology as well as single-cell resolved gene-expression dynamics reported by fluorescence or luminescence. The unprecedented temporal and single cell resolution readings allow the microchemostat to capture dynamics such as delicate oscillations that have eluded detection in conventional settings. Thanks to its unique capability for long-term culturing and suppression of microbial evolution, the microchemostat promises to become integrated as an ingredient of a multicomponent monolithic entity in future applications. The microchemostat would mainly be responsible for in silicone production and supply of genetically homogeneous bacteria for use in various capacities.

Microfluidic flow devices coupled with quantitative Raman spectroscopy are able to provide a deep insight into the reaction mechanism and kinetics of electrocatalytic reactions. With a microfluidic flow device made with glass microscope slides and polymer building blocks, the feasibility of this technique was examined by methanol electrooxidation reaction with a Pt working electrode. Pre-calibration of the Raman peak area was done with solutions of known concentrations of methanol and its major oxidation product, i.e., formate, which enabled the time-dependent Raman spectra taken during the reaction to be converted to time-dependent concentrations. These were interpreted in terms of a model with one-dimensional convection and the reaction kinetics. An improved version of this technique was then applied to a comparative study of different alcohols with Ni-based electrodes. This showed the production of formate as the major product from the oxidation of alcohols with vicinal OH groups, leading to the discovery that C-C bond dissociation is a major reaction pathway for vicinal diols and triols if Ni electrocatalysts are used. It is also suggested that the cleavage of C-C bonds is the rate-determining step. The potential use of printed circuit boards (PCB) in the next generation of a novel microfluidic device was explored, as PCB have advantages over regular electrochemical microfluidic substrates, such as simpler electrode fabrication strategies, more wiring layers, and customization of size and shape of electrodes. Pretreatments and electrodeposition protocols of nickel, silver, palladium and platinum on PCB were successfully developed, together with four types of PCB-based microfluidic devices designed with an open-source PCB design software. This work establishes a new electrochemical microfluidic platform for online and in-situ monitoring of electrocatalytic reactions, which can quickly determine the reaction mechanism and kinetics.
Graduate

碩士
國立雲林科技大學
電子工程系
107
In this thesis, the silver reference electrodes and conductive wires were printed onto a polyethylene terephthalate substrate (PET) by using screen printing technology. Next, aluminium-doped zinc oxide (AZO) or zinc oxide (ZnO) was deposited onto the silver electrodes by using the vacuum radio frequency (RF) sputtering system. The enzyme like glucose oxidase (GOx) or ascorbate oxidase (AO) was immobilized on the AZO or ZnO membranes to fabricate the glucose biosensor or the ascorbic acid biosensor, respectively. After that, graphene oxide (GO) and magnetic beads (MBs) were used to modify the sensing membranes. In terms of the analysis of sensing characteristics, average sensitivity, linearity, response time, limit of detection, drift, hysteresis, interference, lifetime, and temperature effects were investigated. Moreover, electrochemical impedance spectroscopy (EIS) was used to analyze the electrochemical impedance of different membranes. Finally, the sensing characteristics of the biosensor integrating with the microfluidic framework were analyzed, and the wireless sensing system based on ZigBee protocol integrating the biosensor was applied to realizing remote monitoring.

碩士
國立雲林科技大學
電子工程系
106
In this thesis, the screen-printed technology, radio frequency sputtering system and thermal evaporation system were used to integrate indium gallium zinc oxide (IGZO) membrane, Al electrode and silver paste onto the PET (polyethylene terephthalate) substrate. Next, the covalent bonding was used to immobilize ascorbate oxidase (AOX) onto the IGZO sensing membrane, and the flexible arrayed enzymatic L-ascorbic acid (L-AA) biosensor was completed. Besides, the graphene oxide (GO) and magnetic beads (MBs) were used to modify IGZO sensing membrane, and the electrochemical impedance spectroscopy (EIS) was used to confirm whether the GO and MBs were modified onto the sensing membrane successfully. According to the experimental results, the average sensitivity and linearity of MBs-AOX/GO/IGZO/Al L-AA biosensor were 78.9 mV/decade and 0.997, respectively. In this thesis, the response time, drift effect, hysteresis effect, anti-interfering effect and life time were investigated. Moreover, the sensing characteristic of L-AA biosensor which was integrated with microfluidic framework was detected under the different flow rates. Finally, in order to achieve remote monitoring, the L-AA biosensor was integrated with wireless real-time sensing system based on XBee module.

The work presented in this dissertation is focused on integrating organic transistor based circuits with planar microfluidic devices for discrete droplet handling. Discrete droplet based microfluidic systems are being increasingly investigated for lab-on-a-chip type applications. An essential component of a lab-on-a-chip system is the drive circuitry that runs the system. Conventionally, a variety of schemes have been implemented for acting as drivers for microfluidic devices. Organic transistor based circuits offer a viable and cost-effective option for serving as drivers for planar microfluidic devices. The magnitudes of voltages and the time scales involved in implementing these discrete droplet based systems are in good agreement with the values of voltages that can be reliably generated using organic transistor based circuits. Thus, the union of two cost-effective technologies with the ability to perform a wide variety of functions in a lab-on-a-chip type system would be highly desirable. A simple, planar microfluidic device with an open structure is implemented on a glass substrate. The device is optimized for reliable and repeatable performance using Cytop as the insulating dielectric. Cytop provides a highly hydrophobic surface for reversible wetting to take place on the application of electrical voltage. Various organic transistor based circuits are fabricated using Pentacene as the p-type semiconducting material and N,N'-bis(n-octyl)-dicyanoperylene-3,4:9,10-bis(dicarboximide) (PDI-8CN₂) as the n-type material. A top contact inverter, which is the most basic complementary metal oxide semiconductor circuit is fabricated and used as the driver for the planar microfluidic device. The output voltages generated by the inverter are used to actuate discrete water droplets over adjacent electrodes and also to perform merging of droplets, which is another basic functional operation that is performed on lab-on-a-chip type assemblies. Reliable and repeatable performance of the microfluidic device as well as the CMOS circuit is achieved. This work presents the first implementation of a discrete droplet based device driven by electrical voltages generated by an organic transistor based circuit. The physical mechanisms that are responsible for the motion of droplets have been investigated and contributions from electrowetting forces and dielectrophoretic forces have been resolved.

碩士
輔仁大學
物理學系碩士班
106
In this study, I used soft lithography to construct a three-layered microfluidic chip for application as a viscometer. The performance of this viscometer was then tested. This viscometer was made of polydimethylsiloxane (PDMS). The microchannel of this chip has a fixed flow resistance and the liquid circuit is constructed based on the Wheatstone bridge. The microfluidic viscometer was built after bonding three PDMS layers (a liquid-circuit layer, a PDMS thin layer, and a liquid-mixing layer) via oxygen plasma. After flowing ionic liquid into liquid circuit channel, all electrodes were connected to a NI-DAQ board which is controlled via a customized LabVIEW program. This program is also used to control the pressure sensor and the syringe pump. The performance of this viscometer was tested by flowing nitrogen gas with controllable pressures into the device. Through data analysis, the relationship between measured voltage and input pressure was observed to be linear in the pressure range of 0-15psi. Then liquid samples were flowed into the microchannel with flow rates of 0-100μl / min for measuring their viscosities. For glycerol-waters solutions of low concentrations, the experimentally measured viscosities are in good agreement with the theoretical values. Theoretical deduction indicated that the error might come from fluidic slippage of the hydrophobic channel and deformation of the microchannel under high pressure. This microfluidic viscometer can be used to measure samples with low viscosities, and the concentrations of the samples can be controlled by using the customized program (via the liquid-mixing layer). In addition, PDMS has good biocompatibility and is permeable to visible light. In the future, this device can be applied to study cellular behaviors under various physical stimuli such as light, shear stress, and electric field.

碩士
國立清華大學
資訊系統與應用研究所
105
Synthetic biologists design genetic logic circuit using living cells. A challenge in this task is the difficulty in constructing bigger logic circuits with several living cells due to the crosstalk effect among the biological cells. In order to remove the crosstalk effect, current practice is to use separate chambers on a flow-based microfluidic biochip to isolate each reaction zone. A flow-based microfluidic biochip can provide high precision control using microscale devices for the flow of biological substances. Hence, it can contruct more reliable and scalable genetic logic systems for synthetic biology experiments. The state-of-the-art technqiue assumes the reaction rates of different genetic logic gates are identical. This assumption is pessimistic as each genetic logic gate has the reaction rate different from others. Hence, it will cause unnecessary waiting time for fast logic gates and this, in turn, lengthen the whole experiment completion time significantly. In this thesis, we propose a new scheduling scheme for genetic logic circuits in flow-based microfluidic biochips considering different reaction time of each logic gate. Simulation results show that the proposed scheme reduces the experiment completion time. We further minimize the number of control valves and optimize the routing of flow and control layers in the chip layout, which in turn reduces the design cost.

abstract: Synthetic biology is a novel method that reengineers functional parts of natural genes of interest to build new biomolecular devices able to express as designed. There is increasing interest in synthetic biology due to wide potential applications in various fields such as clinics and fuel production. However, there are still many challenges in synthetic biology. For example, many natural biological processes are poorly understood, and these could be more thoroughly studied through model synthetic gene networks. Additionally, since synthetic biology applications may have numerous design constraints, more inducer systems should be developed to satisfy different requirements for genetic design. This thesis covers two topics. First, I attempt to generate stochastic resonance (SR) in a biological system. Synthetic bistable systems were chosen because the inducer range in which they exhibit bistability can satisfy one of the three requirements of SR: a weak periodic force is unable to make the transition between states happen. I synthesized several different bistable systems, including toggle switches and self-activators, to select systems matching another requirement: the system has a clear threshold between the two energy states. Their bistability was verified and characterized. At the same time, I attempted to figure out the third requirement for SR – an effective noise serving as the stochastic force – through one of the most widespread toggles, the mutual inhibition toggle, in both yeast and E. coli. A mathematic model for SR was written and adjusted. Secondly, I began work on designing a new genetic system capable of responding to pulsed magnetic fields. The operators responding to pulsed magnetic stimuli in the rpoH promoter were extracted and reorganized. Different versions of the rpoH promoter were generated and tested, and their varying responsiveness to magnetic fields was recorded. In order to improve efficiency and produce better operators, a directed evolution method was applied with the help of a CRISPR-dCas9 nicking system. The best performing promoters thus far show a five-fold difference in gene expression between trials with and without the magnetic field.
Dissertation/Thesis
Masters Thesis Bioengineering 2016

In this work, a design platform for the modeling, simulation and optimization of fluidic components and their interactions in larger systems is developed. A hydrogel-based stimulus-sensitive microvalve is the core element of the microfluidic toolbox. Essential material properties as swelling-stimuli functions and the cooperative diffusion are extracted from measurements. The results provide necessary input data for finite element simulations in order to extract characteristic properties of the mechanical and fluid domains. Finally, the behavior of the microvalve and other fluidic library elements is implemented in Matlab Simscape for component and system simulations. Case studies and design optimization can be realized in a very short time with high accuracy. The toolbox is suitable for research and development and as software for academic education. The library elements are evaluated for a chemofluidic NAND gate, a chemofluidic decoder and a chemofluidic oscillator.:1 Introduction to Microfluidic Systems 1.1 Chemofluidic Enables Scalable and Logical Microfluidics 1.2 Focus of this Work 2 Fundamentals for Hydrogel-based Lab-on-Chip Systems 2.1 Basic Hydrogel Material Behavior 2.1.1 Basic Swelling Behavior 2.1.2 General Properties of Hydrogels 2.2 Overview of the used Microtechnology 2.2.1 Synthesis of P(NIPAAm-co-SA) 2.2.2 Microfabrication of a Microfluidic Chip 2.3 Introduction to Modeling and Simulation Techniques 2.3.1 Computer-aided Design Methodologies 2.3.2 Model Abstraction Levels for Computer-Aided Design 2.3.3 Modeling Techniques for Microvalves in a Fluidic System 3 Analytical Descriptions of Swelling 3.1 Quasi-Static Description 3.1.1 Physical Static Chemo-Thermal Description 3.1.2 Finite Element Routine for Static Thermo-Elastic Expansion 3.1.3 Static System Level Design for Hydrogel Swelling 3.2 Transient Description 3.2.1 Physical Dynamic Chemo-Thermal Description 3.2.2 Finite Element Routine for Dynamic Thermo-Elastic Expansion 3.2.3 Transient System Level Design for Hydrogel Swelling 3.3 Swelling Hysteresis Effect 3.3.1 Quasi-static Hysteresis 3.3.2 Transient Hysteresis 4 Characterization of Hydrogel 4.1 Data Acquisition through Automated Measurements 4.1.1 Measuring the Swelling of Hydrogels 4.1.2 Contactless Measurement Concept to Determine the Core Stiffness of Hydrogels 4.2 Data Evaluation with Image Recognition 4.3 Data Fitting and Model Adaption 4.3.1 Quasi-static Response 4.3.2 Transient Response 4.3.3 Hysteresis Response 5 Modeling Swelling in Finite Elements 5.1 Validity of the Model and Simulation Approach 5.2 Thermo-Mechanical Model of the Hydrogel Expansion Behavior 5.2.1 Change of the Length by Thermal Expansion 5.2.2 Stress-Strain Relationship for Hydrogels 5.2.3 Thermal Volume Expansion and Parameter Adaptation 5.2.4 Heat Transfer Coefficient 5.3 Volume Phase-Transition of a Hydrogel implemented in ANSYS 5.4 Computational Fluid Dynamics 5.4.1 Analytic Mesh Morphing 5.4.2 One-way Fluid Structure Interaction Modeling 5.4.3 Towards a Two-way Fluid Structure Interaction Model in CFX 6 Lumped Modeling 6.1 The Chemical Volume Phase-transition Transistor Model 6.1.1 Static Hysteresis 6.1.2 Equilibrium Swelling Length – Quasi-static Behavior 6.1.3 Kinematic Swelling Length - Transient Behavior 6.1.4 Stiffness and Maximum Closing Pressure 6.1.5 Calculation of the Fluidic Conductance 6.1.6 Modeling of the Fluid Flow through the Valve 6.2 Circuit Descriptions Analogy for Microfluidic Applications 6.2.1 Advantages and Limitations of Combined Simulink-Simscape Models 6.2.2 Requirements for Microfluidic Circuits 6.2.3 Graphical User Interfaces and Library Element Management 6.3 Modeling Techniques for the Chemical Volume Phase-transition Transistor (CVPT) 6.3.1 Network Description of CVPT 6.3.2 Signal Flow Description of CVPT 6.3.3 Mixed Signal Flow and Network Model for CVPT 7 Micro-Fluidic Toolbox 7.1 Microfluidic Components 7.1.1 Fluid Sources and Stimuli Sources 7.1.2 Fluidic Resistor with Bidirectional Stimulus Transport 7.1.3 Junctions 7.1.4 Chemical Volume Phase-transition Transistor 7.2 Microfluidic Matlab Toolbox 7.3 Modeling Chemofluidic Logic Circuits 7.3.1 Chemofluidic NAND Gate 7.3.2 Chemofluidic Decoder Application 7.3.3 Chemo-Fluidic Oscillator 7.4 Layout Synthesis 8 Summary and Outlook Appendix A 2D Thermo-Mechanical Solid Element for the Finite Element Method B Thermal Expansion Equation for ANSYS C Linear Regression of the Thermal Expansion Equation for ANSYS D Comparing different Mechanical Strain Definitions E Supporting Documents E.1 Analytic Static Swelling E.2 FEM - Matrix Method E.3 8 Node Finite Element Routine E.4 FEM - Script to create the CTEX table data E.5 Comparison of Solid Mechanics
In dieser Arbeit wird eine Entwurfsplattform für die Modellierung, Simulation und Optimierung von fluidischen Komponenten und deren Wechselwirkungen in größeren Systemen entwickelt. Ein Mikroventil auf der Basis von stimuli-sensitiven Hydrogelen ist das Kernelement des Entwurfstools. Wesentliche Materialeigenschaften wie das Quellverhalten und der kooperative Diffusionskoeffizient werden zu Beginn mit Messungen ermittelt. Mit Finite-Elemente-Simulationen werden aus diesen Daten charakteristische Kennwerte für das mechanische und fluidische Verhalten bestimmt. Sie bilden die Basis für komplexe Systemmodelle in Matlab Simscape, welche das Mikroventil und weitere fluidische Grundelemente in ihrem Zusammenwirken beschreiben. Verschiedene Konzepte können in kurzer Zeit und mit hoher Genauigkeit analysiert, optimiert und verglichen werden. Die Toolbox eignet sich für die Forschung und Entwicklung sowie als Software für die akademische Ausbildung. Sie wurde für den Entwurf eines chemofluidischen NAND-Gatters, für einen chemofluidischen Decoder und für einen chemofluidischen Oszillator eingesetzt.:1 Introduction to Microfluidic Systems 1.1 Chemofluidic Enables Scalable and Logical Microfluidics 1.2 Focus of this Work 2 Fundamentals for Hydrogel-based Lab-on-Chip Systems 2.1 Basic Hydrogel Material Behavior 2.1.1 Basic Swelling Behavior 2.1.2 General Properties of Hydrogels 2.2 Overview of the used Microtechnology 2.2.1 Synthesis of P(NIPAAm-co-SA) 2.2.2 Microfabrication of a Microfluidic Chip 2.3 Introduction to Modeling and Simulation Techniques 2.3.1 Computer-aided Design Methodologies 2.3.2 Model Abstraction Levels for Computer-Aided Design 2.3.3 Modeling Techniques for Microvalves in a Fluidic System 3 Analytical Descriptions of Swelling 3.1 Quasi-Static Description 3.1.1 Physical Static Chemo-Thermal Description 3.1.2 Finite Element Routine for Static Thermo-Elastic Expansion 3.1.3 Static System Level Design for Hydrogel Swelling 3.2 Transient Description 3.2.1 Physical Dynamic Chemo-Thermal Description 3.2.2 Finite Element Routine for Dynamic Thermo-Elastic Expansion 3.2.3 Transient System Level Design for Hydrogel Swelling 3.3 Swelling Hysteresis Effect 3.3.1 Quasi-static Hysteresis 3.3.2 Transient Hysteresis 4 Characterization of Hydrogel 4.1 Data Acquisition through Automated Measurements 4.1.1 Measuring the Swelling of Hydrogels 4.1.2 Contactless Measurement Concept to Determine the Core Stiffness of Hydrogels 4.2 Data Evaluation with Image Recognition 4.3 Data Fitting and Model Adaption 4.3.1 Quasi-static Response 4.3.2 Transient Response 4.3.3 Hysteresis Response 5 Modeling Swelling in Finite Elements 5.1 Validity of the Model and Simulation Approach 5.2 Thermo-Mechanical Model of the Hydrogel Expansion Behavior 5.2.1 Change of the Length by Thermal Expansion 5.2.2 Stress-Strain Relationship for Hydrogels 5.2.3 Thermal Volume Expansion and Parameter Adaptation 5.2.4 Heat Transfer Coefficient 5.3 Volume Phase-Transition of a Hydrogel implemented in ANSYS 5.4 Computational Fluid Dynamics 5.4.1 Analytic Mesh Morphing 5.4.2 One-way Fluid Structure Interaction Modeling 5.4.3 Towards a Two-way Fluid Structure Interaction Model in CFX 6 Lumped Modeling 6.1 The Chemical Volume Phase-transition Transistor Model 6.1.1 Static Hysteresis 6.1.2 Equilibrium Swelling Length – Quasi-static Behavior 6.1.3 Kinematic Swelling Length - Transient Behavior 6.1.4 Stiffness and Maximum Closing Pressure 6.1.5 Calculation of the Fluidic Conductance 6.1.6 Modeling of the Fluid Flow through the Valve 6.2 Circuit Descriptions Analogy for Microfluidic Applications 6.2.1 Advantages and Limitations of Combined Simulink-Simscape Models 6.2.2 Requirements for Microfluidic Circuits 6.2.3 Graphical User Interfaces and Library Element Management 6.3 Modeling Techniques for the Chemical Volume Phase-transition Transistor (CVPT) 6.3.1 Network Description of CVPT 6.3.2 Signal Flow Description of CVPT 6.3.3 Mixed Signal Flow and Network Model for CVPT 7 Micro-Fluidic Toolbox 7.1 Microfluidic Components 7.1.1 Fluid Sources and Stimuli Sources 7.1.2 Fluidic Resistor with Bidirectional Stimulus Transport 7.1.3 Junctions 7.1.4 Chemical Volume Phase-transition Transistor 7.2 Microfluidic Matlab Toolbox 7.3 Modeling Chemofluidic Logic Circuits 7.3.1 Chemofluidic NAND Gate 7.3.2 Chemofluidic Decoder Application 7.3.3 Chemo-Fluidic Oscillator 7.4 Layout Synthesis 8 Summary and Outlook Appendix A 2D Thermo-Mechanical Solid Element for the Finite Element Method B Thermal Expansion Equation for ANSYS C Linear Regression of the Thermal Expansion Equation for ANSYS D Comparing different Mechanical Strain Definitions E Supporting Documents E.1 Analytic Static Swelling E.2 FEM - Matrix Method E.3 8 Node Finite Element Routine E.4 FEM - Script to create the CTEX table data E.5 Comparison of Solid Mechanics

Electrophoresis is the migration of charged particles in a heterogeneous fluid under the influence of an electric field. This project is work toward an electrophoretic separation system on a custom CMOS chip. Modeling, fabrication, and testing of an AMI ABN 1.5 um CMOS chip for this application is discussed. The unique approach is to build the entire system using conventional CMOS integrated circuit technology, such that the separation area is fabricated on the chip with integrated control and detection circuitry. To achieve the desired functionality, a novel configuration of an electrophoresis system is implemented. In this system, instead of using only one electrode at each end of the separation area, a multitude of electrodes beneath the entire separation area are utilized, enabling better control of high electric fields using very small voltages over small areas. Electronic circuits control the position and strength of the electric field to drive the separations and to simultaneously detect the location and concentration of samples within the separation area. Ultimately, the project was successful at showing that implementing an electrophoresis system on standard CMOS is possible.

Dissertation