<p>As an increasingly prevalent chronic disease, diabetes represents one of the fastest growing health burdens to both the developed and developing world. In an effort to improve the management and treatment of diabetes, implantable sensors that continuously monitor glucose levels have become popular alternatives to patient-administered finger prick measurements of blood glucose. However, following implantation, the performance of these implants suffers from inaccurate and erratic readings that compromise their useful lives. As a result, implantable glucose sensors remain limited as a platform for the reliable management of diabetes. While the interaction between the sensor and its surrounding tissue has been posited as a culprit for erroneous in vivo sensor performance, there remains little evidence to support that theory.</p><p>This dissertation describes the effects that implant-associated tissue reactions have on implantable sensor function. Since tissue response to an implant changes over time, the overall effect of these tissue reactions is broken into two temporal phases: (1) the phase of weeks to months following implantation when a mature foreign body capsule is present around the sensor and (2) the phase of days to weeks immediately following sensor implantation when a provisional matrix of proteins and inflammatory cells envelops the sensor.</p><p>Late stage sensor responses to implantation are marked by both an attenuated sensor signal and a significant time lag relative to blood glucose readings. For this later stage of sensor response, a computational model of glucose transport through the interstitial space and foreign body capsule was derived and implemented. Utilizing physiologically relevant parameters, the model was used to mechanistically study how each constituent part of the capsular tissue could affect sensor response with respect to signal attenuation and lag. Each parameter was then analyzed using logarithmic sensitivity analysis to study the effects of different transport variables on both lag and attenuation. Results identified capsule thickness as the strongest determinant of sensor time lag, while subcutaneous vessel density and capsule porosity had the largest effects on attenuation of the sensor signal.</p><p>For the phase of early stage tissue response, human whole blood was used as a simple ex vivo experimental system. The impacts of protein accumulation at the sensor surface (biofouling effects) and cellular consumption of glucose in both the biofouling layer and in the bulk (metabolic effects) on sensor response were assessed. Medtronic Minimed SofSensor glucose sensors were incubated in whole blood, plasma diluted whole blood, and cell-free platelet poor plasma (PPP) to analyze the effects of different blood constituents on sensor function. Experimental conditions were then simulated using MATLAB to predict the relative impacts of biofouling and metabolic effects on the observed sensor responses. It was found that the physical barrier to glucose transport presented by protein biofouling did not hinder glucose movement to the sensor surface. Instead, glucose consumption by inflammatory cells was identified as the major culprit for generating poor sensor performance immediately following implantation.</p><p>Lastly, a novel, biomimetic construct was designed to mimic the in vivo 3D cellular setting around the sensor for the focused in vitro investigation of early stage effects of implantation on glucose sensor performance. Results with this construct demonstrate similar trends in sensor signal decline to the ex vivo cases described above, suggesting this construct could be used as an in vitro platform for assessing implantable glucose sensor performance.</p><p>In total, it may be concluded from this dissertation that instead of sensors "failing" in vivo, as is often reported, that different physiological factors mediate long term sensor function by altering the environment around the implant. For times immediately following implantation, sensor signals are mediated by the presence of inflammatory macrophages adhered on the surface. However, at longer times post-implantation, sensor signals are mediated not by the consumptive capacity of macrophages, but instead by the subcutaneous vessel density surrounding the sensor as well as the porosity and thickness of the foreign body capsule itself. Taken in concert, the results of this dissertation provide a temporal framework for outlining the effects of tissue response on sensor performance, hopefully informing more biocompatible glucose sensor designs in the future.</p> / Dissertation

<p>The primary focus of this dissertation is on the assessment of fugitive methane emissions from near and far-field sources. Methane is the second most prevalent greenhouse gas (GHG) emitted in the United States from anthropogenic activities. Due to measurement and model limitations, there is not an accurate assessment of how much methane in the atmosphere is due to anthropogenic sources. This dissertation focuses on measuring the methane emissions from two of the three largest anthropogenic sources -- landfills and natural gas systems. All measurements are made with a single fixed or single mobile sensor. Methods are developed to assess the source strength for both near (i.e. natural gas) and far-field (i.e. landfill) sources using either the fixed or mobile sensor. </p><p> </p><p>For far-field measurements, a standardized version of a mobile tracer correlation measurement method was developed and used for assessment of methane emissions from 15 landfills in 56 field deployments from 2009 to 2013. A total of 1876 mobile tracer correlation measurement transects were attempted over 131 field sampling days. </p><p>Transects were analyzed using signal to noise ratio, plume correlation, and emission rate difference method quality indicators. The application of the method quality indicators yield 456 transects (33\%) that pass data acceptance criteria. </p><p>For near-field sources, techniques are developed for 1) fixed sensors sampling through time downwind of a source and 2) mobile sensors passing across plumes downwind of a source. For the fixed sensor, the lateral plume geometry is reconstructed from the fluctuating wind direction using a derived relationship between the wind direction and crosswind plume position. The crosswind plume spread is estimated with two different methods (modeled and observed), and subsequently used a Gaussian plume inversion to estimate the source strengths. For the fixed sensor, the sensor takes measurements for about 20 minutes and we are able to reconstruct the ensemble average of the plume. </p><p>For the mobile sensor, the vehicle drives through the plume in the crosswind direction. </p><p>The measurements show the lateral plume geometry of an instantaneous plume. The instantaneous plume has a narrowed Gaussian structure. </p><p>Two techniques are tested using data from controlled methane release experiments; these two techniques are 1) linear-squares and 2) a probabilistic approach. For the probabilistic approach, Bayesian inference tools are applied and special attention is paid to the relevant likelihood functions for both short time averaged concentrations from a single fixed sensor and spatial transects of instantaneous concentration measurements from a mobile sensor. The two techniques are also tested on measurements downwind of multiple natural gas production facilities in Wyoming for the fixed sensor and in Colorado for the moving sensor. The results for both the fixed and mobile techniques show promise for use with gas sensors on industry work trucks, opportunistically providing surveillance over a region of well pads.</p> / Dissertation

Currently technologies such as EEG, EMG and EOG recordings are the established methods used in the analysis of sleep. But if these methods are to be employed to study sleep in rodents, extensive surgery and recovery is involved which can be both time consuming and costly. This thesis presents and analyzes a cost effective, non-invasive, high throughput system for detecting the sleep and wake patterns in mice using a piezoelectric sensor. This sensor was placed at the bottom of the mice cages to monitor the movements of the mice. The thesis work included the development of the instrumentation and signal acquisition system for recording the signals critical to sleep and wake classification. Classification of the mouse sleep and wake states were studied for a linear classifier and a Neural Network classifier based on 23 features extracted from the Power Spectrum (PS), Generalized Spectrum (GS), and Autocorrelation (AC) functions of short data intervals. The testing of the classifiers was done on two data sets collected from two mice, with each data set having around 5 hours of data. A scoring of the sleep and wake states was also done via human observation to aid in the training of the classifiers. The performances of these two classifiers were analyzed by looking at the misclassification error of a set of test features when run through a classifier trained by a set of training features. The best performing features were selected by first testing each of the 23 features individually in a linear classifier and ranking them according to their misclassification rate. A test was then done on the 10 best individually performing features where they were grouped in all possible combinations of 5 features to determine the feature combinations leading to the lowest error rates in a multi feature classifier. From this test 5 features were eventually chosen to do the classification. It was found that the features related to the signal energy and the spectral peaks in the 3Hz range gave the lowest errors. Error rates as low as 4% and 9% were achieved from a 5-feature linear classifier for the two data sets. The error rates from a 5-feature Neural Network classifier were found to be 6% and 12% respectively for these two data sets.

Optical fiber sensors have been intensively studied and successfully employed in various human social activities and daily living, such as industrial production, civil engineering, medicine, transportation, national defense and so on. According to different structures, optical sensors could be divided into various categories. This thesis focuses on studying different kinds of in-line fiber Mach-Zehnder interferometers, which have played an important role among the optical interferometric fiber sensors. The structure composition, fabrication process, physical principle and practical applications of two novel in-line fiber Mach-Zehnder interferometers are proposed and discussed in detail in this work. The tapered bend-insensitive fiber Mach-Zehnder interferometer (BIF-MZI) is firstly fabricated and used as a fiber vibrometer. The unique double-cladding structure of bend-insensitive fiber not only provides higher mechanical strength to the sensor, but also guarantees a more uniform transmission spectrum， since only a few inner-cladding modes are left interfering with the core mode. A high sensitivity and fast response intensity demodulation scheme is employed by monitoring the power fluctuation of the BIF-MZI at the operation wavelength. Both damped and continuous vibrations are detected using the proposed sensor. It is demonstrated that this sensor responses to an extremely wide range of frequencies from 1 Hz up to 500 kHz with high signal-to-noise ratios (SNRs). The discrimination of temperature and axial strain is realized based on the dispersion effects of high-order-mode fiber (HOMF) by forming a single mode fiber-high-order-mode fiber-single mode fiber (SMF-HOMF-SMF) structure based in-line Mach-Zehnder interferometer. Unlike some kinds of in-line MZIs such as tapered and core–offset structures whose cladding modes are excited with different types under changing temperature and strain circumstances, the HOMF is capable of supporting three stable core modes, which guarantees a reliable and repeatable measurements within a large temperature or strain range. A new method based on the fast Fourier transform (FFT) is employed to analyze the mode couplings and their chromatic dispersion and intermodal dispersion properties in HOMF. The strong dispersion effects lead to a multi-peak feature in the spatial frequency spectrum. It is found that peaks that denote the waveform periods at positions that are beyond the critical wavelength possess highly sensitive and distinct phase responses to external disturbances, which provides the possibility to realize the discrimination measurements with high sensitivities and smaller errors by selecting appropriate peaks. The phase demodulation scheme is applied to quantify the temperature and strain changes in terms of phase shifts. Appropriate peak selections according to the practical needs would provide an easy access for applications where more than two parameters are required to be discriminated.

This thesis presents a computational analysis of multi-element guard-heated sensors designed to overcome the most severe limitation of conventional thermal sensors for wall shear stress (WSS) measurement in turbulent flows –that of indirect heat conduction through the substrate. The objectives of this thesis are the study of guard-heated sensors {i} to quantify the reduction, over conventional single-element sensors, of substrate heat conduction losses and resultant errors over a range of applied shear and {ii} to examine a range of values of guard heater geometric parameters, in two common fluids, air and water and identify the best designs. Wall-turbulence, the turbulent flow in the vicinity of solid boundaries, has proved difficult to model accurately, due to the lack of accurate WSS measurements. Examples of areas of impact are drag force reduction on transport vehicles in land, sea, air, which today largely translate to reduced fossil fuel use and dependence; aerodynamic noise and control for flight and for wind energy conversion; atmospheric and oceanic transport studies for weather, climate and for pollutant transport; riverbank erosion. Constant-temperature anemometry with MEMS devices, flush-mounted hot-film thermal sensors, is non-intrusive, affords the best temporal resolution and is well-established. However, these hot-film probes suffer from unwanted heat transport to the fluid through the substrate, with errors and nonlinearity large enough to overwhelm quantitative utility of the data. Microfabrication techniques have enabled multi-element guard-heated prototypes to be fabricated. Our results show that errors in sensing-element signals, contributing to spectral distortion, are sensitive to sensor location within the guard heater. These errors can be reduced to below 1% of the signal with proper location of the sensor. Guard heating also reduces the large variation in spatial averaging due to substrate conduction. This makes them suitable for turbulent flows with a large range of fluctuations. / Graduate

The covalent modifications to the histone 2A, 2B, 3, and 4 N-terminal tails that affect gene expression have been deemed the “Histone Code.” Mis-regulation of these signalling pathways is of great interest as are important in human disease. A variety of peptides containing post-translationally modified histone 3 and 4 sequences were read using a supramolecular sensor array approach, where two or three sensors gave a unique response for each analyte when compared to others. These sequences were chosen to determine what type of modifications could be read (phosphorylation, acetylation, methylation) and if this type of array would be suitable for reading analytes on which antibodies—the leading technology—typically perform poorly. It was found that three sensors, which operate in neutral aqueous solution, were able to discriminate 16 different histone analytes. Additionally, it was shown that this array could report simultaneously on both concentration and the identities of histone analytes. / Graduate

This PhD thesis describes the design and development of a new resonator based tactile sensitive probe. This new sensor was proposed because of the increasing need for high-sensitivity, high-speed touch-sensitive probes in coordinate metrology due to the ever-growing demand for precision and reliability at sub-micron level accuracy. Extensive background research on the current development of touch trigger probes has shown that designs based on the resonator principle have potential for minimising lobing effects and the false triggering associated with most commercially available probes. Resonant based sensors have been investigated over many decades and used very successfully in a wide range of applications. However their commercial exploitation in the field of precision engineering has not been particularly successful. One reason for such slow progress is the complexity of the interaction between oscillatory probes and typical engineering surfaces in less than ideal environments. The main aim of this research was to design a high precision resonator based tactile sensitive probe and to investigate the causes of parametric changes on resonant touch sensors both before and during contact with a variety of engineering surfaces in order to achieve a better understanding of contact mechanisms. The four main objectives were: preliminary design and characterisation of a resonator based touch sensor; development of the mathematical model which predicts parametric changes on a resonant probe considering both near surface effects and mechanical contact; experimental verification of mathematical predictions; and an investigation into possible commercial exploitation of the new probe in precision applications. A novel resonator based tactile sensor that utilises the piezoelectric effect was designed and characterised. The design exploits the fact that when a stiff element (probe) oscillating near or at its resonance frequency comes into contact with the surface of another body (workpiece), the frequency of vibrational resonance of the probe changes depending on the properties of the workpiece. The phase-locked loop frequency detection technique was employed to track changes in frequency as well as in the phase of the resonant system. The initial characterisation of the touch sensor has shown a sensitivity to contact of less then 4 mN, a high triggering rate and good repeatability. The potential for application in measuring material properties was also demonstrated. As a result of the characterisation a comprehensive mathematical model was developed. This novel model was based on Hertzian contact mechanics, Rayleigh's approximate energy method and work carried out by Smith and Chetwynd on the analysis of elastic contact of a sphere on a flat. The model predicts that phase and frequency shift of a resonator based sensor can either increase or decrease depending on the dominant phenomena (added mass, stiffness and damping) in the contact region. Observation of dynamic characteristics at either side of the resonant frequency can be used to identify the predominant effect. In order to confirm the model experimentally, another prototype probe was developed. The new sensor was engaged in observations of contact mechanisms with engineering surfaces. The experimental results have showed favourable agreement with the developed mathematical model. This enabled a better understanding of contact phenomena uncovering possibilities for the application of resonant sensors in many other areas. The research has shown that the new probe has potential in contact measurements where it can be used for the quantitative assessment of the physical properties of different materials (modulus of elasticity, density and energy dissipation) and also in non-destructive hardness testing. It was shown that the device can be successfully used in coordinate metrology as a touch trigger probe and as a 3D vector probe. Finally, applications can also be found in surface topography as a surface characterisation instrument. It is intended that the research described in this thesis will make an important contribution in the area of resonator based probes, providing a better understanding of the causes of parametric changes on the oscillatory sensor during contact with the object being measured. Consequently, this will enable a more effective exploitation of resonant probes for a broad range of precision applications.

Engineering particles at the nanoscale demands a high degree of control over process parameters during synthesis. For nanocrystal synthesis, solution-based techniques typically include application of external convective heat. This process often leads to slow heating and allows decomposition of reagents or products over time. Microwave-assisted heating provides faster, localized heating at the molecular level with near instantaneous control over reaction parameters. In this work, microwave-assisted heating has been applied for the synthesis of II-VI semiconductor nanocrystals namely, ZnO nanopods and CdX (X = Se, Te) quantum dots (QDs). Based on factors such as size, surface functionality and charge, optical properties of such nanomaterials can be tuned for application as sensors. ZnO is a direct bandgap semiconductor (3.37 eV) with a large exciton binding energy (60 meV) leading to photoluminescence (PL) at room temperature. A microwave-assisted hydrothermal approach allows the use of sub-5 nm ZnO zero-dimensional nanoparticles as seeds for generation of multi-legged quasi one-dimensional nanopods via heterogeneous nucleation. ZnO nanopods, having individual leg diameters of 13-15 nm and growing along the [0001] direction, can be synthesized in as little as 20 minutes. ZnO nanopods exhibit a broad defect-related PL spanning the visible range with a peak at ~615 nm. Optical sensing based on changes in intensity of the defect PL in response to external environment (e.g., humidity) is demonstrated in this work. Microwave-assisted synthesis was also used for organometallic synthesis of CdX(ZnS) (X = Se, Te) core(shell) QDs. Optical emission of these QDs can be altered ased on their size and can be tailored to specific wavelengths. Further, QDs were incorporated in Enhanced Green-Fluorescent Protein – Ultrabithorax (EGFP-Ubx) fusion protein for the generation of macroscale composite protein fibers via hierarchal self-assembly. Variations in EGFP- Ubx·QD composite fiber surface morphology and internal QD distribution were studied with respect to (i) time of QD addition (i.e., pre or post protein self-assembly) and (ii) QD surface charge — negatively charged QDs with dihydrolipoic acid functionalization and positively charged QDs with polyethyleneimine coating. Elucidating design motifs and understanding factors that impact the protein-nanoparticle interaction enables manipulation of the structure and mechanical properties of composite materials.

Optical biosensors are desired for the monitoring of various biochemical markers, which are relevant indicators in the treatment and diagnosis of diseases. Specifically, luminescence sensors are favorable for optical interrogation since they are highly sensitive to analyte changes and may be implemented in lifetime or intensity-based systems. In order to develop particle-based fluorescent sensors, poly(2-hydroxyethylmethacrylate) (HEMA) microspheres have been fabricated via membrane emulsification and characterized to evaluate the emulsion method and the overall process of tailoring properties to synthesize spheres of specific mean sizes. A pH-sensitive indicator seminaphthorhodafluors-4F 5-(and-6)-carboxylic acid (SNARF) was immobilized within the microspheres, and resulting sensor particles were exposed to various pH buffers to obtain a pH calibration curve based on intensity measurements. PolyHEMA microparticles were fabricated in a systematic study with measured mean sizes ranging from 8-21 um. Optical and scanning electron microscopy images revealed the formation of spherical, porous particles, which were additionally stabilized with polymer coatings. The lowest coefficient of variation value achieved was 50%, indicating the inability to produce monodisperse particles due to the dispersity of pore sizes in the membrane. SNARF was immobilized within the polyHEMA spheres, and fluorescence was observed when exposing the sensors to different pH buffers on a fluorescence microscope. Ratiometric intensity measurements for the sensor particles were obtained on a spectrofluorometer while flowing pH buffers over the immobilized spheres in a reaction chamber. The peak intensity ratio of the microparticle sensors exhibited a change in 0.9 units when decreasing the pH from 8.4 to 5.5. In the future, these pH sensing particles may be implanted alongside glucose sensing materials in order to provide valuable pH information in understanding the immune response to specific biomaterials and sensing components.

ZnO nanowires (NWs) are good candidates for chemical sensing because of their high surface-to-volume ratio. In this work, ZnO nanobridge sensors were fabricated utilizing a novel method which uses carbonized photoresist (C-PR) as a nucleation layer. The use of C-PR allows simultaneous growth and integration of NWs to lithographically-defined features. The nanobridge sensors are shown to be sensitive to the presence of O₂, H₂O, CO, and H₂/N₂ gas. However, since ZnO dissolves in water, a protective layer is necessary for these sensors to be used in the liquid or vapor phase. A chemical vapor deposition (CVD) process for amino-[2,2]paracyclophane (parylene-A) was developed and used to successfully protect the NWs. Gas sensing measurements were performed on bare and parylene-A coated devices with and without UV illumination. The parylene-A layer was found to attenuate sensitivity to O₂ and H₂O, and UV illumination was found to decrease the response time. / Graduation date: 2012