One of the key measurement devices used in characterization of microelectromechanical systems (MEMS) is the interferometric microscope. This device allows remote, noninvasive measurements of the surface shape and deformations of MEMS in full-field-of-view with high spatial resolution and nanometer accuracy in near real-time. As MEMS are becoming more prevalent in the areas of consumer products and national defense, the demand for a versatile and easy to use characterization system is very high. This Thesis describes the design, implementation, and use of an interferometric system that is based on modular components which allow for many loading and measurement capabilities, depending on a specific application. The system has modules for subjecting MEMS to vacuum and dry gas environments, mechanical vibration excitation, thermal loads (both heating and cooling), and electrical loads. Three interferometric measurement modules can be interchanged to spatially measure shape and deformation of micro- and/or meso-scale objects, and temporally measure vibrations of these objects. Representative examples of the measurement and loading capabilities of the system are demonstrated with microcantilevers and a microgyroscope.

"Microelectromechanical systems (MEMS) technology has been evolving for about two decades and, now it is integrated in many designs, including radio frequency (RF) switches characterized by µm dimensions. Today, designers are attempting o develop the ideal RF MEMS switch, yet electro-thermo-mechanical (ETM) effects still limit the design possibilities and adversely affect reliability of these microswitches. The ETM effects are a result of Joule heat generated at the microswitch contact areas. This heat is due to the current passing through the microswitch, characteristics of the contact interfaces, and other parameters characterizing a particular design. It significantly raises temperature of the microswitch, thus affecting the mechanical and electrical properties of the contacts, which may lead to welding, causing a major reliability issue. Advanced research was performed, in this thesis, to minimize the Joule heat effects on the contact areas, thus improving performance of the microswitch. Thermal analyses done computationally on a cantilever-type RF MEMS switch indicate heat-effected zones and the influences that various design parameters have on these zones. Uncertainty analyses were also performed to ensure accuracy of the computational results, which indicate contact temperatures on the order of 700˚C, for the cases considered in this thesis. Although these temperatures are well below the melting temperatures of the materials used, new designs of the microswitches will have to be developed, in order to lower their maximum operating temperatures and reduce temporal effects they cause, to increase reliability of the RF MEMS switches."

"Microelectromechanical systems (MEMS) are integrated mechanical and electrical devices that are fabricated with features micrometers in size. MEMS are used as chemical laboratories on a chip, actuators, sensors, etc. To increase their operational capability, various MEMS sensors are being integrated into sensor systems, whose functionality may not decrease when their size decreases. However, before more advancement can be made in the sensor systems, behavior of individual sensors must be better understood. Without the basic knowledge of how and why MEMS sensors react the way they do, it is impossible to determine how MEMS sensor systems will behave. Out of the many sensors that can be included in the system, a MEMS gyroscope was selected for consideration in this paper. More specifically, the effects that suspension has on the topography of the microgyroscopes were studied. In this thesis, the folded springs that support the MEMS gyroscopes were modeled using analytical and computational methods, whose results were verified using experimentation. The analytical results correlated well with the computational and experimental results. The analytical and computational results for the deformations of the cantilever compared within 0.1%. The differences between the analytical and experimental results were on the order of 10%. Knowledge gained from these studies will help in the development of a through methodology for modeling the microgyroscope. This methodology will facilitate insertion of the microgyroscopes into the sensor systems."

Personalized cancer medicine is a cancer care paradigm in which diagnostic and therapeutic strategies are customized for individual patients. Microsystems that are created by Micro-Electro-Mechanical Systems (MEMS) technology and integrate various diagnostic and therapeutic methods on a single chip hold great potential to enable personalized cancer medicine. Toward ultimate realization of such microsystems, this thesis focuses on developing critical functional building blocks that perform genetic variation identification (single-nucleotide polymorphism (SNP) genotyping) and specific, efficient and flexible cell manipulation on microfluidic surfaces. For the identification of genetic variations, we first present a bead-based approach to detect single-base mutations by performing single-base extension (SBE) of SNP specific primers on solid surfaces. Successful genotyping of the SNP on exon 1 of HBB gene demonstrates the potential of the device for simple, rapid, and accurate detection of SNPs. In addition, a multi-step solution-based approach, which integrates SBE with mass-tagged dideoxynucleotides and solid-phase purification of extension products, is also presented. Rapid, accurate and simultaneous detection of 4 loci on a synthetic template demonstrates the capability of multiplex genotyping with reduced consumption of samples and reagents. For cell manipulation, we first present a microfluidic device for cell purification with surface-immobilized aptamers, exploiting the strong temperature dependence of the affinity binding between aptamers and cells. Further, we demonstrate the feasibility of using aptamers to specifically separate target cells from a heterogeneous solution and employing environmental changes to retrieve purified cells. Moreover, spatially specific capture and selective temperature-mediated release of cells on design-specified areas is presented, which demonstrates the ability to establish cell arrays on pre-defined regions and to collect only specifically selected cell groups for downstream analysis. We also investigate tunable microfluidic trapping of cells by exploiting the large compliance of elastomers to create an array of cell-trapping microstructures, whose dimensions can be mechanically modulated by inducing uniform strain via the application of external force. Cell trapping under different strain modulations has been studied, and capture of a predetermined number of cells, from single cells to multiple cells, has been achieved. In addition, to address the lack of aptamers for targets of interest, which is a major hindrance to aptamer-based cell manipulation, we present a microfluidic device for synthetically isolating cell-targeting aptamers from a randomized single-strand DNA (ssDNA) library, integrating cell culturing with affinity selection and amplification of cell-binding ssDNA. Multi-round aptamer isolation on a single chip has also been realized by using pressure-driven flow. Finally, some perspectives on future work are presented, and strategies and notable issues are discussed for further development of MEMS/microfluidics-based devices for personalized cancer medicine.

Considerable effort has recently been directed toward the miniaturization of quantitative-polymerase-chain-reaction [QPCR] instrumentation in an effort to reduce both cost and form factor for point-of-care applications. Notable gains have been made in shrinking the required volumes of PCR reagents, but resultant prototypes retain their bench-top form factor either due to heavy heating plates or cumbersome optical sensing instrumentation. In this thesis, we describe the use of complementary-metal-oxide semiconductor (CMOS) integrated circuit (IC) technology to produce a fully integrated qPCR lab-on-chip. Exploiting a 0.35-µm high-voltage CMOS process, the IC contains all of the key components for performing qPCR. Integrated resistive heaters and temperature sensors regulate the surface temperature of the chip to 0.45°C. Electrowetting-on-dielectric microfluidic pixels are actively driven from the chip surface, allowing for droplet generation and transport down to volumes of less than 1.2 nanoliters. Integrated single-photon avalanche diodes [SPAD] are used for fluorescent monitoring of the reaction, allowing for the quantification of target DNA with more than four-orders-of-magnitude of dynamic range with sensitivities down to a single copy per droplet. Using this device, reliable and sensitive real-time proof-of-concept detection of Staphylococcus aureus (S. aureus) is demonstrated.

Cardiovascular disease (CVD) is broadly characterized by a loss of global function, exacerbated by a very limited ability for the heart to regenerate itself following injury. CVD remains the leading cause of death in the United States and the leading citation in hospital discharges. The overall concept of this dissertation is to investigate the use of biophysical signals that drive physiologic maturation of myocardium, and lead to its deterioration in disease. By incorporating biophysical signaling into cardiac tissue engineering methods, the aim is to generate high fidelity engineered platforms for cell delivery and maturation of surrogate muscle, while understanding the cues that lead to pathological cell fate in disease. The first part of this thesis describes the development of a composite scaffold, derived from human myocardium, to use as a delivery platform of mesenchymal stem cells to the heart. Through biochemical signaling, we are able to modulate MSC phenotype, and propose a mechanism through which angio- and arteriogenesis of the heart leading to global functional improvements, following myocardial infarction, may be attributed. We further demonstrate cardioprotection of host myocardium in a setting of acute injury by exploiting non-invasive radioimaging techniques. The mechanism through which we can attribute cell mobilization to the infarct bed is further explored in patient-derived myocardium, to understand how this pathway remains relevant in chronic heart failure. The second focus of the thesis is the use of electro-mechanical stimulation to generate high fidelity Engineered Heart Muscle (EHM). We report that electro-mechanical stimulation of EHM at near-physiologic frequency leads to development and maturation of Calcium handling and the T- tubular network, as well as improved functionality and positive force frequency relationship. Lastly, we return to human myocardium as platform understand regulation of cardiomyocyte function by the extracellular matrix. Here, we seek to understand how the ECM from different disease states (eg. non-diseased, ischemic, non-ischemic) affects cell phenotype. Specifically, can bona fide engineered myocardium successfully integrate and remodel diseased ECM? Using stem cell derived cardiomyocytes and patient-derived decellularized myocardium to generated engineered myocardium (hhEMs), we report that hhEMs mimic native myogenic expression patterns representative of their failing- and non-failing heart tissue.

In this thesis, I present numerical simulations that explore the applications of self-propelled particles to the field of self-assembly and to the design of `smart' micromachines. Self-propelled particles, as conceived of here, are colloidal particles that take some energy from their surroundings and turn it into directed motion. These non-equilibrium particles can move persistently for long times in the same direction, a fact that makes the behavior of dense and semi-dilute systems of these particles very different from that of their passive counterparts. The first section of this thesis deals with the interactions between passive components and baths of hard, isotropic self-propelled particles. First, I present simulations showing how the depletion attraction can be made into a short ranged repulsive, or long ranged attractive interaction for passive components with different geometries in a bath of self-propelled particles, and show how the form of these interactions is consistent with how active particles move near fixed walls. In the next chapter, a rigid filament acts as a flexible wall that engages in a feedback loop with an active bath to undergo repeated folding and unfolding events, behavior which would not occur for a filament in a passive environment. The subsequent chapters deal with self-propelled particles that have long ranged and anisotropic interactions. When the orientations of active particles are coupled, they can undergo remarkable collective motion. While the first chapter in this section begins with a discussion of how active disks interacting via an isotropic potential consisting of a long ranged repulsion and short ranged attraction self-assemble into living clusters of controllable size, I show how replacing the disks with anisotropic dumbbells causes these clusters to rotate coherently. In the last chapter, I show that weakly screened active dipoles form lines and clusters that move coherently. These particles can become anchored to the surface of a passive charged colloid in various ways that lead to two different kinds of active motion: rotations of a corona of dipoles around the colloid, and active translation of the colloid, pushed by a tail of dipoles. Finally, a mixture of many charged colloids and dipoles can reproduce the swarming behavior of the pure dipoles at a larger length scale with coherent motion of the colloids. These are all examples of how activity is a useful tool for controlling motion at the micro-scale.

Software cognitive radios and Internet of Things (IoT) are recent interest areas that need low loss and low power consumption hardware. More specifically, the area of software cognitive radios requires that hardware be frequency agile and highly selective. Meanwhile, IoT relies on multiple low power sensor networks. By combining Complementary Metal Oxide Semiconductors (CMOS) technology with piezoelectric Micro-Electro-Mechanical Systems (MEMS), we can fabricate Systems-on-Chip (SoC) that can be used as filters or references (oscillators) and highly selective sensors. In this work we developed a die-level compatible process for the monolithic integration of Bulk Acoustic Resonators (BAWs) on CMOS for low power, reduced area and high-quality passives for radio frequency applications. Using CMOS as a fabrication substrate some stringent requirements were added to maintain the dies and the technology’s integrity. A few of these limitations were the need for a low thermal budget fabrication process, die handling and electro-static discharge (ESD) protection. The devices were first fabricated on glass for modeling extraction that was later used for the design of the integrated circuits (IC). Three integrated circuits were designed as substrates for the integration using IBM’s 180nm and TSMC’s 65nm technology. A monolithic BAW oscillator with a resonance frequency of 1.8GHz was demonstrated with an FOM ~186dBc/Hz, comparable to other academia work. Using the developed process, a membrane BAW structure (FBAR) was integrated as well. Using a susceptor coating and zinc oxide’s (ZnO) high temperature coefficient of frequency (TCF) the device was studied as an alternative uncooled infrared sensor. Finally, a reprogrammable IC and an RF PCB were designed for volatile organic compound (VOC) testing using self-assembled monolayers (SAMs) as the absorber layer.

Microssistemas eletromecânicos ou Micro-Electro-Mechanical Systems (MEMS), representam uma classe de dispositivos que combinam funções mecânicas e eletrônicas em escala micrométrica. Através do uso de técnicas de microfabricação, adaptadas da indústria de semicondutores, é realizada a integração entre estruturas móveis, sensores, atuadores e eletrônica, tornando possível a implementação de sistemas completos miniaturizados. Acelerômetros eletrostáticos estão entre os dispositivos MEMS mais comercializados hoje em dia, com venda anual em todo o mundo superior a 100 milhões de unidades e crescente a cada ano. Eles são geralmente fabricados utilizando-se três lâminas de silício espessas, coladas uma sobre a outra. A camada intermediária é obtida por processos de corrosão e consiste de uma grande massa de prova suspensa por uma ou mais vigas. Ela é separada das lâminas superior e inferior por um pequeno espaço vazio (gap), dando origem a dois conjuntos de capacitores de placas paralelas. A flexibilidade das vigas permite que a massa se mova proporcionalmente à aceleração externa e o seu deslocamento é estimado pela variação da capacitância do conjunto. O projeto destes sensores é uma tarefa complexa, já que os seus diversos requisitos de desempenho são, na maioria das vezes, conflitantes, isto é, se o projeto é modificado para melhorar uma característica, as demais são inevitavelmente afetadas e por isso técnicas de otimização devem ser utilizadas na etapa de projeto. Com o intuito de melhorar o desempenho de micro-acelerômetros capacitivos, são então propostas e avaliadas no atual trabalho duas técnicas de otimização distintas, sendo uma delas baseada em Otimização Paramétrica (OP) e a outra no Método da Otimização Topológica (MOT). A OP parte de uma topologia previamente definida e adota algumas de suas características geométricas como variáveis de projeto. Para levar em consideração incertezas nas dimensões e propriedades dos materiais, que é um elemento-chave na concepção e fabricação de dispositivos MEMS, neste trabalho a OP é combinada com o método da Otimização de Projeto Baseado em Confiabilidade ou Reliability-based Design Optimization (RBDO). Análises de confiabilidade de primeira ordem através do Método de Confiabilidade de Primeira Ordem, ou First-Order Reliability Method (FORM), são utilizadas para o cálculo das probabilidades envolvidas nesta formulação. Já o MOT combina o Método dos Elementos Finitos (MEF) e um modelo de material com algoritmos de otimização para encontrar a distribuição ótima de material em um domínio de projeto pré-estabelecido. As variáveis de projeto são as pseudo-densidades que descrevem a quantidade de material em cada ponto do domínio. Na modelagem pelo MEF utiliza-se elementos de placa estrutural do tipo Mixed Interpolation of Tensorial Components (MITC). Exemplos práticos utilizando ambas as abordagens são apresentados e os seus resultados discutidos com o intuito de se avaliar o potencial de cada técnica para o projeto de micro-acelerômetros capacitivos. / Micro-Electro-Mechanical Systems (MEMS) are a class of devices that combine mechanical and electronic functions on a micrometric scale. Through the use of microfabrication techniques, adapted from the semiconductor industry, the integration of mobile structures, sensors, actuators and electronics is performed, allowing the implementation of fully miniaturized systems. Electrostatic accelerometers are among the highest volume MEMS products nowadays, with worldwide annual sales topping 100 million units and growing steadily. Bulk-type accelerometers are generally manufactured using three thick silicon wafers, bonded together one on top of the other. The intermediate layer is obtained by etching processes and consists of a big proof mass suspended by one or more beams. It is separated from the upper and lower wafers by a small gap, resulting in two sets of parallel plate capacitors. The flexibility of the beams allows the mass to move proportionally to the external acceleration and its displacement is estimated by the change in capacitance of the set. The design of such sensors is a complex task, since they depend on many performance requirements, which are most often conflicting. If a design is modified to improve one characteristic, others are inevitably affected. Therefore, optimization techniques are regularly used in the design stage of MEMS sensors. Aiming to improve the performance of capacitive micro-accelerometers, in the present work two optimization techniques are presented, the first is based on Parametric Optimization (PO) and the other is the Topology Optimization Method (TOM). The PO starts from a predefined topology and uses some of its geometric characteristics as design variables. In order to account for uncertainties in the dimensions and material properties, which is a key element in the design and fabrication of MEMS devices, in this work the PO is combined with the Reliability-based Design Optimization (RBDO) method. The First-Order Reliability Method (FORM) is applied to calculate the probabilities involved in the RBDO formulation. The TOM combines the Finite Element Method (FEM) and a material model with optimization techniques to find the best constrained material distribution in a fixed design domain. The design variables are the pseudo-densities that describe the amount of material at each point of the domain. The FE model is discretized using the Reissner-Mindlin plate element with the Mixed Interpolation of Tensorial Components (MITC) formulation. Practical examples using both approaches are presented and discussed in order to evaluate the potential of each technique to the design of capacitive micro-accelerometers.

Um novo processo de fabricação de dispositivos de emissão de campo (FE) em silício (Si) é apresentado nesta tese, baseado na potencialidade de utilização da técnica de microusinagem denominada HI-PS (Hydrogen Ion Porous Silicon), que trata da combinação entre processos de implantação de hidrogênio e silício poroso. Por meio do procedimento proposto, foram obtidos dispositivos com 2500 emissores (micropontas de Si) integrados e não integrados ao anodo e contidos em uma área de 2,8 x 2,8 mm² (3,2.10\'POT.4\' pontas/cm²). As micropontas de Si fabricadas apresentaram altura de 10 µm, com diâmetro do ápice em torno de 150 nm. A separação entre os emissores (50 µm), na configuração não integrada dos dispositivos, foi limitada pela resolução da máscara litográfica utilizada. Foram propostas etapas de otimização estrutural das micropontas após sua formação, e aplicadas tanto na configuração do sistema anodo-catodo integrado como não integrado. Como resultado destas etapas, constatou-se a redução do ápice das microestruturas para dimensões inferiores a 100 nm. Os dispositivos FE integrados foram obtidos com uma distância de separação entre o anodo e o catodo de aproximadamente 12 µm, distância definida pelas dimensões da máscara litográfica, porém não limitada pelo processo aplicado. Destacam-se, entre as vantagens da utilização da técnica HI-PS em relação às tecnologias usuais de manufatura dos dispositivos FE, a baixa complexidade do processo proposto e a utilização de apenas uma etapa litográfica para obtenção do sistema anodo-catodo integrado e auto alinhado. Para efetuar as caracterizações dos dispositivos, foram implementados uma câmara de vácuo específica, que permite alterar a distância entre as estruturas do anodo e do catodo não integradas, sem a necessidade de se retirar a amostra da câmara, e três sistemas para ensaios elétricos, sendo um destes sistemas desenvolvido especificamente para caracterização elétrica de dispositivos FE. As caracterizações elétricas foram efetuadas por meio de curvas I-V, I-t e V-d, sendo esta última utilizada para extrair o campo elétrico macroscópico E, que foi utilizado como parâmetro de comparação entre amostras submetidas a diferentes processos de otimização estrutural e de recobrimento superficial dos emissores por Al. Todas as amostras caracterizadas apresentaram variação de corrente exponencial com o potencial aplicado, de acordo com o esperado pela teoria proposta por Fowler-Nordheim (F-N). Dispositivos com otimização estrutural ou deposição de Al apresentaram melhores características de emissão (menor valor de E), de acordo com o aprimoramento do modelo de F-N sugerido na literatura para superfícies otimizadas. Constatou-se, pelos gráficos de F-N, o comportamento diferenciado dos emissores de Si tipo p em comparação com outros materiais, estabelecendo uma relação entre as variações da inclinação da curva traçada às distintas fontes de elétrons do Si. Frente aos resultados obtidos, conclui-se que a técnica Hi-PS é altamente promissora para fabricação de emissores microusinados em Si para aplicações em dispositivos FE. / This thesis presents a new silicon (Si) field emission devices (FE) fabrication process based on the potential of the HI-PS (Hydrogen Ion Porous Silicon) micromachining technique, which is a combination of hydrogen implantation and porous silicon. Devices with 2500 emitters (Si microtips), integrated and non-integrated to the anode, enclosed in an area of 2.8 x 2.8 mm² (3.2 x 10\'POT.4\' tips/cm²), were obtained from the proposed technique. The fabricated Si microtips show 10 µm in height, with apex diameter of about 150 nm. The separation distance between emitters (50 µm), considering the non-integrated devices design, was limited by the resolution of the lithographic mask applied. Microtips structural improvement process steps were proposed and applied in both anode-cathode design (integrated and non-integrated). As a result, a reduction in tip apex diameter to dimensions lower than 100 nm was verified. The integrated FE devices were obtained with an anode-cathode separation of about 12 µm, which distance was defined by lithographic mask dimensions, but not limited by the process applied. The outstanding advantages of the HI-PS technique in comparison with usual technologies for FE devices fabrication are the low complexity of the process proposed and the use of a single lithographic step to obtain a selfaligned and integrated anode-cathode system. A dedicated vacuum chamber, which allows the changing of the separation distance between non-integrated anodecathode structures without the need of removing the sample out the chamber, and three systems for electrical test, being one of them developed specifically for FE devices electrical characterization, were implemented. The electrical characterizations were performed by means of I-V, I-t and V-d curves, being the last one used to extract the macroscopic electrical field E, which was applied as comparison parameter between samples obtained from distinct structural improvement process and samples with emitters surface coated with Al. All samples characterized showed exponential-like behavior of current with the potential applied, as expected from theory proposed by Fowler-Nordheim (F-N). Devices with structural improvement or Al coating showed better emission characteristics (lower E value), according with the modified F-N model suggested in the literature for optimized surfaces. From the F-N plots, the distinct behavior of p type Si emitters was verified in comparison with different materials, establishing a relationship between the slope variations of the curve obtained and the electrons source of the Si. Based on the results obtained, the HI-PS technique is very promising to fabricate Si micromachined emitters for use in FE devices.