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Description
Over the past several decades, there has been a growing interest in the use of fluorescent probes in low-cost diagnostic devices for resource-limited environments. This dissertation details the design, development, and deployment of an inexpensive, multiplexed, and quantitative, fluorescence-based lateral flow immunoassay platform, in light of the specific constraints associated with resource-limited settings.
This effort grew out of the need to develop a highly sensitive, field-deployable platform to be used as a primary screening and early detection tool for serologic biomarkers for the high-risk human papillomavirus (hrHPV) infection. A hrHPV infection is a precursor for developing high-grade cervical intraepithelial neoplasia (CIN 2/3+). Early detection requires high sensitivity and a low limit-of-detection (LOD). To this end, the developed platform (DxArray) takes advantage of the specificity of immunoassays and the selectivity of fluorescence for early disease detection. The long term goal is to improve the quality of life for several hundred million women globally, at risk of being infected with hrHPV.
The developed platform uses fluorescent labels over the gold-standard colorimetric labels in a compact, high-sensitivity lateral flow assay configuration. It is also compatible with POC settings as it substitutes expensive and bulky light sources for LEDs, low-light CMOS cameras, and photomultiplier tubes for photodiodes, in a transillumination architecture, and eliminates the need for expensive focusing/transfer optics. The platform uses high-quality interference filters at less than $1 each, enabling a rugged and robust design suitable for field use.
The limit of detection (LOD) of the developed platform is within an order of magnitude of centralized laboratory diagnostic instruments. It enhances the LOD of absorbance or reflectometric and visual readout lateral flow assays by 2 - 3 orders of magnitude. This system could be applied toward any chemical or bioanalytical procedure that requires a high performance at low-cost.
The knowledge and techniques developed in this effort is relevant to the community of researchers and industry developers looking to deploy inexpensive, quantitative, and highly sensitive diagnostic devices to resource-limited settings.
This effort grew out of the need to develop a highly sensitive, field-deployable platform to be used as a primary screening and early detection tool for serologic biomarkers for the high-risk human papillomavirus (hrHPV) infection. A hrHPV infection is a precursor for developing high-grade cervical intraepithelial neoplasia (CIN 2/3+). Early detection requires high sensitivity and a low limit-of-detection (LOD). To this end, the developed platform (DxArray) takes advantage of the specificity of immunoassays and the selectivity of fluorescence for early disease detection. The long term goal is to improve the quality of life for several hundred million women globally, at risk of being infected with hrHPV.
The developed platform uses fluorescent labels over the gold-standard colorimetric labels in a compact, high-sensitivity lateral flow assay configuration. It is also compatible with POC settings as it substitutes expensive and bulky light sources for LEDs, low-light CMOS cameras, and photomultiplier tubes for photodiodes, in a transillumination architecture, and eliminates the need for expensive focusing/transfer optics. The platform uses high-quality interference filters at less than $1 each, enabling a rugged and robust design suitable for field use.
The limit of detection (LOD) of the developed platform is within an order of magnitude of centralized laboratory diagnostic instruments. It enhances the LOD of absorbance or reflectometric and visual readout lateral flow assays by 2 - 3 orders of magnitude. This system could be applied toward any chemical or bioanalytical procedure that requires a high performance at low-cost.
The knowledge and techniques developed in this effort is relevant to the community of researchers and industry developers looking to deploy inexpensive, quantitative, and highly sensitive diagnostic devices to resource-limited settings.
ContributorsObahiagbon, Uwadiae (Author) / Blain Christen, Jennifer M (Thesis advisor) / Anderson, Karen S (Committee member) / Goryll, Michael (Committee member) / Smith, Barbara S. (Committee member) / Arizona State University (Publisher)
Created2018
Description
Readout Integrated Circuits(ROICs) are important components of infrared(IR) imag
ing systems. Performance of ROICs affect the quality of images obtained from IR
imaging systems. Contemporary infrared imaging applications demand ROICs that
can support large dynamic range, high frame rate, high output data rate, at low
cost, size and power. Some of these applications are military surveillance, remote
sensing in space and earth science missions and medical diagnosis. This work focuses
on developing a ROIC unit cell prototype for National Aeronautics and Space Ad
ministration(NASA), Jet Propulsion Laboratory’s(JPL’s) space applications. These
space applications also demand high sensitivity, longer integration times(large well
capacity), wide operating temperature range, wide input current range and immunity
to radiation events such as Single Event Latchup(SEL).
This work proposes a digital ROIC(DROIC) unit cell prototype of 30ux30u size,
to be used mainly with NASA JPL’s High Operating Temperature Barrier Infrared
Detectors(HOT BIRDs). Current state of the art DROICs achieve a dynamic range
of 16 bits using advanced 65-90nm CMOS processes which adds a lot of cost overhead.
The DROIC pixel proposed in this work uses a low cost 180nm CMOS process and
supports a dynamic range of 20 bits operating at a low frame rate of 100 frames per
second(fps), and a dynamic range of 12 bits operating at a high frame rate of 5kfps.
The total electron well capacity of this DROIC pixel is 1.27 billion electrons, enabling
integration times as long as 10ms, to achieve better dynamic range. The DROIC unit
cell uses an in-pixel 12-bit coarse ADC and an external 8-bit DAC based fine ADC.
The proposed DROIC uses layout techniques that make it immune to radiation up to
300krad(Si) of total ionizing dose(TID) and single event latch-up(SEL). It also has a
wide input current range from 10pA to 1uA and supports detectors operating from
Short-wave infrared (SWIR) to longwave infrared (LWIR) regions.
ing systems. Performance of ROICs affect the quality of images obtained from IR
imaging systems. Contemporary infrared imaging applications demand ROICs that
can support large dynamic range, high frame rate, high output data rate, at low
cost, size and power. Some of these applications are military surveillance, remote
sensing in space and earth science missions and medical diagnosis. This work focuses
on developing a ROIC unit cell prototype for National Aeronautics and Space Ad
ministration(NASA), Jet Propulsion Laboratory’s(JPL’s) space applications. These
space applications also demand high sensitivity, longer integration times(large well
capacity), wide operating temperature range, wide input current range and immunity
to radiation events such as Single Event Latchup(SEL).
This work proposes a digital ROIC(DROIC) unit cell prototype of 30ux30u size,
to be used mainly with NASA JPL’s High Operating Temperature Barrier Infrared
Detectors(HOT BIRDs). Current state of the art DROICs achieve a dynamic range
of 16 bits using advanced 65-90nm CMOS processes which adds a lot of cost overhead.
The DROIC pixel proposed in this work uses a low cost 180nm CMOS process and
supports a dynamic range of 20 bits operating at a low frame rate of 100 frames per
second(fps), and a dynamic range of 12 bits operating at a high frame rate of 5kfps.
The total electron well capacity of this DROIC pixel is 1.27 billion electrons, enabling
integration times as long as 10ms, to achieve better dynamic range. The DROIC unit
cell uses an in-pixel 12-bit coarse ADC and an external 8-bit DAC based fine ADC.
The proposed DROIC uses layout techniques that make it immune to radiation up to
300krad(Si) of total ionizing dose(TID) and single event latch-up(SEL). It also has a
wide input current range from 10pA to 1uA and supports detectors operating from
Short-wave infrared (SWIR) to longwave infrared (LWIR) regions.
ContributorsPraveen, Subramanya Chilukuri (Author) / Bakkaloglu, Bertan (Thesis advisor) / Kitchen, Jennifer (Committee member) / Long, Yu (Committee member) / Arizona State University (Publisher)
Created2019
Description
Point of Load (POL) DC-DC converters are increasingly used in space applications, data centres, electric vehicles, portable computers and devices and medical electronics. Heavy computing and processing capabilities of the modern devices have ushered the use of higher battery supply voltage to increase power storage. The need to address this consumer experience driven requirement has propelled the evolution of the next generation of small form-factor power converters which can operate with higher step down ratios while supplying heavy continuous load currents without sacrificing efficiency. Constant On-Time (COT) converter topology is capable of achieving stable operation at high conversion ratio with minimum off-chip components and small silicon area. This work proposes a Constant On-Time buck dc-dc converter for a wide dynamic input range and load currents from 100mA to 10A. Accuracy of this ripple based converter is improved by a unique voltage positioning technique which modulates the reference voltage to lower the average ripple profile close to the nominal output. Adaptive On-time block features a transient enhancement scheme to assist in faster voltage droop recovery when the output voltage dips below a defined threshold. UtilizingGallium Nitride (GaN) power switches enable the proposed converter to achieve very high efficiency while using smaller size inductor-capacitor (LC) power-stage. Use of novel Superjunction devices with higher drain-source blocking voltage simplifies the complex driver design and enables faster frequency of operation. It allows 1.8VComplementary Metal-Oxide Semiconductor (CMOS) devices to effectively drive GaNpower FETs which require 5V gate signal swing. The presented controller circuit uses internal ripple generation which reduces reliance on output cap equivalent series resistance (ESR) for loop stability and facilitates ripples reduction at the output. The ripple generation network is designed to provide ai
optimally stable performance while maintaining load regulation and line regulation accuracy withing specified margin. The chip with ts external Power FET package is proposed to be integrated on a printed circuit board for testing. The designed power converter is expected to operate under 200 MRad of a total ionising dose of radiation enabling it to function within large hadron collider at CERN and space satellite and probe missions.
optimally stable performance while maintaining load regulation and line regulation accuracy withing specified margin. The chip with ts external Power FET package is proposed to be integrated on a printed circuit board for testing. The designed power converter is expected to operate under 200 MRad of a total ionising dose of radiation enabling it to function within large hadron collider at CERN and space satellite and probe missions.
ContributorsJoshi, Omkar (Author) / Bakkaloglu, Bertan (Thesis advisor) / Kitchen, Jennifer (Committee member) / Long, Yu (Committee member) / Arizona State University (Publisher)
Created2019
Description
This thesis describes the development, characterization, and application of new biomedical technologies developed around the photoacoustic effect. The photoacoustic effect is defined as optical absorption-based generation of ultrasound and provides the foundation for a unique method of imaging and molecular detection. The range of applications of the photoacoustic effect have not yet been fully explored. Photoacoustic endoscopy (PAE) has emerged as a minimally invasive tool for imaging internal organs and tissues. One of the main themes of this dissertation involves the first reported dual-intrauterine photoacoustic and ultrasound deep-tissue imaging endoscope. This device was designed to enable physicians at the point-of-care to better elucidate overall gynecological health, by imaging the lining of the human uterus. Intrauterine photoacoustic endoscopy is made possible due to the small diameter of the endoscope (3mm), which allows for complete, 360-degree organ analysis from within the uterine cavity. In certain biomedical applications, however, further minimization is necessary. Sufficiently small diameter endoscopes may allow for the possibility of applying PAE in new areas. To further miniaturize the diameter of our endoscopes, alternative imaging probe designs were investigated. The proposed PAE architecture utilizes a hollow optical waveguide to allow for concentric guiding of both light and sound. This enables imaging depths of up to several millimeters into animal tissue while maintaining an outer diameter of roughly 1mm. In the final focus of this dissertation, these waveguides are further investigated for use in micropipette electrodes, common in the field of single cell electrophysiology. Pulsed light is coupled with these electrodes providing real-time photoacoustic feedback, useful in navigation towards intended targets. Lastly, fluorescence can be generated and collected at the micropipette aperture by utilizing an intra-electrode tapered optical fiber. This allows for a targeted robotic approach to labeled neurons that is independent of microscopy.
ContributorsMiranda, Christopher (Author) / Smith, Barbara S. (Thesis advisor) / Kodibagkar, Vikram (Committee member) / LaBaer, Joshua (Committee member) / Frakes, David (Committee member) / Barkley, Joel (Committee member) / Arizona State University (Publisher)
Created2021