Matching Items (10)
Filtering by

Clear all filters

137147-Thumbnail Image.png
Description
Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize novel smart contrast agents for MRI that respond to temperature changes in tissue microenvironments. Transmission Electron Microscopy, Nuclear Magnetic Resonance,

Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize novel smart contrast agents for MRI that respond to temperature changes in tissue microenvironments. Transmission Electron Microscopy, Nuclear Magnetic Resonance, and cell culture growth assays were used to characterize the physical, magnetic, and cytotoxic properties of candidate nanoprobes. The nanoprobes displayed thermosensitve MR properties with decreasing relaxivity with temperature. Future work will be focused on generating and characterizing photo-active analogues of the nanoprobes that could be used for both treatment of tissues and assessment of therapy.
ContributorsHussain, Khateeb Hyder (Author) / Kodibagkar, Vikram (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2014-05
137180-Thumbnail Image.png
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

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
132413-Thumbnail Image.png
Description
Traumatic brain injury (TBI) is a major cause of disability, with approximately 1.7 million incidents reported annually. Following a TBI, patients are likely to sustain sensorimotor and cognitive impairments and are at an increased risk of developing neurodegenerative diseases later in life. Despite this, robust therapies that treat TBI neuropathology

Traumatic brain injury (TBI) is a major cause of disability, with approximately 1.7 million incidents reported annually. Following a TBI, patients are likely to sustain sensorimotor and cognitive impairments and are at an increased risk of developing neurodegenerative diseases later in life. Despite this, robust therapies that treat TBI neuropathology are not available in the clinic. One emerging therapeutic approach is to target epigenetic mediators that modulate a variety of molecular regulatory events acutely following injury. Specifically, previous studies demonstrated that histone deacetylase inhibitor (HDACi) administration following TBI reduced inflammation, enhanced functional outcomes, and was neuroprotective. Here, we evaluated a novel quisinostat-loaded PLA-PEG nanoparticle (QNP) therapy in treating TBI as modeled by a controlled cortical impact. We evaluated initial pharmacodynamics within the injured cortex via histone acetylation levels following QNP treatment. We observed that QNP administration acutely following injury increased histone acetylation specifically within the injury penumbra, as detected by Western blot analysis. Given this effect, we evaluated QNP therapeutic efficacy. We observed that QNP treatment dampened motor deficits as measured by increased rotarod latency to fall relative to blank nanoparticle- and saline-treated controls. Additionally, open field results show that QNP treatment altered locomotion following injury. These results suggest that HDACi therapies are a beneficial therapeutic strategy following neural injury and demonstrate the utility for nanoparticle formulations as a mode for HDACi delivery following TBI.
ContributorsMousa, Gergey (Author) / Stabenfeldt, Sarah (Thesis director) / Newbern, Jason (Committee member) / Sirianni, Rachael (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
133676-Thumbnail Image.png
Description
Gold nanoparticles are valuable for their distinct properties and nanotechnology applications. Because their properties are controlled in part by nanoparticle size, manipulation of synthesis method is vital, since the chosen synthesis method has a significant effect on nanoparticle size. By aiding mediating synthesis with proteins, unique nanoparticle structures can form,

Gold nanoparticles are valuable for their distinct properties and nanotechnology applications. Because their properties are controlled in part by nanoparticle size, manipulation of synthesis method is vital, since the chosen synthesis method has a significant effect on nanoparticle size. By aiding mediating synthesis with proteins, unique nanoparticle structures can form, which open new possibilities for potential applications. Furthermore, protein-mediated synthesis favors conditions that are more environmentally and biologically friendly than traditional synthesis methods. Thus far, gold particles have been synthesized through mediation with jack bean urease (JBU) and para mercaptobenzoic acid (p-MBA). Nanoparticles synthesized with JBU were 80-90nm diameter in size, while those mediated by p-MBA were revealed by TEM to have a size between 1-3 nm, which was consistent with the expectation based on the black-red color of solution. Future trials will feature replacement of p-MBA by amino acids of similar structure, followed by peptides containing similarly structured amino acids.
ContributorsHathorn, Gregory Michael (Author) / Nannenga, Brent (Thesis director) / Green, Matthew (Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description

Polymeric nanoparticles (NP) consisting of Poly Lactic-co-lactic acid - methyl polyethylene glycol (PLLA-mPEG) or Poly Lactic-co-Glycolic Acid (PLGA) are an emerging field of study for therapeutic and diagnostic applications. NPs have a variety of tunable physical characteristics like size, morphology, and surface topography. They can be loaded with therapeutic and/or

Polymeric nanoparticles (NP) consisting of Poly Lactic-co-lactic acid - methyl polyethylene glycol (PLLA-mPEG) or Poly Lactic-co-Glycolic Acid (PLGA) are an emerging field of study for therapeutic and diagnostic applications. NPs have a variety of tunable physical characteristics like size, morphology, and surface topography. They can be loaded with therapeutic and/or diagnostic agents, either on the surface or within the core. NP size is an important characteristic as it directly impacts clearance and where the particles can travel and bind in the body. To that end, the typical target size for NPs is 30-200 nm for the majority of applications. Fabricating NPs using the typical techniques such as drop emulsion, microfluidics, or traditional nanoprecipitation can be expensive and may not yield the appropriate particle size. Therefore, a need has emerged for low-cost fabrication methods that allow customization of NP physical characteristics with high reproducibility. In this study we manufactured a low-cost (<$210), open-source syringe pump that can be used in nanoprecipitation. A design of experiments was utilized to find the relationship between the independent variables: polymer concentration (mg/mL), agitation rate of aqueous solution (rpm), and injection rate of the polymer solution (mL/min) and the dependent variables: size (nm), zeta potential, and polydispersity index (PDI). The quarter factorial design consisted of 4 experiments, each of which was manufactured in batches of three. Each sample of each batch was measured three times via dynamic light scattering. The particles were made with PLLA-mPEG dissolved in a 50% dichloromethane and 50% acetone solution. The polymer solution was dispensed into the aqueous solution containing 0.3% polyvinyl alcohol (PVA). Data suggests that none of the factors had a statistically significant effect on NP size. However, all interactions and relationships showed that there was a negative correlation between the above defined input parameters and the NP size. The NP sizes ranged from 276.144 ± 14.710 nm at the largest to 185.611 ± 15.634 nm at the smallest. In conclusion, the low-cost syringe pump nanoprecipitation method can achieve small sizes like the ones reported with drop emulsion or microfluidics. While there are trends suggesting predictable tuning of physical characteristics, significant control over the customization has not yet been achieved.

ContributorsDalal, Dhrasti (Author) / Stabenfeldt, Sarah (Thesis director) / Wang, Kuei-Chun (Committee member) / Flores-Prieto, David (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
193396-Thumbnail Image.png
Description
Additive manufacturing, also known as 3D printing, has revolutionized modern manufacturing in several key areas: complex geometry fabrication, rapid prototyping and iteration, customization and personalization, reduced material waste, supply chain flexibility, complex assemblies and consolidated parts, and material innovation. As the technology continues to evolve, its impact on manufacturing is

Additive manufacturing, also known as 3D printing, has revolutionized modern manufacturing in several key areas: complex geometry fabrication, rapid prototyping and iteration, customization and personalization, reduced material waste, supply chain flexibility, complex assemblies and consolidated parts, and material innovation. As the technology continues to evolve, its impact on manufacturing is expected to grow, driving further innovation and reshaping traditional production processes. Some innovation examples in this field are inspired by natural or bio-systems, such as honeycomb structures for internal morphological control to increase strength, bio-mimetic composites for scaffold structures, or shape memory materials in 4D printing for targeted drug delivery. However, the technology is limited by its ability to manipulate multiple materials, especially tuning their submicron characteristics when they show non-compatible chemical or physical features. For example, the deposition and patterning of nanoparticles with different dimensions have seen little success, except in highly precise and slow 3D printing processes like aerojet or electrohydrodynamic. Taking inspiration from the layered patterns and structures found in nature, this research aims to demonstrate the development and versatility of a newly developed ink-based composite 3D printing mechanism called multiphase direct ink writing (MDIW). The MDIW is a multi-materials extrusion system, with a unique nozzle design that can accommodate two immiscible and non-compatible polymer or nano-composite solutions as feedstock. The intricate internal structure of the nozzle enables the rearrangement of the feedstock in alternating layers (i.e., ABAB...) and multiplied within each printed line. This research will first highlight the design and development of the MDIW 3D printing mechanism, followed by laminate processing to establish the requirements of layer formation in the XY-axis and the effect of layer formation on its microstructural and mechanical properties. Next, the versatility of the mechanism is also shown through the one-step fabrication of shape memory polymers with dual stimuli responsiveness, highlighting the 4D printing capabilities. Moreover, the MDIW's capability of dual nanoparticle patterning for manufacturing multi-functional carbon-carbon composites will be highlighted. Comprehensive and in-depth studies are conducted to investigate the morphology-structure-property relationships, demonstrating potential applications in structural engineering, smart and intelligent devices, miniature robotics, and high-temperature systems.
ContributorsRavichandran, Dharneedar (Author) / Nian, Qiong (Thesis advisor) / Song, Kenan (Committee member) / Green, Matthew (Committee member) / Jin, Kailong (Committee member) / Bhate, Dhruv (Committee member) / Arizona State University (Publisher)
Created2024
Description

Falls are known to be a common occurrence and a costly one as well, as they are the second leading cause of unintentional deaths and millions of other injuries worldwide. Falls often occur due to an increase in trunk flexion angle, so this experiment aims to reduce the trunk flexion

Falls are known to be a common occurrence and a costly one as well, as they are the second leading cause of unintentional deaths and millions of other injuries worldwide. Falls often occur due to an increase in trunk flexion angle, so this experiment aims to reduce the trunk flexion received while stepping over an obstacle. To achieve this a soft actuator was attached to the trunk and pressure was sent as subjects walked and stepped over an obstacle presented on a treadmill. The pressure is meant to stiffen the back which should in theory reduce the trunk flexion angle and lower the chances of falling. In this experiment, two groups were tested: three participants from a control group (healthy young adults) and three participants from an experimental group (healthy elderly adults). Since elderly adults have the highest fall risk due to overall lack of stability, they are the experimental group and the focus for this experiment. The results from the study showed that elderly adults had a beneficial effect with the soft actuator as there was a noticeable difference in trunk flexion when the device was attached. The experiment also supported prior research that stated that trunk flexion was greater in elderly adults than younger adults. Despite the positive results, further studies should be done to prove that the soft devices influence lowering trunk flexion angle as well as to see if the device has any noticeable effect on younger adults.

ContributorsFisher, Caleb (Author) / Lee, Hyunglae (Thesis director) / Olivas, Alyssa (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
157255-Thumbnail Image.png
Description
Rapid development of new technology has significantly disrupted the way radiotherapy is planned and delivered. These processes involve delivering high radiation doses to the target tumor while minimizing dose to the surrounding healthy tissue. However, with rapid implementation of these new technologies, there is a need for the detection of

Rapid development of new technology has significantly disrupted the way radiotherapy is planned and delivered. These processes involve delivering high radiation doses to the target tumor while minimizing dose to the surrounding healthy tissue. However, with rapid implementation of these new technologies, there is a need for the detection of prescribed ionizing radiation for radioprotection of the patient and quality assurance of the technique employed. Most available clinical sensors are subjected to various limitations including requirement of extensive training, loss of readout with sequential measurements, sensitivity to light and post-irradiation wait time prior to analysis. Considering these disadvantages, there is still a need for a sensor that can be fabricated with ease and still operate effectively in predicting the delivered radiation dose.



The dissertation discusses the development of a sensor that changes color upon exposure to therapeutic levels of ionizing radiation used during routine radiotherapy. The underlying principle behind the sensor is based on the formation of gold nanoparticles from its colorless precursor salt solution upon exposure to ionizing radiation. Exposure to ionizing radiation generates free radicals which reduce ionic gold to its zerovalent gold form which further nucleate and mature into nanoparticles. The generation of these nanoparticles render a change in color from colorless to a maroon/pink depending on the intensity of incident ionizing radiation. The shade and the intensity of the color developed is used to quantitatively and qualitatively predict the prescribed radiation dose.

The dissertation further describes the applicability of sensor to detect a wide range of ionizing radiation including high energy photons, protons, electrons and emissions from radioactive isotopes while remaining insensitive to non-ionizing radiation. The sensor was further augmented with a capability to differentiate regions that are irradiated and non-irradiated in two dimensions. The dissertation further describes the ability of the sensor to predict dose deposition in all three dimensions. The efficacy of the sensor to predict the prescribed dose delivered to canine patients undergoing radiotherapy was also demonstrated. All these taken together demonstrate the potential of this technology to be translatable to the clinic to ensure patient safety during routine radiotherapy.
ContributorsSubramaniam Pushpavanam, Karthik (Author) / Rege, Kaushal (Thesis advisor) / Sapareto, Stephen (Committee member) / Nannenga, Brent (Committee member) / Green, Matthew (Committee member) / Mu, Bin (Committee member) / Arizona State University (Publisher)
Created2019
155698-Thumbnail Image.png
Description
A comprehensive and systematic investigation on the diffusion and phase behaviors of nanoparticles and macromolecules in two component liquid-liquid systems via Molecule Dynamic (MD) simulations is presented in this dissertation.

The interface of biphasic liquid systems has attracted great attention because it offers a simple, flexible, and highly reproducible template for

A comprehensive and systematic investigation on the diffusion and phase behaviors of nanoparticles and macromolecules in two component liquid-liquid systems via Molecule Dynamic (MD) simulations is presented in this dissertation.

The interface of biphasic liquid systems has attracted great attention because it offers a simple, flexible, and highly reproducible template for the assembly of a variety of nanoscale objects. However, certain important fundamental issues at the interface have not been fully explored, especially when the size of the object is comparable with the liquid molecules. In the first MD simulation system, the diffusion and self-assembly of nanoparticles with different size, shape and surface composition were studied in an oil/water system. It has been found that a highly symmetrical nanoparticle with uniform surface (e.g. buckyball) can lead to a better-defined solvation shell which makes the “effective radius” of the nanoparticle larger than its own radius, and thus, lead to slower transport (diffusion) of the nanoparticles across the oil-water interface. Poly(N-isopropylacrylamide) (PNIPAM) is a thermoresponsive polymer with a Lower Critical Solution Temperature (LCST) of 32°C in pure water. It is one of the most widely studied stimulus-responsive polymers which can be fabricated into various forms of smart materials. However, current understanding about the diffusive and phase behaviors of PNIPAM in ionic liquids/water system is very limited. Therefore, two biphasic water-ionic liquids (ILs) systems were created to investigate the interfacial behavior of PNIPAM in such unique liquid-liquid interface. It was found the phase preference of PNIPAM below/above its LCST is dependent on the nature of ionic liquids. This potentially allows us to manipulate the interfacial behavior of macromolecules by tuning the properties of ionic liquids and minimizing the need for expensive polymer functionalization. In addition, to seek a more comprehensive understanding of the effects of ionic liquids on the phase behavior of PNIPAM, PNIPAM was studied in two miscible ionic liquids/water systems. The thermodynamic origin causes the reduction of LCST of PNIPAM in imidazolium based ionic liquids/water system was found. Energy analysis, hydrogen boding calculation and detailed structural quantification were presented in this study to support the conclusions.
ContributorsGao, Wei (Author) / Dai, Lenore (Thesis advisor) / Jiao, Yang (Committee member) / Liu, Yongming (Committee member) / Green, Matthew (Committee member) / Emady, Heather (Committee member) / Arizona State University (Publisher)
Created2017
135508-Thumbnail Image.png
Description
Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method due to their biocompatibility and ability to be modified by

Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method due to their biocompatibility and ability to be modified by cell penetrating peptides, such as transactivating transciptor (TAT) peptide, which has been shown to increase efficiency of delivery. There are multiple proposed mechanisms of TAT-mediated delivery that also have size restrictions on the molecules that can undergo each BBB crossing mechanism. The effect of nanoparticle size on TAT-mediated delivery in vivo is an important aspect to research in order to better understand the delivery mechanisms and to create more efficient NPs. NPs called FluoSpheres are used because they come in defined diameters unlike polymeric NPs that have a broad distribution of diameters. Both modified and unmodified 100nm and 200nm NPs were able to bypass the BBB and were seen in the brain, spinal cord, liver, and spleen using confocal microscopy and a biodistribution study. Statistically significant differences in delivery rate of the different sized NPs or between TAT-modified and unmodified NPs were not found. Therefore in future work a larger range of diameter size will be evaluated. Also the unmodified NPs will be conjugated with scrambled peptide to ensure that both unmodified and TAT-modified NPs are prepared in identical fashion to better understand the role of size on TAT targeting. Although all the NPs were able to bypass the BBB, future work will hopefully provide a better representation of how NP size effects the rate of TAT-mediated delivery to the CNS.
ContributorsCeton, Ricki Ronea (Author) / Stabenfeldt, Sarah (Thesis director) / Sirianni, Rachael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05