<p dir="ltr">Sterile manufacturing is multifaceted. Each aspect seeks to improve the process of producing drug products absent of impurities. Bacteriophages can benefit greatly from sterile manufacturing which would amplify their already vast range of applications. Novel bacteriophage discovery and annotation, implemented within a classroom setting, can aid in building the foundation of bacteriophages for use in clinical applications. High-Performance Liquid Chromatography (HPLC) can detect impurities and test compatibilities in the final product. Oxytocin and its interaction with tranexamic acid (TXA) provide an excellent example of how HPLC use can be critical in sterile manufacturing as well as build a baseline for which bacteriophages may be utilized in sterile production. A quality scorecard for drug products provides an additional metric that can be used by governing agencies and consumers to analyze drug products of similar bioequivalence and subsequently grade them. The development of a scorecard will provide a guideline to improve the sterile manufacturing of drug products and biologics such as bacteriophages. A literary analysis of lipid nanoparticles presents a future application for synthetically manufactured bacteriophages. The conclusions gathered from this work can be utilized as a case study for working professionals who aim to implement advancements in sterile manufacturing within their industry.</p>

<p>Miniaturization of technologies to milli-, micro- and nanoscale offers numerous advantages for diagnostic and therapeutic biomedical applications. In comparison to their macro-scale counterparts, these small-scale systems are more portable, less invasive and less costly. They can facilitate rapid, sensitive and high throughput detection of abnormalities, help track disease progression, reduce sample consumption and improve therapeutic efficacy of drug delivery while decreasing systemic toxicity. Thus, there is clearly a need for creating innovative milli-, micro- and nanoscale tools that can uncover new possibilities in detection and treatment of various types of diseases. The overall objective of this dissertation was to develop novel small-scale technologies that could help enhance diagnostic and/or therapeutic outcomes in patients with cancer, opioid addiction and inflammatory bowel disease. First, we developed an echogenically stable nanodroplet ultrasound contrast agent with potential applications in extravascular molecular imaging of tumors and targeted cancer therapies. Then, we created a polymer blend microsphere system that could be integrated in prescription opioid tablets to develop an abuse-deterrent formulation against smoking. Finally, we designed a release system for localized delivery of aminosalicylates from magnetically actuated millirobots in the colon to improve therapeutic outcomes in patients suffering from inflammatory bowel disease. Overall, the technologies we developed could serve as a basis for designing diagnostic and therapeutic tools that are superior to currently existing platforms.</p>

<p dir="ltr">In recent years, the world has witnessed a growing trend of record high temperatures, heat waves, and extreme weather events due to climate change. Thus, there is an urgent need to develop technologies that enhance quality of life while mitigating further contributions to climate change. Radiative cooling, a passive cooling technique, offers a promising solution to this challenge. Nature serves as a vast, largely unexplored source of inspiration, with various biological systems utilizing radiative cooling to thrive in extreme environments. This work looks at what can be learned from nature to better develop radiative cooling technologies.</p><p dir="ltr">While nanoparticle-based coatings and biologically-inspired nanocellulose-based structures have shown promise in radiative cooling, each has its limitations. Nanocellulose-based structures exhibit high mechanical strength but lower solar reflectance due to UV absorption. On the other hand, nanoparticle-based coatings require a high volume of nanoparticles, resulting in brittleness. This work introduces a dual-layer system comprising a cellulose-based substrate and a thin nanoparticle-based radiative cooling paint, maximizing both radiative cooling potential and mechanical strength. The relationship is studied between thickness and reflectance of the top coating layer with a consistent thickness of the bottom layer. The saturation point is identified and used to determine the optimal thickness for the top-layer. With the use of cotton paper painted with a 125 microns BaSO⁴-based layer, the cooling performance is enhanced to 149.6 W/m² achieved by the improved total solar reflectance from 80% to 93%.</p><p dir="ltr">Looking at another source of biological inspiration, radiative cooling potential of the white shell of the <a href="" target="_blank"><i>Sphincterochila</i></a><i> zonata</i> desert snail is investigated through experimental techniques, revealing a remarkable 90.8% total solar reflectance and 0.88 sky window emissivity, which is achieved through nanoscale features and layered platelet-like morphologies. This is a record high for a biological system. The porosity, nanostructure, and material composition are analyzed, and compared to relative biological systems in other white shells, including those living in the same Negev desert and highly contrasting ocean dwellers. Structural analysis demonstrates layered platelet-like morphologies that optimize for light scattering in solar wavelengths. We investigate the shell's porosity, nanostructure, and material composition through comparison with other species’ shells in the Negev desert and marine environments. Through this, we gain inspiration from <i>Sphincterochila zonata</i> to develop our own radiative cooling technologies.</p><p dir="ltr">In weight-sensitive applications, thin and lightweight radiative cooling paints are crucial, but achieving high solar reflectance remains a challenge. Using inspiration of the layered structure seen in desert snails, this research introduces ultrawhite <a href="" target="_blank">hBN</a>-Acrylic paints that achieve a remarkable solar reflectance of 97.9% with only 150 µm thickness and 0.029 g/cm² weight. The unique properties of hexagonal boron nitride (hBN), including a high refractive index and nanoplatelet morphology, enable a combination of Mie and Rayleigh scattering, while a 44.3% porosity enhances refractive index contrast. Field tests demonstrate that hBN-Acrylic paints provide full daytime cooling under direct sunlight, reducing temperatures by 5-6℃ below ambient.</p><p dir="ltr">Furthermore, biodegradable chitosan-hBN films are introduced as a promising advancement in sustainable cooling technology. These films, composed of up to 60% hBN nanoplatelets within a chitosan matrix, offer flexibility, mechanical robustness, and significant cooling potential. Preliminary results show that these films achieve high solar reflectance and maintain structural integrity, with further potential for optimization through nanoplatelet alignment techniques like hot pressing. By integrating bio-inspired and synthetic approaches, this work contributes to the broader goal of developing sustainable, high-performance materials for passive cooling.</p>

<p dir="ltr">The exploration of tellurene as a large-area, stable p-type semiconductor has been a key focus of research for several years. In my work, I have made notable strides by successfully fabricating ambipolar Te-FETs using contact engineering techniques. Notably, we observed that the polarity characteristics of Te flakes depend on their thickness: thinner flakes exhibit p-type behavior, while thicker ones show n-FET characteristics.</p><p dir="ltr">To better understand the carrier transport mechanism in 2D Te FETs, we developed a novel "sandwich" model. This model accounts for the differing properties of the surface layer compared to the inner layers, combining insights from both experimental data and advanced simulations. By addressing the variations between the surface and the body layers, we have gained new insights into the thickness-dependent polarity of Te FETs—an area previously explained through band structure alignment theory in other 2D semiconductors.</p><p dir="ltr">Surface native oxide's influence on FET transport has often been neglected in similar materials. However, in our research, we specifically focused on charge transfer doping caused by Te's native oxide. By directly reducing the surface oxide layer, we highlighted the importance of environment-induced surface defects, like native oxide, which are almost unavoidable in nanoelectronics based on 2D materials. These defects result in a chemically distinct surface composition, causing band bending in the out-of-plane direction near the surface.</p><p dir="ltr">In addition to these fundamental findings, we reached a significant practical milestone by successfully constructing a monolithic CMOS inverter. This was achieved through careful control of Te thickness and contact design, ensuring optimal device performance. We also advanced polarity engineering by demonstrating a homojunction based on Te flakes of different thicknesses, showcasing the versatility and potential of polarity control in 2D materials. This has exciting implications for the development of photodetectors and photovoltaic devices.</p><p dir="ltr">Overall, our research provides important insights into the transport mechanisms and polarity engineering of 2D semiconductors, with a particular focus on tellurene. Our findings not only enhance the understanding of Te FETs but also have broader implications for the field of 2D materials and their applications in advanced electronics.</p>

<p>The use of silicon nanoneedles provides a unique and versatile biointerface for a range of biomedical applications. In this work, we propose a rational design for vertical Si nanoneedles that are printed on a polymer substrate for ocular drug delivery, intracellular recording, and intra-organoid sensing. To enable minimally invasive and long-term sustained delivery of ocular drugs, we integrate vertical Si nanoneedles with a tear-soluble contact lens for ocular drug delivery. We demonstrate the effectiveness of this platform in treating corneal neovascularization in an in vivo rabbit model, surpassing the current gold standard surgical therapy. This platform has the potential to revolutionize the management of various chronic ocular diseases without causing significant side effects.</p> <p>To enable intracellular recording, we present a unique platform consisting of vertical Si nanoneedles coated with a thin, transparent network of Au-Ag nanowires. This platform is held in place and enclosed by a soft, transparent elastomer, providing simultaneous intracellular recording and live imaging with applications in neuroscience, cardiology, muscle physiology, and drug screening. To demonstrate the utility of this platform, we monitored electrical potentials from cardiomyocyte cells and cardiovascular organoids. Additionally, we propose an intra-organoid sensing platform with vertical Si nanoneedles transfer printed into a soft scaffold. This platform can be adjusted and tailored for various organoids and tumor tissues of interest, or used to deliver bioactive molecules of interest into organoids in response to external stimuli.</p> <p>Our proposed designs of vertical Si nanoneedles based platforms demonstrate their significant potential for a broad range of biomedical applications, including ocular drug delivery, intracellular recording, and intraorganoid sensing. These platforms have the potential to revolutionize current approaches and pave the way for future developments in biomedical research and clinical applications, offering new possibilities for the diagnosis and treatment of a wide range of diseases.</p>

<p dir="ltr">This doctoral thesis investigates how wave phenomena, including light and acoustic waves, can be harnessed to characterize and manipulate fluids, suspensions, and nanoparticles. It explores light-matter interactions and their role in material characterization, leveraging the complex refractive index as a material fingerprint. Additionally, it examines acoustic wave interactions to enhance particle separation and manipulation in fluid media.</p><p dir="ltr">The research introduces a portable Schlieren imaging system for real-time detection of refractive index gradients in pharmaceutical solutions, providing insights into heterogeneity and diffusion during thawing. A novel method based on Rayleigh-Sommerfeld diffraction theory is developed to size and determine the refractive index of sub-micron particles from holographic data, enabling precise particle characterization. Enhanced filtration performance in fiber filters is demonstrated using standing acoustic waves, with observed efficiency improvements through different fiber arrangements. Finally, the thesis presents Spectral Interferometric SCATtering (SiSCAT) microscopy, a label-free system that combines interferometry and wavelength-dependent scattering to achieve chemically dependent nanoparticle characterization. </p><p dir="ltr">These findings advance the fields of biophysics, materials science, and nanotechnology, offering innovative tools for material and particle analysis.</p>

<p dir="ltr">Ultra-scaled, always-on, smart, wearable and implantable (WI) therapeutic platforms define the research frontier of modern personalized medicine. The WI platform integrates real-time sensing with on-demand therapy and is ideally suited for real-time management of chronic diseases like diabetes. Traditional blood tracking methods, such as glucometers, are insufficient due to their once-in-a-while measurements and the imprecision of insulin injections, which can lead to severe complications. To address these challenges, researchers have been developing smart and minimally invasive microneedle (MN) components for pain-free glucose detection and drug delivery, potentially functioning as an "artificial pancreas". Inspired by natural body homeostasis, these platforms must be accurate and responsive for immediate corrective interventions. However, artificial MN patches often have slow readings due to factors like MN morphology and composition that remain poorly understood, hindering their optimization and integration into real-time monitoring devices. Despite extensive, iterative experimental efforts worldwide, a holistic framework incorporating the interaction between MN sensing and therapy with fluctuating natural body functions is missing. In this thesis, we propose a generalized framework for glycemic management based on the interaction between biological processes and MN-based operations. The results, incorporating theoretical insights from the 1960s and recent advancements in MN technology, are platform-agnostic. This generality offers a unique template to interpret experimental observations, justify the recent introduction of drugs like GLP-1 cocktails, and optimize platforms for accurate and fast disease management. </p>