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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
Flow measurement has always been one of the most critical processes in many industrial and clinical applications. The dynamic behavior of flow helps to define the state of a process. An industrial example would be that in an aircraft, where the rate of airflow passing the aircraft is used to

Flow measurement has always been one of the most critical processes in many industrial and clinical applications. The dynamic behavior of flow helps to define the state of a process. An industrial example would be that in an aircraft, where the rate of airflow passing the aircraft is used to determine the speed of the plane. A clinical example would be that the flow of a patient's breath which could help determine the state of the patient's lungs. This project is focused on the flow-meter that are used for airflow measurement in human lungs. In order to do these measurements, resistive-type flow-meters are commonly used in respiratory measurement systems. This method consists of passing the respiratory flow through a fluid resistive component, while measuring the resulting pressure drop, which is linearly related to volumetric flow rate. These types of flow-meters typically have a low frequency response but are adequate for most applications, including spirometry and respiration monitoring. In the case of lung parameter estimation methods, such as the Quick Obstruction Method, it becomes important to have a higher frequency response in the flow-meter so that the high frequency components in the flow are measurable. The following three types of flow-meters were: a. Capillary type b. Screen Pneumotach type c. Square Edge orifice type To measure the frequency response, a sinusoidal flow is generated with a small speaker and passed through the flow-meter that is connected to a large, rigid container. True flow is proportional to the derivative of the pressure inside the container. True flow is then compared with the measured flow, which is proportional to the pressure drop across the flow-meter. In order to do the characterization, two LabVIEW data acquisition programs have been developed, one for transducer calibration, and another one that records flow and pressure data for frequency response testing of the flow-meter. In addition, a model that explains the behavior exhibited by the flow-meter has been proposed and simulated. This model contains a fluid resistor and inductor in series. The final step in this project was to approximate the frequency response data to the developed model expressed as a transfer function.
ContributorsHu, Jianchen (Author) / Macia, Narciso (Thesis advisor) / Pollat, Scott (Committee member) / Rogers, Bradley (Committee member) / Arizona State University (Publisher)
Created2013
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Description
The partially-depleted (PD) silicon Metal Semiconductor Field Effect Transistor (MESFET) is becoming more and more attractive for analog and RF applications due to its high breakdown voltage. Compared to conventional CMOS high voltage transistors, the silicon MESFET can be fabricated in commercial standard Silicon-on-Insulator (SOI) CMOS foundries without any change

The partially-depleted (PD) silicon Metal Semiconductor Field Effect Transistor (MESFET) is becoming more and more attractive for analog and RF applications due to its high breakdown voltage. Compared to conventional CMOS high voltage transistors, the silicon MESFET can be fabricated in commercial standard Silicon-on-Insulator (SOI) CMOS foundries without any change to the process. The transition frequency of the device is demonstrated to be 45GHz, which makes the MESFET suitable for applications in high power RF power amplifier designs. Also, high breakdown voltage and low turn-on resistance make it the ideal choice for switches in the switching regulator designs. One of the anticipated applications of the MESFET is for the pass device for a low dropout linear regulator. Conventional NMOS and PMOS linear regulators suffer from high dropout voltage, low bandwidth and poor stability issues. In contrast, the N-MESFET pass transistor can provide an ultra-low dropout voltage and high bandwidth without the need for an external compensation capacitor to ensure stability. In this thesis, the design theory and problems of the conventional linear regulators are discussed. N-MESFET low dropout regulators are evaluated and characterized. The error amplifier used a folded cascode architecture with gain boosting. The source follower topology is utilized as the buffer to sink the gate leakage current from the MESFET. A shunt-feedback transistor is added to reduce the output impedance and provide the current adaptively. Measurement results show that the dropout voltage is less than 150 mV for a 1A load current at 1.8V output. Radiation measurements were done for discrete MESFET and fully integrated LDO regulators, which demonstrate their radiation tolerance ability for aerospace applications.
ContributorsChen, Bo (Author) / Thornton, Trevor (Thesis advisor) / Bakkaloglu, Bertan (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2013
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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
The efficacy of deep brain stimulation (DBS) in Parkinson's disease (PD) has been convincingly demonstrated in studies that compare motor performance with and without stimulation, but characterization of performance at intermediate stimulation amplitudes has been limited. This study investigated the effects of changing DBS amplitude in order to assess dose-response

The efficacy of deep brain stimulation (DBS) in Parkinson's disease (PD) has been convincingly demonstrated in studies that compare motor performance with and without stimulation, but characterization of performance at intermediate stimulation amplitudes has been limited. This study investigated the effects of changing DBS amplitude in order to assess dose-response characteristics, inter-subject variability, consistency of effect across outcome measures, and day-to-day variability. Eight subjects with PD and bilateral DBS systems were evaluated at their clinically determined stimulation (CDS) and at three reduced amplitude conditions: approximately 70%, 30%, and 0% of the CDS (MOD, LOW, and OFF, respectively). Overall symptom severity and performance on a battery of motor tasks - gait, postural control, single-joint flexion-extension, postural tremor, and tapping - were assessed at each condition using the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and quantitative measures. Data were analyzed to determine whether subjects demonstrated a threshold response (one decrement in stimulation resulted in ≥ 70% of the maximum change) or a graded response to reduced stimulation. Day-to-day variability was assessed using the CDS data from the three testing sessions. Although the cohort as a whole demonstrated a graded response on several measures, there was high variability across subjects, with subsets exhibiting graded, threshold, or minimal responses. Some subjects experienced greater variability in their CDS performance across the three days than the change induced by reducing stimulation. For several tasks, a subset of subjects exhibited improved performance at one or more of the reduced conditions. Reducing stimulation did not affect all subjects equally, nor did it uniformly affect each subject's performance across tasks. These results indicate that altered recruitment of neural structures can differentially affect motor capabilities and demonstrate the need for clinical consideration of the effects on multiple symptoms across several days when selecting DBS parameters.
ContributorsConovaloff, Alison (Author) / Abbas, James (Thesis advisor) / Krishnamurthi, Narayanan (Committee member) / Mahant, Padma (Committee member) / Jung, Ranu (Committee member) / Helms Tillery, Stephen (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
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Description
Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the

Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the desired skill level. It would result in more reliable and adaptive neural interfaces that could record optimal neural activity 24/7 with high fidelity signals, high yield and increased throughput. The main contribution here is validating adaptive strategies to overcome challenges in autonomous navigation of microelectrodes inside the brain. The following issues pose significant challenges as brain tissue is both functionally and structurally dynamic: a) time varying mechanical properties of the brain tissue-microelectrode interface due to the hyperelastic, viscoelastic nature of brain tissue b) non-stationarities in the neural signal caused by mechanical and physiological events in the interface and c) the lack of visual feedback of microelectrode position in brain tissue. A closed loop control algorithm is proposed here for autonomous navigation of microelectrodes in brain tissue while optimizing the signal-to-noise ratio of multi-unit neural recordings. The algorithm incorporates a quantitative understanding of constitutive mechanical properties of soft viscoelastic tissue like the brain and is guided by models that predict stresses developed in brain tissue during movement of the microelectrode. An optimal movement strategy is developed that achieves precise positioning of microelectrodes in the brain by minimizing the stresses developed in the surrounding tissue during navigation and maximizing the speed of movement. Results of testing the closed-loop control paradigm in short-term rodent experiments validated that it was possible to achieve a consistently high quality SNR throughout the duration of the experiment. At the systems level, new generation of MEMS actuators for movable microelectrode array are characterized and the MEMS device operation parameters are optimized for improved performance and reliability. Further, recommendations for packaging to minimize the form factor of the implant; design of device mounting and implantation techniques of MEMS microelectrode array to enhance the longevity of the implant are also included in a top-down approach to achieve a reliable brain interface.
ContributorsAnand, Sindhu (Author) / Muthuswamy, Jitendran (Thesis advisor) / Tillery, Stephen H (Committee member) / Buneo, Christopher (Committee member) / Abbas, James (Committee member) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
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
Spinal cord injury (SCI) disrupts the communication between supraspinal circuits and spinal circuits distal to the injury. This disruption causes changes in the motor abilities of the affected individual, but it can also be used as an opportunity to study motor control in the absence or limited presence of control

Spinal cord injury (SCI) disrupts the communication between supraspinal circuits and spinal circuits distal to the injury. This disruption causes changes in the motor abilities of the affected individual, but it can also be used as an opportunity to study motor control in the absence or limited presence of control from the brain. In the case of incomplete paraplegia, locomotion is impaired and often results in increased incidence of foot drag and decreased postural stability after injury. The overall goal of this work is to understand how changes in kinematics of movement and neural control of muscles effect locomotor coordination following SCI. Toward this end, we examined musculoskeletal parameters and kinematics of gait in rats with and without incomplete SCI (iSCI) and used an empirically developed computational model to test related hypotheses. The first study tested the hypothesis that iSCI causes a decrease in locomotor and joint angle movement complexity. A rat model was used to measure musculoskeletal properties and gait kinematics following mild iSCI. The data indicated joint-specific changes in kinematics in the absence of measurable muscle atrophy, particularly at the ankle as a result of the injury. Kinematic changes manifested as a decrease in complexity of ankle motion as indicated by measures of permutation entropy. In the second study, a new 2-dimensional computational model of the rat ankle combining forward and inverse dynamics was developed using the previously collected data. This model was used to test the hypothesis that altered coordination of flexor and extensor muscles (specifically alteration in burst shape and timing) acting at the ankle joint could be responsible for increases in incidence of foot drag following injury. Simulation results suggest a time course for changes in neural control following injury that begins with foot drag and decreased delay between antagonistic muscle activations. Following this, beneficial adaptations in muscle activation profile and ankle kinematics counteract the decreased delay to allow foot swing. In both studies, small changes in neural control caused large changes in behavior, particularly at the ankle. Future work will further examine the role of neural control of hindlimb in rat locomotion following iSCI.
ContributorsHillen, Brian (Author) / Jung, Ranu (Thesis advisor) / Abbas, James (Committee member) / Muthuswamy, Jit (Committee member) / Jindrich, Devin (Committee member) / Yamaguchi, Gary (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