Published ETD Collection
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Browsing Published ETD Collection by Author "Abidian, Mohammad Reza"
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Item 3D Printing of Composite Organic Semiconductor Microdevices for Biosensors and Organic Bioelectronics(2022-05-12) Dadras, Omid; Abidian, Mohammad Reza; Mohan, Chandra; Majd, Sheereen; Raghunathan, Vijaykrishna; Chen, Tai-YenBioelectronic devices aim to alleviate symptoms or return function to patients suffering from neural disorders / injuries. Choice of functional material and employment of advanced fabrication techniques constitute key elements in ultimate success of these devices. As an alternative to traditional metallic platforms, organic electroactive materials have garnered tremendous attention in neural devices. Consequently, the emerging field of organic bioelectronics has sought to interface the organic-based devices with the soft and ion-dominated neural tissue. Organic semiconductor materials (OSs), i.e. conjugated polymers, have emerged as one of the ideal candidates for neural interfaces, owing to their biocompatibility, soft mechanical properties, and mixed electronic / ionic conductivity. This thesis is primarily focused on development of soft and conductive micron-scale platforms for applications in organic bioelectronics and biosensors. In the course of the projects, much attention has been devoted towards design of microelectronic devices, employing advanced fabrication techniques, and formulation of composite biomaterials based on two common OSs; poly(3,4-ethylenedioxythiophene) and polypyrrole. The theme of research projects falls into two main categories: 1. Soft and bioactive platforms for neural regeneration, and 2. 3D-printed conductive microelectronic devices for organic bioelectronics and biosensors. In the first category, we have developed a micro-patterning technique and have created various profiles of laminin gradients on surface of OS thin films, which can be potentially employed for neural regeneration. The second category deals with design, fabrication and characterization of 3D-printed microelectronic devices. First, we have explored 3D printing of soft, conductive, and bioactive microstructures via direct laser writing, also known as multi-photon polymerization lithography (MPL). We have formulated conductive photosensitive inks, and fabrication and characterization of microelectronic devices such as hybrid neural microelectrodes, bioactive microstructures and high-performance glucose biosensors have been successfully demonstrated. We also report on development of an in-house 3D printing technique for fabrication of OS microdevices based on in-situ electrochemical polymerization. Microelectronic devices, bioactive structures and glucose biosensors have been fabricated using this technique. Overall, we envision that these microelectronic devices and platforms pave the way towards development of next-generation neural interfaces for organic bioelectronics and biosensing applications.Item An in Vitro Investigation on Polymeric-Core Lipid Nano-carriers’ Transport across Biological Barriers and Use for Delivery of Cancer Therapeutics(2022-12-13) Kuo, Chung-Fan; Majd, Sheereen; Mohan, Chandra; Abidian, Mohammad Reza; Raghunathan, Vijaykrishna; Sirianni, Rachael W.Delivery of therapeutic and diagnostic compounds to specific sites in the body often faces several challenges. Among these challenges are crossing the obstacles created by biological barriers, such as the blood-brain barrier (BBB) and lymphatic endothelial layer, cell selectivity and efficient uptake, and retaining activity. In recent decades, nanoparticles (NPs) particularly those composed of biocompatible materials such as lipids and polymers have shown the ability to overcome these hurdles to some extent and have thus, become attractive candidates for delivery purposes in various medical applications. To date, several intrinsic physicochemical properties of NPs, such as size and surface charge, have proven to be critical in modulating NPs’ bio-distribution including their transport across biological barriers. Recent studies have suggested that NP bio-distribution is also affected by NP mechanical properties including rigidity. Such effect may in part be due to the impact of NP’s rigidity on crossing the above-mentioned barriers in the body. Centered around this hypothesis, the first part of this thesis investigates the influence of NPs’ rigidity on their ability to cross BBB and lymphatic endothelium in vitro. This part further examines the impact of NP rigidity on their interactions with brain tumor cells, for the first time. To this end, we first optimized an in vitro BBB trans-well model by evaluating several culture conditions individually and in combination, characterized by trans-endothelial electric resistance (TEER), tight junction protein expression, and barrier permeability. NPs with different elastic moduli were then prepared and evaluated for their transport across the optimized BBB model, using a new approach that relied on nanoparticle tracking analysis (NTA). We also assessed the uptake of these NPs by human glioblastoma U87 cells, as a model target. Next, we investigated the impact of rigidity on NPs traveling through the initial lymphatics under physiological conditions in vitro. These transport studies were conducted using an in vitro lymphatic endothelium trans-well model that we developed under either static or dynamic conditions. The influence of the particle elasticity along with the particle size was investigated. The second part of this thesis focuses on development and assessment of a nano-carrier for delivery of a potent cancer therapeutic, di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), to enable its safe and targeted delivery to cancerous cells. To this end, we applied NPs of poly(lactic-co-glycolic acid) (PLGA) modified with either lipids or PVA (polyvinyl alcohol) to encapsulate DpC and characterized the resultant NP for size, charge, stability, encapsulation efficiency and release of DpC. Finally, the cytotoxicity of these DpC-loaded NPs were studied in three different cancer cell lines of human glioblastoma (U87), breast cancer (MCF7), and colorectal cancer cells (HT29).Item Coaxial Electrospinning of Protein-Encapsulated Core-Shell Nanofibers: Process Optimization and Release Modeling(2019-12) Hariprasad, Bhoomija; Abidian, Mohammad Reza; Mohan, Chandra; Majd, SheereenCoaxial electrospinning is a novel method for encapsulation of protein drugs into polymeric materials for use in drug delivery systems. In this study, coaxial electrospinning was used to fabricate aligned polyethylene oxide/poly(lactic-co-glycolic acid) core-shell nanofibers encapsulated with nerve growth factor (NGF), a trophic agent for axonal regeneration. Electrospinning processing parameters, namely inner and outer flow rates, wheel speed, needle-wheel distance, and applied voltage, were optimized using design of experiment (DOE) methodology to achieve nanofibers with minimized diameter and size distribution. The resulting prediction models were validated using analysis of variance. Optimized fibers were incubated in phosphate-buffered saline (PBS) for 3 days, and the released NGF was characterized at different time points using ELISA. The NGF release profile was mathematically modeled utilizing the Korsmeyer-Peppas and zero-order models. The results of this study can be applied to drug delivery systems for neural regeneration.Item CONJUGATED POLYMER NANOFIBERS FOR ORGANIC BIOELECTRONICS AND BIOACTUATORS(2021-05) Eslamian, Mohammadjavad; Abidian, Mohammad Reza; Mohan, Chandra; Romero-Ortega, Mario I.; Majd, Sheereen; Raghunathan, VijaykrishnaThe emerging field of organic bioelectronics bridges the electronic world of organic-semiconductor-based devices with the soft, predominantly ionic world of biology. Conjugated polymers (CPs) are one of the most promising organic materials for biointerfaces owing to their biologically relevant mechanical characteristics, ability to be chemically modified, mixed electronic and ionic charge transport, and facile and versatile fabrication routes. CP nanofibers have been of great attention because of their extensive porosity and extremely high surface area to volume ratio that result in their high electronic/ionic conductivity and unique electro-chemo-mechanical properties. Thus far, CP nanofibers have been employed for biomedical applications such as biosensors, nerve tissue regeneration, controlled drug delivery devices, and surface modification of neural interfaces. This thesis is mainly focused on the state-of-the-art utilization of CP nanofibers for development of high performance organic bioactuators and for articulating flexible neural microelectrodes with movable recording sites. We first explored the ion transportation mechanisms in actuation of the two most versatile CPs, poly(pyrrole) and poly(3,4-ethylenedioxythiophene), in the form of randomly oriented nanofibers through direct mass measurement under cyclic voltammetry coupled with electrochemical quartz crystal microbalance. Understanding the actuation behavior of the CP nanofibers, we developed a high-performance bilayer beam actuator based on poly(pyrrole) nanofibers (PPy NFs) that efficiently operate in liquid and gel-polymer electrolytes. We studied the dynamics of the actuator using theoretical analysis and experimental measurements of motion and mass transport. The actuator demonstrated an impressive performance, including low power consumption per strain percentage, large deformation, fast response, and excellent actuation stability. Ultimately, the concept of PPy NFs actuators was deployed for microfabrication of flexible neural microelectrodes with movable projections that enable to control the position of electrode recording sites in cerebral environment. We anticipate that the CP nanofiber-based actuators will be utilized for advancement of next generation actuators in the fields of soft robotics, artificial muscles, and biomedical devices.Item DESIGN AND DEVELOPMENT OF PATCHY LIPOSOMES AS POTENTIAL DELIVERY CARRIERS WITH ENHANCED FUSOGENICITY OR BINDING ABILITY(2023-05-11) Wang, Yifei; Majd, Sheereen; Abidian, Mohammad Reza; Wu, Tianfu; Chow, Diana Shu-Lian; Du, GuangweiNanoliposomes are one of the most commonly used delivery nanocarriers due to their biocompatibility, biodegradability, and low toxicity. To achieve high levels of cellular uptake, liposomes often require large doses of fusion-promoting molecules or targeting ligands that can lead to undesired side effects, including toxicity and immunogenicity. To address this challenge, this project aims to utilize the biological process of membrane phase-separation to design and develop liposomes that can offer highly efficient cellular internalization with minimal toxicity. First part of this dissertation combines experimental and computational tools to investigate the phase behavior of multi-component lipid membranes. The experimental studies focused on studying phase-separation on micron-sized liposomes of various compositions using fluorescence microscopy. In collaboration with mathematicians, two continuum phase-field models were then developed to simulate the phase-separation examined in experiments. Great agreement between experiments and simulations validated the computational models and demonstrated their potential use for the design of phase-separating and patchy liposomes. Second part of this dissertation explores the use of phase-separation to create highly fusogenic liposomal nanocarriers with minimal toxicity. The impact of charged lipids on membrane’s phase behavior was first investigated in multi-component micron-sized liposomes. The findings of this work were then applied towards designing fusogenitic liposomes with cationic patches that showed enhanced fusogenicity compared to their homogenous counterparts. This work demonstrated that phase-separation can be applied to enhance the performance of cationic delivery liposomes. The last part of this dissertation seeks to use phase-separation to enhance cellular uptake of ligand-conjugated liposomes. Focusing on biotin-streptavidin binding, as a model system, biotinylated liposomes were designed to respond to acidic pH in tumor environment to undergo phase-separation and present their ligands in highly-dense patches. We are further investigating the application in cell studies. Together, this study provides an insight into the use of phase-separation to control the functionality of lipid membranes and it hence, offers new possibilities to overcome the shortcomings of current liposomal nanocarriers.Item Design and Fabrication of Ultra-Thin Soft Sensors Based on Electrospun Metal Oxide Semiconductors(2018-05) Enan, Nada; Yu, Cunjiang; Zhang, Yingchun; Abidian, Mohammad RezaThe advancement of bioelectronics in the health care field has increased in recent years. To better their use, non-invasive continuous monitoring patch-sensors have been developed by increasing conformal mounting and developing ultralight weight devices. The convoluted surface of these sensors allow for better conformity to the human body due to the micro-ridges on the surface of the patches. The ultra-thin design of the patch reduces the surface adhesion energy for patch to skin conformity, and increases bending insensitivity to mechanical deformations which allows for continuous monitoring. These epidermal sensors can be utilized for better diagnostics in the health care field as well as implemented in future research for artificial skin needs. Using one-dimensional metal-oxide material and an ultra-thin mechanical design, temperature and glucose epidermal patches were fabricated with bending insensitive, environmentally inert, ultra-thin and non-invasive characteristics.Item Electrospinning of Core-Shell Fibers for Encapsulation of Biomolecules(2019-05) Patel, Nihir; Abidian, Mohammad Reza; Wu, Tianfu; Majd, SheereenAxonal regeneration, particularly that of the neurons found in the Central Nervous System, is of great interest in tissue engineering. Diseases due to damaged nerves found in this system include Alzheimer’s, Parkinson’s and even paralysis. These affect millions of people. One way to achieve axonal regeneration is to use NGF (Nerve Growth Factors) that can guide the 2 ends of the damaged nerve into rejoining and potentially cure diseases that arise from this. The main issue is having a vessel that can produce controlled release of these NGF. One potential solution is to make a core-shell fiber, from the co-axial electro-spinning process, with the NGF incorporated in the core and PLGA (polylactic-co-glycolic-acid) acting as the shell. PLGA is biocompatible and biodegradable, making it suitable for this role. This structure could allow for a more controlled release of NGF and provides a shape that promotes axonal regeneration in the Central Nervous System. Such a structure was made in this paper with PLGA as a shell and BSA (an NGF substitute) present in the core.Item Encapsulation of an Anti-tumor Chelator in Polymeric Nanoparticles: Development, Optimization, and Assessment(2022-05-12) Phillips, Spencer Geoffrey; Majd, Sheereen; Abidian, Mohammad Reza; Naash, Muna I.Neoplastic cells require extensive amounts of iron, a vital element for normal cellular growth, for supporting their rapid proliferation. Metal chelators that have long been used to remove heavy metals from the body, have also been utilized in treatment of neurodegenerative diseases and cancer. Thiosemicarbazones are a novel class of chelators that bind to both iron and copper and have been explored for cancer therapy. Di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), a second-generation thiosemicarbazone, has proven to be a particularly promising anti-proliferative agent. However, this chelator has only been explored in its free from in previous studies, limiting its applications. To further advance the application of DpC as a chemotherapeutic, here we aim to develop and optimize a formulation of DpC-loaded nanoparticles (NPs) by using poly(lactic-co-glycolic acid) (PLGA), an FDA-approved biodegradable polymeric material. To this end, we prepared DpC-encapsulated PLGA NPs (PLGA-DpC-NPs) via the nanoprecipitation method and investigated the effect various parameters had on the resultant NPs, including drug-to-polymer ratio, injection rate, stirring rate, and surfactant type and concentration used during nanoprecipitation. The NPs were characterized for size distribution, zeta potential, encapsulation efficiency, and loading capacity to determine the optimal fabrication conditions. Next, we studied the drug release from PLGA-DpC-NPs and the particles’ colloidal and serum stability. Discharge of DpC from NPs showed a more rapid release when NPs were made with PVA than those made with F-127, reaching ~ 90% released after 48 hours compared to ~ 70% released, respectively. All the examined NP formulations showed stability for 24 hours under physiological conditions. Finally, we assessed the in vitro toxicity of PLGA-DpC-NPs against various types of cancer cells. These DpC-loaded NPs were highly toxic with IC50 values of ~ 51 nM, 83 nM, and 178 nM in malignant human breast cancer, human glioblastoma, and human colorectal adenocarcinoma, respectively. This study is the first to report the encapsulation of DpC in a nanocarrier that may advance the use of this anti-proliferative chelator in oncological treatments in the future.Item Fabrication and Characterization of Bioactive Conjugated Polymer 3D Microstructures for Organic Bioelectronics(2019-05) Khorrami, Milad; Abidian, Mohammad Reza; Mohan, Chandra; Francis, Joseph T.; Majd, Sheereen; Borhan, AliThe emerging field of organic bioelectronics bridges the electronic world of organic based devices with the soft and predominantly ionic world of biology. This crosstalk can occur in both directions. For example, a biochemical reaction may change the doping state of an organic material leading to generate an electronic signal. Conversely, an electrical signal from a device may stimulate a biological event. Cutting-edge researches in the field of organic bioelectronics result in development of wide range of biomedical applications including neural interfaces, biochemical delivery and drug release, biosensors and field-effective transistors. The current bioelectronics devices are mainly limited by the mechanical mismatch between the soft tissue and hard metallic materials, high electrical resistivity of materials which inhibits the signal-to-noise ratio, the none-biocompatibility that produces the acute and chronic inflammatory reaction and etc. To that end, conjugated polymers (CPs) may be a great candidate for fabrication of organic bioelectronics due to their similarities in chemical structures with biological molecules and can be engineered in various forms, including films, microcups, nanotubes, nanogrooves or any 3D structures. Additionally, conjugated polymers can be tuned through synthetic chemistry for variety of bioelectronics applications. This dissertation is focused on fabrication and characterization electrically conductive and bioactive 3D structures for organic bioelectronics applications. Two of the most common CPs poly(3,4-ethylenedioxythiophene) and polypyrrole were utilized to fabricate conductive 3D structures in various shape and geometry including microcups, aligned nanotubes, aligned nanogrooves using electrochemical polymerization and two-photon polymerization techniques. Additionally, the chemical structure of some of those CPs was chemically functionalized using laminin protein to potentially improve its biocompatibilities and the cell adhesion properties. We also introduced a novel equivalent circuit model to investigate the dependence of electrode impedance of conjugated polymers microcups on properties of CP/electrolyte interface. It was found that the morphology (i.e. height and surface area) of CPs could be precisely tuned during electrochemical polymerization. We were able to demonstrate a sustain release of anti-inflammatory agent from microcups and aligned fibers. We also showed the fabrication of highly conductive and laminin-incorporated 3D structures using two-photon polymerization. The fabricated microstructures have tremendous potential for bioelectronics applications.Item Fabrication and Characterization of Tunable Conducting Polymer Micro- and Nano-Structures for Bioelectronics(2022-05-11) Kisucky, Anthony M.; Abidian, Mohammad Reza; Mohan, Chandra; Francis, Joseph T.; Majd, Sheereen; Chang, LongThe three novel investigations comprising this dissertation focus tightly on detailing the relationship between conditions of electrochemical deposition and the properties of the resulting CP films or microstructures. The first project elucidated the quantitative relationships between electrochemical deposition parameters and the surface nanostructure of poly(3,4-ethylenedioxythiophene) (PEDOT) and poly(pyrrole) (PPy) films doped with poly(styrene sulfonate) (PSS), and demonstrates how physical and electrical properties can be reliably tuned through adjustments of deposition parameters. By developing a model of how CP film properties can be controlled by their deposition parameters, a “toolbox” of sorts may be developed to ensure that PEDOT and PPy components in neural interface applications can most easily possess the most optimal parameters for their intended application. The second project built upon some of the relationships discovered in the first, moving away from classical electrochemical “bath” modalities and using a hydrogel mediator to allow for greater spatial freedom in electrodeposition of PPy:PSS films. Leveraging the relationship between deposition time and resultant film properties created a technique by which PPy:PSS films could be created with surface properties that change over the length of the film. Linear and non-linear gradients of surface roughness were created, and are intended to synergize with the known influence of chemical gradients on axonal guidance. The third project is a further refinement of the hydrogel modality into a system by which PPy:PSS can be electropolymerized in-situ along a path. Known informally as the “gel pen”, this system behaves somewhat like a conventional 3d printer, and it incorporates all the film-property-control lessons learned from the previous two projects. Using commercial software, rather than ad-hoc solutions as in prior projects, this system can accept and execute arbitrary design files.Item Fabrication and Investigation of Conducting Polymer Micro and Nano Structures for Bioelectronics Applications(2018-05) Antensteiner, Martin; Abidian, Mohammad Reza; Mohan, Chandra; Francis, Joseph T.; Majd, Sheereen; Borhan, AliConducting polymers (CPs), especially poly(3,4-ethylenedioxythiophthene) (PEDOT) and poly(pyrrole) (PPy), are ideal materials for bioelectronics devices because of their biocompatibility, mechanical properties that are similar to those of biological structures, their ability to transduce signals through both ionic and electronic conductivity, and their facile and versatile fabrication routes. CPs have been shown to improve the electrical performance of neural recording/stimulation electrodes, deliver compounds to suppress unfavorable biological reactive responses, and enhance axon regeneration. CP structures have also been shown to create stable biocompatible actuators in the form of micro-robots and other controllable structures. However, much remains to be investigated with regard to CP micro and nano structures, especially those intended for bioelectronics applications. The purpose of this dissertation is to expand upon this knowledge with five novel investigations comprised of (1) explicitly determining the relationship between electrochemical deposition parameters and the resulting surface structure of PEDOT and PPy films doped with poly(styrene-sulfonate) (PSS), (2) investigating and comparing the ion exchange behavior and impact on surface roughness of PEDOT and PPy nanotubes as a function of voltage driven actuation, (3) fabrication of PPy microcups (MCs) with customizable geometries, and an investigation of the resulting electrode performance and drug release capabilities, (4) equivalent circuit modeling of PPy MCs electrodes to investigate the dependence of electrode impedance on the properties of the CP/electrolyte interface, and (5) development of a novel deposition methodology to create customizable linear and non-linear roughness gradients of PPy films for axon guidance applications. It was found that for both PEDOT and PPy, the surface topography (especially surface roughness) can be controlled through careful selection of deposition time and current/potential during electrochemical deposition. This allows for the tuning of the resultant impedance and charge storage capacity of bioelectronics devices. It also allows for controllable fabrication of novel CP structures including microcups and nanofibers. These structures were employed for the sustained release of dexamethasone, and an in-depth study of the actuation behavior of both CPs. Finally, a novel fabrication route allows for the reproducible deposition of nanostructured PPy gradients with arbitrary shapes for future applications in controlling nerve regeneration behavior.Item Fabrication and Optimization of Dp44mT-loaded Polymeric Nanoparticles for Treatment of Malignant Cells(2020-05) Holley, Claire Katherine; Majd, Sheereen; Abidian, Mohammad Reza; Lee, T. Randall; Liu, Xinli; Mohan, ChandraCancer is the second leading cause of mortality worldwide, resulting in over eight million deaths per year. In the fight against cancer, traditional chemotherapeutics are not very effective due to poor delivery, toxicity to healthy tissues, and ever-increasing cancer resistance. Since neoplastic cells require increased levels of iron (Fe) to proliferate, a promising strategy for cancer treatment is Fe deprivation using metal chelators. One such chelator, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), has been shown to be extremely toxic towards many types of cancer in its free form (IC50 of 4 - 500 nM), due to its ability to chelate both Fe and copper (Cu), produce reactive oxygen species (ROS) through redox cycling, and overcome multi-drug resistance in malignant cells. Therefore, Dp44mT presents a promising candidate for the treatment of highly aggressive tumors. However, due to the hydrophobicity and toxicity of this compound, encapsulating Dp44mT into a nano-carrier will enhance its therapeutic effectiveness, while also preventing premature drug degradation, improving biodistribution and drug release to the tumor, and mitigating negative side effects to healthy tissues. The objective of this project was the development of a new anti-cancer nano-formulation based on Dp44mT and the in vitro evaluation of this formulation against malignant cells. To this end, we first utilized two distinct techniques, nanoprecipitation and single emulsion, to fabricate nanoparticle of poly(lactic-co-glycolic acid)(PLGA) loaded with Dp44mT (referred to as “Dp44mT-NPs”). During fabrication, Dp44mT encapsulation efficiency and NP size was optimized through the adjustment of the polymer, drug, and surfactant concentrations, as well as injection rate. The resultant Dp44mT-NPs were also characterized for shape, surface potential, colloidal stability and drug release. Next, we assessed, for the first time, the therapeutic effectiveness of both free and encapsulated Dp44mT in glioma (U251, U87) cells, as compared to healthy astrocytes. We further applied our Dp44mT-NPs to other malignant cells, namely breast (MCF7) and colorectal (HT29) cancer cells, to evaluate this nano-formulation as a universal anti-cancer platform. Finally, we modified this nano-formulation, via surface PEGylation and conjugation of a cancer-specific targeting ligand, to improve nanoparticle stability, biodistribution, and delivery for future in vivo applications. We then re-evaluated the efficacy of our PEGylated Dp44mT-NPs against malignant cells, both with and without targeting. Lastly, we assessed the ability of these PEGylated NPs to bypass the endothelial layer of an in vitro Blood-Brain Barrier model. In summary, this dissertation presents the fabrication, optimization, and assessment of a novel nano-formulation, containing anti-cancer chelator Dp44mT, for future application as a chemotherapeutic against malignant cells.Item Investigation on Conducting Polymers-Doped with Laminin(2017-12) Guo, Zhilin; Abidian, Mohammad Reza; Majd, Sheereen; Wu, TianfuConducting polymers (CPs) have been used in biomedical science and engineering research field with wide applications such as biosensors/ actuators, drug delivery systems, and implantable devices. Some biocompatible CPs like PEDOT and PPy and their nanostructures have been designed to make devices and further functionalized with biomolecules to increase the attachment and viability of cells. In this thesis, EDOT monomers have been doped with laminin peptides to generate biomolecule doped PEDOT films by electropolymerization experiment. Furthermore, EDOT/ laminin peptide CP films were then coated on PLLA polymer microfibers template to form PEDOT/ laminin nanotubes. The laminin doped PEDOT nanotubes will be tested with experiments of cell attachment and neurite outgrowth in future research.Item Laminin Microdroplet Deposition on Conducting Polymer Films for Neural Regeneration(2019-05) Sharma, Kartik; Abidian, Mohammad Reza; Majd, Sheereen; Wu, TianfuConducting polymers are valuable tools in tissue engineering as they can play an important role in enhancing cellular response to guidance cues due to their electrical conductivity. Extracellular matrix proteins like laminin can provide a strong guidance cue to direct cellular regrowth. When combined, these two can prove to be unbeatable alternative for tissue regeneration applications. However, the biggest challenge lies in depositing these proteins on the surface of conducting polymer to get the best response out of neurons for neural regeneration. In this study, various parameters have been optimized to idealize the deposition of laminin on conducting polymer’s surface. From this study, an optimized patterning technique can be established to deposit laminin on PEDOT substrates such that minimum volume of laminin is used, the pattern has very well-balanced distances between adjacent rows and columns, and there is least possible void space between the droplets both in horizontal and vertical directions.Item Materials and Manufacture of Soft and Curvilinear Electronics(2018-08) Sim, Kyoseung; Yu, Cunjiang; Bao, Jiming; Ruchhoeft, Paul; Zhang, Yingchun; Abidian, Mohammad RezaUnconventional electronic devices in soft and three-dimensional (3D) curvilinear formats hold promise in a broad range of applications, such as wearable computers, stretchable displays, biomedical instruments, and personal health-care devices, etc. To create such a type of electronic devices, dedicated materials and manufacturing technologies are needed. Although a lot of knowledge in these and related aspects currently exists, the realization of soft and 3D curvilinear electronics still faces many challenges. For instance, no versatile manufacturing technology is available to effectively manufacture 3D curvilinear electronics; the existing strategies for building soft and stretchable electronics associated with complicated structural designs and sophisticated fabrication processes limits their future development and implementation for many applications. To this end, this dissertation aims to provide both fundamental and application studies to address some of the existing material and manufacturing challenges and to validate them through various device evaluation and demonstrations. This dissertation mainly covers four major topics. The first topic introduces a new manufacturing approach, namely conformal additive stamp (CAS) printing, which utilizes a deformable balloon stamp to pick up and print element or components of interest, to fabricate 3D curvilinear electronics. The second topic is to introduce a dedicated example of 3D curvilinear electronics, specifically a multifunctional smart contact lens, by utilizing CAS printing. The demonstrated smart contact lens allows continuous health monitoring including eye intraocular pressure, ocular surface temperature, tear glucose level, etc. The third topic introduces sol-gel-on-polymer processed indium zinc oxide (IZO) semiconductor nanomembrane based ultra-thin stretchable electronics with advantages of multifunctionality, simple manufacturing, imperceptible wearing, and robust interfacing, which is employed as wearable closed-loop HMI system. The fourth topic introduces high performance rubbery electronics based on intrinsically stretchable semiconductor with enhanced carrier mobility. The rubbery electronics retain electrical performance without significant loss under mechanical stretching of 50%. Overall, this dissertation includes a whole set of results in materials, manufacturing technologies, mechanical studies, and devices to illustrate the associated novel aspects in these soft and curvilinear electronics that have been developed or can be developed in the future.Item Microfluidic Device Design Informed by Red Blood Cell Morphology for Global Blood Diagnostics and Banking(2020-05) Torabian, Kian; Shevkoplyas, Sergey S.; Majd, Sheereen; Abidian, Mohammad Reza; Gifford, Howard C.; Wu, Tianfu; Sheehan, Vivien A.Just as blood diagnostic tests are ubiquitous in the clinic, blood component transfusions are among the most commonly performed medical procedures at the bedside. The many devices designed to process blood often rely on microscale flow of the complex non-Newtonian fluid. With approximately 40% of human blood comprised of red blood cells, flow dynamics are largely influenced by these relatively dense particles. Their delicate biconcave shape is essential to their deformability, aggregability, and overall viability, allowing them to bend, shear, expand, and stack as they navigate the microvasculature to deliver oxygen to surrounding tissues. As a result, shape and its many surrogates not only serve as biomarkers for their quality, but also can be exploited to improve diagnostic and blood banking devices. In this work we study red blood cells with altered morphology in various forms of sickle cell disease and in animal models with uniquely adapted vascular systems, and use our findings to develop three devices with applications in blood banking and diagnostics: a simple gravity-based device to replace industrial centrifuges that wash stored red blood cells prior to transfusion, a multi-layered microfluidic platform to separate whole blood into its component blood transfusion products, and a paper-based diagnostic device for the altered hemoglobin molecule responsible for sickle cell disease. We explore the limitations and challenges associated with current technologies used to study red blood cell deformability and aggregation, ranging from micropipettes to ektacytometers and aggregometers, with respect to balancing diagnostic robustness, methodological throughput, and access and affordability. Additionally, we take advantage of inexpensive and biomimetic microfluidic platforms to inform a design process for global health applications, considering the potential scope of these devices to improve access to some of the most widely used biomedical tools.Item Preparation and Characterization of Hydrogel-Core Liposomes for Drug Delivery Applications(2019-05) Farhadi, Hanieh; Majd, Sheereen; Abidian, Mohammad Reza; Wu, TianfuLiposomes are amongst the most effective delivery vehicles developed to date. Despite many advantages including biocompatibility, biodegradability, and the ability to carry both hydrophilic and lipophilic compounds, liposomes suffer from low physical stability and controlled drug release. Inclusion of a polymeric scaffold within the core of liposomes can effectively address this limitation. Given the versatility of poly(ethylene glycol) (PEG) hydrogels, these polymers are particularly attractive for the use in liposomal core. Towards development of robust liposomal delivery systems, here we aim to develop a simple and reliable technique for the fabrication of liposomes with hydrogel cores. We assess the resultant nanoparticles (NPs) using scanning electron microscopy and dynamic light scattering and demonstrate that the presented approach can successfully produce gel-liposome nanoparticles with spherical shape and 100-300 nm size. These nanoparticles are further evaluated for colloidal stability in physiological solution. Moreover, we demonstrate the versatility of this method by studying the effect of changing (A) the membrane composition in liposomes, (B) the polymer and cross-linker concentration in liposomal core, and (C) the polymer content on the formation of hydrogel-core liposomes.Item Studying The Membrane Fusion of Cationic Nanoliposomes Using a Simple Fusion Assay(2022-05-10) Dang, Dang T.; Majd, Sheereen; Abidian, Mohammad Reza; Horton, RenitaLiposomes are spherical vesicles that can encapsulate and deliver drugs into the body. Moreover, the liposomal membrane resembles the cell membrane since they both have lipids as the main building blocks. Due to this property, liposomes can fuse into cell membranes with the help of fusogenic lipids and deliver their cargo straight into the cytosol of cells. However, this process is complicated to investigate in living cells, where there is a variety of proteins and lipids. In this study, we designed a simple experimental fusion assay that relies only on liposomes to study the fusion of nanoliposomes to micron-scale liposomes, where nanoliposomes acted as drug delivery vehicles, and micron-scale liposomes mimicked model cell membranes. Specifically, we investigated the influence of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), a cationic lipid, on the fusogenicity of nanoliposomes. Using this assay, we studied how the surface distribution of DOTAP on nanoliposomes contributes to membrane fusion. We utilized membrane phase separation to control the surface distribution of DOTAP on the liposomal membrane. We applied confocal scanning microscopy to monitor the process of membrane fusion over time through fluorescent signals. Images captured during this process were analyzed using ZEN imaging software and a personally developed MATLAB code. The results of these studies show that an increase in the amount of DOTAP in nanoliposomes’ lipid composition led to an increase in their ability to fuse into micron-scale liposomes. The results also reveal that concentrating DOTAP lipid into small regions on the surface of nanoliposomes enhanced the fusogenicity of the nanoliposomes.Item Using Agarose-Assisted Formation as an Alternative to Electroformation for Producing Phase Separating Vesicles(2022-08-09) Keith, Khasey Marina; Majd, Sheereen; Abidian, Mohammad Reza; Wu, TianfuGiant unilamellar vesicles (GUVs) are often used as models to study lipid membrane structure and function. The most common method for GUV formation is electroformation, though this technique has its own inherent drawbacks such as low yield in ionic solutions or in the presence of charged lipids. In recent years, gel-assisted swelling has been explored as an alternative to electroformation and has been reported to overcome some of the limitations of this technique. This study aims to assess the ability of gel-assisted swelling to form GUVs of ternary lipid compositions that are known to undergo phase separation. To this end, we utilize five different ratios of a 3-component mixture of DOPC/DPPC/Cholesterol to form vesicles capable of separating into phases of liquid-ordered (Lo) and liquid-disordered (Ld). This lipid composition was chosen as previous studies have shown that at room temperature, many of its possible compositions exhibit distinct phase separation. We apply confocal fluorescence microscopy to evaluate the resultant GUVs, in terms of yield, size, and phase behavior. We compare the results of agarose-assisted swelling to that of electroformation with a focus on GUV size and quantity, as well as the number of lipid domains formed, the lipid domain area fraction, and the lipid domain perimeter on GUVs. Here, we show that the phase behavior of giant liposomes formed from the gentle hydration of hybrid films of agarose and lipids is comparable to the phase behavior of giant liposomes formed from electroformation. This work shows that agarose-assisted swelling is a simple, rapid, reproducible, and affordable approach to generate phase-separating giant liposomes of ternary lipid compositions.