Matching Items (14)
Description
Biosensors offer excellent diagnostic methods through precise quantification of bodily fluid biomarkers and could fill an important niche in diagnostic screening. The long term goal of this research is the development of an impedance immunosensor for easy-to-use, rapid, sensitive and selective simultaneously multiplexed quantification of bodily fluid disease biomarkers. To test the hypothesis that various cytokines induce empirically determinable response frequencies when captured by printed circuit board (PCB) impedance immunosensor surface, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods were used to test PCB biosensors versus multiple cytokine biomarkers to determine limits of detection, background interaction and response at all sweep frequencies. Results indicated that sensors for cytokine Interleukin-12 (IL-12) detected their target over three decades of concentration and were tolerant to high levels of background protein. Further, the hypothesis that cytokine analytes may be rapidly detected via constant frequency impedance immunosensing without sacrificing undue sensitivity, CV, EIS, impedance-time (Zt) methods and modeling were used to test CHITM gold electrodes versus IL-12 over different lengths of time to determine limits of detection, detection time, frequency of response and consistent cross-platform sensor performance. Modeling and Zt studies indicate interrogation of the electrode with optimum frequency could be used for detection of different target concentrations within 90 seconds of sensor exposure and that interrogating the immunosensor with fixed, optimum frequency could be used for sensing target antigen. This informs usability of fixed-frequency impedance methods for biosensor research and particularly for clinical biosensor use. Finally, a multiplexing impedance immunosensor prototype for quantification of biomarkers in various body fluids was designed for increased automation of sample handling and testing. This enables variability due to exogenous factors and increased rapidity of assay with eased sensor fabrication. Methods were provided for simultaneous multiplexing through multisine perturbation of a sensor, and subsequent data processing. This demonstrated ways to observe multiple types of antibody-antigen affinity binding events in real time, reducing the number of sensors and target sample used in the detection and quantification of multiple biomarkers. These features would also improve the suitability of the sensor for clinical multiplex detection of disease biomarkers.
ContributorsFairchild, Aaron (Author) / La Belle, Jeffrey T (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Nagaraj, Vinay (Committee member) / Pizziconi, Vince (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2012
Description
This dissertation provides a fundamental understanding of the properties of mesoporous carbon based materials and the utilization of those properties into different applications such as electrodes materials for super capacitors, adsorbents for water treatments and biosensors. The thickness of mesoporous carbon films on Si substrates are measured by Ellipsometry method and pore size distribution has been calculated by Kelvin equation based on toluene adsorption and desorption isotherms monitored by Ellipsometer. The addition of organometallics cobalt and vanalyl acetylacetonate in the synthesis precursor leads to the metal oxides in the carbon framework, which largely decreased the shrink of the framework during carbonization, resulting in an increase in the average pore size. In addition to the structural changes, the introduction of metal oxides into mesoporous carbon framework greatly enhances the electrochemical performance as a result of their pseudocapacitance. Also, after the addition of Co into the framework, the contraction of mesoporous powders decreased significantly and the capacitance increased prominently because of the solidification function of CoO nanoparticles. When carbon-cobalt composites are used as adsorbent, the adsorption capacity of dye pollutant in water is remarkably higher (90 mg/g) after adding Co than the mesoporous carbon powder (2 mg/g). Furthermore, the surface area and pore size of mesoporous composites can be greatly increased by addition of tetraethyl orthosilicate into the precursor with subsequent etching, which leads to a dramatic increase in the adsorption capacity from 90 mg/g up to 1151 mg/g. When used as electrode materials for amperometric biosensors, mesoporous carbons showed good sensitivity, selectivity and stability. And fluorine-free and low-cost poly (methacrylate)s have been developed as binders for screen printed biosensors. With using only 5wt% of poly (hydroxybutyl methacrylate), the glucose sensor maintained mechanical integrity and exhibited excellent sensitivity on detecting glucose level in whole rabbit blood. Furthermore, extremely high surface area mesoporous carbons have been synthesized by introducing inorganic Si precursor during self-assembly, which effectively determined norepinephrine at very low concentrations.
ContributorsDai, Mingzhi (Author) / Vogt, Bryan D (Thesis advisor) / La Belle, Jeffrey T (Committee member) / Dai, Lenore (Committee member) / Nielsen, David R (Committee member) / Torres, César I (Committee member) / Arizona State University (Publisher)
Created2012
Description
Monitoring complex diseases and their comorbidities requires accurate and convenient measurements of multiple biomarkers. However, many state-of-the-art bioassays not only require complicated and time-consuming procedures, but also measure only one biomarker at a time. This noncomprehensive single-biomarker monitoring, as well as the cost and complexity of these bioassays advocate for a simple, rapid multi-marker sensing platform suitable for point-of-care or self-monitoring settings. To address this need, diabetes mellitus was selected as the example complex disease, with dry eye disease and cardiovascular disease as the example comorbidities. Seven vital biomarkers from these diseases were selected to investigate the platform technology: lactoferrin (Lfn), immunoglobulin E (IgE), insulin, glucose, lactate, low density lipoprotein (LDL), and high density lipoprotein (HDL). Using electrochemical techniques such as amperometry and electrochemical impedance spectroscopy (EIS), various single- and dual-marker sensing prototypes were studied. First, by focusing on the imaginary impedance of EIS, an analytical algorithm for the determination of optimal frequency and signal deconvolution was first developed. This algorithm helped overcome the challenge of signal overlapping in EIS multi-marker sensors, while providing a means to study the optimal frequency of a biomarker. The algorithm was then applied to develop various single- and dual-marker prototypes by exploring different kinds of molecular recognition elements (MRE) while studying the optimal frequencies of various biomarkers with respect to their biological properties. Throughout the exploration, 5 single-marker biosensors (glucose, lactate, insulin, IgE, and Lfn) and one dual-marker (LDL and HDL) biosensor were successfully developed. With the aid of nanoparticles and the engineering design of experiments, the zeta potential, conductivity, and molecular weight of a biomarker were found to be three example factors that contribute to a biomarker’s optimal frequency. The study platforms used in the study did not achieve dual-enzymatic marker biosensors (glucose and lactate) due to signal contamination from localized accumulation of reduced electron mediators on self-assembled monolayer. However, amperometric biosensors for glucose and lactate with disposable test strips and integrated samplers were successfully developed as a back-up solution to the multi-marker sensing platform. This work has resulted in twelve publications, five patents, and one submitted manuscripts at the time of submission.
ContributorsLin, Chi En (Author) / La Belle, Jeffrey T (Thesis advisor) / Caplan, Michael (Committee member) / Cook, Curtiss B (Committee member) / Stabenfeldt, Sarah (Committee member) / Spano, Mark (Committee member) / Arizona State University (Publisher)
Created2018
Description
The purpose of this project was to examine the viability of protein biomarkers in pre-symptomatic detection of lung cancer. Regular screening has been shown to vastly improve patient survival outcome. Lung cancer currently has the highest occurrence and mortality of all cancers and so a means of screening would be highly beneficial. In this research, the biomarker neuron-specific enolase (Enolase-2, eno2), a marker of small-cell lung cancer, was detected at varying concentrations using electrochemical impedance spectroscopy in order to develop a mathematical model of predicting protein expression based on a measured impedance value at a determined optimum frequency. The extent of protein expression would indicate the possibility of the patient having small-cell lung cancer. The optimum frequency was found to be 459 Hz, and the mathematical model to determine eno2 concentration based on impedance was found to be y = 40.246x + 719.5 with an R2 value of 0.82237. These results suggest that this approach could provide an option for the development of small-cell lung cancer screening utilizing electrochemical technology.
ContributorsEvans, William Ian (Author) / LaBelle, Jeffrey (Thesis director) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Electrical stimulation has previously been effective in neural cells activation within retinas affected by degenerative retinal disease. However current technology has at most allowed blind individuals to perceive light without significant resolution, as implants are limited by the spatial constraints of the eye. Photoreactive nanoparticles may provide a solution to this issue, as their small size would allow for the incorporation of higher numbers of stimulatory elements, thus increasing visual resolution. Semiconductive nanocrystal quantum dots (QDs) and gold nanoparticles (AuNPs) both exhibit photoreactive properties which may result in sufficient electrical stimulation to activate neural cells in the retina. This study investigated the electrochemistry and photoreactivity of QDs and AuNPs encapsulated within the hydrophobic region of small unilamellar lipid vesicles (SUVs) to evaluate their potential for application in retinal stimulation. Absorbance of the constructs was evaluated on the day of fabrication and 24 hours later to determine the ability of the particles to react to light while encapsulated, as well as to evaluate stability of the construct over time. Electrical impedance spectroscopy (EIS) was conducted at both time points to determine the electrochemical character of the bilayer and further evaluate construct stability. Although quantum dots may increase the stability of the bilayer over time and improve its capacitative properties, lipid encapsulation appears to obscure the photoreactive properties of the quantum dots. In the case of gold nanoparticles, the construct is initially stabilized but deteriorates more quickly than those SUVs containing quantum dots, as evidenced by an increase in substrate diffusion. Additionally, although these constructs are more photoreactive than those containing QDs, the increase in absorbance is observed primarily in a range below that of the visible spectrum, a feature which is of limited use for the proposed application. Further studies should investigate alternative methods of nanoparticle capping to improve stability and absorbance in this system.
ContributorsReidell, Olivia Rose (Author) / La Belle, Jeffrey T (Thesis director) / Coursen, Jerry (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
In this paper, β-estradiol was characterized utilizing electrochemical impedance spectroscopy (EIS) techniques for the purpose of developing a multi-marker fertility sensor. β-estradiol was immobilized onto the surface of gold disk electrodes to find the optimal binding frequency of estradiol and its respective antibody, anti-17β-estradiol, which was determined to be 37.46Hz. At this frequency a logarithmic relationship between concentration and impedance (Z/ohm) was established creating a concentration calibration curve with a slope of 211 ohm/ln(pg mL-1), an R-squared value of 0.986 and a lower limit of detection of 742 fg mL-1. The specificity and cross-reactivity of the antibody with other hormones was tested through interferent and non-target experiments. Signal-to-noise ratio analysis verified that anti-17β-estradiol exhibited minimal chemical reactions with other hormones (SNR< 3) in non-target experiments. Additionally, there were minimal changes in the amount of signal collected during interferent testing, with albumin and follicle stimulating hormone having SNR values greater than 3. These results, along with the unique frequency response of the antibody-target binding reaction, allow for the possibility of using anti-17β-estradiol and β-estradiol for detecting multiple fertility biomarkers on a single sensor.
ContributorsSmith, Victoria Ann (Author) / LaBelle, Jeffrey (Thesis director) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Volume depletion can lead to migraines, dizziness, and significant decreases in a subject's ability to physically perform. A major cause of volume depletion is dehydration, or loss in fluids due to an imbalance in fluid intake to fluid excretion. Because proper levels of hydration are necessary in order to maintain both short and long term health, the ability to monitor hydration levels is growing in clinical demand. Although devices capable of monitoring hydration level exist, these devices are expensive, invasive, or inaccurate and do not offer a continuous mode of measurement. The ideal hydration monitor for consumer use needs to be characterized by its portability, affordability, and accuracy. Also, this device would need to be noninvasive and offer continuous hydration monitoring in order to accurately assess fluctuations in hydration data throughout a specified time period. One particular method for hydration monitoring that fits the majority of these criteria is known as bioelectric impedance analysis (BIA). Although current devices using BIA do not provide acceptable levels of accuracy, portability, or continuity in data collection, BIA could potentially be modified to fit many, if not all, desired customer specifications. The analysis presented here assesses the viability of using BIA as a new standard in hydration level measurement. The analysis uses data collected from 22 subjects using an existing device that employs BIA. A regression derived for estimating TBW based on the parameters of age, weight, height, sex, and impedance is presented. Using impedance data collected for each subject, a regression was also derived for estimating impedance based on the factors of age, weight, height, and sex. The derived regression was then used to calculate a new impedance value for each subject, and these new impedance values were used to estimate TBW. Through a paired-t test between the TBW values derived by using the direct measurements versus the calculated measurements of impedance, the two samples were found to be comparable. Considerations for BIA as a noninvasive measurement of hydration are discussed.
ContributorsTenorio, Jorge Antonio (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / W. P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
A great deal of research has been done on communication barriers between patient and doctor, but due to the complexity of the relationship, little successful solutions have been suggested to bridge interdisciplinary communication between the two persons. This project explores a solution to aid both patient and doctor as they seek to communicate with each other regarding the patient's prognosis and treatment with a medical device. By creating a website, the information found therein can be accessed in the doctor's office by using a smartphone or tablet so that both patient and doctor can use it as a resource before, during, and after a doctor's visit. The website, Medical Devices 4 U (MD4U), gives background information on a large selection of medical devices, allows primary sources to share their information with potential consumers of the medical device, permits users to ask questions and comment on other user's comments, and gives a list of questions that a patient can ask a healthcare professional during a doctor's visit. In this report, the nature of doctor and patient communication is exposed and the steps taken to alleviate the communication barriers by way of creating a website are explained.
ContributorsHalls, Sarah Koy (Author) / Spano, Mark (Thesis director) / Garcia, Antonio (Committee member) / Brandon, Tedd (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
The action/adventure game Grad School: HGH is the final, extended version of a BME Prototyping class project in which the goal was to produce a zombie-themed game that teaches biomedical engineering concepts. The gameplay provides fast paced, exciting, and mildly addicting rooms that the player must battle and survive through, followed by an engineering puzzle that must be solved in order to advance to the next room. The objective of this project was to introduce the core concepts of BME to prospective students, rather than attempt to teach an entire BME curriculum. Based on user testing at various phases in the project, we concluded that the gameplay was engaging enough to keep most users' interest through the educational puzzles, and the potential for expanding this project to reach an even greater audience is vast.
ContributorsNitescu, George (Co-author) / Medawar, Alexandre (Co-author) / Spano, Mark (Thesis director) / LaBelle, Jeffrey (Committee member) / Guiang, Kristoffer (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
According to sources of the Centers for Disease Control and Prevention, approximately 1.7 million traumatic brain injury (TBI) cases occur annually in the United States. TBI results in 50 thousand deaths, nearly 300 thousand hospitalizations and 2.2 million emergency room visits causing a $76 billion economic burden in direct and indirect costs. Furthermore, it is estimated that over 5 million TBI survivors in the US are struggling with long-term disabilities. And yet, a point-of-care TBI diagnostic has not replaced the non-quantitative cognitive and physiological methods used today. Presently, pupil dilation and the Glasgow Coma Scale (GCS) are clinically used to diagnose TBI. However, GSC presents difficulties in detecting subtle patient changes, oftentimes leaving mild TBI undiagnosed. Given the long-term deficits associated with TBIs, a quantitative method that enables capturing of subtle and changing TBI pathologies is of great interest to the field.
The goal of this research is to work towards a test strip and meter point-of-care technology (similar to the glucose meter) that will quantify several TBI biomarkers in a drop of whole blood simultaneously. It is generally understood that measuring only one blood biomarker may not accurately diagnose TBI, thus this work lays the foundation to develop a multi-analyte approach to detect four promising TBI biomarkers: glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE), S-100β protein, and tumor necrosis factor-α (TNF-α). To achieve this, each biomarker was individually assessed and modeled using sensitive and label-free electrochemical impedance techniques first in purified, then in blood solutions using standard electrochemical electrodes. Next, the biomarkers were individually characterized using novel mesoporous carbon electrode materials to facilitate detection in blood solutions and compared to the commercial standard Nafion coating. Finally, the feasibility of measuring these biomarkers in the same sample simultaneously was explored in purified and blood solutions. This work shows that a handheld TBI blood diagnostic is feasible if the electronics can be miniaturized and large quantity production of these sensors can be achieved.
The goal of this research is to work towards a test strip and meter point-of-care technology (similar to the glucose meter) that will quantify several TBI biomarkers in a drop of whole blood simultaneously. It is generally understood that measuring only one blood biomarker may not accurately diagnose TBI, thus this work lays the foundation to develop a multi-analyte approach to detect four promising TBI biomarkers: glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE), S-100β protein, and tumor necrosis factor-α (TNF-α). To achieve this, each biomarker was individually assessed and modeled using sensitive and label-free electrochemical impedance techniques first in purified, then in blood solutions using standard electrochemical electrodes. Next, the biomarkers were individually characterized using novel mesoporous carbon electrode materials to facilitate detection in blood solutions and compared to the commercial standard Nafion coating. Finally, the feasibility of measuring these biomarkers in the same sample simultaneously was explored in purified and blood solutions. This work shows that a handheld TBI blood diagnostic is feasible if the electronics can be miniaturized and large quantity production of these sensors can be achieved.
ContributorsCardinell, Brittney Ann (Author) / La Belle, Jeffrey T (Thesis advisor) / Spano, Mark L (Committee member) / Stabenfeldt, Sarah E (Committee member) / Kleim, Jeffrey A (Committee member) / Cook, Curtiss B (Committee member) / Arizona State University (Publisher)
Created2017