Matching Items (28)
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- All Subjects: Biomedical Engineering
- Creators: Nikkhah, Mehdi
- Member of: Theses and Dissertations
- Resource Type: Text
Description
With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending on the conditions in which polymers are used, they are modified to accommodate a specific need. For instance, polymers used in drug delivery are more efficient if they are biodegradable. This ensures that the delivery system does not remain in the body after releasing the drug. It is therefore crucial that the polymer used in the drug system possess biodegradable properties. Such modification can be done in different ways including the use of peptides to make copolymers that will degrade in the presence of enzymes. In this work, we studied the effect of a polypeptide GAPGLL on the polymer NIPAAm and compare with the previously studied Poly(NIPAAm-co-GAPGLF). Both copolymers Poly(NIPAAm-co-GAPGLL) were first synthesized from Poly(NIPAAm-co-NASI) through nucleophilic substitution by the two peptides. The synthesis of these copolymers was confirmed by 1H NMR spectra and through cloud point measurement, the corresponding LCST was determined. Both copolymers were degraded by collagenase enzyme at 25 ° C and their 1H NMR spectra confirmed this process. Both copolymers were cleaved by collagenase, leading to an increase in solubility which yielded a higher LCST compared to before enzyme degradation. Future studies will focus on evaluating other peptides and also using other techniques such as Differential Scanning Microcalorimetry (DSC) to better observe the LCST behavior. Moreover, enzyme kinetics studies is also crucial to evaluate how fast the enzyme degrades each of the copolymers.
ContributorsUwiringiyimana, Mahoro Marie Chantal (Author) / Vernon, Brent (Thesis director) / Nikkhah, Mehdi (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Encapsulation is a promising technology to deliver cell-based therapies to patients safely and with reduced need for immunosuppression. Macroencapsulation devices are advantageous due to their ease of retrieval, and thus enhanced safety profile, relative to microencapsulation techniques. A major challenge in macroencapsulation device design is ensuring sufficient oxygen transport to encapsulated cells, requiring high surface area-to-volume device geometries. In this work, a hydrogel injection molding biofabrication method was modified to design and generate complex three-dimensional macroencapsulation devices that have greater complexity in the z-axis. The rheological properties of diverse hydrogels were evaluated and used to perform computational flow modeling within injection mold devices to evaluate pressure regimes suitable for cell viability. 3D printed device designs were evaluated for the reproducibility of hydrogel filling and extraction. This work demonstrated that injection molding biofabrication to construct complex three-dimensional geometries is feasible in pressure regimes consistent with preserving cell viability. Future work will evaluate encapsulated cell viability after injection molding.
ContributorsBrowning, Blake (Author) / Weaver, Jessica D (Thesis advisor) / Vernon, Brent (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2022
Description
Evolving knowledge about the tumor microenvironment (TME) is driving innovation in designing novel therapies against hard-to-treat breast cancer. Addressing the immune elements within the tumor microenvironment (TME) has emerged as a highly encouraging strategy for treating cancer. Although current immunotherapies have made advancements in reinstating the body's ability to fight tumors, the search for effective cancer treatments to combat tumor evasion remains a formidable challenge. In line with this objective, there is a pressing need to better understand the complex tumor-immune dynamics and crosstalk within the TME. To evaluate the cancer-immune interaction, this study aimed at investigating the crosstalk between naïve macrophages and cytotoxic T cells in driving tumor progression using an organotypic 3D ex vivo tumor on-a-chip model. The presented microfluidic platform consists of two distinct regions namely: The tumor region and the stroma region separated by trapezoidal microposts to ensure interconnectivity between regions thereby incorporating high spatial organization. In the established triculture platform, the complex Tumor Immune Microenvironment was successfully recapitulated by incorporating naïve macrophage and T cells within an appropriate 3D matrix. Through invasion and morphometric analyses, definitive outcomes were obtained that underscore the significant contribution of macrophages in facilitating tumor progression. Furthermore, the inclusion of T cells led to a notable decrease in the migratory speed of cancer cells and macrophages, underscoring the reciprocal communication between these two immune cell populations in the regulation of tumor advancement. Overall, this study highlights the complexity of TME and underscores the critical role of immune cells in regulating cancer progression.
ContributorsManoharan, Twinkle Jina Minette (Author) / Nikkhah, Mehdi (Thesis advisor) / Acharya, Abhinav P (Committee member) / Wang, Shaopeng (Committee member) / Arizona State University (Publisher)
Created2023
Description
DNA methylation (DNAm) is an epigenetic mark with a critical role in regulating gene expression. Altered clinical states, including toxin exposure and viral infections, can cause aberrant DNA methylation in cells, which may persist during cell division. Current methods to study genome-wide methylome profiles of the cells require a long processing time and are expensive. Here, a novel technique called Multiplexed Methylated DNA Immunoprecipitation Sequencing (Mx-MeDIP-Seq), which is amenable to automation. Up to 15 different samples can be combined into the same run of Mx-MeDIP-Seq, using only 25 ng of DNA per sample. Mx-MeDIP-Seq was used to study DNAm profiles of peripheral blood mononuclear cells (PBMCs) in two biologically distinct RNA viral infections with different modes of transmission, symptoms, and interaction with the host immune system: human immunodeficiency virus1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Analysis of 90 hospitalized patients with SARS-CoV-2 and 57 healthy controls revealed that SARS-CoV-2 infection led to alterations in 920 methylated regions in PBMCs, resulting in a change in transcription that affects host immune response and cell survival. Analysis of publicly available RNA-Sequencing data in COVID-19 correlated with DNAm in several key pathways. These findings provide a mechanistic view toward further understanding of viral infections. Genome-wide DNAm changes post HIV-1-infection from 37 chronically ill patients compared to 17 controls revealed dysregulation of the actin cytoskeleton, which could contribute to the establishment of latency in HIV-1 infections. Longitudinal DNAm analysis identified several potentially protective and harmful genes that could contribute to disease suppression or progression.
ContributorsRidha, Inam (Author) / LaBaer, Joshua (Thesis advisor) / Murugan, Vel (Thesis advisor) / Plaisier, Christopher (Committee member) / Nikkhah, Mehdi (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2022
Description
The blood-brain-barrier (BBB) is a significant obstacle for treating many neurological disorders. Bubble-assisted focused ultrasound (BAFUS) medicated BBB disruption is a promising technology that enables the delivery of large drug doses at targeted locations across the BBB. However, the current lack of an in vitro model of this process hinders the full understanding of BAFUS BBB disruption for better translation into clinics. In this work, a US-transparent organ-on-chip device has been fabricated that can be critical for the in vitro modeling of the BAFUS BBB disruption. The transparency of the device window to focused ultrasound (FUS) was calculated theoretically and demonstrated by experiments. Nanobubbles were fabricated, characterized by cryogenic transmission electron microscopy (cryo-TEM), and showed bubble cavitation under FUS. Human colorectal adenocarcinoma (Caco-2) cells were used to form a good cellular barrier for BAFUS barrier disruption, as suggested by the measured permeability and transepithelial electrical resistance (TEER). Finally, barrier disruption and recovery were observed in BAFUS disrupted US-transparent organ-on-chips with Caco-2 barriers, showing great promise of the platform for future modeling BAFUS BBB disruption in vitro.
ContributorsAkkad, Adam Rifat (Author) / Gu, Jian (Thesis advisor) / Nikkhah, Mehdi (Thesis advisor) / Belohlavek, Marek (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2022
Description
The development of biosensing platforms not only has an immediate lifesaving effect but also has a significant socio-economic impact. In this dissertation, three very important biomarkers with immense importance were chosen for further investigation, reducing the technological gap and improving their sensing platform.Firstly, gold nanoparticles (AuNP) aggregation and sedimentation-based assays were developed for the sensitive, specific, and rapid detection of Ebola virus secreted glycoprotein (sGP)and severe acute respiratory syndrome coronavirus 2 (SARS-COV2) receptor-binding domain (RBD) antigens. An extensive study was done to develop a complete assay workflow from critical nanobody generation to optimization of AuNP size for rapid detection. A rapid portable electronic reader costing (<$5, <100 cm3), and digital data output was developed. Together with the developed workflow, this portable electronic reader showed a high sensitivity (limit of detection of ~10 pg/mL, or 0.13 pM for sGP and ~40 pg/mL, or ~1.3 pM for RBD in diluted human serum), a high specificity, a large dynamic range (~7 logs), and accelerated readout within minutes. Secondly, A general framework was established for small molecule detection using plasmonic metal nanoparticles through wide-ranging investigation and optimization of assay parameters with demonstrated detection of Cannabidiol (CBD). An unfiltered assay suitable for personalized dosage monitoring was developed and demonstrated. A portable electronic reader demonstrated optoelectronic detection of CBD with a limit of detection (LOD) of <100 pM in urine and saliva, a large dynamic range (5 logs), and a high specificity that differentiates closely related Tetrahydrocannabinol (THC). Finally, with careful biomolecular design and expansion of the portable reader to a dual-wavelength detector the classification of antibodies based on their affinity to SARS-COV2 RBD and their ability to neutralize the RBD from binding to the human Angiotensin-Converting Enzyme 2 (ACE2) was demonstrated with the capability to detect antibody concentration as low as 1 pM and observed neutralization starting as low as 10 pM with different viral load and variant. This portable, low-cost, and versatile readout system holds great promise for rapid, digital, and portable data collection in the field of biosensing.
ContributorsIkbal, Md Ashif (Author) / Wang, Chao (Thesis advisor) / Goryll, Michael (Committee member) / Zhao, Yuji (Committee member) / Wang, Shaopeng (Committee member) / Arizona State University (Publisher)
Created2022
Description
Non-invasive biosensors enable rapid, real-time measurement and quantification of biological processes, such as metabolic state. Currently, the most accurate metabolic sensors are invasive, and significant cost is required, with few exceptions, to achieve similar accuracy using non-invasive methods. This research, conducted within the Biodesign Institute Center for Bioelectronics and Biosensors, leverages the selective reactivity of a chemical sensing solution to develop a sensor which measures acetone in the breath for ketosis and ketoacidosis diagnostics, which is relevant to body weight management and type I diabetes. The sensor displays a gradient of color changes, and the absorbance change is proportional to the acetone concentration in the part- per-million range, making applicable for detection ketosis and ketoacidosis in human breath samples. The colorimetric sensor response can be fitted to a Langmuir-like model for sensor calibration. The sensors best performance comes with turbulent, continuous exposure to the samples, rather than batch sample exposure. With that configuration, these novel sensors offer significant improvements to clinical and at- home measurement of ketosis and ketoacidosis.
ContributorsDenham, Landon (Author) / Forzani, Erica (Thesis advisor) / Wang, Shaopeng (Committee member) / Kulick, Doina (Committee member) / Arizona State University (Publisher)
Created2023
Description
Chimeric antigen receptor (CAR)-T cell therapy is a type of cancer immunotherapy has shown promising results in engineering the T cells which targets a specific antigen. Despite their success rate, there are certain limitations to the use of CAR-T therapies that includes cytokine release syndrome (CRS), neurologic toxicity, lack of response in approximately 50% of treated patients, monitoring of patients treated with CAR-T therapy. However, rapid point- of- care testing helps in quantifying the circulating CAR T cells and can enhance the safety of patients, minimize the cost of CAR-T cell therapy, and ease the management process. Currently, the standard method to quantify CAR-T cell in patient blood samples are flow cytometry and quantitative polymerase chain reaction (qPCR). But these techniques are expensive and are not easily accessible and suitable for point- of- care testing to assist real- time clinical decisions. To overcome these hurdles, here I propose a solution to these problems by rapid optical imaging (ROI)- based principle to monitor and detect CAR-T cells. In this project, a microfluidic device is developed and integrated with two functions: (1) Centrifuge free, filter- based separation of white blood cells and plasma; (2) Optical imaging- based technique for digital counting of CAR T- cells. Here, I carried out proof- of- concept test on the laser cut prototype microfluidic chips as well as the surface chemistry for specific capture of CAR-T cells. These data show that the microfluidic chip can specifically capture CAR-T positive cells with concentration dependent counts of captured cells. Further development of the technology could lead to a new tool to monitor the CAR-T cells and help the clinicians to effectively measure the efficacy of CAR-T therapy treatment in a faster and safer manner.
ContributorsElanghovan, Praveena (Author) / Wang, Shaopeng (Thesis advisor) / Forzani, Erica (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2023
Description
Recent breakthroughs in optical scattering-based imaging have enabledvisualization of entities as small as single proteins. Leveraging our innovation, Surface Enhanced Scattering Microscopy (SESM), detection of single protein binding kinetics and single DNA conformational changes have been achieved, showcasing the feasibility of single molecule imaging. In this dissertation, I aim to harness the potential of SESM and extend its relevance in the biomedical realm. My first goal is to conduct multiplexed protein detection and parallel binding kinetics analysis with label-free digital single- molecule counting. My second goal is focused on accurate quantification of cell force. An elastic model has been developed to quantify the cell-substrate interactions and have continuously tracked cell force evolutions upon small-molecule drugs (for example, acetylcholine) stimulation, achieving a temporal resolution of approximately 60 ms over the course of 30 min without attenuating the signals. The third goal is to achieve real- time tracking of DNA self-assembly dynamics. I have demonstrated SESM's capability to image individual DNA origami monomers and established an on-chip temperature annealing system to monitor the real-time progression of DNA self-assembly. The applications of the imaging method, spanning single proteins, single DNA origami, and single cells, are poised to impact the field of biology
ContributorsZhou, Xinyu (Author) / Wang, Shaopeng (Thesis advisor) / Nikkhah, Mehdi (Committee member) / Lindsay, Stuart (Committee member) / Presse, Steve (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2024
Description
Cardiovascular diseases (CVDs), including myocardial infarction (MI), are the major cause of death globally. Considerable research has been devoted in recent years to developing in vitro cardiac tissue models utilizing human induced pluripotent stem cells (hiPSCs) for regenerative medicine, disease modeling, and drug discovery applications. Notably, electroconductive hydrogel scaffolds have shown great promise in the development of functional hiPSC-derived cardiac tissues for both in vitro and in vivo cardiac research. However, the underlying mechanism(s) by which these nanoparticles contribute to the function and fate of stem cell-derived cardiac tissues have not been fully investigated. To address these knowledge gaps, this Ph.D. dissertation focuses on the mechanistic analysis of the impact of nanoengineered electroconductive hydrogel scaffolds on 2D and 3D hiPSC-derived cardiac tissues. Specifically, within the first phase of the project, hydrogel scaffolds were nanoengineered using either electroconductive or non-conductive nanoparticles to dissect the role of electroconductivity features of gold nanorods (GNRs) in the functionality of isogenic 2D hiPSC-derived cardiac patches. Extensive biological and electrophysiological assessments revealed that, while biophysical cues from the presence of nanoparticles could potentially play a role in cardiac tissue development, electroconductivity cues played a major role in enhancing the functional maturation of hiPSC-derived cardiac tissues in 2D cell-seeded cardiac patches. This dissertation further describes the application of GNRs in developing a biomimetic 3D electroconductive Heart-on-a-chip (eHOC) model. The 3D eHOC model was then leveraged to comprehensively investigate the cellular and molecular responses of isogenic human cardiac tissues to the electroconductive microenvironment through single-cell RNA sequencing (scRNAseq), an aspect not addressed in previous studies. The enhanced functional maturation of the 3D eHOC was demonstrated through extensive tissue-level and molecular-level assays. It was revealed that the GNR-based electroconductive microenvironment contributes to cardiac tissue development through the enrichment of calcium handling and cardiac contractile pathways.Overall, these findings offer additional insights into the role of electroconductive hydrogel scaffolds in regulating the functionalities of hiPSC-derived cardiac tissues. Furthermore, the proposed 3D eHOC platform could also serve as a more physiologically representative model of the in vivo microenvironment for in vitro applications, such as drug testing and disease modeling studies.
ContributorsEsmaeili, Hamid (Author) / Nikkhah, Mehdi (Thesis advisor) / Migrino, Raymond (Committee member) / Zhu, Wuqiang (Committee member) / Vernon, Brent (Committee member) / Weaver, Jessica (Committee member) / Arizona State University (Publisher)
Created2024