Matching Items (21)
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- All Subjects: Traumatic Brain Injury
- All Subjects: electrochemistry
- Creators: Harrington Bioengineering Program
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Description
Traumatic brain injury (TBI) may result in numerous pathologies that cannot currently be mitigated by clinical interventions. Stem cell therapies are widely researched to address TBI-related pathologies with limited success in pre-clinical models due to limitations in transplant survival rates. To address this issue, the use of tissue engineered scaffolds as a delivery mechanism has been explored to improve survival and engraftment rates. Previous work with hyaluronic acid \u2014 laminin (HA-Lm) gels found high viability and engraftment rates of mouse fetal derived neural progenitor/stem cells (NPSCs) cultured on the gel. Furthermore, NPSCs exposed to the HA-Lm gels exhibit increased expression of CXCR4, a critical surface receptor that promotes cell migration. We hypothesized that culturing hNPCs on the HA-Lm gel would increase CXCR4 expression, and thus enhance their ability to migrate into sites of tissue damage. In order to test this hypothesis, we designed gel scaffolds with mechanical properties that were optimized to match that of the natural extracellular matrix. A live/dead assay showed that hNPCs preferred the gel with this optimized formulation, compared to a stiffer gel that was used in the CXCR4 expression experiment. We found that there may be increased CXCR4 expression of hNPCs plated on the HA-Lm gel after 24 hours, indicating that HA-Lm gels may provide a valuable scaffold to support viability and migration of hNPCs to the injury site. Future studies aimed at verifying increased CXCR4 expression of hNPCs cultured on HA-Lm gels are necessary to determine if HA-Lm gels can provide a beneficial scaffold for stem cell engraftment therapy for treating TBI.
ContributorsHemphill, Kathryn Elizabeth (Author) / Stabenfeldt, Sarah (Thesis director) / Brafman, David (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
DescriptionMy main goal for my thesis is in conjunction with the research I started in the summer of 2010 regarding the creation of a TBI continuous-time sensor. Such goals include: characterizing the proteins in sensing targets while immobilized, while free in solution, and while in free solution in the blood.
ContributorsHaselwood, Brittney (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Cook, Curtiss (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2011-12
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
The endogenous response of neural stem cell/progenitor (NPSC) recruitment to the brain injury environment following a traumatic brain injury (TBI) is currently under heavy investigation. Mechanisms controlling NPSC proliferation and migration to the brain injury environment remain unclear; however, it is thought that the vascular extracellular matrix proteins (e.g. laminin, fibronectin, and vitronectin) and vascular endothelial growth factor (VEGF) play a role in mediating NPSC behavior through vasophillic interactions. This project attempts to uncover potential VEGF-ECM crosstalk in mediating migration and proliferation. To investigate migration, neurospheres were seeded on ECM-coated wells supplemented with VEGF and without VEGF, and neural outgrowth was measured at days 0, 1, 3, and 8 using differential interference contrast microscopy. Furthermore, single-cell NPSCs were seeded on ECM-coated Transwell membranes with VEGF supplemented media on one side and without VEGF to look at chemotactic migration. Migrated NPSCs were visualized with DAPI nuclear stain and imaged with an inverted fluorescent microscope. To investigate NPSC proliferation, NPSCs were seeded on ECM coated plates as in the radial migration assay and visualized with EdU on day 8. Total proliferation was measured by seeding NPSCs on ECM coated 96-well plates and incubating them with MTT on days 3 and 6. Proliferation was measured using a spectrophotometer at 630nm and 570nm wavelengths. It was found that VEGF-laminin crosstalk synergistically increased radial migration, but may not play a role in chemotactic migration. Understanding the mechanisms behind VEGF-laminin crosstalk in NPSC proliferation and migration may provide crucial information for the design of stem cell transplantation therapies in the future.
ContributorsMillar-Haskell, Catherine Susan (Author) / Stabenfeldt, Sarah (Thesis director) / Addington, Caroline (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (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
Diabetes mellitus is a disease characterized by many chronic and acute conditions. With the prevalence and cost quickly increasing, we seek to improve on the current standard of care and create a rapid, label free sensor for glycated albumin (GA) index using electrochemical impedance spectroscopy (EIS). The antibody, anti-HA, was fixed to gold electrodes and a sine wave of sweeping frequencies was induced with a range of HA, GA, and GA with HA concentrations. Each frequency in the impedance sweep was analyzed for highest response and R-squared value. The frequency with both factors optimized is specific for both the antibody-antigen binding interactions with HA and GA and was determined to be 1476 Hz and 1.18 Hz respectively in purified solutions. The correlation slope between the impedance response and concentration for albumin (0 \u2014 5400 mg/dL of albumin) was determined to be 72.28 ohm/ln(mg/dL) with an R-square value of 0.89 with a 2.27 lower limit of detection. The correlation slope between the impedance response and concentration for glycated albumin (0 \u2014 108 mg/dL) was determined to be -876.96 ohm/ln(mg/dL) with an R-squared value of 0.70 with a 0.92 mg/dL lower limit of detection (LLD). The above data confirms that EIS offers a new method of GA detection by providing unique correlation with albumin as well as glycated albumin. The unique frequency response of GA and HA allows for modulation of alternating current signals so that several other markers important in the management of diabetes could be measured with a single sensor. Future work will be necessary to establish multimarker sensing on one electrode.
ContributorsEusebio, Francis Ang (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
The main objective of this research is to develop and characterize a targeted contrast agent that will recognize acute neural injury pathology (i.e. fibrin) after traumatic brain injury (TBI). Single chain fragment variable antibodies (scFv) that bind specifically to fibrin have been produced and purified. DSPE-PEG micelles have been produced and the scFv has been conjugated to the surface of the micelles; this nanoparticle system will be used to overcome limitations in diagnosing TBI. The binding and imaging properties will be analyzed in the future to determine functionality of the nanoparticle system in vivo.
ContributorsRumbo, Kailey Michelle (Author) / Stabenfeldt, Sarah (Thesis director) / Kodibagkar, Vikram (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Acetaminophen, commonly found in Tylenol and other over the counter (OTC) pharmaceuticals, was electrochemically characterized on custom made, flexible, screen printed electrodes (SPEs) to serve as a model target pharmaceutical found in flowing water lines. Carbon, silver/silver chloride, and insulator paste inks were printed onto polyethylene naphthalateolyester (PEN) using custom made stencils for a 4x1 array of 3-electrode electrochemical cells. Cyclic voltammetry was performed to find the electrical potential corresponding to the greatest current response and the experiments were conducted using amperometric current-time mode (AMP*i-t). The physical limitations of SPEs as well as the detection limitations of the target, such as pH and temperature were tested. A concentration gradient of the target was fitted with a linear curve (R2 0.99), and a lower limit of detection of 14.5 μM. It was also found that both pH and temperature affect the current produced by acetaminophen at a fixed concentration, and that the sensors can detect target in a continuous flow. A flow apparatus consisting of an inlet and effluent pipe served as the flow model into which a rolled up flexible electrode array was inserted. The broader goal of this research is to develop a highly sensitive electrode array on flexible substrates which can detect multiple targets simultaneously. Acetaminophen was chosen due to its electro-active properties and its presence in most public water lines in the United States.
ContributorsMaxwell, Stephanie Ann (Author) / LaBelle, Jeffrey (Thesis director) / Allee, David (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Traumatic brain injury (TBI) can result in many pathologies, one of which being coagulopathy. TBI can progress to hemorrhagic lesions and increased intercranial pressure leading to coagulopathy. The coagulopathy has been linked to poor clinical outcomes and occurs in 60% of severe TBI cases. To improve hemostasis, synthetic platelets (SPs) have been repurposed. SPs are composed of a poly(N-isopropylacrylamide-co-acrylic-acid) microgel, conjugated with a fibrin-specific antibody and are biomimetic in their ability to deform and collapse within a fibrin matrix. The objective of this study is to diminish coagulopathy with a single, intravenous injection of SPs, and subsequently decrease neuropathologies. TBI was modeled in animal cohorts using the well-established controlled cortical impact and SPs were injected 2-3 hours post-injury. Control cohorts received no injection. Brain tissue was harvested at acute (24h) and delayed (7 days) time points post-TBI, and fluorescently imaged to quantify reactive astrocytes (GFAP+), microglial morphology and presence (Iba1+), and tissue lesion spared. SP-treatment resulted in significant reduction of GFAP expression at 7 days post-TBI. Furthermore, SP-treatment significantly reduced the percent difference from 24h to 7 days in microglia/macrophage per field compared to the control. For microglial morphology, SP-treated cohorts observed a significant percent difference in endpoints per soma from 24h to 7 days compared to untreated cohorts. However, microglial branch length significantly decreased in percent difference from 24h to 7 days when compared to the control. Finally, tissue sparing did not significantly decrease between 24h and 7 day for SP-treated cohorts as was observed in untreated cohorts, implying inhibition of delayed necrosis. Overall, these results suggest decreased neuroinflammation by 7 days, supporting SPs as potentially therapeutic post-TBI.
ContributorsTodd, Jordan Cecile (Author) / Stabenfeldt, Sarah (Thesis director) / Bharadwaj, Vimala (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Previous studies have found that the detection of near-threshold stimuli is decreased immediately before movement and throughout movement production. This has been suggested to occur through the use of the internal forward model processing an efferent copy of the motor command and creating a prediction that is used to cancel out the resulting sensory feedback. Currently, there are no published accounts of the perception of tactile signals for motor tasks and contexts related to the lips during both speech planning and production. In this study, we measured the responsiveness of the somatosensory system during speech planning using light electrical stimulation below the lower lip by comparing perception during mixed speaking and silent reading conditions. Participants were asked to judge whether a constant near-threshold electrical stimulation (subject-specific intensity, 85% detected at rest) was present during different time points relative to an initial visual cue. In the speaking condition, participants overtly produced target words shown on a computer monitor. In the reading condition, participants read the same target words silently to themselves without any movement or sound. We found that detection of the stimulus was attenuated during speaking conditions while remaining at a constant level close to the perceptual threshold throughout the silent reading condition. Perceptual modulation was most intense during speech production and showed some attenuation just prior to speech production during the planning period of speech. This demonstrates that there is a significant decrease in the responsiveness of the somatosensory system during speech production as well as milliseconds before speech is even produced which has implications for speech disorders such as stuttering and schizophrenia with pronounced deficits in the somatosensory system.
ContributorsMcguffin, Brianna Jean (Author) / Daliri, Ayoub (Thesis director) / Liss, Julie (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05