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Description
In this thesis, I present a lab-on-a-chip (LOC) that can separate and detect Escherichia Coli (E. coli) in simulated urine samples for Urinary Tract Infection (UTI) diagnosis. The LOC consists of two (concentration and sensing) chambers connected in series and an integrated impedance detector. The two-chamber approach is designed to

In this thesis, I present a lab-on-a-chip (LOC) that can separate and detect Escherichia Coli (E. coli) in simulated urine samples for Urinary Tract Infection (UTI) diagnosis. The LOC consists of two (concentration and sensing) chambers connected in series and an integrated impedance detector. The two-chamber approach is designed to reduce the non-specific absorption of proteins, e.g. albumin, that potentially co-exist with E. coli in urine. I directly separate E. coli K-12 from a urine cocktail in a concentration chamber containing micro-sized magnetic beads (5 µm in diameter) conjugated with anti-E. coli antibodies. The immobilized E. coli are transferred to a sensing chamber for the impedance measurement. The measurement at the concentration chamber suffers from non-specific absorption of albumin on the gold electrode, which may lead to a false positive response. By contrast, the measured impedance at the sensing chamber shows ~60 kÙ impedance change between 6.4x104 and 6.4x105 CFU/mL, covering the threshold of UTI (105 CFU/mL). The sensitivity of the LOC for detecting E. coli is characterized to be at least 3.4x104 CFU/mL. I also characterized the LOC for different age groups and white blood cell spiked samples. These preliminary data show promising potential for application in portable LOC devices for UTI detection.
ContributorsKim, Sangpyeong (Author) / Chae, Junseok (Thesis advisor) / Phillips, Stephen M. (Committee member) / Blain Christen, Jennifer M. (Committee member) / Arizona State University (Publisher)
Created2011
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Description
There is a tremendous need for wireless biological signals acquisition for the microelectrode-based neural interface to reduce the mechanical impacts introduced by wire-interconnects system. Long wire connections impede the ability to continuously record the neural signal for chronic application from the rodent's brain. Furthermore, connecting and/or disconnecting Omnetics interconnects often

There is a tremendous need for wireless biological signals acquisition for the microelectrode-based neural interface to reduce the mechanical impacts introduced by wire-interconnects system. Long wire connections impede the ability to continuously record the neural signal for chronic application from the rodent's brain. Furthermore, connecting and/or disconnecting Omnetics interconnects often introduces mechanical stress which causes blood vessel to rupture and leads to trauma to the brain tissue. Following the initial implantation trauma, glial tissue formation around the microelectrode and may possibly lead to the microelectrode signal degradation. The aim of this project is to design, develop, and test a compact and power efficient integrated system (IS) that is able to (a) wirelessly transmit triggering signal from the computer to the signal generator which supplies voltage waveforms that move the MEMS microelectrodes, (b) wirelessly transmit neural data from the brain to the external computer, and (c) provide an electrical interface for a closed loop control to continuously move the microelectrode till a proper quality of neural signal is achieved. One of the main challenges of this project is the limited data transmission rate of the commercially available wireless system to transmit 400 kbps of digitized neural signals/electrode, which include spikes, local field potential (LFP), and noise. A commercially available Bluetooth module is only capable to transmit at a total of 115 kbps data transfer rate. The approach to this challenge is to digitize the analog neural signal with a lower accuracy ADC to lower the data rate, so that is reasonable to wirelessly transfer neural data of one channel. In addition, due to the limited space and weight bearing capability to the rodent's head, a compact and power efficient integrated system is needed to reduce the packaged volume and power consumption. 3D SoP technology has been used to stack the PCBs in a 3D form-factor, proper routing designs and techniques are implemented to reduce the electrical routing resistances and the parasitic RC delay. It is expected that this 3D design will reduce the power consumption significantly in comparison to the 2D one. The progress of this project is divided into three different phases, which can be outlined as follow: a) Design, develop, and test Bluetooth wireless system to transmit the triggering signal from the computer to the signal generator. The system is designed for three moveable microelectrodes. b) Design, develop, and test Bluetooth wireless system to wirelessly transmit an amplified (200 gain) neural signal from one single electrode to an external computer. c) Design, develop, and test a closed loop control system that continuously moves a microelectrode in searching of an acceptable quality of neural spikes. The outcome of this project can be used not only for the need of neural application but also for a wider and general applications that requires customized signal generations and wireless data transmission.
ContributorsZhou, Li (Author) / Muthuswamy, Jitendran (Thesis advisor) / Sutanto, Jemmy (Thesis advisor) / Yu, Hongyu (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Detecting anatomical structures, such as the carina, the pulmonary trunk and the aortic arch, is an important step in designing a CAD system of detection Pulmonary Embolism. The presented CAD system gets rid of the high-level prior defined knowledge to become a system which can easily extend to detect other

Detecting anatomical structures, such as the carina, the pulmonary trunk and the aortic arch, is an important step in designing a CAD system of detection Pulmonary Embolism. The presented CAD system gets rid of the high-level prior defined knowledge to become a system which can easily extend to detect other anatomic structures. The system is based on a machine learning algorithm --- AdaBoost and a general feature --- Haar. This study emphasizes on off-line and on-line AdaBoost learning. And in on-line AdaBoost, the thesis further deals with extremely imbalanced condition. The thesis first reviews several knowledge-based detection methods, which are relied on human being's understanding of the relationship between anatomic structures. Then the thesis introduces a classic off-line AdaBoost learning. The thesis applies different cascading scheme, namely multi-exit cascading scheme. The comparison between the two methods will be provided and discussed. Both of the off-line AdaBoost methods have problems in memory usage and time consuming. Off-line AdaBoost methods need to store all the training samples and the dataset need to be set before training. The dataset cannot be enlarged dynamically. Different training dataset requires retraining the whole process. The retraining is very time consuming and even not realistic. To deal with the shortcomings of off-line learning, the study exploited on-line AdaBoost learning approach. The thesis proposed a novel pool based on-line method with Kalman filters and histogram to better represent the distribution of the samples' weight. Analysis of the performance, the stability and the computational complexity will be provided in the thesis. Furthermore, the original on-line AdaBoost performs badly in imbalanced conditions, which occur frequently in medical image processing. In image dataset, positive samples are limited and negative samples are countless. A novel Self-Adaptive Asymmetric On-line Boosting method is presented. The method utilized a new asymmetric loss criterion with self-adaptability according to the ratio of exposed positive and negative samples and it has an advanced rule to update sample's importance weight taking account of both classification result and sample's label. Compared to traditional on-line AdaBoost Learning method, the new method can achieve far more accuracy in imbalanced conditions.
ContributorsWu, Hong (Author) / Liang, Jianming (Thesis advisor) / Farin, Gerald (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2011
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Description
In recent years, the field of nanomedicine has progressed at an astonishing rate, particularly with respect to applications in cancer treatment and molecular imaging. Although organic systems have been the frontrunners, inorganic systems have also begun to show promise, especially those based upon silica and magnetic nanoparticles (NPs). Many of

In recent years, the field of nanomedicine has progressed at an astonishing rate, particularly with respect to applications in cancer treatment and molecular imaging. Although organic systems have been the frontrunners, inorganic systems have also begun to show promise, especially those based upon silica and magnetic nanoparticles (NPs). Many of these systems are being designed for simultaneous therapeutic and diagnostic capabilities, thus coining the term, theranostics. A unique class of inorganic systems that shows great promise as theranostics is that of layered double hydroxides (LDH). By synthesis of a core/shell structures, e.g. a gold nanoparticle (NP) core and LDH shell, the multifunctional theranostic may be developed without a drastic increase in the structural complexity. To demonstrate initial proof-of-concept of a potential (inorganic) theranostic platform, a Au-core/LDH-shell nanovector has been synthesized and characterized. The LDH shell was heterogeneously nucleated and grown on the surface of silica coated gold NPs via a coprecipitation method. Polyethylene glycol (PEG) was introduced in the initial synthesis steps to improve crystallinity and colloidal stability. Additionally, during synthesis, fluorescein isothiocyanate (FITC) was intercalated into the interlayer spacing of the LDH. In contrast to the PEG stabilization, a post synthesis citric acid treatment was used as a method to control the size and short-term stability. The heterogeneous core-shell system was characterized with scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (EDX), dynamic light scattering (DLS), and powder x-ray diffraction (PXRD). A preliminary in vitro study carried out with the assistance of Dr. Kaushal Rege's group at Arizona State University was to demonstrate the endocytosis capability of homogeneously-grown LDH NPs. The DLS measurements of the core-shell NPs indicated an average particle size of 212nm. The PXRD analysis showed that PEG greatly improved the crystallinity of the system while simultaneously preventing aggregation of the NPs. The preliminary in vitro fluorescence microscopy revealed a moderate uptake of homogeneous LDH NPs into the cells.
ContributorsRearick, Colton (Author) / Dey, Sandwip K (Thesis advisor) / Krause, Stephen (Committee member) / Ramakrishna, B (Committee member) / Arizona State University (Publisher)
Created2011
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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
Development of post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) is a major health concern (5% - 50% of TBI cases). A significant problem in TBI management is the inability to predict which patients will develop PTE. Such prediction, followed by timely treatment, could be highly beneficial to TBI patients.

Development of post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) is a major health concern (5% - 50% of TBI cases). A significant problem in TBI management is the inability to predict which patients will develop PTE. Such prediction, followed by timely treatment, could be highly beneficial to TBI patients. Six male Sprague-Dawley rats were subjected to a controlled cortical impact (CCI). A 6mm piston was pneumatically driven 3mm into the right parietal cortex with velocity of 5.5m/s. The rats were subsequently implanted with 6 intracranial electroencephalographic (EEG) electrodes. Long-term (14-week) continuous EEG recordings were conducted. Using linear (coherence) and non-linear (Lyapunov exponents) measures of EEG dynamics in conjunction with measures of network connectivity, we studied the evolution over time of the functional connectivity between brain sites in order to identify early precursors of development of epilepsy. Four of the six TBI rats developed PTE 6 to 10 weeks after the initial insult to the brain. Analysis of the continuous EEG from these rats showed a gradual increase of the connectivity between critical brain sites in terms of their EEG dynamics, starting at least 2 weeks prior to their first spontaneous seizure. In contrast, for the rats that did not develop epilepsy, connectivity levels did not change, or decreased during the whole course of the experiment across pairs of brain sites. Consistent behavior of functional connectivity changes between brain sites and the "focus" (site of impact) over time was demonstrated for coherence in three out of the four epileptic and in both non-epileptic rats, while for STLmax in all four epileptic and in both non-epileptic rats. This study provided us with the opportunity to quantitatively investigate several aspects of epileptogenesis following traumatic brain injury. Our results strongly support a network pathology that worsens with time. It is conceivable that the observed changes in spatiotemporal dynamics after an initial brain insult, and long before the development of epilepsy, could constitute a basis for predictors of epileptogenesis in TBI patients.
ContributorsTobin, Edward (Author) / Iasemidis, Leonidas (Thesis advisor) / Tsakalis, Konstantinos (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2012
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Description
The world of healthcare can be seen as dynamic, often an area where technology and science meet to consummate a greater good for humanity. This relationship has been working well for the last century as evident by the average life expectancy change. For the greater of the last five decades

The world of healthcare can be seen as dynamic, often an area where technology and science meet to consummate a greater good for humanity. This relationship has been working well for the last century as evident by the average life expectancy change. For the greater of the last five decades the average life expectancy at birth increased globally by almost 20 years. In the United States specifically, life expectancy has grown from 50 years in 1900 to 78 years in 2009. That is a 76% increase in just over a century. As great as this increase sounds for humanity it means there are soon to be real issues in the healthcare world. A larger older population will need more healthcare services but have fewer young professionals to provide those services. Technology and science will need to continue to push the boundaries in order to develop and provide the solutions needed to continue providing the aging world population sufficient healthcare. One solution sure to help provide a brighter future for healthcare is mobile health (m-health). M-health can help provide a means for healthcare professionals to treat more patients with less work expenditure and do so with more personalized healthcare advice which will lead to better treatments. This paper discusses one area of m-health devices specifically; human breath analysis devices. The current laboratory methods of breath analysis and why these methods are not adequate for common healthcare practices will be discussed in more detail. Then more specifically, mobile breath analysis devices are discussed. The topic will encompass the challenges that need to be met in developing such devices, possible solutions to these challenges, two real examples of mobile breath analysis devices and finally possible future directions for m-health technologies.
ContributorsLester, Bryan (Author) / Forzani, Erica (Thesis advisor) / Xian, Xiaojun (Committee member) / Trimble, Steve (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Approximately 1.7 million people in the United States are living with limb loss and are in need of more sophisticated devices that better mimic human function. In the Human Machine Integration Laboratory, a powered, transtibial prosthetic ankle was designed and build that allows a person to regain ankle function with

Approximately 1.7 million people in the United States are living with limb loss and are in need of more sophisticated devices that better mimic human function. In the Human Machine Integration Laboratory, a powered, transtibial prosthetic ankle was designed and build that allows a person to regain ankle function with improved ankle kinematics and kinetics. The ankle allows a person to walk normally and up and down stairs, but volitional control is still an issue. This research tackled the problem of giving the user more control over the prosthetic ankle using a force/torque circuit. When the user presses against a force/torque sensor located inside the socket the prosthetic foot plantar flexes or moves downward. This will help the user add additional push-off force when walking up slopes or stairs. It also gives the user a sense of control over the device.
ContributorsFronczyk, Adam (Author) / Sugar, Thomas G. (Thesis advisor) / Helms-Tillery, Stephen (Thesis advisor) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Approximately 1% of the world population suffers from epilepsy. Continuous long-term electroencephalographic (EEG) monitoring is the gold-standard for recording epileptic seizures and assisting in the diagnosis and treatment of patients with epilepsy. However, this process still requires that seizures are visually detected and marked by experienced and trained electroencephalographers. The

Approximately 1% of the world population suffers from epilepsy. Continuous long-term electroencephalographic (EEG) monitoring is the gold-standard for recording epileptic seizures and assisting in the diagnosis and treatment of patients with epilepsy. However, this process still requires that seizures are visually detected and marked by experienced and trained electroencephalographers. The motivation for the development of an automated seizure detection algorithm in this research was to assist physicians in such a laborious, time consuming and expensive task. Seizures in the EEG vary in duration (seconds to minutes), morphology and severity (clinical to subclinical, occurrence rate) within the same patient and across patients. The task of seizure detection is also made difficult due to the presence of movement and other recording artifacts. An early approach towards the development of automated seizure detection algorithms utilizing both EEG changes and clinical manifestations resulted to a sensitivity of 70-80% and 1 false detection per hour. Approaches based on artificial neural networks have improved the detection performance at the cost of algorithm's training. Measures of nonlinear dynamics, such as Lyapunov exponents, have been applied successfully to seizure prediction. Within the framework of this MS research, a seizure detection algorithm based on measures of linear and nonlinear dynamics, i.e., the adaptive short-term maximum Lyapunov exponent (ASTLmax) and the adaptive Teager energy (ATE) was developed and tested. The algorithm was tested on long-term (0.5-11.7 days) continuous EEG recordings from five patients (3 with intracranial and 2 with scalp EEG) and a total of 56 seizures, producing a mean sensitivity of 93% and mean specificity of 0.048 false positives per hour. The developed seizure detection algorithm is data-adaptive, training-free and patient-independent. It is expected that this algorithm will assist physicians in reducing the time spent on detecting seizures, lead to faster and more accurate diagnosis, better evaluation of treatment, and possibly to better treatments if it is incorporated on-line and real-time with advanced neuromodulation therapies for epilepsy.
ContributorsVenkataraman, Vinay (Author) / Jassemidis, Leonidas (Thesis advisor) / Spanias, Andreas (Thesis advisor) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Due to heterogeneity at the cellular level, single cell analysis (SCA) has become a necessity to study cellomics for the early detection of diseases like cancer. Development of single cell manipulation systems is very critical for performing SCA. In this thesis, electrorotation (ROT) chips to trap and rotate single cells

Due to heterogeneity at the cellular level, single cell analysis (SCA) has become a necessity to study cellomics for the early detection of diseases like cancer. Development of single cell manipulation systems is very critical for performing SCA. In this thesis, electrorotation (ROT) chips to trap and rotate single cells using electrokinetic forces have been developed. The ROT chip mainly consists of a set of closely spaced metal electrodes (60µm interspacing between opposite electrodes) that forms a closed electric field cage (electrocage) when driven with high frequency AC voltages. Cells were flowed through a microchannel to the electrocage where they could be precisely trapped, levitated and rotated in 3-D along the axis of interest. The dielectrophoresis based ROT chip design and relevant electrokinetic effects have been simulated using COMSOL 3.4 to optimize the design parameters. Also, various semiconductor technology fabrication process steps have been developed and optimized for better yield and repeatability in the manufacture of the ROT chip. The ROT chip thus fabricated was used to characterize rotation of single cells with respect to the control parameters namely excitation voltage, frequency and cell line. The longevity of cell rotation under electric fields has been probed. Also, the Joule heating inside the ROT chip due to applied voltage has been characterized to know the thermal stress on the cells. The major advantages of the ROT chip developed are precise electrorotation of cells, simple design and straight forward fabrication process.
ContributorsSoundappa Elango, Iniyan (Author) / Meldrum, Deirdre R (Thesis advisor) / Christen, Jennifer Blain (Committee member) / Johnson, Roger H (Committee member) / Arizona State University (Publisher)
Created2012