This thesis presents some experimental work in the area of manipulation of microparticles. Manipulation of both magnetic and non magnetic beads as well as microorganisms are addressed. The work on magnetic bead manipulation is focused on controlled transport and release, on a micrometer level, of proteins bound to the bead surface. Experimental results for protein transport and release using a method based on magnetization/demagnetization of micron-sized magnetic elements patterned on a modified chip-surface are presented. Special attention has been placed on minimizing bead-surface interactions since sticking problems have shown to be of major importance when protein-coated beads are used. The work with non-magnetic microparticles is focused on the dielectrophoretic manipulation of microorganisms. Preliminary experimental results for trapping and spatial separation of bacteria, yeast and non-magnetic beads are presented. The overall goal was to investigate the use of dielectrophoresis for the separation of sub-populations of bacteria differing in, for example, protein content. This was, however, not possible to demonstrate using our methods.Within the non-magnetic microparticle work, a method for determining the conductivity of bacteria in bulk was also developed. The method is based on the continuous lowering of medium conductivity of a bacterialsuspension while monitoring the medium and suspension conductivities.

Attitude and Heading angles are crucial parameters for navigation. Conventional navigation methods mostly uses IMU and GPS devices to calculate these angles. MEMS technology offers small sized, low cost IMU sensors with moderate performance. However, GPS cannot be used in underwater. Therefore, different aiding sensors are used in underwater vehicles in order to increase the accuracy. As the accuracy of devices increases, the cost of these devices also increases. In this thesis, rather than using GPS and high quality IMU sensors, low cost MEMS IMU sensor is used together with a magnetometer and a pressure sensor as aiding sensors. Considering the IMU error model and motion dynamics, two systems are designed and simulated using real data. The results seem to be satisfactory and using pressure sensor as an aiding sensor improves the attitude angles estimation.

Patch-based transdermal drug delivery offers a convenient way to administer drugs without the drawbacks of standard hypodermic injections relating to issues such as patient acceptability and injection safety. However, conventional transdermal drug delivery is limited to therapeutics where the drug can diffuse across the skin barrier. By using miniaturized needles, a pathway into the human body can be established which allow transport of macromolecular drugs such as insulins or vaccines. These microneedles only penetrate the outermost skin layers, superficial enough not to reach the nerve receptors of the lower skin. Thus, microneedle insertions are perceived as painless. The thesis presents research in the field of microneedle-based drug delivery with the specific aim of investigating a microneedle-based transdermal patch concept. To enable controllable drug infusion and still maintain an unobtrusive and easy-to-use, patch-like design, the system includes a small active dispenser mechanism. The dispenser is based on a novel thermal actuator consisting of highly expandable microspheres. When actuated, the microspheres expand into a liquid reservoir and, subsequently, dispense stored liquid through outlet holes. The microneedles are fabricated in monocrystalline silicon by Deep Reactive Ion Etching. The needles are organized in arrays situated on a chip. To allow active delivery, the microneedles are hollow with the needle bore-opening located on the side of the needle. This way, the needle can have a sharp and well-defined needle tip. A sharp needle is a further requirement to achieve microneedle insertion into skin by hand. The thesis presents fabrication and evaluation of both the microneedle structure and the transdermal patch as such. Issues such as penetration reliability, liquid delivery into the skin and microneedle packaging are discussed. The microneedle patch was also tested and studied in vivo for insulin delivery. Results show that intradermal administration with microneedles give rise to similar insulin concentration as standard subcutaneous delivery with the same dose rate. / QC 20100623

Hasomed GmbH, a German company in the Field of medicine technology, intends to introduce a gait analysis system on the market. The system includes an inertial sensor which collects data used for generating movement patterns of the feet. This thesis describes the development and evaluation of a new version of the sensor, aimed at minimizing costs, maximizing performance and facilitating production. Algorithms used in the gait analysis system are sensitive to noise. Noise sources and precautions taken in order to minimize noise levels are described and discussed. By minimizing the physical size of analogue electronics blocks, static noise and occasional high frequency components were substantially reduced. New features including internal temperature sensors, firmware update via serial interface, self-test functions and a wireless link were implemented. Additional improvements are e.g. lower power consumption and an extension of the interface from 2 to 256 (theoretical limit) attached devices. By reducing the number of included components and PCB (Printed Circuit Board) layers, together with use of components that do not require advanced soldering techniques, easier and cheaper production was obtained. Research and development presented in this thesis resulted in a sensor with overall good performance and new features.

This thesis presents the design of an inertial measurement data acquisition system intended for use in sailboats. The variables of interest are 3-axis acceleration, 3-axis rotation, GPS position/velocity, magnetic compass bearing and wind speed/direction. The design focus is on low-cost micro-electromechanical systems (MEMS) based technology and demonstrating the validity of these technologies in a scientific application. A prototype is constructed and submitted to a series of tests to demonstrate functionality and soundness of the design. These tests range from bench tests to full scale application. Contributions of this thesis include the novel application of inertial measurement unit (IMU) technology to a sailboat racing application, the integration of all instrumentation, creative ruggedised packaging and emphasising the use of low-cost commercial off-the-shelf (COTS) technology.

The mechanical properties of biomaterials play important roles in performing their specialized functions: synthesizing, storing, and transporting biomolecules; maintaining internal structures; and responding to external environments. Besides biological cells, there are also many other biomaterials that are highly deformable and have a diameter between 1μm and 100μm, comparable to that of most biological cells. For example, many polymeric microcapsules for drug delivery use are spherical particles of micrometers size. In order to mechanically characterize individual micrometer-sized biomaterials, the capability of capturing high-resolution and low-magnitude force feedback is required. This research focuses on the development of micro devices and experimental techniques for quantifying the mechanical properties of alginate-chitosan microcapsules. The micro devices include microelectromechanical systems (MEMS) capacitive force sensors and force-feedback microgrippers, capable of measuring sub-μN forces. Employing the MEMS devices, systems were constructed to perform the micro-scale compression testing of microcapsules. The force sensors are capable of resolving forces up to 110μN with a resolution of 33.2nN along two independent axes. The force sensors were applied to characterizing the mechanical properties of hydrogel microparticles without assembling additional end-effectors. The microcapsules were immobilized by a PDMS holding device and compressed between the sensor probe and holding device. Young's modulus values of individual microcapsules with 1%, 2%, and 3% chitosan coating were determined through the micro-scale compression testing in both distilled deionized (DDI) water and pH 7.4 phosphate buffered saline (PBS). The Young's modulus values were also correlated to protein release rates. Instead of compressing the microcapsule against the wall of the holding device, a force-feedback MEMS microgripper with the capability of directly compressing the microcapsule between two gripping arms has been used for characterizing both the elastic and viscoelastic properties of the microcapsules during micromanipulation. The single-chip microgripper integrates an electrothermal microactuator and two capacitive force sensors, one for contact detection (force resolution: 38.5nN) and the other for gripping force measurements (force resolution: 19.9nN). Through nanoNewton force measurements, closed-loop force control, and visual tracking, the system quantified the Young's modulus values and viscoelastic parameters of alginate microcapsules, demonstrating an easy-to-operate, accurate compression testing technique for characterizing soft, micrometer-sized biomaterials.

Ce travail de thèse porte sur l'étude de composites magnétoélectriques laminaires dans le but de réaliser des dispositifs innovants intégrés sur silicium tel que l'inductance RF variable. Grâce au couplage mécanique entre des couches adjacentes magnétostrictive ultra douce et piézoélectrique, il est possible d'obtenir un couplage magnétoélectrique indirect qui est supérieur de plusieurs ordres de grandeur à celui des matériaux multiferroïques naturels. Dans un premier temps, nous avons utilisé l'approche phénoménologique basée sur les énergies pour décrire le panorama des effets attendus dans des composites magnétoélectriques laminaires (multicouches). Ensuite, des composites magnétoélectriques macroscopiques à base de substrats piézoélectriques de type MFC et de couches minces de FeCoB ont été réalisés. L'étude du couplage magnétoélectrique en fonction de la composition de FeCoB a permis de déterminer les propriétés clés des matériaux, notamment le rapport λs/Ms, qui sont essentielles pour obtenir un effet magnétoélectrique élevé. Un coefficient magnétoélectrique record de 250 V∙cm‐1Oe‐1 a été obtenu. Par ailleurs, un microscope à effet Kerr a été spécialement développé pour pouvoir observer de manière quasi-instantanée la modification de la structure en domaines sous l'effet de la tension électrique dans ces composites. Pour la première fois, l'observation directe de la rotation de l'axe facile d'aimantation sous commande électrique a été réalisée. La deuxième partie de ce manuscrit est consacrée à la conception, simulation, fabrication et caractérisation d'un dispositif MEMS hybride d'inductance variable intégrée. Ce dispositif exploite l'effet magnétoélectrique indirect entre un élément moteur en PZT (sol gel) et un élément inductif à base de FeCoB. Etant donné le caractère multiphysique hors norme de ce dispositif, un ensemble de tests électriques, mécaniques, optiques et magnétiques a été déployé tout au long de la fabrication. Les résultats concluent à une preuve de concept partiellement fonctionnelle en raison principalement d'une mauvaise gestion des contraintes internes liées à la fabrication. Les pistes d'amélioration aux niveaux du design, des matériaux et des procédés sont identifiées.

Au cours des dernières années, l'essor spectaculaire des microsystèmes (ou MEMS), qui touche tous les domaines industriels, est à l'origine de nombreux et nouveaux progrès technologiques. Néanmoins, dans ce contexte prometteur de large envergure, la fiabilité des MEMS s'avère être la problématique à améliorer pour franchir la phase d'industrialisation à grande échelle. C'est dans le cadre de cette thématique de fiabilité des microsystèmes, que s'inscrit ce travail.La température étant un paramètre majeur entrant dans de nombreux mécanismes d'endommagement des MEMS, notre étude présente la conception et la réalisation d'un banc de thermographie infrarouge de haute résolution (2 µm), associé à la mise en œuvre d'une méthodologie d'analyse et de traitement des mesures infrarouges.Ce dispositif innovant permet un diagnostic in-situ, sans contact et rapide des défaillances des MEMS par mesures locales et quantitatives des pertes thermiques associées. Cet outil constitue une avancée importante pour détecter, mesurer et comprendre les mécanismes d'endommagement des MEMS. Il nous permet de reconstituer des images thermiques de tout type de microsystème en cours de fonctionnement ou soumis à des tests de vieillissement accéléré, et ceci afin de réaliser une analyse fine et rapide de leur fiabilité.Ce travail apporte de nouveaux résultats en ce qui concerne la détection des mécanismes de défaillance de différents types de MEMS-RF et tout particulièrement des MEMS-RF avec contact électrique.

Nano-FET biosensors are an emerging nanoelectronic technology capable of real-time and label-free quantification of soluble biological molecules. This technology promises to enable novel in vitro experimental approaches for investigating complex biological systems. In this study, we first explored osteocyte mechanosensitivity under different mechanical stimuli and found that osteocytes are exquisitely sensitive to different oscillatory fluid flow conditions. We therefore aimed to characterize protein-mediated intercellular communication between mechanically-stimulated osteocytes and other bone cell populations in vitro to elucidate the underlying mechanisms of load-induced bone remodeling. To this end, we devised a novel nano-manipulation based fabrication method for manufacturing nano-FET biosensors with precisely controlled device parameters, and further investigated the effect of these parameters on sensor performance.

Nano-FET biosensors are an emerging nanoelectronic technology capable of real-time and label-free quantification of soluble biological molecules. This technology promises to enable novel in vitro experimental approaches for investigating complex biological systems. In this study, we first explored osteocyte mechanosensitivity under different mechanical stimuli and found that osteocytes are exquisitely sensitive to different oscillatory fluid flow conditions. We therefore aimed to characterize protein-mediated intercellular communication between mechanically-stimulated osteocytes and other bone cell populations in vitro to elucidate the underlying mechanisms of load-induced bone remodeling. To this end, we devised a novel nano-manipulation based fabrication method for manufacturing nano-FET biosensors with precisely controlled device parameters, and further investigated the effect of these parameters on sensor performance.