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Description
The past two decades have been monumental in the advancement of microchips designed for a diverse range of medical applications and bio-analysis. Owing to the remarkable progress in micro-fabrication technology, complex chemical and electro-mechanical features can now be integrated into chip-scale devices for use in biosensing and physiological measurements. Some

The past two decades have been monumental in the advancement of microchips designed for a diverse range of medical applications and bio-analysis. Owing to the remarkable progress in micro-fabrication technology, complex chemical and electro-mechanical features can now be integrated into chip-scale devices for use in biosensing and physiological measurements. Some of these devices have made enormous contributions in the study of complex biochemical processes occurring at the molecular and cellular levels while others overcame the challenges of replicating various functions of human organs as implant systems. This thesis presents test data and analysis of two such systems. First, an ISFET based pH sensor is characterized for its performance in a continuous pH monitoring application. Many of the basic properties of ISFETs including I-V characteristics, pH sensitivity and more importantly, its long term drift behavior have been investigated. A new theory based on frequent switching of electric field across the gate oxide to decrease the rate of current drift has been successfully implemented with the help of an automated data acquisition and switching system. The system was further tested for a range of duty cycles in order to accurately determine the minimum length of time required to fully reset the drift. Second, a microfluidic based vestibular implant system was tested for its underlying characteristics as a light sensor. A computer controlled tilt platform was then implemented to further test its sensitivity to inclinations and thus it‟s more important role as a tilt sensor. The sensor operates through means of optoelectronics and relies on the signals generated from photodiode arrays as a result of light being incident on them. ISFET results show a significant drop in the overall drift and good linear characteristics. The drift was seen to reset at less than an hour. The photodiodes show ideal I-V comparison between photoconductive and photovoltaic modes of operation with maximum responsivity at 400nm and a shunt resistance of 394 MΩ. Additionally, post-processing of the tilt sensor to incorporate the sensing fluids is outlined. Based on several test and fabrication results, a possible method of sealing the open cavity of the chip using a UV curable epoxy has been discussed.
ContributorsMamun, Samiha (Author) / Christen, Jennifer Blain (Thesis advisor) / Goryll, Michael (Committee member) / Yu, Hongyu (Committee member) / Arizona State University (Publisher)
Created2011
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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

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
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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

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
This research investigated using impedance as a minimally invasive oral cancer-screening tool by modeling healthy and diseased tissue. This research developed an ultra-structurally based tissue model for oral mucosa that is versatile enough to be easily modified to mimic the passive electrical impedance responses of multiple benign and cancerous tissue

This research investigated using impedance as a minimally invasive oral cancer-screening tool by modeling healthy and diseased tissue. This research developed an ultra-structurally based tissue model for oral mucosa that is versatile enough to be easily modified to mimic the passive electrical impedance responses of multiple benign and cancerous tissue types. This new model provides answers to biologically meaningful questions related to the impedance response of healthy and diseased tissues. This model breaks away from the old empirical top down "black box" Thèvinin equivalent model. The new tissue model developed here was created from a bottom up perspective resulting in a model that is analogous to having a "Transparent Box" where each network element relating to a specific structural component is known. This new model was developed starting with sub cellular ultra-structural components such as membranes, proteins and electrolytes. These components formed the basic network elements and topology of the organelles. The organelle networks combine to form the cell networks. The cell networks combine to make networks of cell layers and the cell layers were combined into tissue networks. This produced the complete "Transparent Box" model for normal tissue. This normal tissue model was modified for disease based on the ultra-structural pathology of each disease. The diseased tissues evaluated include cancers type one through type three; necrotic-inflammation, hyperkeratosis and the compound condition of hyperkeratosis over cancer type two. The impedance responses for each of the disease were compared side by side with the response of normal healthy tissue. Comparative evidence from the models showed the structural changes in cancer produce a unique identifiable impedance "finger print." The evaluation of the "Transparent Box" model for normal tissues and diseased tissues show clear support for using comparative impedance measurements as a clinical tool for oral cancer screening.
ContributorsPelletier, Peter Robert (Author) / Kozicki, Michael (Thesis advisor) / Towe, Bruce (Committee member) / Saraniti, Marco (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Electronic devices are gaining an increasing market share in the medical field. Medical devices are becoming more sophisticated, and encompassing more applications. Unlike consumer electronics, medical devices have far more limitations when it comes to area, power and most importantly reliability. The medical devices industry has recently seen the advantages

Electronic devices are gaining an increasing market share in the medical field. Medical devices are becoming more sophisticated, and encompassing more applications. Unlike consumer electronics, medical devices have far more limitations when it comes to area, power and most importantly reliability. The medical devices industry has recently seen the advantages of using Flash memory instead of Read Only Memory (ROM) for firmware storage, and in some cases to replace Electrically Programmable Read Only Memories (EEPROMs) in medical devices for frequent data storage. There are direct advantages to using Flash memory instead of Read Only Memory, most importantly the fact that firmware can be rewritten along the development cycle and in the field. However, Flash technology requires high voltage circuitry that makes it harder to integrate into low power devices. There have been a lot of advances in Non-Volatile Memory (NVM) technologies, and many Flash rivals are starting to gain attention. The purpose of this thesis is to evaluate these new technologies against Flash to determine the feasibility as well as the advantages of each technology. The focus is on embedded memory in a medical device micro-controller and application specific integrated circuits (ASIC). A behavioral model of a Programmable Metallization Cell (PMC) was used to simulate the behavior and determine the advantages of using PMC technology versus flash. When compared to flash test data, PMC based embedded memory showed a reduction in power consumption by many orders of magnitude. Analysis showed that an approximated 20% device longevity increase can be achieved by using embedded PMC technology.
ContributorsHag, Eslam E (Author) / Kozicki, Michael N (Thesis advisor) / Schroder, Dieter K. (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2010
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Description
Interdigitated back contact (IBC) solar cells have achieved the highest single junction silicon wafer-based solar cell power conversion efficiencies reported to date. This thesis is about the fabrication of a high-efficiency silicon heterojunction IBC solar cell for potential use as the bottom cell for a 3-terminal lattice-matched dilute-nitride Ga (In)NP(As)/Si

Interdigitated back contact (IBC) solar cells have achieved the highest single junction silicon wafer-based solar cell power conversion efficiencies reported to date. This thesis is about the fabrication of a high-efficiency silicon heterojunction IBC solar cell for potential use as the bottom cell for a 3-terminal lattice-matched dilute-nitride Ga (In)NP(As)/Si monolithic tandem solar cell. An effective fabrication process has been developed and the process challenges related to open circuit voltage (Voc), series resistance (Rs), and fill factor (FF) are experimentally analyzed. While wet etching, the sample lost the initial passivation, and by changing the etchant solution and passivation process, the voltage at maximum power recovered to an initial value of over 710 mV before metallization. The factors reducing the series resistance loss in IBC cells were also studied. One of these factors was the Indium Tin Oxide (ITO) sputtering parameters, which impact the conductivity of the ITO layer and transport across the a-Si:H/ITO interface. For the standard recipe, the chamber pressure was 3.5 mTorr with no oxygen partial pressure, and the thickness of the ITO layer in contact with the a-Si:H layers, was optimized to 150 nm. The patterning method for the metal contacts and final annealing also change the contact resistance of the base and emitter stack layers. The final annealing step is necessary to recover the sputtering damage; however, the higher the annealing time the higher the final IBC series resistance. The best efficiency achieved was 19.3% (Jsc = 37 mA/cm2, Voc = 691 mV, FF = 71.7%) on 200 µm thick 1-15 Ω-cm n-type CZ C-Si with a designated area of 4 cm2.
ContributorsMoeini Rizi, Mansoure (Author) / Goodnick, Stephen (Thesis advisor) / Honsberg, Christina (Committee member) / Goryll, Michael (Committee member) / Smith, David (Committee member) / Bowden, Stuart (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Portable health diagnostic systems seek to perform medical grade diagnostics in non-ideal environments. This work details a robust fault tolerant portable health diagnostic design implemented in hardware, firmware and software for the detectionof HPV in low-income countries. The device under device under test (DUT) is a fluorescence based lateral flow

Portable health diagnostic systems seek to perform medical grade diagnostics in non-ideal environments. This work details a robust fault tolerant portable health diagnostic design implemented in hardware, firmware and software for the detectionof HPV in low-income countries. The device under device under test (DUT) is a fluorescence based lateral flow assay (LFA) point-of-care (POC) device. This work’s contributions are: firmware and software development, calibration routine implementation, device performance characterization and a proposed method of in-software fault detection. Firmware was refactored from the original implementation of the POC fluorescence reader to expose an application programming interface (API) via USB. Companion software available for desktop environments (Windows, Mac and Linux) was created to interface with this firmware API and conduct macro level routines to request and receive fluorescence data while presenting a user-friendly interface to clinical technicians. Lastly, an environmental chamber was constructed to conduct sequential diagnostic reads in order to observe sensor drift and other deviations that might present themselves in real-world usage. The results from these evaluations show a standard deviation of less than 1% in fluorescence readings in nominal temperature environments (approx. 25C) suggesting that this system will have a favorable signal-to-noise (SNR) ratio in such a setting. In non-ideal over heated environments (≥38C), the evaluation results showed performance degradation with standard deviations as large as 15%.
ContributorsLue Sang, Christopher David (Author) / Blain Christen, Jennifer M (Thesis advisor) / Ozev, Sule (Committee member) / Goryll, Michael (Committee member) / Raupp, Gregory (Committee member) / Arizona State University (Publisher)
Created2022
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Description
The development of biosensing platforms not only has an immediate lifesaving effect but also has a significant socio-economic impact. In this dissertation, three very important biomarkers with immense importance were chosen for further investigation, reducing the technological gap and improving their sensing platform.Firstly, gold nanoparticles (AuNP) aggregation and sedimentation-based assays

The development of biosensing platforms not only has an immediate lifesaving effect but also has a significant socio-economic impact. In this dissertation, three very important biomarkers with immense importance were chosen for further investigation, reducing the technological gap and improving their sensing platform.Firstly, gold nanoparticles (AuNP) aggregation and sedimentation-based assays were developed for the sensitive, specific, and rapid detection of Ebola virus secreted glycoprotein (sGP)and severe acute respiratory syndrome coronavirus 2 (SARS-COV2) receptor-binding domain (RBD) antigens. An extensive study was done to develop a complete assay workflow from critical nanobody generation to optimization of AuNP size for rapid detection. A rapid portable electronic reader costing (<$5, <100 cm3), and digital data output was developed. Together with the developed workflow, this portable electronic reader showed a high sensitivity (limit of detection of ~10 pg/mL, or 0.13 pM for sGP and ~40 pg/mL, or ~1.3 pM for RBD in diluted human serum), a high specificity, a large dynamic range (~7 logs), and accelerated readout within minutes. Secondly, A general framework was established for small molecule detection using plasmonic metal nanoparticles through wide-ranging investigation and optimization of assay parameters with demonstrated detection of Cannabidiol (CBD). An unfiltered assay suitable for personalized dosage monitoring was developed and demonstrated. A portable electronic reader demonstrated optoelectronic detection of CBD with a limit of detection (LOD) of <100 pM in urine and saliva, a large dynamic range (5 logs), and a high specificity that differentiates closely related Tetrahydrocannabinol (THC). Finally, with careful biomolecular design and expansion of the portable reader to a dual-wavelength detector the classification of antibodies based on their affinity to SARS-COV2 RBD and their ability to neutralize the RBD from binding to the human Angiotensin-Converting Enzyme 2 (ACE2) was demonstrated with the capability to detect antibody concentration as low as 1 pM and observed neutralization starting as low as 10 pM with different viral load and variant. This portable, low-cost, and versatile readout system holds great promise for rapid, digital, and portable data collection in the field of biosensing.
ContributorsIkbal, Md Ashif (Author) / Wang, Chao (Thesis advisor) / Goryll, Michael (Committee member) / Zhao, Yuji (Committee member) / Wang, Shaopeng (Committee member) / Arizona State University (Publisher)
Created2022
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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

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
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Description
This work describes efforts made toward the development of a compact, quantitative fluorescence-based multiplexed detection platform for point-of-care diagnostics. This includes the development of a microfluidic delivery and actuation system for multistep detection assays. Early detection of infectious diseases requires high sensitivity dependent on the precise actuation of fluids.

Methods

This work describes efforts made toward the development of a compact, quantitative fluorescence-based multiplexed detection platform for point-of-care diagnostics. This includes the development of a microfluidic delivery and actuation system for multistep detection assays. Early detection of infectious diseases requires high sensitivity dependent on the precise actuation of fluids.

Methods of fluid actuation were explored to allow delayed delivery of fluidic reagents in multistep detection lateral flow assays (LFAs). Certain hydrophobic materials such as wax were successfully implemented in the LFA with the use of precision dispensed valves. Sublimating materials such as naphthalene were also characterized along with the implementation of a heating system for precision printing of the valves.

Various techniques of blood fractionation were also investigated and this work demonstrates successful blood fractionation in an LFA. The fluid flow of reagents was also characterized and validated with the use of mathematical models and multiphysics modeling software. Lastly intuitive, user-friendly mobile and desktop applications were developed to interface the underlying Arduino software. The work advances the development of a system which successfully integrates all components of fluid separation and delivery along with highly sensitive detection and a user-friendly interface; the system will ultimately provide clinically significant diagnostics in a of point-of-care device.
ContributorsArafa, Hany M (Author) / Blain Christen, Jennifer M (Thesis advisor) / Goryll, Michael (Committee member) / Smith, Barbara (Committee member) / Arizona State University (Publisher)
Created2018