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Aquesta tesi ha estat realitzada al Centre Nacional de Microelectrònica, Institut de Microelectrònica de Barcelona (CNM-IMB) que és un institut d'investigació que forma part del Consell Superior d'Investigacions Científiques (CSIC). La memòria és un recull de la feina realitzada per en Luis Guillermo Villanueva Torrijo sota la direcció del Professor d'Investigació Joan Bausells Roigé al període comprès entre setembre de 2002 i octubre de 2006. El treball queda dividit en tres apartats, tots tres relacionats amb el disseny i la fabricació de bigues de mida micromètrica (micro-cantilevers en anglès) per a diferents aplicacions. Al segon capítol es descriu la feina realitzada amb bigues piezoresistives. L'objectiu fonamental d'aquesta part del treball consistia en la fabricació d'un element sensor capaç de detectar forces dins del rang de 10 a 100 pN. Per això, en primer lloc, es va realitzar una anàlisi teòrica del comportament d'aquestes estructures mecàniques quan se les hi aplica una força al seu extrem lliure. També es va estudiar el soroll (tant electrònic com mecànic) que presentaven. D'aquesta manera, es van establir uns criteris per a la maximització de la sensibilitat i la resolució del sensor. Els resultats analítics es van comparar amb els resultats de simulacions per elements finits, obtenint divergències molt baixes. Això va ser interpretat com una validació dels resultats analítics. Es van dissenyar i fabricar unes bigues piezoresistives de polisilici amb forma de "U". Les dimensions i la resta de paràmetres es van determinar mitjançant els criteris obtinguts per l'optimització del comportament de les bigues. Aquestes es van fabricar a la Sala Blanca del CNM i també fent servir una tecnologia CMOS comercial (0.8 m de AustriaMicroSystems). Els processos de fabricació dins de la Sala Blanca del CNM es van optimitzar per augmentar el rendiment de les oblies. Així, finalment, es va arribar a un rendiment que estava a prop del 95% (aproximadament 95 de cada 100 dispositius es van obtenir correctament). Es va optimitzar el post procés dels xips CMOS al CNM per obtenir un alt rendiment. En aquest cas no només es va considerar la supervivència de les estructures, sinó també la dels circuits CMOS integrats al costat de les bigues. Aquests circuits, dissenyats al ETH de Zürich, consisteixen en un filtre i un amplificador per a millorar la resolució del sensor. Una vegada fabricats, els dispositius es van caracteritzar. La part principal d'aquesta caracterització recollia dos aspectes: la mesura del soroll del senyal de sortida del circuit i la determinació de la sensibilitat dels dispositius. Considerant tots dos resultats es va calcular la resolució dels sensors. Els millors resultats obtinguts van ser aproximadament 30 nN per a les bigues fabricades al CNM i 30 pN per les bigues fetes amb tecnologia CMOS. Aquesta diferència de tres ordres de magnitud a la resolució és deguda als circuits amplificadors i ens permetria mesurar forces al rang requerit. Per altra banda, amb l'objectiu de realitzar mesures de conducció en un ambient líquid, es van fabricar unes bigues conductores però aïllades. La capa conductora en aquestes bigues (una capa d'or) ha d'estar aïllada del exterior per una capa dielèctrica (nitrur de silici) per disminuir d'aquesta manera les capacitats paràsites. Al extrem lliure, s'ha de situar una punta de polisilici afilada per poder escanejar superfícies. La punta ha d'estar coberta per or i, sobre l'or, tenir nitrur a tot arreu menys al vèrtex. Per obtenir aquests dispositius, es va optimitzar el gravat de puntes de polisilici obtenint finalment puntes amb un diàmetre de vèrtex més petit que 20 nm (fent servir un atac sec en un equip DRIE seguit d'unes oxidacions per esmolar). A més, es va realitzar un estudi dels esforços interns per intentar obtenir bigues planes. A l'última part del treball, es va dur a terme la fabricació de sondes per AFM (bigues amb una punta esmolada al seu extrem lliure). Aquests dispositius es fan servir moltíssim actualment per caracteritzar superfícies i realitzar experiments que requereixen molta precisió i/o resolució. L'objectiu fonamental d'aquesta feina era el possibilitar la fabricació de sondes per AFM al nostre centre de manera que els dissenys poguessin ser triats pels investigadors d'acord amb les necessitats de cadascú d'ells. Per això, es van considerar diferents materials i processos de fabricació de puntes. La millor opció va ser el gravat sec amb un equip DRIE d'unes puntes "tipus coet" amb una part superior afilada, situada al cim d'una columna cilíndrica. Els processos de gravat es van optimitzar per així obtenir una alta uniformitat arreu de l'oblia, així com uns perfils de puntes apropiats per poder fer-les servir en un AFM. A continuació, es van fabricar sondes completes. Per comprovar com de bona era la tecnologia de fabricació que havíem dissenyat, es van fabricar dispositius de dos tipus diferents: per fer-les servir en mode contacte (constant elàstica baixa) i per fer-les servir en mode dinàmic (constant elàstica alta). Aquests dispositius es van utilitzar per escanejar unes mostres d'alumini i es van comparar amb els resultats obtinguts amb sondes comercials, obtenint resultats similars en ambdós casos. Finalment, es van fabricar sondes per a aplicacions específiques: sondes amb puntes amb la part superior plana per l'estudi de la elasticitat de polímers i materials biològics (molt baix mòdul de Young) i sondes amb bigues d'una geometria especial per a que les freqüències de ressonància del mode fonamental i del primer harmònic transversal estiguessin més juntes, per així millorar la detecció del potencial de superfície en la tècnica KPFM. Amb la fabricació d'aquestes puntes, es va demostrar que el disposar d'una tecnologia que permetés la fabricació de sondes pot ser molt útil per al desenvolupament de noves aplicacions de l'AFM. / Este trabajo queda dividido en tres apartados, todos ellos relacionados con el diseño y fabricación de vigas en voladizo de tamaño micrométrico (micro-cantilevers en inglés) para diferentes aplicaciones. En el segundo capítulo se describe el trabajo realizado con vigas piezorresistivas. El objetivo fundamental de esa parte del trabajo consistía en la consecución de un elemento sensor capaz de detectar fuerzas en el rango de 10 a 100 pN. Para ello, en primer lugar, se realizó un detallado análisis teórico del comportamiento de estas estructuras mecánicas cuando se les aplica una fuerza en su extremo libre. Se estudió asimismo el ruido (tanto eléctrico como mecánico) presente en ellas. De esta manera se establecieron unos criterios para la maximización de la sensibilidad y la resolución del sensor. Los resultados analíticos se compararon con los resultados de simulaciones por elementos finitos, obteniendo divergencias muy bajas, lo cual fue interpretado como una validación de los primeros. Se diseñaron y fabricaron unas vigas piezorresistivas de polisilicio con forma de U. Las dimensiones y demás parámetros se fijaron mediante los criterios obtenidos para la optimización del comportamiento de las vigas. Las vigas se fabricaron tanto en la Sala Blanca del CNM como usando una tecnología CMOS comercial (0.8 m de AustriaMicroSystems). Los procesos de fabricación dentro de la Sala Blanca del CNM se optimizaron para aumentar el rendimiento de las obleas. De esta forma, finalmente, se alcanzó un rendimiento cercano al 95% (aproximadamente 95 de cada 100 dispositivos se obtuvieron correctamente). Se optimizó asimismo el post proceso de los chips CMOS en el CNM para obtener un alto rendimiento. En este caso, se consideró la supervivencia de las estructuras mecánicas así como de la circuitería CMOS integrada junto con las vigas. Esta circuitería, diseñada en el ETH de Zürich, consistía en un filtro y un amplificador para mejorar la resolución del sensor. Una vez fabricados, los dispositivos se caracterizaron. La parte central de esta caracterización englobó dos aspectos: la medida del ruido de la señal de salida del circuito y la determinación de la sensibilidad de los dispositivos. Teniendo en cuenta ambos resultados se calculó la resolución de nuestros sensores. Los mejores resultados obtenidos fueron de unos 30 nN para las vigas fabricadas en el CNM y de unos 30 pN para las provenientes de la tecnología CMOS. Esta diferencia de tres órdenes de magnitud en la resolución es debida a la circuitería adjunta a los dispositivos transductores (vigas) y nos permitiría medir fuerzas del orden de magnitud requerido. Por otro lado, con el objetivo de realizar medidas de conducción en medio líquido, se fabricaron unas vigas conductoras pero aisladas. La capa conductora en dichas vigas (capa de oro) ha de estar aislada del exterior por medio de una capa dieléctrica (nitruro de silicio) para así disminuir las capacidades parásitas. En el extremo libre, se ha de situar una punta de polisilicio afilada para poder escanear superficies. Dicha punta ha de estar cubierta por oro y, sobre el oro, tener nitruro en todas partes salvo en el vértice. Para obtener estos dispositivos, se optimizó el grabado de puntas de polisilicio, obteniendo finalmente puntas con un diámetro de vértice menor que 20 nm (usando un ataque en un equipo DRIE seguido por unas oxidaciones para afilar). Además, se realizó un estudio de los esfuerzos internos para intentar obtener vigas lo más planas posible. En la última parte del trabajo, se llevó a cabo la fabricación de sondas para AFM (vigas con una punta afilada en su extremo libre). Estos dispositivos son ampliamente usados en la actualidad para caracterizar muestras y para realizar experimentos en los que se requiere una alta precisión y/o resolución. El objetivo fundamental de este trabajo era el posibilitar la fabricación de sondas para AFM en nuestro centro de manera que los diseños pudieran ser elegidos a voluntad y acordes con las necesidades de cada investigador. Para ello se consideraron diferentes materiales y procesos de fabricación de puntas. La mejor opción fue la definición por medio de un equipo DRIE de puntas "tipo cohete" con una parte superior afilada, situada sobre una columna cilíndrica. Los procesos de grabado se optimizaron para así obtener una alta uniformidad a lo largo y ancho de la oblea así como unos perfiles de puntas apropiados para poder ser usadas después en un AFM. A continuación, se fabricaron sondas completas. Para comprobar cómo de buena era la tecnología de fabricación que habíamos diseñado, se fabricaron puntas de dos tipos diferentes: para ser usadas en modo contacto (constante elástica baja) y para ser usadas en modo dinámico (constante elástica alta). Dichos dispositivos se usaron para escanear algunas muestras y se compararon con algunos disponibles comercialmente, obteniendo resultados similares tanto para modo contacto como para dinámico. Finalmente, se fabricaron sondas para aplicaciones específicas: sondas con puntas con la parte superior plana para el estudio de la elasticidad de polímeros y materiales biológicos (con bajo módulo de Young) y sondas con vigas de una geometría especial para que las frecuencias de resonancia del modo fundamental y del primer harmónico transversal estuvieran más juntas, para así mejorar la detección del potencial de superficie en la técnica KPFM. Con la fabricación de estas puntas, se demostró que el disponer de una tecnología que permita la consecución de puntas puede ser muy útil para el desarrollo de nuevas aplicaciones del AFM. / The main objective of this thesis has been the research in the design and fabrication of micro-cantilevers that are one of the most used mechanical transducers because of their versatility. The use of polysilicon piezoresistive cantilevers has been explored in order to detect binding forces between biomolecules. Force resolution under 100 pN was required. A detailed analytical study has been performed in order to calculate sensitivity and resolution when applying a force at their free end. The results obtained with this analysis have been confirmed by the use of FEM simulations and hence used to determine the optimum design of the piezoresistive sensor. U-shaped polysilicon cantilevers have been fabricated at CNM clean room facilities using a novel and dedicated technology. Designs were made following the criteria imposed by the previously obtained analytical results. The high force resolution required implied the fabrication of some cantilevers among the softest piezoresistive cantilevers reported up to date (elastic constants down to 0.5 mN/m). With the final optimized fabrication process, a yield of 95% has been achieved. Using a commercial CMOS technology (0.8 m from AustriaMicroSystems), polysilicon piezoresistive cantilevers have been designed and fabricated following again the criteria imposed by the theoretical analysis and, in this case, also design rules from the CMOS technology. Cantilevers were integrated with a filtering and amplifying circuitry to reduce noise. The softest piezoresistive CMOS integrated cantilevers have been obtained with a high yield and with an undamaged circuitry. In order to determine the actual sensitivity of such soft sensors and their gauge factor, a characterization method (consisting in AFM actuation) has been developed. Gauge factor for polysilicon deposited at CNM and at AustriaMicroSystems was -12 and -9 respectively. The maximum force sensitivity and force resolution obtained for CNM fabricated sensors have been 11 V/nN and 28 nN respectively. The maximum force sensitivity and force resolution obtained for CMOS fabricated sensors have been 11 V/pN and 27 pN respectively. In both cases, resolution is limited by the noise in the circuit, whose main contributions are Hooge noise (or 1/f) and Johnson noise (or thermoelectric). Conductive, but isolated, nitride cantilevers (with a wrapped gold layer) with a sharp tip (that has an opened contact) have been designed and fabricated to be used in conductive measurements in liquid environments. Polysilicon tips definition has been optimized to improve the whole probes fabrication process, achieving apex radii smaller than 20 nm using a dry etching by means of a DRIE equipment followed by sharpening oxidation. A complete and novel technological process has been developed for the fabrication of AFM cantilevers. Different tip materials and machining processes have been analyzed, obtaining the best results for crystalline silicon tips defined using a DRIE equipment to machine rocket tips. Isotropic processes with low cross-wafer dispersion and anisotropic processes with low cross-wafer dispersion and low scalloping have been achieved. After a sharpening oxidation, apex radii smaller than 5 nm have been achieved. Complete AFM probes have been fabricated. In order to test the developed technology, probes with similar characteristics to commercial ones were fabricated and used to raster scan some samples (in contact and non-contact mode) yielding results similar to those obtained with commercial probes. In addition, some special probes have been fabricated for nanoindentation over polymers and also to improve Kelvin Probe Force Microscopy (KPFM) performance. Thus, the availability of a technology that allows the fabrication of customized cantilevers is very useful for the development of new SPM applications.

An understanding of the fluid coupled dynamics of micro and nanotechnology has the potential to yield significant advances yet many open and interesting questions remain. As an important example we consider the coupling of two closely spaced cantilevers immersed in a viscous fluid subject to an external driving. While one cantilever is driven to oscillate, the adjacent cantilever is passive. This system is modeled as two simple harmonic oscillators in an array whose motion is coupled through the fluid. Using simplified geometries and the unsteady Stokes equations, an analytical expression is developed that describes the dynamics of the passive cantilever. Full numerical simulations of the fluid-solid interactions that include the precise geometries of interest are performed. The analytical expressions are compared with the numerical simulations to develop insight into the fluid-coupled dynamics over a range of experimentally relevant parameters including the cantilever separation and frequency based Reynolds number. In addition, a shaker-based actuation device is investigated in order to demonstrate its feasibility for use with micro and nanoscale systems. / Master of Science

Thermochemical Nanolithography (TCNL) is a scanning probe microscope (SPM) based lithographic technique modified with a semi-conducting cantilever. This cantilever is capable of locally heating a surface and with a well-engineered substrate, this spatially confined heating induces chemical or physical transformation. While previous works focused primarily on proof of principle and binary studies, there is limited research on controlling and understanding the underlying mechanisms governing the technique. In this thesis, a chemical kinetics model is employed to explain the driving mechanisms and to control the technique. The first part focuses on studying surface reactions. By coupling a thermally activated organic polymer with fluorescence microscopy, the chemical kinetics model is not only verified but also applied to control the surface reactions. The work is then expanded to include 3D effects, and some preliminary results are introduced. Finally, applications are discussed.

The goal of this research is to measure viscosity via the analysis of amplitude response of a piezo driven vibrating cantilevers partially immersed in a viscous medium. As a driving frequency is applied to a piezoceramic material, the external forces acting on the system will affect its maximum amplitude. This thesis applies this principle through experimental and analytical analyses of the proportional relationship between viscosity and the amplitude response of the first natural frequency mode of the sinusoidal vibration. Currently, the few cantilever-based viscometer designs that exist employ resonant frequency response as the parameter by which the viscosity is correlated. The proposed piezoelectric viscometer employs amplitude response in lieu of resonant frequency response. The goal of this aspect of the research was to provide data confirming amplitude response as a viable method for determining viscosity. A miniature piezoelectric plate was mounted to a small stainless-steel cantilever beam. The tip of the cantilever was immersed within various fluid test samples. The cantilever was then swept through a range of frequencies in which the first frequency mode resided. The operating principle being as the viscosity of the fluid increases the amplitude response of cantilever vibration will decrease relatively. What was found was in fact an inversely exponential relationship between dynamic viscosity and the cantilever beam's vibrational amplitude response. The experiment was performed using three types of cantilevers as to experimentally test the sensitivity of each.

Student Number : 8701355N - MDent research report - School of Oral Health Sciences - Faculty of Health Sciences / Purpose: The aim of this research project was to determine the fracture resistance to linear vertical compressive forces of acrylic and metal-reinforced acrylic fixed implant supported prosthesis cantilever arms. Methods: Ten non-reinforced and 10 reinforced acrylic superstructures were secured on five evenly distributed implants and subjected to linear axial compressive forces utilising an Instron® materials testing machine. The reinforcement consisted of commercially available preformed titanium metal strengthener bars. Force was applied to the cantilever arms 15mm distal to the distal most implant and two tests were conducted on each sample. The first drop in load recorded was noted as a fracture of the sample. Results: Fracture of the acrylic was noted at the distal most implant in both non-reinforced and the reinforced samples. The mean fracture value for the non-reinforced samples was 679N and for the reinforced samples, 628N. Conclusion: No significant difference between the fracture resistance of the two designs was noted.

Les propriétés physiques et chimiques exceptionnelles du matériau diamant ont suscité l'intérêt des chercheurs pour le développement d'applications industrielles, comme par exemple dans les domaines de la dissipation thermique ou de l'électronique de puissance. En particulier, les propriétés mécaniques remarquables de ce matériau peuvent être exploitées avantageusement pour la conception de résonateurs MEMS (Micro-Electro-Mechanical Systems). Même si certains dispositifs MEMS à base de diamant avaient été décrits dans la littérature, les propriétés mécaniques de ce matériau n'avaient jamais été associées à ses propriétés chimiques pour la réalisation de transducteurs chimiques ou biochimiques à base de résonateurs MEMS. Ainsi, l'objectif cette thèse a été de démontrer l'intérêt de ce matériau innovant pour la fabrication de ces capteurs. Les MEMS offrent la possibilité de faire de la détection en temps réel de manière directe (sans marqueur), rapide et sensible, sur de faibles quantités d'analytes. De plus ils permettent d'adresser des cibles non électro-actives qui ne peuvent pas être détectées par des capteurs électrochimiques. Dans cette étude, nous avons développé dans un premier temps des procédés de micro-structuration spécifiques du diamant. Ces procédés entièrement compatibles avec des techniques de salle blanche ont permis d'aboutir à la réalisation de nombreux transducteurs à base de micro-leviers en diamant sur des substrats en silicium de 4 pouces. De plus les approches développées permettent d'éviter la gravure fastidieuse du matériau diamant. Leur caractérisation mécanique en régime dynamique a permis de caractériser le module d'Young E du matériau diamant synthétisé en fonction des conditions de croissance. Dans le meilleur cas une valeur de E très élevée de l'ordre de 1100 GPa a été obtenue, ce qui est très proche de la valeur du diamant monocristallin (1200GPa). Par ailleurs, nous avons pu vérifier que les propriétés de résonance (fréquence de résonance et facteur de qualité) des structures en diamant réalisées étaient supérieures à celles de structures identiques en silicium. En particulier, cela rend ces résonateurs plus aptes à être exploités en milieux liquides. Nous avons montré que dans de tels milieux les micro-leviers en diamant étaient très peu sensibles à une variation massique. En revanche leur sensibilité à une variation de masse volumique du liquide est de l'ordre de 3Hz.kg-1.m3 et donc significative. Par ailleurs, en fonctionnalisant des micro-leviers en diamant par de l'acide caproïque, nous avons mis en évidence que des variations de densité de charges à la surface des micro-leviers pouvaient induire des variations de fréquence de résonance de plusieurs dizaines de Hz dans le cas de structures vibrant à quelques kHz. Ceci a permis de mettre en évidence la grande sensibilité de nos transducteurs en diamant à des interactions moléculaires. Dans ce contexte nous avons pu réaliser un capteur d'ADN permettant la reconnaissance spécifique en temps réel de brins d'ADN cibles de 24 paires de bases sans marqueur. En parallèle de ces travaux, des structures d'actionnement et de lecture ont été intégrées et évalué sur des dispositifs résonants à base de diamant. Ceci a permis de les interfacer à un premier prototype de système d'acquisition électronique portable dédié réalisé au cours de cette thèse / Diamond material is very promising for future technological applications due to its outstanding physical and chemical properties. In particular, its remarkable mechanical features may be used advantageously for MEMS (Micro-Electro-Mechanical Systems) devices development. However, even though several diamond-based MEMS devices have been reported in the literature, the mechanical properties of this material have never been combined to its chemical properties for developing resonating MEMS-based biochemical transducers. Thus, the purpose of this study was to demonstrate the interest of such diamond transducers for chemical or biochemical sensing applications. MEMS devices are indeed attractive because they allow fast, label free and sensitive detection in real time on small volumes due to their miniaturized size. Moreover they offer the possibility to address non electroactive target species which are undetectable using classical electrochemical methods. In this study, we developed specific clean room compatible processes for diamond micro-structuring. The bottom-up approaches undertaken here were based on diamond patterns growth. Hence they avoid time consuming diamond etching steps. These processes allowed fabricating several diamond micro-cantilever transducers over 4-inches substrates. The mechanical characterization of the cantilevers in oscillating regime was performed in order to extract the material Young's modulus E when the structures were made of different polycrystalline diamond qualities. In the best case, a value of E as high as 1100 GPa and very close to the Young's modulus of monocrystalline diamond (1200 GPa) was achieved. In parallel, we verified that both cantilevers resonance frequency and Q-factor were significantly higher than those of identical silicon structures (on average twice higher). This makes diamond mechanical structures more suitable for use in liquid media. In such damping media a very poor sensitivity to mass changes was determined. Nevertheless, their sensitivity to liquid density changes was found to be significant (-3Hz.kg-1.m3). More importantly, by functionalizing diamond micro-cantilevers with caproic acid, an evidence of these transducers high sensitivity to surface molecular interactions was shown. Especially, when charge density variations occurs several tens Hz changes were measured on kHz-range oscillating cantilevers. In this context, a label free DNA sensor was achieved and allowed the specific detection of 24-mer target DNA in real time. In parallel to this work, actuation and boron doped diamond-based readout gauges were integrated to the resonant cantilevers and characterized. They allowed interfacing the cantilevers to a dedicated acquisition electronic prototype developed in the course of this study

The invention of the atomic force microscope (AFM) revolutionized the scientific world by providing researchers with the ability to make topographical maps of both conducting and non-conducting surfaces with nanometer resolution. As an alternative to optical AFM methods, thermal cantilevers have been investigated as a method to measure topography. This study reports the fabrication and testing of heated AFM cantilevers. This study transfers a fabrication process first developed at Stanford University to the Georgia Institute of Technology micro-fabrication facility and fabricates six different heated AFM cantilever designs. Selective impurity doping of a silicon cantilever allows it to become electrically conductive with a resistive element near the cantilever free end. Voltage applied across the cantilever legs induces current flow through the cantilever that generates heat in the resistive element. A deep understanding of the operational behavior and limits of the AFM cantilever is required to use the cantilever as an experimental tool. Characterization experiments determined the cantilever electrical resistance and temperature response. Experiments were conducted that electrically test heated AFM cantilevers at various system input voltages. Electrical and thermal responses of these cantilevers were compared against a theoretical model. The model utilizes heat transfer fundamentals and links the thermal response to the cantilever temperature-dependent electrical characteristics. Results of this study show that the fabricated heated AFM cantilevers have a tip with a radius of curvature as small as 20nm. Cantilever temperatures can exceed 700㠩n short pulses and, because the resistive heating element is also a temperature sensor, calibration of the cantilever temperature response is possible to within 1㮍

The human body is an intricate network of many highly regulated biochemical processes and cell adhesion is one of them. Cell adhesion is mediated by specific interactions between molecules on apposing cell surfaces and is critical to many physiological and pathological processes like inflammation and cancer metastasis. During inflammation, blood-borne circulating leukocytes regularly stick to and roll on the vessel walls, which consist in part, adhesive contacts mediated by the selectin family of adhesion receptors (P-, E- and L-selectin). This is the beginning of a multi-step cascade that ultimately leads to leukocyte recruitment in areas of injury or infection. In vivo, selectin-mediated interactions take place in a hydrodynamic milieu and hence, it becomes imperative to study these interactions under very similar conditions in vitro. The goal of this project was to characterize the kinetic and mechanical properties of selectin interactions with different physiologically relevant ligands and selectin-specific monoclonal antibodies (mAbs) under a mechanically stressful milieu, using atomic force microscopy (AFM). Elasticity studies revealed that bulk of the complex compliance came from the selectins, with the ligands or mAbs acting as relatively stiffer components in the stretch experiments. Furthermore, molecular elasticity was inversely related to selectin length with the Consensus Repeats (CRs) behaving as Hookean springs in series. Besides, monomeric vs. dimeric interactions could be clearly distinguished from the elasticity measurements. L-selectin dissociation studies with P-selectin Glycoprotein Ligand 1 (PSGL-1) and Endoglycan revealed that catch bonds operated at low forces while slip bonds were observed at higher forces. These results were consistent with previous P-selectin studies and suggested that catch bonds could contribute to the shear threshold for L-selectin-mediated rolling By contrast, only slip bonds were observed for L-selectin-antibody interactions, suggesting that catch bonds could be a common characteristic of selectin-ligand interactions. Force History studies revealed that off-rates of L-selectin-sPSGL-1 (or 2-GSP-6) interactions were not just dependent on applied force, as has been widely accepted but in fact, depended on the entire history of force application, thus providing a new paradigm for how force could regulate bio-molecular interactions. Characterizing selectin-ligand interactions at the molecular level, devoid of cellular contributions, is essential in understanding the role played by molecular properties in leukocyte adhesion kinetics. In this aspect, data obtained from this project will not only add to the existing body of knowledge but also provide new insights into mechanisms by which selectins initiate leukocyte adhesion in shear.

The purpose of this work is the development of MEMS-based resonant sensors for liquid-phase biochemical sensing applications. Specifically, the sensors developed here are aimed at embedded or point-of-sampling applications: (1) when there is not enough time to send a sample to a lab for analysis, (2) in resource-poor settings, (3) when collecting analyte and shipping it to a lab would damage the sample, or (4) for in-situ monitoring. To this end, a bulk micromachined resonant cantilever sensor and a surface micromachined sensor based on the spring-softening effect are investigated as transducer elements. The developed cantilever resonators are operated in an in-plane vibration mode to reduce fluid damping and mass loading by the surrounding fluid. The surface of the resonator is either coated with a chemically sensitive polymer film for chemical sensing or with a layer of protein or antibody for biosensor testing. Chemical tests for sensing volatile organic compounds using polymer-coated in-plane resonators in the liquid-phase give estimated limits of detection below 100 ppb. In addition, biosensor tests for the detection of anti-IgG yield estimated limits of detection around 100 ng/ml. In an attempt to further improve sensor reliability and to further lower the limits of detection, a second sensing concept has been investigated. The presented sensing scheme is capacitive with a resonator acting as an analog-to-digital converter. The resonator and the sensing capacitors are coupled via the spring softening effect. Through this mechanism a change in capacitance causes a shift in resonant frequency. Extensive device modeling has been performed and a process has been developed allowing for fabrication and on-chip packaging of these sensor structures. Initial mechanical characterization data show that the resonators do in fact vibrate.