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There is a strong medical need and important therapeutic applications for improved wireless bioelectric interfaces to the nervous system. Multichannel devices are desired for neural control of robotic prosthetics that interface to remaining nerves in limb stumps of amputees and as alternatives to traditional wired arrays used in for some

There is a strong medical need and important therapeutic applications for improved wireless bioelectric interfaces to the nervous system. Multichannel devices are desired for neural control of robotic prosthetics that interface to remaining nerves in limb stumps of amputees and as alternatives to traditional wired arrays used in for some types of brain stimulation. This present work investigates a new approach to ultrasound-powering of implantable microelectronic devices within the tissue that may better support such applications. These devices are of ultra-miniature size that is enabled by a wireless technique. This study investigates two types of ultrasound-powered neural interfaces for multichannel sensory feedback in neurostimulation. The piezoceramics lead zirconate titanate (PZT) ceramic and polyvinylidene fluoride (PVDF) polymer were the primary materials used to build the devices. They convert ultrasound to electricity that when rectified by a diode produce a current output that is neuro stimulatory to peripheral nerve or the neurons in the brain. Multichannel devices employ a form of spatial multiplexing that directs focused ultrasound towards localized and segmented regions of PVDF or PZT that allows independent channels of nerve actuation. Different frequencies of ultrasound were evaluated for best results. Firstly, a 2.25 MHz frequency signal that is reasonably penetrating through body tissue to an implant several centimeters deep and also a 5 MHz frequency more suited to application for actuation of devices within a less than a centimeter of nerve. Results show multichannel device performance to have a complex inter-relationship with frequency, size and thickness, angular incidence, channel separations, and number of folds (layers connected in series and parallel). The output electrical port impedances of PVDF devices were examined in relationship to that of stimulating electrodes and tissue interfaces. Miniature multichannel devices were constructed using an unreported method of employing state of the art laser cutting systems. The results show that PVDF based devices have advantages over PZT, because of better acoustic coupling with tissue, known better biocompatibility, and better separation between multiple channels. However, the PZT devices proved to be better overall in terms of compactness and higher outputs for a given ultrasound power level.
ContributorsNanda Kumar, Yashwanth (Author) / Towe, Bruce (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Early detection and treatment of disease is paramount for improving human health and wellness. Micro-scale devices promote new opportunities for the rapid, cost-effective, and accurate identification of altered biological states indicative of disease early-onset; these devices function at a scale more sensitive to numerous biological processes. The application of Micro-Electro-Mechanical

Early detection and treatment of disease is paramount for improving human health and wellness. Micro-scale devices promote new opportunities for the rapid, cost-effective, and accurate identification of altered biological states indicative of disease early-onset; these devices function at a scale more sensitive to numerous biological processes. The application of Micro-Electro-Mechanical Systems (MEMS) in biomedical settings has recently emerged and flourished over course of the last two decades, requiring a deep understanding of material biocompatibility, biosensing sensitively/selectively, biological constraints for artificial tissue/organ replacement, and the regulations in place to ensure device safety. Capitalizing on the inherent physical differences between cancerous and healthy cells, our ultra-thin silicone membrane enables earlier identification of bladder cancer—with a 70% recurrence rate. Building on this breakthrough, we have devised an array to multiplex this sample-analysis in real-time as well as expanding beyond bladder cancer. The introduction of new materials—with novel properties—to augment current and create innovative medical implants requires the careful analysis of material impact on cellular toxicity, mutagenicity, reactivity, and stability. Finally, the achievement of replacing defective biological systems with implanted artificial equivalents that must function within the same biological constraints, have consistent reliability, and ultimately show the promise of improving human health as demonstrated by our hydrogel check valve. The ongoing proliferation, expanding prevalence, and persistent improvement in MEMS devices through greater sensitivity, specificity, and integration with biological processes will undoubtedly bolster medical science with novel MEMS-based diagnostics and therapeutics.
ContributorsPodlevsky, Jennie Hewitt Appel (Author) / Chae, Junseok (Thesis advisor) / Goryll, Michael (Committee member) / Kozicki, Michael (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2018
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

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
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Description
Severe cases of congenital heart defect (CHD) require surgeries to fix the structural problem, in which artificial grafts are often used. Although outcome of surgeries has improved over the past decades, there remains to be patients who require re-operations due to graft-related complications and the growth of patients which results

Severe cases of congenital heart defect (CHD) require surgeries to fix the structural problem, in which artificial grafts are often used. Although outcome of surgeries has improved over the past decades, there remains to be patients who require re-operations due to graft-related complications and the growth of patients which results in a mismatch in size between the patient’s anatomy and the implanted graft. A graft in which cells of the patient could infiltrate, facilitating transformation of the graft to a native-like tissue, and allow the graft to grow with the patient heart would be ideal. Cardiac tissue engineering (CTE) technologies, including extracellular matrix (ECM)-based hydrogels has emerged as a promising approach for the repair of cardiac damage. However, most of the previous studies have mainly focused on treatments for ischemic heart disease and related heart failure in adults, therefore the potential of CTE for CHD treatment is underexplored. In this study, a hybrid hydrogel was developed by combining the ECM derived from cardiac tissue of pediatric CHD patients and gelatin methacrylate (GelMA). In addition, the influence of incorporating gold nanorods (GNRs) within the hybrid hydrogels was studied. The functionalities of the ECM-GelMA-GNR hydrogels as a CTE scaffold were assessed by culturing neonatal rat cardiomyocytes on the hydrogel. After 8 days of cell culture, highly organized sarcomeric alpha-actinin structures and connexin 43 expression were evident in ECM- and GNR-incorporated hydrogels compared to pristine GelMA hydrogel, indicating cell maturation and formation of cardiac tissue. The findings of this study indicate the promising potential of ECM-GelMA-GNR hybrid hydrogels as a CTE approach for CHD treatment.

As another approach to improve CHD treatment, this study sought the possibility of performing a proteomic analysis on cardiac ECM of pediatric CHD patient tissue. As the ECM play important roles in regulating cell signaling, there is an increasing interest in studying the ECM proteome and the influences caused by diseases. Proteomics on ECM is challenging due to the insoluble nature of ECM proteins which makes protein extraction and digestion difficult. In this study, as a first step to perform proteomics, optimization on sample preparation procedure was attempted.
ContributorsSugamura, Yuka (Author) / Nikkhah, Mehdi (Thesis advisor) / Smith, Barbara (Committee member) / Willis, Brigham (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Many developing countries do not have health care systems that can afford technological biomedical devices or supplies to make such devices operational. To fill this void, nonprofit organizations, like Project C.U.R.E., recondition retired biomedical instrumentation so they can send medical supplies to help these developing countries. One of the issues

Many developing countries do not have health care systems that can afford technological biomedical devices or supplies to make such devices operational. To fill this void, nonprofit organizations, like Project C.U.R.E., recondition retired biomedical instrumentation so they can send medical supplies to help these developing countries. One of the issues with this is that sometimes the devices are unusable because components or expendable supplies are not available (Bhadelia). This issue has also been shown in the Impact Evaluations that Project C.U.R.E. receives from the clinics that explain the reasons why certain devices are no longer in use. That need underlies the idea on which this honors thesis has come into being. The purpose of this honors project was to create packing lists for biomedical instruments that Project C.U.R.E. recycles. This packing list would decrease the likelihood of important items being forgotten when sending devices. If an extra fuse, battery, light bulb, cuff or transducer is the difference between a functional or a nonfunctional medical device, such a list would be of benefit to Project C.U.R.E and these developing countries. In order to make this packing list, manuals for each device were used to determine what supplies were required, what was necessary for cleaning, and what supplies were desirable but functionally optional. This list was then added into a database that could be easily navigated and could help when packing up boxes for a shipment. The database also makes adding and editing the packing list simple and easy so that as Project C.U.R.E. gets more donated devices the packing list can grow.
ContributorsGraft, Kelsey Anne (Author) / Coursen, Jerry (Thesis director) / Walters, Danielle (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
The Hippo signaling pathway is responsible for regulating organ size through cell proliferation, stemness, and apoptosis. Through targeting proteins Yes-associated kinase 1(YAP) and transcriptional co-activator with a PDZ-binding domain(TAZ), YAP/TAZ are unable to enter the nucleus and bind with coactivators to express target genes. To understand YAP/TAZ dynamics and its

The Hippo signaling pathway is responsible for regulating organ size through cell proliferation, stemness, and apoptosis. Through targeting proteins Yes-associated kinase 1(YAP) and transcriptional co-activator with a PDZ-binding domain(TAZ), YAP/TAZ are unable to enter the nucleus and bind with coactivators to express target genes. To understand YAP/TAZ dynamics and its role in tumorigenesis, tissue regeneration, and tissue degeneration, a regulatory network was modeled by ordinary differential equations. Using MATLAB, the deterministic behavior of the network was observed to determine YAP/TAZ activity in different states. Performing the bifurcation analysis of the system through Oscill8, three states were identified: tumorigenic/regenerative, degenerative, and homeostatic states. Further analysis through parameter modification allowed a better understanding of which proteins can be targeted for cancer and degenerative disease.
ContributorsBarra Avila, Diego Rodrigo (Author) / Tian, Xiaojun (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Based on James Marcia's theory, identity development in youth is the degree to which one has explored and committed to a vocation [1], [2]. During the path to an engineering identity, students will experience a crisis, when one's values and choices are examined and reevaluated, and a commitment, when the

Based on James Marcia's theory, identity development in youth is the degree to which one has explored and committed to a vocation [1], [2]. During the path to an engineering identity, students will experience a crisis, when one's values and choices are examined and reevaluated, and a commitment, when the outcome of the crisis leads the student to commit to becoming an engineer. During the crisis phase, students are offered a multitude of experiences to shape their values and choices to influence commitment to becoming an engineering student. Student's identities in engineering are fostered through mentoring from industry, alumni, and peer coaching [3], [4]; experiences that emphasize awareness of the importance of professional interactions [5]; and experiences that show creativity, collaboration, and communication as crucial components to engineering. Further strategies to increase students' persistence include support in their transition to becoming an engineering student, education about professional engineers and the workplace [6], and engagement in engineering activities beyond the classroom. Though these strategies are applied to all students, there are challenges students face in confronting their current identity and beliefs before they can understand their value to society and achieve personal satisfaction. To understand student's progression in developing their engineering identity, first year engineering students were surveyed at the beginning and end of their first semester. Students were asked to rate their level of agreement with 22 statements about their engineering experience. Data included 840 cases. Items with factor loading less than 0.6 suggesting no sufficient explanation were removed in successive factor analysis to identify the four factors. Factor analysis indicated that 60.69% of the total variance was explained by the successive factors. Survey questions were categorized into three factors: engineering identity as defined by sense of belonging and self-efficacy, doubts about becoming an engineer, and exploring engineering. Statements in exploring engineering indicated student awareness, interest and enjoyment within engineering. Students were asked to think about whether they spent time learning what engineers do and participating in engineering activities. Statements about doubts about engineering to engineering indicated whether students had formed opinions about their engineering experience and had understanding about their environment. Engineering identity required thought in belonging and self-efficacy. Belonging statements called for thought about one's opinion in the importance of being an engineer, the meaning of engineering, an attachment to engineering, and self-identification as an engineer. Statements about self-efficacy required students to contemplate their personal judgement of whether they would be able to succeed and their ability to become an engineer. Effort in engineering indicated student willingness to invest time and effort and their choices and effort in their engineering discipline.
ContributorsNguyen, Amanda (Author) / Ganesh, Tirupalavanam (Thesis director) / Robinson, Carrie (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related

Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related mutations, have provided important insights into the disease. However, these models do not display important disease-related pathologies and have been limited in their ability to model the complex genetics associated with SAD.

Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.

It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
ContributorsBounds, Lexi Rose (Author) / Brafman, David (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
The combination of immunohistochemical (IHC) stainings and optical microscopy has allowed for the visualization of specific microscopic structures within tissue; however, limitations in light and antibody penetration mitigate the scale on which these images can be taken (Alshammari et al, 2016; Marx, 2014). Tissue clearing, specifically the removal of lipids

The combination of immunohistochemical (IHC) stainings and optical microscopy has allowed for the visualization of specific microscopic structures within tissue; however, limitations in light and antibody penetration mitigate the scale on which these images can be taken (Alshammari et al, 2016; Marx, 2014). Tissue clearing, specifically the removal of lipids to improve sample transparency, solves the former weakness well, but does not improve antibody penetration significantly (Chung et al, 2013; Treweek et al, 2015). Therefore, there is a need to equalize the maximum depth that light can pass through a section with the depth at which there is recognizable fluorescence. This is particularly important when staining blood vessels as traditional size limitations exclusively allows for cross sectional visualization. Passive CLARITY Technique (PACT) has been at the forefront of tissue clearing protocols, utilizing an acrylamide hydrogel solution to maintain structure and sodium dodecyl sulfate to wash out lipids (Tomer et al, 2014). PACT is limited in its ability to clear larger sections and is not conducive to IHC antibody diffusion (Treweek et al, 2015). In order to circumvent these drawbacks, CUBIC was developed as an alternative passive protocol, aimed at being scalable to any tissue size (Richardson, 2015; Susaki et al, 2015). This study compared the effectiveness of both protocols in high and low lipid tissues in the context of blood vessel staining efficacy. Upon initial comparison, it became apparent that there was a statistically significant difference in mean DAPI intensity at all depths, up to 200 micrometers, between CUBIC and PACT \u2014 the former showcasing brighter stainings. Moreover, it was found that PACT does not remove erythrocytes from the tissue meaning that their auto-fluorescence is seen during imaging. Therefore, for blood vessel stainings, only CUBIC was optimized and quantitatively analyzed. In both tissue conditions as well as for two stainings, DAPI and fibronectin (FNCT), optimized CUBIC demonstrated a statistically significant difference from standard CUBIC with regards to mean fluorescent intensity.
ContributorsSidhu, Gurpaul Singh (Author) / VanAuker, Michael (Thesis director) / Kodibagkar, Vikram (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
This creative project created and implemented a seven-day STEM curriculum that ultimately encouraged engagement in STEM subjects in students ages 5 through 11. The activities were incorporated into Arizona State University's Kids' Camp over the summer of 2017, every Tuesday afternoon from 4 to 6 p.m. with each activity running

This creative project created and implemented a seven-day STEM curriculum that ultimately encouraged engagement in STEM subjects in students ages 5 through 11. The activities were incorporated into Arizona State University's Kids' Camp over the summer of 2017, every Tuesday afternoon from 4 to 6 p.m. with each activity running for roughly 40 minutes. The lesson plans were created to cover a myriad of scientific topics to account for varied student interest. The topics covered were plant biology, aerodynamics, zoology, geology, chemistry, physics, and astronomy. Each lesson was scaffolded to match the learning needs of the three age groups (5-6 year olds, 7-8 year olds, 9-11 year olds) and to encourage engagement. "Engagement" was measured by pre- and post-activity surveys approved by IRB. The surveys were in the form of statements where the children would totally agree, agree, be undecided, disagree, or totally disagree with it. To more accurately test engagement, the smiley face Likert scale was incorporated with the answer choices. After implementation of the intervention, two-tailed paired t-tests showed that student engagement significantly increased for the two lesson plans of Aerodynamics and Chemistry.
ContributorsHunt, Allison Rene (Co-author) / Belko, Sara (Co-author) / Merritt, Eileen (Thesis director) / Ankeny, Casey (Committee member) / Division of Teacher Preparation (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12