The surface roughness of a few asperities and their influence on the work of adhesion is of scientific interest. Macroscale and nanoscale adhesion data have given seemingly inconsistent results. Despite the importance of bridging the gap between the two regimes, little experimental work has been done, presumably due to the difficulty of the experiment needed to determine how small amounts of surface roughness might influence adhesion data lying in between the two scales. To investigate the role of few-asperity contacts in adhesion, the pull-off force was measured between different sized AFM (Atomic-Force Microscope) tips that had different roughnesses and sample surfaces that had well-controlled material properties. The spring constant of the cantilever, the deflection of the cantilever, and the radius of the cantilever tip were measured before each experiment. There were seventeen tips of four different types, with radii from 200 nm to 60 ìm. The samples were unpatterned amorphous silicon dioxide die with two types of surface conditions: untreated and treated with a few angstroms of vapor deposited diphenylsiloxane. We observed that the pull-off force was independent of the radius of the AFM tip, which was contrary to all continuum-mechanics model predictions. To explain this behavior, we assumed that the interactions between the AFM tip and sample were additive, material properties were constant, and that the AFM tip, asperities, and sample surfaces were of uniform density. Based on these assumptions, we calculated a simple correction due to the measured Root Mean Square (RMS) surface roughness of the AFM tips. The simple correction for the RMS surface roughness resulted in the expected dependence of the pull-off force on radius, but the magnitudes were higher than expected. Commercial and heat-treated AFM tips had minimal surface roughness and result in magnitudes that were more reliable. The relative uncertainty for the pull-off force was estimated to be 10% and the work of adhesion was estimated to be 15%. In this thesis, we derive how the cantilever and tip parameters contribute to the measured pull-off force, show how the corrected results compare with theory, and demonstrate how the AFM probes were calibrated. Although much work is still needed, the work presented here should expand the understanding of adhesion between the nanoscale and macroscale.

The focus of this work is to present in detail the implementation of a three dimensional direct simulation Monte Carlo methodology on unstructured Delaunay meshes (U-DSMC). The validation and verification of the implementation are shown using a series of fundamental flow cases. The numerical error associated with the implementation is also studied using a fundamental flow configuration. Gas expansion from microtubes is studied using the U-DSMC code for tube diameters ranging from 100Æ’ÃÂ�m down to 100nm. Simulations are carried out for a range of inlet Knudsen numbers and the effect of aspect ratio and inlet Reynolds number on the plume structure is investigated. The effect of scaling the geometry is also examined. Gas expansion from a conical nozzle is studied using the U-DSMC code for throat diameters ranging from 250 Æ’ÃÂ�m down to 250 nm. Simulations are carried out for a range of inlet Knudsen numbers and the effect of inlet speed ratio and inlet Reynolds number on the plume structure is investigated. The effect of scaling the geometry is examined. Results of a numerical study using the U-DSMC code are employed to guide the design of a micropitot probe intended for use in analyzing rarefied gaseous microjet flow. The flow conditions considered correspond to anticipated experimental test cases for a probe that is currently under development. The expansion of nitrogen from an orifice with a diameter of 100Æ’ÃÂ�m is modeled using U-DSMC. From these results, local ¡¥free stream¡¦ conditions are obtained for use in U-DSMC simulations of the flow in the vicinity of the micropitot probe. Predictions of the pressure within the probe are made for a number of locations in the orifice plume. The predictions from the U-DSMC simulations are used for evaluating the geometrical design of the probe as well as aiding in pressure sensor selection. The effect of scale on the statistical fluctuation of the U-DSMC data is studied using Poiseuille flow. The error in the predicted velocity profile is calculated with respect to both first and second-order slip formulations. Simulations are carried out for a range of channel heights and the error between the U-DSMC predictions and theory are calculated for each case. From this error, a functional dependence is shown between the scale-induced statistical fluctuations and the decreasing channel height.

This Thesis proposes phase modulating interferometry as an alternative to phase stepping and phase-shifting interferometry for use in the shape and displacement characterization of microelectromechanical systems (MEMS) [Creath, 1988; de Groot, 1995a; Furlong and Pryputniewicz, 2003]. A phase modulating interferometer is developed theoretically with the use of a stroboscopic illumination source and implemented on a Linnik configured interferometer using a software control package developed in the LabVIEWâ„¢ programming environment. Optimization of the amplitude and phase of the sinusoidal modulation source is accomplished through the investigation and minimization of errors created by additive noise effects on the recovered optical phase. A spatial resolution of 2.762 µm over a 2.97x2.37 mm field of view has been demonstrated with 4x magnification objectives within the developed interferometer. The measurement resolution lays within the design tolerance of a 500Ã… ±2.5% thick NIST traceable gold film and within 0.2 nm of data acquired under low modulation frequency phase stepping interferometry on the same physical system. The environmental stability of the phase modulating interferometer is contrasted to the phase stepping interferometer, exhibiting a mean wrapped phase drift of 40.1 mrad versus 91 mrad under similar modulation frequencies. Shape and displacement characterization of failed µHexFlex devices from MIT's Precision Compliant Systems Laboratory is presented under phase modulating and phase stepping interferometry. Shape characterization indicates a central stage displacement of up to 7.6 µm. With a linear displacement rate of 0.75 Ã…/mV under time variant load conditions as compared to a nominal rate of 1.0 Ã…/mV in an undamaged structure [Chen and Culpepper, 2006].

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.