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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

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
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Description
The development of the Diabetic Physiological state is influenced by the Receptor for Advanced Glycation End Products (RAGE). This receptor was discovered in 1992, and the accumulation of research on this subject has been extensive. Structural characterization studies of the RAGE protein have shown that it is a transmembrane protein

The development of the Diabetic Physiological state is influenced by the Receptor for Advanced Glycation End Products (RAGE). This receptor was discovered in 1992, and the accumulation of research on this subject has been extensive. Structural characterization studies of the RAGE protein have shown that it is a transmembrane protein that binds a number of different motile ligands. The diversity of ligands that can attach to the binding domain is the primary factor that allows for RAGE to exhibit its wide-range effects on host cells. Two different studies were completed: one study dealt with the role of IAPP in beta cell death, and the second study was related to RAGE influence on cardiomyocytes and, more specifically, it was related to cardiac cell death. After the completion of the two studies, a comprehensive report was written for each topic. The two papers were merged into a single document. Molecular studies are important for understanding the underlying mechanisms that motivate pathophysiological presentation. In addition to a molecular understanding of the development of diabetes, a clinical research study was completed through the examination of appropriate literature sources. This clinical aspect allowed for the progression of different phases in the research process. A relationship between vinegar and lower plasma glucose was found. The exact mechanism behind this relationship will be studied in the future.
ContributorsGonzalez, Matthew Joseph (Author) / Johnston, Carol (Thesis director) / Collins, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
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Description

The purpose of this study, which was done in conjunction with the Arizona Heart Foundation, was to evaluate whether pyridoxine accelerates ulcer wound healing in diabetic patients with ulcers in the lower extremities. In this study, 100 mg of pyridoxine per day was given to patients in the experimental grou

The purpose of this study, which was done in conjunction with the Arizona Heart Foundation, was to evaluate whether pyridoxine accelerates ulcer wound healing in diabetic patients with ulcers in the lower extremities. In this study, 100 mg of pyridoxine per day was given to patients in the experimental group (while they receive normal wound treatment) while patients in the control group received normal treatment of wounds without the pyridoxine. Over time, wound healing was evaluated by photographing and then measuring the size of patients' ulcer wounds on the photographs. Results from the experimental group were compared with those of the control group to evaluate the efficacy of the pyridoxine treatment. In addition, comparisons of the healing rates were made with respect to whether the patients smoked, had hypertension or hypotension, and the patients' body mass indexes. It has been found that there was no statistically significant difference in the mean healing rates between the control groups and experimental groups. In addition, it has been found that smoking, BMI and blood pressure did not have a statistically appreciable effect on the difference in mean healing rates between the control and experimental groups. This is evidence that pyridoxine did not have a statistically significant effect on wound healing rates.

ContributorsHaupt, Shawn Anthony (Author) / Caplan, Michael (Thesis director) / Pauken, Christine (Committee member) / Pagan, Pedro (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
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Description
Diabetes is a growing epidemic in developing countries, specifically in rural Kenya. In addition to the high cost of glucose testing, many diabetics in Kenya do not understand the importance of testing their blood glucose, let alone the nature of the disease. This project addresses the insufficiency of educational materials

Diabetes is a growing epidemic in developing countries, specifically in rural Kenya. In addition to the high cost of glucose testing, many diabetics in Kenya do not understand the importance of testing their blood glucose, let alone the nature of the disease. This project addresses the insufficiency of educational materials regarding diabetes in rural Kenya. The resulting documents can easily be adjusted for use in other developing countries.
ContributorsBuchak, Jacqueline (Author) / Caplan, Michael (Thesis director) / Snyder, Jan (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Type II diabetes is a serious, chronic metabolic disease that has serious impacts on both the health and quality of life in patients diagnosed with the disease. Type II diabetes is also a very prevalent disease both in the United States and around the world. There is still a lot

Type II diabetes is a serious, chronic metabolic disease that has serious impacts on both the health and quality of life in patients diagnosed with the disease. Type II diabetes is also a very prevalent disease both in the United States and around the world. There is still a lot that is unknown about Type II diabetes, and this study will aim to answer some of these questions. The question posed in this study is whether insulin resistance changes as a function of time after the start of a high fat diet. We hypothesized that peripheral insulin resistance would be observed in animals placed on a high fat diet; and peripheral insulin resistance would have a positive correlation with time. In order to test the hypotheses, four Sprague-Dawley male rats were placed on a high fat diet for 8 weeks, during which time they were subjected to three intraperitonal insulin tolerance tests ((NovoLogTM 1 U/kg). These three tests were conducted at baseline (week 1), week 4, and week 8 of the high fat diet. The test consisted of serially determining plasma glucose levels via a pin prick methodology, and exposing a droplet of blood to the test strip of a glucometer (ACCUCHEKTM, Roche Diagnostics). Two plasma glucose baselines were taken, and then every 15 minutes following insulin injection for one hour. Glucose disposal rates were then calculated by simply dividing the glucose levels at each time point by the baseline value, and multiplying by 100. Area under the curve data was calculated via definite integral. The area under the curve data was then subjected to a single analysis of variance (ANOVA), with a statistical significance threshold of p<0.05. The results of the study did not indicate the development of peripheral insulin resistance in the animals placed on a high fat diet. Insulin-mediated glucose disposal was about 50% at 30 minutes in all four animals, during all three testing periods. Furthermore, the ANOVA resulted in p=0.92, meaning that the data was not statistically significant. In conclusion, peripheral insulin resistance was not observed in the animals, meaning no determination could be made on the relation between time and insulin resistance.
ContributorsBrown, Kellen Andrew (Author) / Caplan, Michael (Thesis director) / Herman, Richard (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05