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3D printing for microfluidic device fabrication has received considerable interest in recent years, in part driven by the potential to dramatically speed up device development by reducing device fabrication time to the minutes timescale. Moreover, in contrast to traditional cleanroom-based fabrication processes that require manual production and stacking of a limited number of layers, 3D printing allows full use of the 3D fabrication volume to lay out microfluidic elements with complex yet compact 3D geometries. The Nordin group has successfully developed multiple generations of high resolution printers and materials for microfluidic devices that achieve this vision. However, because of the customizability of design in the Nordin microfluidics lab, finding settings that lead to a successful print can involve a taxing cycle of adjustments. The current 3D microfluidics design flow, which requires each student to find settings for each design, makes it difficult for new students to rapidly print successful designs with new components. In this thesis I present an Improved Microfluidic Design Approach (IMDA) that is based on a pre-defined component library. It allows students to reuse a library of components such that a new designer can utilize the work of more experienced predecessors, allowing the lab to avoid repeating the same parameter tuning process with each student. So far the tool has shown the feasibility of printing new designs based on previously tested components. Ultimately, my work demonstrates an attractive path to make the 3D printed microfluidic design experience more robust, repeatable, and easier for newcomers to learn.

The Nordin group at Brigham Young University has been focused on developing 3D printing technology for fabrication of lab-on-a-chip (microfluidic) devices since 2013. As we showed in 2015, commercial 3D printers and resins have not been developed to meet the highly specialized needs of microfluidic device fabrication. We have therefore created custom 3D printers and resins specifically designed to meet these needs. As part of this development process, ad hoc 3D printer control software has been developed. However, the software is difficult to modify and maintain to support the numerous experimental iterations of hardware used in our custom 3D printers. This highlights the need for modular yet reliable system software that is easy to use, learn, and work with to adapt to the unique challenges of a student workforce. This thesis details the design and implementation of new 3D printer system software that meets these needs. In particular, a software engineering principle-based design approach is taken that lends itself to several specific development patterns that permit easy incorporation of new hardware into a 3D printer to enable rapid evaluation of and development with such new hardware.

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23155号 / 工博第4799号 / 新制||工||1750(附属図書館) / 京都大学大学院工学研究科マイクロエンジニアリング専攻 / (主査)教授 横川 隆司, 教授 井上 康博, 教授 中部 主敬 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

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At the cutting edge of the chemical and biological research, innovation takes place in a field referred to as Lab on Chip (LoC), a multi-disciplinary area that combines biology, chemistry, electronics, microfabrication, and fluid mechanics. Within this field, droplets have been used as microreactors to produce advanced materials like quantum dots, micro and nanoparticles, active pharmaceutical ingredients, etc. The size of these microreactors offers distinct advantages, which were not possible using batch technologies. For example, they allow for lower reagent waste, minimal energy consumption, increased safety, as well as better process control of reaction conditions like temperature regulation, residence times, and response times among others. One of the biggest drawbacks associated with this technology is its limited production volume that prevents it from reaching industrial applications. The standard production rates for a single droplet microfluidic device is in the range of 1-10mLh-1, whereas industrial applications usually demand production rates several orders of magnitude higher. Although substantial work has been recently undertaken in the development scaled-out solutions, which run in parallel several droplet generators. Complex fluid mechanics and limitations on the manufacturing capacity have constrained these works to explore only in-plane parallelization. This thesis investigates a three-dimensional parallelization by proposing a microfluidic system that is comprised of a stack of droplet generation layers working on the liquid-liquid ow regime. Its realization implied a study of the characteristics of conventional droplet generators and the development of a fabrication process for 3D networks of microchannels. Finally, the combination of these studies resulted in a functional 3D parallelization system with the highest production rate (i.e. 1 Lh-1) at the time of its publication. Additionally, this architecture can reach industrially relevant production rates as more devices can be integrated into the same chip and many chips can compose a manufacturing plant. The thesis also addresses the concerns about system reliability and quality control by proposing capacitive and radio frequency resonator sensors that can measure accurately increments as small as 2.4% in the water-in-oil volume fraction and identify errors during droplet production.

Au cours de ma thèse, j'ai développé un procédé de fabrication spécifique capable de produire un biocapteur qui combine deux techniques de biodétection différentes, la réponse plasmonique basée sur la résonance de plasmon de surface localisée (LSPR) et la réponse électrochimique. Les méthodes et les résultats qui sont présentés dans ce manuscrit ont été définis pour converger vers un dispositif fluidique unique combinant ces deux approches de détection différentes. Afin de trouver la configuration permettant l'excitation des résonances plasmoniques, la géométrie des nanocavités MIM (métal/isolant/métal) en réseau de lignes interdigitées a été optimisée par des simulations électromagnétiques. La fabrication par nanoimpression douce assistée UV (SoftUV-NIL) a été optimisée et, finalement, la caractérisation optique de ces nanocavités a été comparée avec succès aux simulations théoriques. Parallèlement à la réalisation de ce dispositif nanostructuré, des dispositifs électrochimiques fluidiques plus simples qui intègrent des microélectrodes classiques ont également été développés. L'objectif était d'abord de développer une chimie innovante pour le couple « biotine/streptavidine » et de comprendre ensuite comment les paramètres fluidiques peuvent affecter l'efficacité de capture des biomolécules. Ce manuscrit se termine par une discussion sur le rôle des paramètres fluidiques concernant l’efficacité de la biodétection sur la base de la théorie de Squires. / During my thesis, I worked on the development of a specific fabrication process able to produce a device that combines two different biodetection techniques, plasmonic response based on Localized Surface Plasmon Resonance (LSPR) and electrochemical response. Methods and results that are presented in this manuscript were defined to converge towards a unique fluidic device combining these two different sensing approaches. This device integrates interdigitated array of MIM nanocavities. In order to find the easier working configuration allowing the excitation of plasmonic resonances, their geometry has been optimized through electromagnetic simulations. The fabrication of these dual devices has been optimized based on Soft-UV NIL and, finally, optical characterization of these nanocavities has been successfully compared with theoretical simulations. In parallel to this challenging goal, simpler fluidic electrochemical devices that integrate conventional microelectrodes have also been developed. The goal was first to develop an innovative chemistry for the couple biotin/streptavidin and secondly to learn how fluidic parameters can affect the capture efficiency of molecules. This manuscript ends with a discussion on the role of the fluidic parameters on the biodetection efficiency based on the theory of Squires.

Les nanosciences représentent, actuellement, un domaine de recherche en pleine expansion grâce aux nombreuses applications auxquelles elles peuvent être associées, et en particulier à la course à la miniaturisation des systèmes. De plus, il a rapidement été montré que les propriétés physico-chimiques des matériaux à l’échelle nanométrique sont modifiées parfois de manière drastique, à cause par exemple des effets quantiques apparaissant à des tailles aussi petites, mais aussi en raison des effets de confinement. Le confinement de molécules ou de particules à l’échelle nanoscopique nécessite donc la fabrication de matériaux hôtes possédant ce qu’il convient d’appeler des sites de confinement, c’est-à-dire des sites possédant une taille voisine de celle du système à insérer. Ce type de matériau est désormais relativement connu, et deux familles monopolisent l’intérêt, à savoir la silice mésoporeuse, aussi et récemment utilisé, les verres bioactifs à base de silice ayant des caractéristiques contrôlées qui constituent des matériaux hôtes de confinement qui peuvent être immergés dans des fluides complexes tel que le plasma sanguin synthétique. Pour réaliser ces travaux on a besoins d’appliquer plusieurs techniques de caractérisations telles que la diffusion des Rayons X et des Neutrons, la Microscopie Electronique à Balayage et à Transmission, la spectroscopie Infrarouge à Transformé de Fourier etc...De plus, ces dernières années, des systèmes microfluidiques ont été utilisés pour élaborer des émulsions doubles, des microcapsules ou des microparticules, avec la particularité d’obtenir des populations très monodisperses par rapport à celles obtenues avec des techniques plus traditionnelles et de morphologie contrôlée. Dans le domaine pharmaceutique, ces capacités sont particulièrement intéressantes pour la synthèse de médicaments à libération contrôlée. Elles permettent d’obtenir des particules monodisperses de polymère encapsulantes pour lesquelles l’effet de relargage brutal est diminué et qui possèdent des vitesses de relargage plus lentes que celles observées avec des procédés de fabrication conventionnels. / Nanoscience currently represent a growing area of research through the many applications for which they may be associated, particularly in the race for miniaturization of systems. In addition, it was quickly demonstrated that the physico-chemical properties of nanoscale materials are sometimes changed drastically, for example because of quantum effects occurring at sizes as small, but also because of confinement effects .Confinement of molecules or particles at the nanoscale therefore requires the manufacture of host materials with what to call containment sites, that is to say, sites with a size close to that of the system insert. This type of material is now relatively well known, and two families monopolize the interest, ie the mesoporous silica, and also recently used bioactive glasses based on silica having controlled characteristics that are host materials containment can be immersed in complex fluids such as synthetic blood plasma.To do this work several characterization techniques we need to apply, including the spread of X-rays and neutrons, the Scanning Electron Microscopy and Transmission, Infrared spectroscopy Transformed Fourier etc ...Moreover, in recent years, microfluidic systems were used to prepare double emulsions, microcapsules or microparticles, with the particularity to obtain highly monodisperse populations compared to those obtained with more traditional and controlled morphology techniques. In the pharmaceutical field, these capabilities are particularly interesting for the synthesis of controlled release to drugs. They enable polymer monodisperse particles encapsulating why the sudden release effect is decreased and have slower release rates than those observed with conventional manufacturing processes

A moving contact line is the idealized line of intersection between two immiscible fluids as one displaces the other along a solid boundary. The displacement process has been the subject of a large amount of theoretical and experimental research; however, the fundamental processes that govern contact line motion are still unknown. The challenge from an experimental perspective is to make measurements with high enough resolution to validate competing theories. An experimental method has been developed to simultaneously measure interface motion, dynamic contact angles, and local fluid velocity fields using micron-resolution Particle Image Velocimetry (µPIV). Capillary numbers range from 1.7 x 10^(⁻⁴) to 6.2 x 10^(⁻⁴). Interface velocities were measured between 1.7 µm/s and 33 µm/s. Dynamic contact angles were manually measured between 1.1 µm and 120 µm from the contact line, and calculated from µPIV data to within several hundred nanometers from the contact line. Fluid velocities were measured over two orders of magnitude closer to the contact line than published values with an increase in resolution of over 3400%. The appearance of a recirculation zone similar to controversial prediction below previously published limits demonstrates the power and significance of the method.

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