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- Creators: Harrington Bioengineering Program
- Member of: Theses and Dissertations
Description
Abstract: The delivery of a drug or gene payload inside an individual neuron has been highly sought after and studied as a means of treating a large variety of neurological diseases and disorders such as cancer and Alzheimer’s. Current technology for these applications remains imperfect particularly with respect to matters of precision and cell viability. Thus, the use of MEMS (micro electro mechanical systems) based systems have become more prevalent in order to conduct these processes with higher precision and automation. Penetrating these specific cells while also maintaining their structural integrity during the process, remain as two major hurdles still being explored today. Electrical stimulation has been used to drive the delivery of a payload at the microscale but to do so with a voltage that keeps the neuron viable is imperative. In order to find a means for optimizing the voltage and ejection of the payload while maintaining cell viability, the goal of this project is to explore the use of pulsed waveforms for driving the delivery. In doing so, lower to moderate voltage amplitudes may potentially be used while also avoiding hydrolysis of the cell. This study was done by ejecting dye dextran from glass micropipettes with an agar and artificial seawater well using both DC and pulsed waveforms. Successful ejection of the payload was achieved and confirmed using fluorescent microscopy. While the methods used for this voltage based delivery require further optimization, the successful ejection utilizing pulsed voltages suggest that this may lead to an improved technique for MEMS based delivery of payloads into single cells in the future.
ContributorsStamm, Steven Jeffrey (Author) / Muthuswamy, Jitendran (Thesis director) / Sridharan, Arati (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Time-Lapse Visualization of Microglia Cell Processes using Fluorescent Miniature (Miniscope) Imaging
Description
In the United States, an estimated 2 million cases of traumatic brain injury (TBI) resulting in more than 50,000 deaths occur every year. TBI induces an immediate primary injury resulting in local or diffuse cell death in the brain. Then a secondary injury occurs through neuroinflammation from immune cells in response to primary injury. Microglia, the resident immune cell of the central nervous system, play a critical role in neuroinflammation following TBI. Microglia make up 10% of all cells in the nervous system and are the fastest moving cells in the brain, scanning the entire parenchyma every several hours. Microglia have roles in both the healthy and injured brain. In the healthy brain, microglia can produce neuroprotective factors, clear cellular debris, and organize neurorestorative processes to recover from TBI. However, microglia mediated neuroinflammation during secondary injury produces pro-inflammatory and cytotoxic mediators contributing to neuronal dysfunction, inhibition of CNS repair, and cell death. Furthermore, neuroinflammation is a prominent feature in many neurodegenerative diseases such as Alzheimer’s, and Parkinson’s disease, of which include overactive microglia function. Microglia cell morphology, activation, and response to TBI is poorly understood. Currently, imaging microglia can only be performed while the animal is stationary and under anesthesia. The Miniscope technology allows for real-time visualization of microglia in awake behaving animals. The Miniscope is a miniature fluorescent microscope that can be implanted over a craniectomy to image microglia. Currently, the goals of Miniscope imaging are to improve image quality and develop time-lapse imaging capabilities. There were five main sub-projects that focused on these goals including surgical nose cone design, surgical holder design, improved GRIN lens setup, improved magnification through achromatic lenses, and time-lapse imaging hardware development. Completing these goals would allow for the visualization of microglia function in the healthy and injured brain, elucidating important immune functions that could provide new strategies for treating brain diseases.
ContributorsNelson, Andrew Frederick (Author) / Stabenfeldt, Sarah (Thesis director) / Lifshitz, Jonathan (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Octopus arms employ a complex three dimensional array of musculature, called a
muscular hydrostat, which allows for nearly infinite degrees of freedom of movement without
the structure of a skeletal system. This study employed Magnetic Resonance Imaging with a
Gadoteridol-based contrast agent to image the octopus arm and view the internal tissues. Muscle
layering was mapped and area was measured using AMIRA image processing and the trends in
these layers at the proximal, middle, and distal portions of the arms were analyzed. A total of 39
arms from 6 specimens were scanned to give 112 total imaged sections (38 proximal, 37 middle,
37 distal), from which to ascertain and study the possible differences in musculature. The
images revealed significant increases in the internal longitudinal muscle layer percentages
between the proximal and middle, proximal and distal, and middle and distal sections of the
arms. These structural differences are hypothesized to be used for rapid retraction of the distal
segment when encountering predators or noxious stimuli. In contrast, a significant decrease in
the transverse muscle layer was found when comparing the same sections. These structural
differences are hypothesized to be a result of bending behaviors during retraction. Additionally,
the internal longitudinal layer was separately studied orally, toward the sucker, and aborally,
away from the sucker. The significant differences in oral and aboral internal longitudinal
musculature in proximal, middle, and distal sections is hypothesized to support the pseudo-joint
functionality displayed in octopus fetching behaviors. The results indicate that individual
octopus arm morphology is more unique than previously thought and supports that internal
structural differences exist to support behavioral functionality.
muscular hydrostat, which allows for nearly infinite degrees of freedom of movement without
the structure of a skeletal system. This study employed Magnetic Resonance Imaging with a
Gadoteridol-based contrast agent to image the octopus arm and view the internal tissues. Muscle
layering was mapped and area was measured using AMIRA image processing and the trends in
these layers at the proximal, middle, and distal portions of the arms were analyzed. A total of 39
arms from 6 specimens were scanned to give 112 total imaged sections (38 proximal, 37 middle,
37 distal), from which to ascertain and study the possible differences in musculature. The
images revealed significant increases in the internal longitudinal muscle layer percentages
between the proximal and middle, proximal and distal, and middle and distal sections of the
arms. These structural differences are hypothesized to be used for rapid retraction of the distal
segment when encountering predators or noxious stimuli. In contrast, a significant decrease in
the transverse muscle layer was found when comparing the same sections. These structural
differences are hypothesized to be a result of bending behaviors during retraction. Additionally,
the internal longitudinal layer was separately studied orally, toward the sucker, and aborally,
away from the sucker. The significant differences in oral and aboral internal longitudinal
musculature in proximal, middle, and distal sections is hypothesized to support the pseudo-joint
functionality displayed in octopus fetching behaviors. The results indicate that individual
octopus arm morphology is more unique than previously thought and supports that internal
structural differences exist to support behavioral functionality.
ContributorsCummings, Sheldon Daniel (Author) / Fisher, Rebecca (Thesis director) / Marvi, Hamidreza (Committee member) / Cherry, Brian (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
To date, there have been few, if any, studies evaluating the venom toxin levels in dogs that have been naturally envenomated by pit vipers. Understanding venom toxin pharmacokinetics in a clinical setting is important for a variety of reasons, including the potential to better elucidate treatment options, prognosis, and other factors associated with pit viper envenomation. In addition, dogs serve as a comparative species to humans for evaluating pit viper envenomations. This pilot study’s primary objective was to address the question of “What do we see?” in dogs presenting for rattlesnake envenomation. To answer this question, we obtained serum from envenomated dogs presenting at three veterinary clinics, then used enzyme-linked immunosorbent assay (ELISA) and western blot analysis to measure total venom and key toxins in sera. Phospholipase A2, a primary venom toxin, was identified in a few samples by the western blot, and contributed to the positive correlation between percent echinocytes in the blood and venom concentration. Medical data records were compared to venom concentrations measured using ELISA to determine whether there were any significant correlations. First, the hematological results were compared. Clotting times showed a strong positive correlation, clotting times and platelets showed a negative correlation, while echinocytes and platelets showed no correlation. When compared to venom concentration, clotting times showed a negative correlation, while age showed a positive correlation. Weight and platelets were also compared to venom concentration, but no significant correlations were found. The logistics of this study provided a real-world model where time elapsed between envenomation and hospital admission, thus giving a realistic look at what occurs in both animal and human medicine.
ContributorsNelson, Alexis (Co-author, Co-author) / DeNardo, Dale (Thesis director) / Woods, Craig (Thesis director) / Varsani, Arvind (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
When an individual is conceived there is a metaphorical roll of the dice. A game of chance is played with their genetics to which they cannot consent. Unlucky players could have inherited mild conditions such as chronic allergies to terrible diseases such as Cystic Fibrosis or Tay-Sachs. Controlling the genetics of an individual through the use of gene editing technology could be the key to ending this cycle of genetic diseases. Once detrimental diseases are now being cured through direct applications of genetic engineering. Even as we see the uses of genetic engineering technologies change the world, the more “sci-fi” applications have yet to be fully realized or explored. Editing hereditary genes before birth may have the ability to eliminate diseases from entire genetic lines, reduce the possibility for certain cancers and diseases, and perhaps even modify phenotypes in humans to create enhanced humans. Although this scientific field shows promise, it does have its reservations. Like any other scientific field, its ability to benefit humanity depends on its use.
ContributorsSchuler, Jacob (Co-author) / Silva, Anthony (Co-author) / Brian, Jennifer (Thesis director) / Ross, Christian (Committee member) / Harrington Bioengineering Program (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Homeopathy is a brand of alternative medicine that has enjoyed a unique form of regulation for many years. This work aims to understand the regulation of homeopathic drugs in the United States by performing a literature review focused on three fronts: (i) homeopathy (theory, history in the United States and criticisms), (ii) U.S Food and Drug Administration (history and relationship to homeopathy), and (iii) interpretation of the law through reading guidance documents and the Code of Federal Regulations.
In 2015, the FDA began a process to reevaluate and update the regulations surrounding homeopathic products to better fit their present risk-based model. Past regulations were set in 1938; and as the world evolved, these have been found to set inadequate standards. By reviewing the agency’s guidance drafts and core regulatory documents, we come to understand that these changes are motivated by a desire for homeopathic remedies to follow high standards that apply to other products for the benefit of the U.S. consumers. FDA has made significant advances by proposing new Guidances on homeopathic products, listening to homeopathic community and consumers, and withdrawing the Compliance Policy Guide 400.400 issued in 1988.
We recommend for homeopathic manufacturers and practitioners to see the FDA as an ally and cooperate fully with the proposed changes for the regulation the agency gives out. Doing so will give the homeopathic community the best chance at continuing to sell their products and reach their consumers in the United States. In the same token, the FDA should do their best to involve homeopathic professionals in some way in this regulatory process, to encourage participation and compliance by the broader homeopathic community. Doing so ensures a climate of teamwork among different facets of the medical community in the United States.
In 2015, the FDA began a process to reevaluate and update the regulations surrounding homeopathic products to better fit their present risk-based model. Past regulations were set in 1938; and as the world evolved, these have been found to set inadequate standards. By reviewing the agency’s guidance drafts and core regulatory documents, we come to understand that these changes are motivated by a desire for homeopathic remedies to follow high standards that apply to other products for the benefit of the U.S. consumers. FDA has made significant advances by proposing new Guidances on homeopathic products, listening to homeopathic community and consumers, and withdrawing the Compliance Policy Guide 400.400 issued in 1988.
We recommend for homeopathic manufacturers and practitioners to see the FDA as an ally and cooperate fully with the proposed changes for the regulation the agency gives out. Doing so will give the homeopathic community the best chance at continuing to sell their products and reach their consumers in the United States. In the same token, the FDA should do their best to involve homeopathic professionals in some way in this regulatory process, to encourage participation and compliance by the broader homeopathic community. Doing so ensures a climate of teamwork among different facets of the medical community in the United States.
ContributorsRobayo, Juan Pablo (Author) / Pizziconi, Vincent (Thesis director) / Feigal, David (Committee member) / Frow, Emma (Committee member) / School of International Letters and Cultures (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Markov Chain Monte-Carlo methods are a Bayesian approach to predictive statistics, which takes advantage of prior beliefs and conditions as well as the existing data to produce posterior distributions of relevant parameters. This approach, implementable through the JAGS packaging in R, is promising for its impact on the diagnostics space, which is a critical bottleneck for pandemic planning and rapid response. Specifically, these methods provide the means to optimize diagnostic testing, for example, by determining whether it is best to test individuals in a certain locale once or multiple times. This study compares the expected accuracy of single and double testing under two specific conditions, a general and Icelandic test case, in order to ascertain the validity of MCMC methods in this space and inform decisionmakers and future research in the space. Models based on this platform may eventually be tailored to the priors of specific locales. Additionally, the ability to test multiple regimes of real or simulated data while maintaining uncertainty widens the pool of researchers that can impact the space. In future studies, ensemble methods investigating the full range of parameters and their combinations can be studied.
ContributorsSuresh, Tarun (Author) / Naufel, Mark (Thesis director) / Panchanathan, Sethuraman (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Post-truth has become a household word since the start of 2016. Post-truth is the concept that facts are becoming less useful towards swaying popular opinion. Post-truth is based off the ideation that the truth is laced in the metaphysical, which means that facts are independent of the human mind. Post-truth states two methods in which we derive truth: one is an objective truth, or a statement based on scientific and statistical analysis; the other is or a subjective truth, or a statement based on a feeling or value. Objective truth and subjective truth are interpretations of the “truth”: where objective truths use objective methods, such as research and statistics, and subjective truths use subjective methods, such as emotions or values. Further interpretations of post-truth interpret post-truth being a struggle between the objective truth and the subjective truth, and that objective truths are the correct interpretation of the truth. However, the current interpretation of post-truth becomes problematic. The case studies presented show that something that could be considered a subjective truth is grounded in reality, even though it is objectively wrong. There are instances where statistical analysis fails in its goals to represent reality in both war and science. There are also instances where capitalizing on the strongest emotional aspect of an issue creates a better understanding of that issue. The objective and subjective truths may not conflict with each other, in fact they may inform each other. The thesis concludes that a different interpretation of truth should be used to understand post-truth.
ContributorsSora, Nicholas (Author) / Fette, Donald (Thesis director) / O'Neill, Joseph (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Interictal spikes have been used to diagnose idiopathic seizure disorder and localize the seizure onset zone. Interictal spikes are thought to arise primarily from large excitatory postsynaptic potentials, and the role of interictal spikes in idiopathic seizure disorder and epileptogenesis remains unclear. We evaluated how local voltage changes due to interictal spikes impact action potential generation and firing using intracellular recordings from human tissue and the Hodgkin-Huxley model. During interictal spikes, bursts of action potentials underwent variable degrees of depolarization-induced inactivation in the intracellular data. Intracellular recordings in neocortical slices of human brain tissue confirmed that bursts of inactivated action potentials occurred during spontaneous paroxysmal depolarization shifts. These ex vitro findings were predicted using the Hodgkin-Huxley model and showed inactivated action potentials being generated by large depolarizations. As the amplitude of the interictal spike increased, there was a progression from low firing rate normal action potentials to higher firing rate normal action potentials to inactivated action potentials. The results show that the Hodgkin-Huxley model confirmed the effect of large interictal spike depolarizations on action potential firing and inactivation. This supports a key element in the hypothesis that interictal spikes, and the associated action potential firing, may alter the electrical environment of the brain and contribute to idiopathic seizure disorder.
ContributorsLossner, Lauren Nicole (Author) / Greger, Bradley (Thesis director) / Foldes, Stephen (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
Description
Eosinophilic Esophagitis (EoE) is a chronic autoimmune disease that causes inflammation of the esophagus due to food allergy. In pediatric EoE, remission can be reduced by 95% through the use of hypoallergenic amino acid formulas (AAF), however its bitter taste gives it poor palatability, making nutrition difficult. This thesis highlights the problem of poor palatability of AAF's and explores the idea of prototyping a new flavor enhanced recipe to minimize bitterness for EoE patients and how to evaluate it through sensory evaluation practices. Along the way, I also discovered that quail egg homogenate has novel therapeutic potential to reduce EoE symptoms.
ContributorsBorah, Priya Anjali (Co-author) / Holmes, Katherine (Co-author) / Serrano, Osvin (Co-author) / Spackman, Christy (Thesis director) / Schroeder, Shauna (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12