Matching Items (49)
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- All Subjects: Biomedical Engineering
- Creators: Harrington Bioengineering Program
- Creators: Brafman, David
- Member of: Theses and Dissertations
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Description
The portability of genetic tools from one organism to another is a cornerstone of synthetic biology. The shared biological language of DNA-to-RNA-to-protein allows for expression of polypeptide chains in phylogenetically distant organisms with little modification. The tools and contexts are diverse, ranging from catalytic RNAs in cell-free systems to bacterial proteins expressed in human cell lines, yet they exhibit an organizing principle: that genes and proteins may be treated as modular units that can be moved from their native organism to a novel one. However, protein behavior is always unpredictable; drop-in functionality is not guaranteed.
My work characterizes how two different classes of tools behave in new contexts and explores methods to improve their functionality: 1. CRISPR/Cas9 in human cells and 2. quorum sensing networks in Escherichia coli.
1. The genome-editing tool CRISPR/Cas9 has facilitated easily targeted, effective, high throughput genome editing. However, Cas9 is a bacterially derived protein and its behavior in the complex microenvironment of the eukaryotic nucleus is not well understood. Using transgenic human cell lines, I found that gene-silencing heterochromatin impacts Cas9’s ability to bind and cut DNA in a site-specific manner and I investigated ways to improve CRISPR/Cas9 function in heterochromatin.
2. Bacteria use quorum sensing to monitor population density and regulate group behaviors such as virulence, motility, and biofilm formation. Homoserine lactone (HSL) quorum sensing networks are of particular interest to synthetic biologists because they can function as “wires” to connect multiple genetic circuits. However, only four of these networks have been widely implemented in engineered systems. I selected ten quorum sensing networks based on their HSL production profiles and confirmed their functionality in E. coli, significantly expanding the quorum sensing toolset available to synthetic biologists.
My work characterizes how two different classes of tools behave in new contexts and explores methods to improve their functionality: 1. CRISPR/Cas9 in human cells and 2. quorum sensing networks in Escherichia coli.
1. The genome-editing tool CRISPR/Cas9 has facilitated easily targeted, effective, high throughput genome editing. However, Cas9 is a bacterially derived protein and its behavior in the complex microenvironment of the eukaryotic nucleus is not well understood. Using transgenic human cell lines, I found that gene-silencing heterochromatin impacts Cas9’s ability to bind and cut DNA in a site-specific manner and I investigated ways to improve CRISPR/Cas9 function in heterochromatin.
2. Bacteria use quorum sensing to monitor population density and regulate group behaviors such as virulence, motility, and biofilm formation. Homoserine lactone (HSL) quorum sensing networks are of particular interest to synthetic biologists because they can function as “wires” to connect multiple genetic circuits. However, only four of these networks have been widely implemented in engineered systems. I selected ten quorum sensing networks based on their HSL production profiles and confirmed their functionality in E. coli, significantly expanding the quorum sensing toolset available to synthetic biologists.
ContributorsDaer, René (Author) / Haynes, Karmella (Thesis advisor) / Brafman, David (Committee member) / Nielsen, David (Committee member) / Kiani, Samira (Committee member) / Arizona State University (Publisher)
Created2017
Description
Myocardial infarction (MI) remains the leading cause of mortality and morbidity in the U.S., accounting for nearly 140,000 deaths per year. Heart transplantation and implantation of mechanical assist devices are the options of last resort for intractable heart failure, but these are limited by lack of organ donors and potential surgical complications. In this regard, there is an urgent need for developing new effective therapeutic strategies to induce regeneration and restore the loss contractility of infarcted myocardium. Over the past decades, regenerative medicine has emerged as a promising strategy to develop scaffold-free cell therapies and scaffold-based cardiac patches as potential approaches for MI treatment. Despite the progress, there are still critical shortcomings associated with these approaches regarding low cell retention, lack of global cardiomyocytes (CMs) synchronicity, as well as poor maturation and engraftment of the transplanted cells within the native myocardium. The overarching objective of this dissertation was to develop two classes of nanoengineered cardiac patches and scaffold-free microtissues with superior electrical, structural, and biological characteristics to address the limitations of previously developed tissue models. An integrated strategy, based on micro- and nanoscale technologies, was utilized to fabricate the proposed tissue models using functionalized gold nanomaterials (GNMs). Furthermore, comprehensive mechanistic studies were carried out to assess the influence of conductive GNMs on the electrophysiology and maturity of the engineered cardiac tissues. Specifically, the role of mechanical stiffness and nano-scale topographies of the scaffold, due to the incorporation of GNMs, on cardiac cells phenotype, contractility, and excitability were dissected from the scaffold’s electrical conductivity. In addition, the influence of GNMs on conduction velocity of CMs was investigated in both coupled and uncoupled gap junctions using microelectrode array technology. Overall, the key contributions of this work were to generate new classes of electrically conductive cardiac patches and scaffold-free microtissues and to mechanistically investigate the influence of conductive GNMs on maturation and electrophysiology of the engineered tissues.
ContributorsNavaei, Ali (Author) / Nikkhah, Mehdi (Thesis advisor) / Brafman, David (Committee member) / Migrino, Raymond Q. (Committee member) / Stabenfeldt, Sarah (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2018
Description
The importance of efficient design and development teams in in 21st century is evident after the compressive literate review was performed to digest various aspects of benefits and foundation of teamwork. Although teamwork may have variety of applications in many different industries, the new emerging biomedical engineering is growing significantly using principles of teamwork. Studying attributes and mechanism of creating successful biomedical engineering teams may even contribute more to the fast paste growth of this industry. In comprehensive literate review performed, general importance of teamwork was studied. Also specific hard and soft attributes which may contribute to teamwork was studied. Currently, there are number of general assessment tools which assists managements in industry and academia to systematically bring qualified people together to flourish their talents and skills as members of a biomedical engineering teams. These assessment tools, although are useful, but are not comprehensive, incorporating literature review attributes, and also doesn't not contain student perspective who have experience as being part of a design and development team. Although there are many scientific researches and papers designated to this matter, but there is no study which purposefully studies development of an assessment tool which is designated to biomedical engineering workforce and is constructed of both literature, current assessment tools, and also student perspective. It is hypothesized that a more comprehensive composite assessment tool that incorporate both soft and hard team attributes from a combined professional and student perspective could be implemented in the development of successful Biomedical Engineering Design and Development teams and subsequently used in 21st century workforce.
ContributorsAfzalian Naini, Nima (Author) / Pizziconi, Vincent (Thesis director) / Ankeny, Casey (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Abstract
The aim of the research performed was to increase research potential in the field of cell stimulation by developing a method to adhere human neural progenitor cells (hNPC’s) to a sterilized stretchable microelectrode array (SMEA). The two primary objectives of our research were to develop methods of sterilizing the polydimethylsiloxane (PDMS) substrate being used for the SMEA, and to derive a functional procedure for adhering hNPC’s to the PDMS. The proven method of sterilization was to plasma treat the sample and then soak it in 70% ethanol for one hour. The most successful method for cell adhesion was plasma treating the PDMS, followed by treating the surface of the PDMS with 0.01 mg/mL poly-l-lysine (PLL) and 3 µg/cm2 laminin. The development of these methods was an iterative process; as the methods were tested, any problems found with the method were corrected for the next round of testing until a final method was confirmed. Moving forward, the findings will allow for cell behavior to be researched in a unique fashion to better understand the response of adherent cells to physical stimulation by measuring changes in their electrical activity.
The aim of the research performed was to increase research potential in the field of cell stimulation by developing a method to adhere human neural progenitor cells (hNPC’s) to a sterilized stretchable microelectrode array (SMEA). The two primary objectives of our research were to develop methods of sterilizing the polydimethylsiloxane (PDMS) substrate being used for the SMEA, and to derive a functional procedure for adhering hNPC’s to the PDMS. The proven method of sterilization was to plasma treat the sample and then soak it in 70% ethanol for one hour. The most successful method for cell adhesion was plasma treating the PDMS, followed by treating the surface of the PDMS with 0.01 mg/mL poly-l-lysine (PLL) and 3 µg/cm2 laminin. The development of these methods was an iterative process; as the methods were tested, any problems found with the method were corrected for the next round of testing until a final method was confirmed. Moving forward, the findings will allow for cell behavior to be researched in a unique fashion to better understand the response of adherent cells to physical stimulation by measuring changes in their electrical activity.
ContributorsBridgers, Carson (Co-author) / Peterson, Mara (Co-author) / Stabenfeldt, Sarah (Thesis director) / Graudejus, Oliver (Committee member) / Harrington Bioengineering Program (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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
Determining the characteristics of an object during a grasping task requires a combination of mechanoreceptors in the muscles and fingertips. The width of a person's finger aperture during the grasp may affect the accuracy of how that person determines hardness, as well. These experiments aim to investigate how an individual perceives hardness amongst a gradient of varying hardness levels. The trend in the responses is assumed to follow a general psychometric function. This will provide information about subjects' abilities to differentiate between two largely different objects, and their tendencies towards guess-chances upon the presentation of two similar objects. After obtaining this data, it is then important to additionally test varying finger apertures in an object-grasping task. This will allow an insight into the effect of aperture on the obtained psychometric function, thus ultimately providing information about tactile and haptic feedback for further application in neuroprosthetic devices. Three separate experiments were performed in order to test the effect of finger aperture on object hardness differentiation. The first experiment tested a one-finger pressing motion among a hardness gradient of ballistic gelatin cubes. Subjects were asked to compare the hardness of one cube to another, which produced the S-curve that accurately portrayed the psychometric function. The second experiment utilized the Phantom haptic device in a similar setup, using the precision grip grasping motion, instead. This showed a more linear curve; the percentage reported harder increased as the hardness of the second presented cube increased, which was attributed to both the experimental setup limitations and the scale of the general hardness gradient. The third experiment then progressed to test the effect of three finger apertures in the same experimental setup. By providing three separate testing scenarios in the precision grip task, the experiment demonstrated that the level of finger aperture has no significant effect on an individual's ability to perceive hardness.
ContributorsMaestas, Gabrielle Elise (Author) / Helms Tillery, Stephen (Thesis director) / Tanner, Justin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending on the conditions in which polymers are used, they are modified to accommodate a specific need. For instance, polymers used in drug delivery are more efficient if they are biodegradable. This ensures that the delivery system does not remain in the body after releasing the drug. It is therefore crucial that the polymer used in the drug system possess biodegradable properties. Such modification can be done in different ways including the use of peptides to make copolymers that will degrade in the presence of enzymes. In this work, we studied the effect of a polypeptide GAPGLL on the polymer NIPAAm and compare with the previously studied Poly(NIPAAm-co-GAPGLF). Both copolymers Poly(NIPAAm-co-GAPGLL) were first synthesized from Poly(NIPAAm-co-NASI) through nucleophilic substitution by the two peptides. The synthesis of these copolymers was confirmed by 1H NMR spectra and through cloud point measurement, the corresponding LCST was determined. Both copolymers were degraded by collagenase enzyme at 25 ° C and their 1H NMR spectra confirmed this process. Both copolymers were cleaved by collagenase, leading to an increase in solubility which yielded a higher LCST compared to before enzyme degradation. Future studies will focus on evaluating other peptides and also using other techniques such as Differential Scanning Microcalorimetry (DSC) to better observe the LCST behavior. Moreover, enzyme kinetics studies is also crucial to evaluate how fast the enzyme degrades each of the copolymers.
ContributorsUwiringiyimana, Mahoro Marie Chantal (Author) / Vernon, Brent (Thesis director) / Nikkhah, Mehdi (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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
Oxygen delivery is crucial for the development of healthy, functional tissue. Low tissue oxygenation, or hypoxia, is a characteristic that is common in many tumors. Hypoxia contributes to tumor malignancy and can reduce the success of chemotherapy and radiation treatment. There is a current need to noninvasively measure tumor oxygenation or pO2 in patients to determine a personalized treatment method. This project focuses on creating and characterizing nanoemulsions using a pO2 reporter molecule hexamethyldisiloxane (HMDSO) and its longer chain variants as well as assessing their cytotoxicity. We also explored creating multi-modal (MRI/Fluorescence) nanoemulsions.
ContributorsGrucky, Marian Louise (Author) / Kodibagkar, Vikram (Thesis director) / Rege, Kaushal (Committee member) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
Science fiction has a unique ability to express, analyze, and critique concepts in a subtle way that emphasizes a point but is still entertaining to the audience. Because of science fiction's ability to do this it has long been a powerful way to ask questions that would normally not be addressed. As such, this paper provides an overview of the effects of biomedical technology in science fiction films. The discussions in this paper will analyze the different portrayals of the technology in the viewed cinematic pieces and the effects they have on the characters in the film. The discussion will begin with the films that have technology based in Genetic Engineering. This will then be followed by a discussion of the biomedical technology based in the fields of Endocrinology; Reanimation; Preservation; Prosthetics; Physical Metamorphosis; Super-Drugs and Super-Viruses; and Diagnostic, Surgical, and Monitoring Equipment. At the end of this paper movie summaries are provided to assist in clarifying plot details.
ContributorsGrzybowski, Amanda Ann (Author) / Foy, Joseph (Thesis director) / Facinelli, Diane (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05