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Item Study of New Functionalized Nanomaterials for Non-Invasive Point-of-Care Biosensor Devices(North Dakota State University, 2021) Johnson, MichaelEarly disease detection and in-time health monitoring via novel sensing systems is highly demanded for modern medicine and health management. Recent development in nanotechnology and nanomaterials such as functionalized nanostructured metal-oxide semiconductors and newly discovered two-dimensional Ti3C2 MXenes have offered exciting areas of research as nanomaterial-based biomedical sensing devices. In this thesis, two major nanomaterials, KWO for application in diabetes and MXene for cancer management and further improvement of the KWO diabetes sensor, are intensively researched. KWO shows great potential as a breath acetone sensor, which can be utilized to monitor and diagnose diabetes. It also shows the unique ferroelectric property, which allows for a room-temperature sensing operation. Synthesis methods and characterization are done to further the understanding of KWO as an acetone sensor and further improve its capability towards becoming the cornerstone of a handheld biomedical sensor that is non-invasive, portable, and easy-to-use. Continuing, Ti3C2 MXenes are studied and characterized under various synthesis conditions to create both accordion-like structures with varying gap widths, and single-to-few layered nanosheets created by the intercalation of Li+ ions. Additionally, a new sensor based on 2D nanosheets, Ti3C2 MXene, has been designed and used for the sensing response to 8-HOA and PGE2 in lung cancer cells. The preliminary results indicate an important conclusion: this new Ti3C2-based sensor can provide a convenient and simple method for anti-cancer treatment guidance. Finally, a nanocomposite is synthesized using both KWO and Ti3C2 MXenes to improve the acetone sensor’s sensitivity and selectivity by majorly reducing humidity cross-interference.Item Dynamic 3D In Vitro Bone Metastatic Testbeds for Prostate and Breast Cancer(North Dakota State University, 2022) Jasuja, HaneeshMetastatic prostate cancer spreads preferentially to the bone, causing skeletal complications associated with significant morbidity and a poor prognosis, despite current therapeutic approaches. Increasing evidence suggests the synergistic role of biochemical and biophysical cues in cancer progression at metastases. However, the mechanism underlying the crosstalk between interstitial flow-induced mechanical stimuli and prostate cancer progression in the bone microenvironment remains poorly understood. To this end, we have developed 3D in vitro dynamic models of prostate cancer bone metastasis using perfusion bioreactor and horizontal flow bioreactor to delineate the role of flow-induced shear stress on prostate cancer progression and migration, respectively at metastases. Using a perfusion bioreactor, we observed changes in the expressions of MET biomarkers and the tumoroid morphologies of prostate cancer cells under dynamic culture. Evaluation of cell adhesion proteins indicated that the altered cancer cell morphologies resulted from the constant force pulling due to increased E-cadherin and FAK proteins under shear stress. Using a horizontal flow bioreactor, we demonstrated that the percent cell migration rate of prostate cancer cells was increased in the presence of bone under dynamic conditions. The results showed that interstitial fluid flow did not alter the CXCR4 level, but bone upregulated CXCR4 levels, leading to increased MMP-9 levels. In addition, both αvβ3 integrins and MMP-9 levels were upregulated by fluid flow conditions, contributing to an increased migration rate under dynamic conditions. Breast cancer cells also tend to preferentially disseminate to bone and colonize within the remodeling bone site to cause bone metastases. We have previously developed a 3D in vitro breast cancer bone metastasis model using hMSCs and commercial breast cancer cells (MCF-7 and MDAMB231), recapitulating late-stage breast cancer metastasis to bone. In the present study, we have validated our model using patient-derived breast cancer cell lines- NT013 and NT023, exhibiting hormone-positive and triple-negative characteristics, respectively that showed MET and formed tumors in the presence of bone. In addition, the results showed ET-1 (NT013) and DKK-1 (NT023) mediated stimulation and abrogation of the osteogenesis via Wnt/β catenin pathway, in line with our previous results with MCF-7 and MDAMB231 cell lines.Item Manipulation and Isolation of Biomolecules Using Dielectrophoretic and Hydrodynamic Methods(North Dakota State University, 2021) Oh, MyungkeunNovel particle manipulation techniques are developed to separate, isolate, and control a wide range biomolecules from DNA to cells in complex solution such as whole blood. First, we show that integrating an insulating tip with dielectrophoresis allows us to trap, carry, reposition, and relocate nanoscale objects, which can be used as molecular tweezers without fouling, electrolysis, and joule heating issues associated with conventional dielectrophoretic methods. In addition, we find that two theoretical force calculations (Clausius-Mossotti model and counter ion fluctuation model) result in a factor of 2-40 difference, but the magnitude of both is 4 orders stronger than the thermal force, which is strong enough to manipulate objects in the medium. Second, we perform sedimentation and size-based particle separation methods in a microfluidic device configuration. Using polydimethylsiloxane and its high gas solubility, we demonstrate a sedimentation-based, blood cell separation method. To further isolate small biomarkers such as exosomes utilizing a deterministic lateral displacement principle, we fabricate nanoscale pillar structures on a silicon wafer using multiple nanolithography processes and explore possibilities for size-dependent particle separation on the device.Item Enhanced Bone Tissue Regeneration Enabled with Tissue-Engineered Interlocking Nanoclay Scaffolds and Bone Morphogenic Proteins(North Dakota State University, 2022) Kundu, KrishnaAbout 6 million bone fractures occur annually in the US; 30% require bone grafting transplants to aid bone healing. Well-established clinical therapy techniques for bone regeneration suffer from limited availability, higher infection risk, donor site morbidity, and poor transplant integration. Delay in healing or nonunion of critical-sized defects is another concern in orthopedics. This dissertation focuses on constructing an interlocking scaffold structure to speed bone regeneration. In this thesis, a BMP-2 & 7 coated PCL-nanoclay-hydroxyapatite interlocking scaffold was developed to accelerate bone regeneration. Developed nano clay polymer interlocking scaffolds retain the scaffold's structural integrity and provide a large surface area while allowing for media interaction. Mesenchymal stem cells (MSCs) and osteoblast cells seeded at a 1:1 ratio boost cell viability and enable calcium deposition on day three and collagen production on day 7 with BMP-2 and BMP-7 coated scaffolds. In addition, BMPs, interlocking, and co-culturing of osteoblasts and MSCs promote osteogenic differentiation. In this dissertation, The long-term effect of BMP-2/BMP-7 on in-vitro utilizing interlocking scaffold blocks was evaluated. Changes to the nanomechanical properties of scaffolds and bone tissue during osteogenesis with the progression of ECM formation were reported. Gene expression results and Alizarin Red S staining images indicate a significant increase in mineralized bone nodules with BMPs coated samples compared with uncoated samples. Results suggest BMPs played a critical role in mineralized ECM production, which increased the scaffolds' elastic modulus. This research provides valuable insight into understanding how BMPs affect bone growth. In this dissertation, polymer clay nanocomposites fibers were constructed utilizing a pressured gyration setup and observed improved cell viability, osteogenic differentiation, ECM development, and collagen formation for PCL HAP MMT-Clay nanocomposite fiber scaffolds compared to pure PCL fibers. In this dissertation, the in-silico design of the unnatural amino acids modified clays and fabricated unnatural amino acids modified scaffolds were reported for application as cancer testbeds. This dissertation also reported the design of the in situ hydroxy apatite and tri-calcium phosphate incorporated nano clays polymer scaffolds for bone tissue engineering applications. These studies represent a new opportunity to design manufacturable composite nanoclay polymer scaffolds for bone tissue engineering applications.Item Adhesion With Slender Structures: Tape Loops, Crumples, and Origami(North Dakota State University, 2021) Elder, Theresa MarieThe desire for improved adhesive systems led us to examine three geometries: tape loops, crumples, and origami shapes. The tape loop is mechanically interesting because it is stable in more than one configuration. For example, the first configuration is a circular loop. The second is an elongated oval shape that occurs after the loop is pushed into a surface. In this work we examined this cycle and derive a simple mathematical model. We found a solution to the model that only needs one input measurement, that of the loop radius, to determine a tape loop’s adhesion. We explored how a sticky but crumpled film adhered to smooth and rough surfaces. To do this we crumpled inextensible sheets because crumples have been shown to maintain a high compliance while increasing contact area through deforming around obstacles. We found that there was no significant difference in the adhesive behavior of the crumples on rough surfaces compared to flat surfaces. Finally, we designed a switchable adhesive based on thin film origami. We examined a unit cell of the Ron Resch pattern which had two different configurations (open and closed) aided by a 3-D printed device In the closed state the device had a high pull off force, and in the open state a different style of peel off occurred, lowering the peak force. We present promising results that show this to be the case.Item In-Silico Investigation of Geological and Biological Materials by Molecular Dynamics Simulations(North Dakota State University, 2021) Faisal, H M NasrullahMolecular dynamics (MD) simulation is a computational technique that predicts the time-dependent behavior of a molecular system utilizing molecular mechanics. MD simulations are extensively employed in the scientific arena to investigate a wide range of material systems at the nanoscale (atoms and molecules), including organics, inorganics, polymer, composites, biomacromolecules, etc. This work investigates the properties of a range of geological (Green River oil shale and swelling clays) and biological materials (coronaviral proteins) at the molecular level using MD simulations. Oil shale, a sedimentary rock containing organic crude oil precursor named kerogen trapped in an inorganic mineral matrix, has long been considered an alternative source of petroleum. Molecular dynamics simulation of Green River oil shale Type I kerogen has been performed in the proximity of predominantly present calcite and quartz minerals to identify their binding interactions with trapped kerogen from the mineral matrix for efficient crude oil production. Sodium-montmorillonite (Na-MMT), a member of the smectite group, is one of the swelling clay minerals components that find various geo-environmental and industrial applications due to its high swelling capacity. Steered molecular dynamics (SMD) simulations have been performed to determine the nanomechanical properties of both dry and hydrated Na-MMT clay tactoid. Besides the geological materials, MD and SMD simulations have also been used to computationally inspect the coronaviral protein-ACE2 protein interactions to elucidate the potential reasons why COVID-19 results in significantly more infections and deaths compared to other coronaviruses. The coronaviral attachment to host cell through spike-ACE2 interactions and coronaviral replication mechanism through tri non-structural protein (nsp12-nsp7-nsp8) interactions have been simulated to understand the differences between SARS-CoV and SARSCoV-2 (COVID-19). The major findings obtained from coronaviral protein interactions may point towards the underlying reasons behind the severity of COVID-19. Moreover, the potency of different phytochemicals has been examined for breast cancer treatment. Compounds commonly found in Rhodiola, and Oregano plants extracts have been targeted against a series of breast cancer proteins utilizing molecular docking to determine the most potent phytochemical for breast cancer treatment.Item Investigating the Reduction of Fogging Behavior of Natural Fiber-Filled Polymers(North Dakota State University, 2021) Thanki, Nidhi ModhaSynthetic fibers such as glass and carbon are used as reinforcement in polymer composites due to their high strength and modulus. However, synthetic fibers are non-biodegradable and contribute to high costs. In literature, various natural fibers, including banana and sisal fiber, as reinforcement in a polymer matrix, are investigated for mechanical and thermal properties to overcome this challenge. Nevertheless, natural fibers bring their issues such as degradation and emissions of Volatiles Organic Compounds (VOCs), resulting in the fogging phenomena when exposed to heating-cooling cycles. In this study, effectiveness of addition of porous fillers in reducing VOCs emissions in biocomposites reinforced with natural fibers is investigated. Mechanical testing exhibited that adding the porous filler into the biocomposites did not hinder mechanical properties. It is hypothesized that adding the porous filler in the biocomposites could reduce the VOCs emission due to the pore structures absorbing the VOCs.Item Lignin and Cellulose Nanofibers Enhanced Corn-Based Thermoplastic Composites(North Dakota State University, 2021) Chen, YanlinThe goal of this project is to develop biobased thermoplastics and composites using corn as the main raw material. Corn contains mainly starch, zein, and oil. Thermoplastic starch/zein blends were prepared through internal mixing and extrusion. Lignin was used as a compatibilizer to refine the phase structure of the blend and increase the mechanical properties of the product. Scanning electron microscopy study showed that the incorporation of lignin significantly reduced the domain size of the zein phase in the blends. Modulus and tensile strength of the blend were increased greatly. Thermogravimetric analysis showed that the thermal stability of the blends was slightly improved after the incorporation of lignin. Cellulose nanofibrils (CNFs), a biobased nanomaterial, were also tested as a reinforcement for the blend. The incorporation of CNFs further enhanced the modulus and strength of the blends, suggesting a strong synergy between lignin and CNFs in reinforcing the corn-based thermoplastics.Item Tissue-Engineered Nanoclay-Based Bone-Mimetic 3D In Vitro Testbed for Studying Breast Cancer Metastasis to Bone(North Dakota State University, 2020) Kar, SumantaBreast cancer shows a high affinity towards the bone, causing bone-related complications leading to poor clinical prognosis. Approximately 80% of breast cancer patients die within five years after primary cancer has metastasized to the bones. The tumor stage strongly influences the survival rates of patients with breast cancer that has spread to bone at the time of diagnosis. There are currently no effective therapeutics available for bone metastases due to the failure of animal models and the scarcity of human bone metastasized samples, as most patients with advance stages of cancer are already in palliative care. Therefore, it is imperative to develop translational models to elucidate disease mechanisms at the cellular and molecular level. Here, we report the development of tissue-engineered nanoclay-based bone-mimetic three-dimensional (3D) in vitro model for studying later stages of cancer pathogenesis at the metastatic bone site using osteogenically-differentiated human mesenchymal stem cells (MSCs) and human breast cancer cells (MDA-MB-231 and MCF-7). This 3D model provides an ideal microenvironment suitable for cell-cell and cell-matrix interactions while retaining the behavior of breast cancer cells with different metastatic potential along with mimicking mesenchymal to epithelial transition (MET) of breast cancer cells. Sequential cultures of MSCs with MCF-7 gave rise to tumoroids, while sequential cultures of MSCs with MDA-MB-231 formed disorganized clusters of cells with poor cell-cell adhesion. We further evaluated how cancer-derived factors and cytokines affect bone leading to up to metastasis and conferring drug resistance, respectively. Results showed that Wnt/β-catenin and interleukin-6 (IL-6) mediated IL-6/STAT3 pathways are responsible for bone-related complications and conferring drug resistance, respectively. Furthermore, we have utilized the 3D in vitro model to develop methods for non-invasive and rapid prediction of cancer progression using various biophysical techniques such as spectroscopy and nanoindentation. Spectroscopy methods showed significant contributions of proteins, lipids, and nucleic acids, while the nanoindentation method showed F-actin mediated softening of cancer cells during cancer progression at the metastatic bone site, respectively. Collectively, 3D in vitro model provides an ideal platform for studying the molecular mechanism of breast cancer progression at the metastatic bone site, drug development, and discovery of biomarkers for cancer progression.Item Lead Halide Perovskite Nanocrystals: Photophysical and Photochemical Dynamics(North Dakota State University, 2021) Forde, Aaron ArthurLead halide perovskites nanocrystals (LHP NCs) are a recent novel material of ‘high-defect tolerance’ that has been synthesized which have provided a new platform for opto-electronic devices, such as photovoltaics and light-emitting diodes. Development of these materials for commercial devices requires a thorough understanding of their photo-physical properties. A comprehensive understanding of photo-physical properties involves studying the interplay between light-matter interactions, which produce photo-excited charge carriers and govern radiative recombination mechanism, carrier-lattice interactions, which play a dominate role in non-radiative dynamics such as hot-carrier cooling and recombination, and the NC surface chemistry which plays an important role in passivating surface sites which can potentially act as non-radiative recombination centers. In chapter 1 a review of the photo-physical phenomena and electronic processes which occur in materials is established and the motivation for incorporating nanomaterials into opto-electronic devise is provided. Chapter 2 describes in formal details the theoretical methods used to compute electronic structure, light-matter interactions, and carrier-lattice interactions are. Chapter 3 overviews simple physical models, such as particle-in-a-box photo-physics and two-level Redfield theory, which give intuition on how to understand the results of the research. Finally chapters 4-7 are devoted to original research on charge-carrier dynamics within a LHP NC atomistic model as free carriers, bound polarons, in the presence of surface defects, and finally in the presence of transition metal dopants. Chapter 4 provides computational evidence of slow electron cooling due to strong electronic confinement and large spin-orbit coupling contributed from Pb2+ 6p orbitals. Chapter 5 considers the effect of polaron formation on hot-carrier dynamics with the prediction of low efficiency polaron infrared photoluminescence. Chapter 6 provides mechanism for ‘defect tolerance’ due to bright electron surface trap states that form due to polaron reorganization. Chapter 7 models dual exciton-dopant luminescence due to Mn2+ doping.