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- Genre: Academic theses
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Description
Continuous monitoring in the adequate temporal and spatial scale is necessary for a better understanding of environmental variations. But field deployments of molecular biological analysis platforms in that scale are currently hindered because of issues with power, throughput and automation. Currently, such analysis is performed by the collection of large sample volumes from over a wide area and transporting them to laboratory testing facilities, which fail to provide any real-time information. This dissertation evaluates the systems currently utilized for in-situ field analyses and the issues hampering the successful deployment of such bioanalytial instruments for environmental applications. The design and development of high throughput, low power, and autonomous Polymerase Chain Reaction (PCR) instruments, amenable for portable field operations capable of providing quantitative results is presented here as part of this dissertation. A number of novel innovations have been reported here as part of this work in microfluidic design, PCR thermocycler design, optical design and systems integration. Emulsion microfluidics in conjunction with fluorinated oils and Teflon tubing have been used for the fluidic module that reduces cross-contamination eliminating the need for disposable components or constant cleaning. A cylindrical heater has been designed with the tubing wrapped around fixed temperature zones enabling continuous operation. Fluorescence excitation and detection have been achieved by using a light emitting diode (LED) as the excitation source and a photomultiplier tube (PMT) as the detector. Real-time quantitative PCR results were obtained by using multi-channel fluorescence excitation and detection using LED, optical fibers and a 64-channel multi-anode PMT for measuring continuous real-time fluorescence. The instrument was evaluated by comparing the results obtained with those obtained from a commercial instrument and found to be comparable. To further improve the design and enhance its field portability, this dissertation also presents a framework for the instrumentation necessary for a portable digital PCR platform to achieve higher throughputs with lower power. Both systems were designed such that it can easily couple with any upstream platform capable of providing nucleic acid for analysis using standard fluidic connections. Consequently, these instruments can be used not only in environmental applications, but portable diagnostics applications as well.
ContributorsRay, Tathagata (Author) / Youngbull, Cody (Thesis advisor) / Goryll, Michael (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Yu, Hongyu (Committee member) / Arizona State University (Publisher)
Created2013
Description
Over the past fifty years, the development of sensors for biological applications has increased dramatically. This rapid growth can be attributed in part to the reduction in feature size, which the electronics industry has pioneered over the same period. The decrease in feature size has led to the production of microscale sensors that are used for sensing applications, ranging from whole-body monitoring down to molecular sensing. Unfortunately, sensors are often developed without regard to how they will be integrated into biological systems. The complexities of integration are underappreciated. Integration involves more than simply making electrical connections. Interfacing microscale sensors with biological environments requires numerous considerations with respect to the creation of compatible packaging, the management of biological reagents, and the act of combining technologies with different dimensions and material properties. Recent advances in microfluidics, especially the proliferation of soft lithography manufacturing methods, have established the groundwork for creating systems that may solve many of the problems inherent to sensor-fluidic interaction. The adaptation of microelectronics manufacturing methods, such as Complementary Metal-Oxide-Semiconductor (CMOS) and Microelectromechanical Systems (MEMS) processes, allows the creation of a complete biological sensing system with integrated sensors and readout circuits. Combining these technologies is an obstacle to forming complete sensor systems. This dissertation presents new approaches for the design, fabrication, and integration of microscale sensors and microelectronics with microfluidics. The work addresses specific challenges, such as combining commercial manufacturing processes into biological systems and developing microscale sensors in these processes. This work is exemplified through a feedback-controlled microfluidic pH system to demonstrate the integration capabilities of microscale sensors for autonomous microenvironment control.
ContributorsWelch, David (Author) / Blain Christen, Jennifer (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Frakes, David (Committee member) / LaBelle, Jeffrey (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2012
Description
The design and development of analog/mixed-signal (AMS) integrated circuits (ICs) is becoming increasingly expensive, complex, and lengthy. Rapid prototyping and emulation of analog ICs will be significant in the design and testing of complex analog systems. A new approach, Programmable ANalog Device Array (PANDA) that maps any AMS design problem to a transistor-level programmable hardware, is proposed. This approach enables fast system level validation and a reduction in post-Silicon bugs, minimizing design risk and cost. The unique features of the approach include 1) transistor-level programmability that emulates each transistor behavior in an analog design, achieving very fine granularity of reconfiguration; 2) programmable switches that are treated as a design component during analog transistor emulating, and optimized with the reconfiguration matrix; 3) compensation of AC performance degradation through boosting the bias current. Based on these principles, a digitally controlled PANDA platform is designed at 45nm node that can map AMS modules across 22nm to 90nm technology nodes. A systematic emulation approach to map any analog transistor to PANDA cell is proposed, which achieves transistor level matching accuracy of less than 5% for ID and less than 10% for Rout and Gm. Circuit level analog metrics of a voltage-controlled oscillator (VCO) emulated by PANDA, match to those of the original designs in 90nm nodes with less than a 5% error. Voltage-controlled delay lines at 65nm and 90nm are emulated by 32nm PANDA, which successfully match important analog metrics. And at-speed emulation is achieved as well. Several other 90nm analog blocks are successfully emulated by the 45nm PANDA platform, including a folded-cascode operational amplifier and a sample-and-hold module (S/H)
ContributorsXu, Cheng (Author) / Cao, Yu (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Bakkaloglu, Bertan (Committee member) / Arizona State University (Publisher)
Created2012
Description
In this thesis two methodologies have been proposed for evaluating the fault response of analog/RF circuits. These proposed approaches are used to evaluate the response of the faulty circuit in terms of specifications/measurements. Faulty response can be used to evaluate important test metrics like fail probability, fault coverage and yield coverage of given measurements under process variations. Once the models for faulty and fault free circuit are generated, one needs to perform Monte Carlo sampling (as opposed to Monte Carlo simulations) to compute these statistical parameters with high accuracy. The first method is based on adaptively determining the order of the model based on the error budget in terms of computing the statistical metrics and position of the threshold(s) to decide how precisely necessary models need to be extracted. In the second method, using hierarchy in process variations a hybrid of heuristics and localized linear models have been proposed. Experiments on LNA and Mixer using the adaptive model order selection procedure can reduce the number of necessary simulations by 7.54x and 7.03x respectively in the computation of fail probability for an error budget of 2%. Experiments on LNA using the hybrid approach can reduce the number of necessary simulations by 21.9x and 17x for four and six output parameters cases for improved accuracy in test statistics estimation.
ContributorsSubrahmaniyan Radhakrishnan, Gurusubrahmaniyan (Author) / Ozev, Sule (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Cao, Yu (Committee member) / Arizona State University (Publisher)
Created2010
Description
For two centuries, electrical stimulation has been the conventional method for interfacing with the nervous system. As interfaces with the peripheral nervous system become more refined and higher-resolution, several challenges appear, including immune responses to invasive electrode application, large-to-small axon recruitment order, and electrode size-dependent spatial selectivity. Optogenetics offers a solution that is less invasive, more tissue-selective, and has small-to-large axon recruitment order. By adding genes to express photosensitive proteins optogenetics provides neuroscientists the ability to genetically select cell populations to stimulate with simple illumination. However, optogenetic stimulation of peripheral nerves uses diffuse light to activate the photosensitive neural cell lines. To increase the specificity of stimulus response, research was conducted to test the hypothesis that multiple, focused light emissions placed around the circumference of optogenetic mouse sciatic nerve could be driven to produce differential responses in hindlimb motor movement depending on the pattern of light presented. A Monte Carlo computer simulation was created to model the number of emitters, the light emission size, and the focal power of accompanying micro-lenses to provide targeted stimulation to select regions within the sciatic nerve. The computer simulation results were used to parameterize the design of micro-lenses. By modeling multiple focused beams, only fascicles within a nerve diameter less than 1 mm are expected to be fully accessible to focused optical stimulation; a minimum of 4 light sources is required to generate a photon intensity at a point in a nerve over the initial contact along its surface. To elicit the same effect in larger nerves, focusing lenses would require a numerical aperture > 1. Microlenses which met the simulation requirements were fabricated and deployed on a flexible nerve cuff which was used to stimulate the sciatic nerve in optogenetic mice. Motor neuron responses from this stimulation were compared to global illumination; stimulation using the optical cuff resulted in fine motor movement of the extensor muscles of the digits in the hindlimb. Increasing optical power resulted in a shift to gross motor movement of hindlimb. Finally, varying illumination intensity across the cuff showed changes in the extension of individual digits.
ContributorsFritz, Nicholas (Author) / Blain Christen, Jennifer (Thesis advisor) / Abbas, James (Committee member) / Goryll, Michael (Committee member) / Sadleir, Rosalind (Committee member) / Helms-Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2021
Description
This work focuses on qualifying the performance of an optoelectrical measurement system designed to analyze ribonucleic acid (RNA) within a micro sample. The system is capable of measuring light intensity converted to voltage versus time and is a fast, inexpensive, and portable method for rapid detection of biologics such as SARS-CoV-2 virus, or Covid-19 disease. The measurement system consists of a microfluidic chip and a point of care fluorescent reader.The intent of this research is to measure consistency and robustness of the fluorescent reader combined with the microfluidic chip. The consistency and the robustness of the fluorescent reader within the duty cycle of the system power and the measurement system were analyzed with Six Sigma methods. Control charts, analysis of variance (ANOVAs), and variance components calculations were implemented to characterize the reader system. Through the process of this analysis, baseline characteristics were measured and documented providing valuable data for the improved instrument design.
The existing microfluidic chip is a prototype that works in combination with the reader based on fluorescent detection. Baseline studies were required to define any issues related to microfluidic autofluorescence. Multiple designs were tested to measure reduction in autofluorescence in the microfluidics. It was found that certain designs performed better than others. One approach for improvement in the microfluidic chip may be achieved by characterizing and source controlling materials, optimizing layers, mask apertures, and mask orientations to determine reliability in the measurable output through the fluorescent reader. Since the reader and the microfluidic are designed to work together, any future studies should explore testing where the two components are considered a coupled system.
ContributorsShabtai, Bat-El (Author) / Blain Christen, Jennifer (Thesis advisor) / Abbas, James (Thesis advisor) / Maass, Eric (Committee member) / Beeman, Scott (Committee member) / Arizona State University (Publisher)
Created2021
Description
Human papillomavirus (HPV) infection has a large burden on society. It is a causal agent of 99.7% of all cervical cancer cases. The prevalence of HPV infection worldwide is high, but the burden of HPV infections lies on less developed regions. Cervical cancer is not associated with immediate symptoms, screening methods are needed to detect HPV disease presence before lesions progress to cervical cancer. Protein biomarkers are a growing area of diagnostic medicine and facilitate the detection of disease at an early and treatable stage. Technologies for healthcare diagnostics often require laboratory space or expensive instrumentation, which are not feasible for point of care applications. In order for clinical diagnostics to advance in developing countries, low cost, rapid, portable, and easy to use point of care diagnostic tests are needed. The project adapts the Enzyme Linked Immunosorbent Assays (ELISA) and Nucleic Acid-Programmable Protein Array (NAPPA) to a proof of concept assay for use in magnetic bead based microfluidics. The biomarker used for analyte detection was E7, as a strong correlation has been found between presence of E7 antibodies and development of advanced cervical cancer. It is demonstrated that magnetic microfluidic assay design for rapid detection of antibodies is amenable to fluorescence detection in point of care settings. The data demonstrates that the microfluidic assay is rapid, low-cost, specific, and relevant to serology detection. The assay detects antibody responses to analytes with the point of care reader system and is realized in an on chip capacity. With the integration of anti-GST capture antibodies conjugated to the magnetic beads in the microfluidic system, many analytes can be detected without large changes to the existing assay structure, which gives the ability to adapt the system to analytes of interest rapidly.
ContributorsSnow, Kylie (Author) / Anderson, Karen (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2022
Description
Nanoelectronics are electronic components that are often only a few nanometers in size. The field of nanoelectronics encompasses a wide range of products and materials that share the trait of being so small that physical forces can modify their characteristics on a nanoscale. These nanoscale devices are dominated by quantum processes including atomistic disorder and tunneling.In contrast to nanoelectronics, which involves the scaling down of devices to nanoscale levels, molecular electronics is concerned with electronic activities that take place within molecule structures. Detection of molecular conductance plays a vital role in the field of molecular electronics and nanotechnology. The ability to measure the conductive behavior of molecules is necessary to study their surface properties, defects, electronic structures, and for bio-sensing. To determine the conductance of the molecule, it is necessary to deduce the current passing through it. This is achieved by applying a voltage bias across the molecule and the detection instrument. Instruments like Scanning Tunneling Microscope (STM) and chip-based characterization (Probe Station) are used to fetch the amount of current flowing through the molecules. The current through molecules can be very small to measure and needs to be amplified. Linear amplifiers are widely used for amplifying these small currents, but due to their low dynamic range they are being replaced by logarithmic amplifiers. This thesis project aims to customize a logarithmic amplifier design to the interface with these instruments to measure the current flowing through these molecules.
This thesis starts with a review of a linear- current amplifier-based technology that is used for measuring small currents and its challenges. It then introduces logarithmic amplifier for overcoming those obstacles. This thesis involves design, fabrication, and characterization of the built logarithmic amplifier.
Furthermore, the setup includes a custom designed logarithmic amplifier that can be used with instruments like Scanning Tunneling Microscope (STM) and probe station. The key objective of the research is to accurately calibrate the logarithmic amplifier for measurement of currents over a wide range from picoamperes to milliamperes. Dummy resistors with different resistance values are used to replace the sample of which the conductance is to be measured, for testing and calibrating purposes. Bandwidth of the circuit is tested using these different values of resistors.
ContributorsYeole, Aishwarya Yogesh (Author) / Hihath, Josh (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2024
Description
Neurological disorders are the leading cause of physical and cognitive declineglobally and affect nearly 15% of the current worldwide population. These disorders
include, but are not limited to, epilepsy, Alzheimer’s disease, Parkinson’s disease,
and multiple sclerosis. With the aging population, an increase in the prevalence of
neurodegenerative disorders is expected. Electrophysiological monitoring of neural
signals has been the gold standard for clinicians in diagnosing and treating neurological
disorders. However, advances in detection and stimulation techniques have paved the
way for relevant information not seen by standard procedures to be captured and
used in patient treatment. Amongst these advances have been improved analysis of
higher frequency activity and the increased concentration of alternative biomarkers,
specifically pH change, during states of increased neural activity. The design and
fabrication of devices with the ability to reliably interface with the brain on multiple
scales and modalities has been a significant challenge.
This dissertation introduces a novel, concentric, multi-scale micro-ECoG array
for neural applications specifically designed for seizure detection in epileptic patients.
This work investigates simultaneous detection and recording of adjacent neural tissue
using electrodes of different sizes during neural events. Signal fidelity from electrodes
of different sizes during in vivo experimentation are explored and analyzed to highlight
the advantages and disadvantages of using varying electrode sizes. Furthermore, the
novel multi-scale array was modified to perform multi-analyte detection experiments
of pH change and electrophysiological activity on the cortical surface during epileptic
events. This device highlights the ability to accurately monitor relevant information
from multiple electrode sizes and concurrently monitor multiple biomarkers during
clinical periods in one procedure that typically requires multiple surgeries.
ContributorsAkamine, Ian (Author) / Blain Christen, Jennifer (Thesis advisor) / Abbas, Jimmy (Committee member) / Muthuswamy, Jitendran (Committee member) / Goryll, Michael (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2024
Description
The study of soft magnetic materials has been growing in popularity in recent years. Driving this interest are new applications for traditional electrical power-management components, such as inductors and transformers, which must be scaled down to the micro and nano scale while the frequencies of operation have been scaling up to the gigahertz range and beyond. The exceptional magnetic properties of the materials make them highly effective in these small-component applications, but the ability of these materials to provide highly-effective shielding has not been so thoroughly considered. Most shielding is done with traditional metals, such as aluminum, because of the relatively low cost of the material and high workability in shaping the material to meet size and dimensional requirements.
This research project focuses on analyzing the variance in shielding effectiveness and electromagnetic field effects of a thin film of Cobalt Zirconium Tantalum Boron (CZTB) in the band of frequencies most likely to require innovative solutions to long-standing problems of noise and interference. The measurements include Near H-Field attenuation and field effects, Far Field shielding, and Backscatter. Minor variances in the thickness and layering of sputter deposition can have significant changes electromagnetic signature of devices which radiate energy through the material.
The material properties presented in this research are H-Field attenuation, H-Field Flux Orientation, Far-Field Approximation, E Field Vector Directivity, H Field Vector Directivity, and Backscatter Magnitude. The results are presented, analyzed and explained using characterization techniques. Future work includes the effect of sputter deposition orientation, application to devices, and applicability in mitigating specific noise signals beyond the 5G band.
This research project focuses on analyzing the variance in shielding effectiveness and electromagnetic field effects of a thin film of Cobalt Zirconium Tantalum Boron (CZTB) in the band of frequencies most likely to require innovative solutions to long-standing problems of noise and interference. The measurements include Near H-Field attenuation and field effects, Far Field shielding, and Backscatter. Minor variances in the thickness and layering of sputter deposition can have significant changes electromagnetic signature of devices which radiate energy through the material.
The material properties presented in this research are H-Field attenuation, H-Field Flux Orientation, Far-Field Approximation, E Field Vector Directivity, H Field Vector Directivity, and Backscatter Magnitude. The results are presented, analyzed and explained using characterization techniques. Future work includes the effect of sputter deposition orientation, application to devices, and applicability in mitigating specific noise signals beyond the 5G band.
ContributorsMiller, Phillip Carl (Author) / Yu, Hongbin (Thesis advisor) / Aberle, James T., 1961- (Committee member) / Blain Christen, Jennifer (Committee member) / Arizona State University (Publisher)
Created2019