By implementing the rolled-up microfabrication method based on strain engineering, several systems are investigated within the contents of this thesis. The structural morphing of planar geometries into three-dimensional structures opens up many doors for the creation of unique material configurations and devices. An exploration into several novel microsystems, encompassing various scientific subjects, is made and methods for on-chip integration of these devices are presented. The roll-up of a metal and oxide allows for a cylindrical hollow-core structure with a cladding layer composed of a multilayer stack, plasmonic metamaterial. This structure can be used as a platform for a number of optical metamaterial devices. By guiding light radially through this structure, a theoretical investigation into the system makeup of a rolled-up hyperlens, is given. Using the same design, but rather propagating light parallel to the cylinder, a novel device known as a metamaterial optical fiber is defined. This fiber allows light to be guided classically and plasmonically within a single device. These fibers are developed experimentally and are integrated into preexisting on-chip structures and characterized. A system known as lab-in-a-tube is introduced. The idea of lab-in-a-tube combines various rolled-up components into a single all-encompassing biosensor that can be used to detect and monitor single bio-organisms. The first device specifically tailored to this system is developed, flexible split-wall microtube resonator sensors. A method for the capturing of embryonic mouse cells into on-chip optical resonators is introduced. The sensor can optically detect, via photoluminescence, living cells confined within the resonator through the compression and expansion of a nanogap built within its walls. The rolled-up fabrication method is not limited to the well-investigated systems based on the roll-up from semiconductor material or from a photoresist layer. A new approach, relying on the delamination of polymers, is presented. This offers never-before-realized microscale structures and configurations. This includes novel magnetic configurations and flexible fluidic sensors which can be designed for on-chip and roving detector applications.

Rolled-up nanotechnology based on strain-engineering is a powerful tool to manufacture three-dimensional hollow structures made of virtually any kind of material on a large variety of substrates. The aim of this thesis is to address the key features of different on- and off-chip applications of rolled-up microtubes through modification of their basic framework. The modification of the framework pertains to the tubular structure, in particular the diameter of the microtube, and the material which it is made of, hence achieving different functionalities of the final rolled-up structure. The tuning of the microtube diameter which is adjusted to the individual size of an object allows on-chip studies of single cells in artificial narrow cavities, for example. Another modification of the framework is the addition of a catalytic layer which turns the microtube into a self-propelled catalytic micro-engine. Furthermore, the tuneability of the diameter can have applications ranging from nanotools for drilling into cells, to cargo transporters in microfluidic channels. Especially rolled-up microtubes based on low-cost and easy to deposit materials, such as silicon oxides, can enable the exploration of novel systems for several scientific topics. The main objective of this thesis is to combine microfluidic features of rolled-up structures with optical sensor capabilities of silicon oxide microtubes acting as optical ring resonators, and to integrate these into a Lab-on-a-Chip system. Therefore, a new concept of microfluidic integration is developed in order to establish an inexpensive, reliable and reproducible fabrication process which also sustains the optical capabilities of the microtubes. These integrated microtubes act as optofluidic refractrometric sensors which detect changes in the refractive index of analytes using photoluminescence spectroscopy. The thesis concludes with a demonstration of a functional portable sensor device with several integrated optofluidic sensors. / Die auf verspannten Dünnschichten basierende „rolled-up nanotechnologie“ ist eine leistungsfähige Methode um dreidimensionale hohle Strukturen (Mikroröhrchen) aus nahezu jeder Art von Material auf einer großen Vielfalt von Substraten herzustellen. Ausgehend von der Möglichkeit der Skalierung des Röhrchendurchmessers und der Modifikation der Funktionalität des Röhrchens durch Einsatz verschiedener Materialien und Oberflächenfunktionalisierungen kann eine große Anzahl an verschiedenen Anwendungen ermöglicht werden. Eine Anwendung behandelt unter anderem on-chip Studien einzelner Zellen wobei die Mikroröhrchen, an die Größe der Zelle angepasste, Reaktionscontainer darstellen. Eine weitere Modifikation der Funktionalität der Mikroröhrchen kann durch das Aufbringen einer katalytischen Schicht realisiert werden, wodurch das Mikroröhrchen zu einem selbstangetriebenen katalytischen Mikro-Motor wird. Hauptziel dieser Arbeit ist es Mikrometer große optisch aktive Glasröhrchen herzustellen, diese mikrofluidisch zu kontaktieren und als Sensoren in Lab-on-a-Chip Systeme zu integrieren. Die integrierten Glasröhrchen arbeiten als optofluidische Ringresonatoren, welche die Veränderungen des Brechungsindex von Fluiden im inneren des Röhrchens durch Änderungen im Evaneszenzfeld detektieren können. Die Funktionsfähigkeit eines Demonstrators wird mit verschiedenen Flüssigkeiten gezeigt, dabei kommt ein Fotolumineszenz Spektrometer zum Anregen des Evaneszenzfeldes und Auslesen des Signals zum Einsatz. Die entwickelte Integrationsmethode ist eine Basis für ein kostengünstiges, zuverlässiges und reproduzierbares Herstellungsverfahren von optofluidischen Mikrochips basierend auf optisch aktiven Mikroröhrchen.

Lab-on-a-Chip-Systeme sind mikrofluidische, portable Systeme mit denen bioanalytische Reaktionen und Auswertungen an kleinen Probenvolumina vor Ort durchführbar sind. In der vorliegenden Arbeit wird eine Entwurfsstrategie für das integrierte, resistive Heizen in einem solchen System auf Basis einer polymerbasierten, modularen Technologieplattform entwickelt. Dabei wird eine Modellierung als Feldmodell, die Ableitung eines reduzierten Makromodells sowie die experimentelle Untersuchung und Verifikation beschrieben. Verschiedene Ansätze für die Abbildung temperaturunabhängiger und -abhängiger elektrisch-thermischer Wandler sind berücksichtigt. Der Einflüsse von Aufbau, Widerstandsverhalten, Randbedingungen, sowie der elektrischen Ansteuerung auf die Temperatur der Biosensorfläche, in der die bioanalytische Reaktion erfolgt, werden dargelegt. / Lab on a chip systems are portable microfluidic systems which enable bioanalytical reactions and the appropriate analysis at the point of need using small sample volumes. In this publication a design strategy for integrated resistive heating in such a polymer based system is developed. The modelling comprises a field model, a derived reduced macro model and the experimental characterisation. Approaches to describe temperature dependent as well as independent electric-thermal converters are taken into account. The effects of the assembly, resistive behaviour, boundary conditions as well as the drive electronics on the temperature of the biosensor are presented.

By implementing the rolled-up microfabrication method based on strain engineering, several systems are investigated within the contents of this thesis. The structural morphing of planar geometries into three-dimensional structures opens up many doors for the creation of unique material configurations and devices. An exploration into several novel microsystems, encompassing various scientific subjects, is made and methods for on-chip integration of these devices are presented. The roll-up of a metal and oxide allows for a cylindrical hollow-core structure with a cladding layer composed of a multilayer stack, plasmonic metamaterial. This structure can be used as a platform for a number of optical metamaterial devices. By guiding light radially through this structure, a theoretical investigation into the system makeup of a rolled-up hyperlens, is given. Using the same design, but rather propagating light parallel to the cylinder, a novel device known as a metamaterial optical fiber is defined. This fiber allows light to be guided classically and plasmonically within a single device. These fibers are developed experimentally and are integrated into preexisting on-chip structures and characterized. A system known as lab-in-a-tube is introduced. The idea of lab-in-a-tube combines various rolled-up components into a single all-encompassing biosensor that can be used to detect and monitor single bio-organisms. The first device specifically tailored to this system is developed, flexible split-wall microtube resonator sensors. A method for the capturing of embryonic mouse cells into on-chip optical resonators is introduced. The sensor can optically detect, via photoluminescence, living cells confined within the resonator through the compression and expansion of a nanogap built within its walls. The rolled-up fabrication method is not limited to the well-investigated systems based on the roll-up from semiconductor material or from a photoresist layer. A new approach, relying on the delamination of polymers, is presented. This offers never-before-realized microscale structures and configurations. This includes novel magnetic configurations and flexible fluidic sensors which can be designed for on-chip and roving detector applications.

Much of recent progress in medical research and diagnostics has been enabled through the advances in molecular analysis technologies, which now permit the detection and analysis of single molecules with high sensitivity and specificity. Assay sensitivity is fundamentally limited by the efficiency of the detection method used for read-out. Inefficient detection systems are usually compensated for by molecular amplification at the cost of elevated assay complexity. This thesis presents microfluidic automation and digital quantification of targeted nucleic acid detection methods based on padlock and selector probes and rolling circle amplification (RCA). In paper I, the highly sensitive, yet complex circle-to-circle amplification assay was automated on a digital microfluidic chip. In paper II, a new RCA product (RCP) sensing principle was developed based on resistive pulse sensing that allows label free digital RCP quantification. In paper III, a microfluidic chip for spatial RCP enrichment was developed, which enables the detection of RCPs with an unprecedented efficiency and allows for deeper analysis of enriched RCPs through next generation sequencing chemistry. In paper IV, a smart phone was converted into a multiplex fluorescent imaging device that enables imaging and quantification of RCPs on slides as well as within cells and tissues. KRAS point mutations were detected (i) in situ, directly in tumor tissue, and (ii) by targeted sequencing of extracted tumor DNA, imaged with the smart phone RCP imager. This thesis describes the building blocks required for the development of highly sensitive low-cost RCA-based nucleic acid analysis devices for utilization in research and diagnostics.

Résumé : Ce travail de thèse a pour but de développer un dispositif intégré de photodétection pour des applications biomédicales nécessitant une grande sensibilité de détection et une discrimination spectrale (sélectivité). Ce dispositif peut être appliqué, par exemple, à la mesure simultanée de plusieurs marqueurs fluorescents dans les laboratoires sur puce mettant en œuvre de très faibles volumes de réactifs (inférieurs au microlitre). Le travail de thèse se focalise sur la conception, la réalisation et le test de ce dispositif intégré de photodétection. Ce travail se décline selon deux axes principaux : d’une part, la conception d’un photodétecteur CMOS avec préamplificateurs intégrés, et d’autre part la conception, la réalisation et la caractérisation de filtres optiques intégrés performants pour la détection de fluorescence. Le dispositif de détection conçu implémente un photodétecteur à quatre jonctions enterrées (Buried Quad Junction photodetector – BQJ) et un étage de préamplification de charge pour le traitement simultané des quatre sorties de ce photodétecteur. L’ensemble a été fabriqué en technologie Haut-Voltage CMOS Teledyne-DALSA 0,8μm. Son fonctionnement a été démontré et ses performances, notamment en termes de bruit et de sensibilité, ont été caractérisées. En parallèle, des filtres optiques coupe-bande ont été développés à l’aide d’un procédé compatible avec la technologie CMOS utilisée pour le photodétecteur. Ainsi, le dépôt de ces filtres sur le photodétecteur pourra être intégré dans le process de fabrication industriel. Les filtres interférentiels développés sont fabriqués en alternant des dépôts de couches minces de nitrure et d’oxyde de silicium par PECVD. La mesure des indices optiques de ces matériaux a été utilisée pour optimiser ces filtres à partir de simulations. Les filtres déposés sur lame de verre ou sur le photodétecteur BQJ ont été caractérisés. Des méthodes de traitement des signaux spécifiques pour le BQJ sont également proposées pour améliorer la sensibilité et/ou la sélectivité de détection. Leurs performances ont été évaluées. Enfin, des mesures de fluorescence avec le système de photodétection conçu ont été réalisées sur des mélanges de nanocristaux fluorescents (quantum dots) ou de fluorophores organiques. Ces résultats préliminaires permettent de valider le fonctionnement applicatif du système de photodétection développé. // Abstract : This thesis aims to develop an integrated photosensor device for biomedical applications requiring high detection sensitivity and spectral discrimination (selectivity). For example, this system can be applied to mesure simultaneous emissions of several fluorescent labels in lab-on-a-chip implementing very small volumes of reagents (less than one microliter). The thesis focuses on the design, implementation and testing of this integrated photodetector device. The work is divided in two main parts: first, the design of a CMOS photodetector with integrated preamplifiers, and secondly the design, realization and characterization of integrated optical filters for fluorescence detection. The detection device implements a Buried Quad Junction photodetector (BQJ) and charge sensitive preamplifiers for the simultaneous treatment of its four outputs. The chip was made in 0.8μm High Voltage CMOS technology from Teledyne-DALSA. Its operation has been demonstrated and its performances, especially in terms of noise and sensitivity, have been characterized. In parallel, optical notch filters have been developed using a process compatible with the CMOS technology used for the photodetector fabrication. Thus, deposition of these filters on the photodetector can be integrated during industrial process. Developed interference filters are made by alternating deposition of thin layers of nitride and silicon oxide by PECVD. Measurements of refractive index of these materials were used to optimize these filters through simulations. The filters implemented on a glass cover or on the BQJ photodetector were characterized. Signal processing methods specific to BQJ are also proposed to improve the detection’s sensitivity and/or selectivity. Their performances were evaluated. Finally, fluorescence measurements with the designed photodetection device were performed on mixtures of fluorescent nanocrystals (quantum dots) or of organic fluorophores. These preliminary results validate the performances in terms of photodetection of the designed integrated photodetection device.

生活實驗室(Living Lab)是一種以使用者為中心(User-centric)的研究方法，設立於一多元脈絡(Multi-context)的真實(Real)生活情境中，使所有利益關係人(Stakeholders)主動(Active)參與共同創造(Co-creation)，透過使用者需求研究，測試、驗證新產品服務原型、系統、以及商業模式，並持續給予產品服務提供者回饋，以提供複雜問題的解決方案，創造有價的創新產品服務。 　　本研究選定台灣的四間生活實驗室為研究對象，包括：資策會Living Lab Taiwan、台大INSIGHT Center、交大Eco-City、以及成大TOUCH Center；本研採用Gulliksen等人(2009)所提出的生活實驗室共創原則，並結合Voss(1992)提出的服務創新流程為本研究之研究架構，藉此研究生活實驗室，在不同時期下，與使用者共同創造之達成度，並對分析所見結果的成因，研究結論概述於下： 一、採用本研究所提出的「結合創新服務流程之使用者共創原則」架構，可呈現生活實驗室共創原則，分析各時期是否達成要求，適合做為分析生活實驗室在共創運作上的操作準則。 二、根據本研究分析，資策會Living Lab Taiwan，相較台灣其他三間生活實驗室，與使用者共創的達成度最高。其設立真實生活實驗室場域，並自行開發商業驗證方法論；其他生活實驗室則尚無建立。 三、台灣各生活實驗室在「概念期」與「發展期」尚位涉足。因各生活實驗室仍屬於技術本位，未真正以使用者需求為出發，仍是由產品服務提供者自己的想法進行發展。

Clusters/nanoparticles are aggregates of a “small” number of building blocks, atoms or molecules, ranging from two up to millions of atoms. Two main groups of clusters have been studied using photoelectron spectroscopy based on synchrotron radiation. They are dry/wet alkali-halide clusters, including pure water clusters, and metal-based nanoparticles. For the dry alkali halide clusters, analysis of the data and theoretical modeling has allowed us insights into the local electronic properties at nanoscale: a change of polarizability of ions in the alkali-halide clusters due to the varying environment has been suggested. The study of the wet salt clusters shows that the alkali-halides are already solvated at the nanoscale reached by water clusters doped with salt vapor. The photoelectron angular distribution of water cluster shows lower anisotropy parameters as compared to the separate monomers. A model based on intracluster scattering has been built to partly explain the reduction. In the last part of the thesis, metal-based multi-component nanoparticles have been produced by self-assembly processes using reactive magnetron sputtering. Depending on the specific metal element, oxidation processes have been applied before or after the aggregation. Clearly radial distributions such as core-shell and “sandwich-like” structures have unambiguously determined by photoelectron spectroscopy.

Precise manipulation of heterogeneous droplets on an open droplet microfluidic platform could have numerous practical advantages in a broad range of applications, from proton exchange membrane (PEM) fuel cells and microreactors, to medical diagnostic platforms capable of assaying complex biological analytes. Toward the aim of developing electrically controllable micropost arrays for use in open droplet manipulation, custom-designed titanium dioxide (TiO2)- loaded poly(dimethylsiloxane) (PDMS) micropost arrays were developed in this work and indirectly mechanically actuated by applying an electric field. Initial experiments explored the bulk properties of TiO2-loaded PDMS films, with scanning electron microscopy (SEM) confirming a uniform TiO2 particle distribution in the PDMS, and tensile testing of bulk films showing an inverse relationship between TiO2 % (w/w) and Young’s Modulus with the Young’s Moduli quantified as 4.22 ± 0.51 MPa for unloaded PDMS, 2.27 ± 0.18 MPa for 10 % (w/w) TiO2, and 1.39 ± 0.20 MPa for 20 % (w/w) TiO2. Following bulk material evaluation, soft lithography methods were developed to fabricate TiO2- loaded PDMS micropost arrays. Mathematical predictions were applied to design microposts of varying shape, length, and gap spacing to yield super-hydrophobic surfaces actuatable by an electric field. Visual inspection and optical microscopy of the resulting arrays confirmed a non- collapsed micropost geometry. Overall, round microposts that were 100, 200, and 300 μm in length, 15 μm in diameter, and spaced 50 μm apart were produced largely free of defects, and used in contact angle measurements and micropost deflection experiments. Droplet contact angles measured on the arrays remained above 120° indicating the arrays successfully provided super- hydrophobic surfaces. Individual microposts deflected most notably above an electric field strength of 520 kV/m (12.5 kV nominal voltage). The ability to mechanically deflect customized microposts using an electric field demonstrated by this work is promising for translating this technology to precise droplet manipulation applications. Indirect actuation of droplets could enable the manipulation of liquids with varying electrical properties, which is a limitation of current micropumping technologies. Once optimized, electrically actuated micropost arrays could significantly contribute to the micro- handling of heterogeneous, highly ionic, and/or deionized fluids. / Thesis (Master, Chemical Engineering) -- Queen's University, 2013-03-03 17:25:49.785

1-Microevaporation - Microfluidics is the branch of fluid mechanics dedicated to the study of flows in the channel withdimensions between 1 micron and 100 micron. The object of this chapter is to illustrate the basicprinciples and possible applications of microfluidic chip, called microevaporator. In the first part ofthe chapter, we present a detailed description of the physics of microevaporators using analyticalarguments, and describe some applications. In the second part of the chapter, we present theexperimental protocol of engineering of micro evaporator and different type of microfluidics device.2- On-chip microspectroscopy - The object of this chapter is to illustrate a method to measure absorption spectra during theprocess of growth of our materials in our microfluidic tools. The aim is to make an opticalcharacterization of our micro materials and to carry-out a spatio-temporal study of kineticproperties of our dispersion under study. This instrumental chapter presents the theoretical basis !of the method we used.3-Role of colloidal stability in the growth of micromaterials - We used combined microspectroscopy and videomicroscopy to follow the nucleation and growth ofmaterials made of core-shell Ag@SiO2 NPs in micro evaporators.!We evidence that the growth is actually not always possible, and instead precipitation may occurduring the concentration process. This event is governed by the concentration of dispersion in thereservoir and we assume that its origin come from ionic species that are concentrated all togetherwith the NPs and may alter the colloidal stability en route towards high concentration. 4-Microfluidic-induced growth and shape-up of three-dimensional extended arrays of denselypacked nano particles - In this chapter I present in details microfluidic evaporation experiments to engineer various denselypacked 3D arrays of NPs.5-Bulk metamaterials assembled by microfluidic evaporation - In this chapter I introduced the technique we used (microspot ellipsometry) in close collaborationswith V.Kravets and A.Grigorenko(University of Manchester) and with A.Aradian, P.Barois, A.Baron,K.Ehrhardt(CRPP, Pessac) to characterized the solids made of densely packed NPs. I describe theconstraints that emerge from the coupling between the small size of our materials and the opticalrequirements, the analysis and interpretation of the ellipsometry experiments show that for thematerial with high volume fraction of metal exists the strong electrical coupling between the NPsand the materials display an extremely high refraction index in the near infra-red regime.