published_or_final_version / abstract / Physics / Master / Master of Philosophy

published_or_final_version / abstract / toc / Surgery / Master / Master of Philosophy

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The manipulation of molecular structures is an important enabling technology for future advances in nanotechnology. The ability to control the synthesis of nanostructured materials, such as the bond formation and geometry of a molecule is of great significance to nanoscience as nanosystems are constructed from these smaller units. Influencing the assembly of molecular structures at the early stages of material formation can modify the ensuing molecular aggregate structure with the potential for impact in a broad range of optical, chemical, and biological applications. Heteroleptic titanium metal alkoxides (OPy)₂Ti(4MP) ₂ and (OPy)₂Ti(TAP)₂, where OPy = OC₆H₆N, 4MP = OC₆H₄(SH)-4, and TAP = OC₆H₂(CH₂N(CH₃)₂)₃-2,4,6 were investigated as precursors for thin film and solution-based synthesis of oxide materials via the photoactivation of intermolecular reactions (e.g. hydrolysis/condensation) at selected ligand sites about the metal center. Manipulation of the molecular structure of these photosensitive metal alkoxides was achieved through the use of optical irradiation parameters, such as the tuning of the excitation wavelength, total optical fluence, and pulse energy intensity. Irradiating these metal alkoxides with UV-light was seen to cause photodisruption in the ligand groups leading to the formation of Ti-O-Ti linking via hydrolysis and condensation reactions. In spin-coated (OPy)₂Ti(TAP)₂ films, these photoinduced bridge bond formations resulted in an increase in refractive index and film densification as well as produced an insoluble film when rinsed in pyridine. By making use of these photoinduced film properties, the formation of physical relief structures from spin-coated (OPy)₂Ti(TAP)₂ films was demonstrated along with the ability to photopattern sub-micron and nanometer features. In addition, the micro- and nanostructure of thin films were optically manipulated through several deposition methods; a novel dip-coated in-situ photodeposition technique was utilized by illuminating at specific distances above the meniscus to further control the early stages of material formation due to changes in the mobility of the reactants from the evaporation and gravitational draining of the solvent. The ability to manipulate molecular development at the on-set of material formation through different deposition techniques and optical parameters allowed for the creation of several thin film optical devices, such as gratings, micro-optic lenslet arrays, and binary "on-off" patterned devices.

An important research area in medicine is molecular diagnostics of cancers and infectious diseases, which can be diagnosed, managed and treated more effectively with genetic information. We have developed an integrated sample to answer bacterial detection platform combining a simple, universal bacterial lysis approach and sensitive nanomaterial electrochemical biosensors. Lysis is rapid and effective at releasing intercellular nucleic acid targets. The platform was directly challenged with unpurified lysates and successful at determining the presence of clinically relevant concentrations within 30min from sample to answer. Another important aspect of biosensor development is the development of cheap and efficient methods for manufacturing nanostructured microelectrodes. Previously, we have used costly silicon wafers for fabrication. Here we explored alternate inexpensive materials for fabrication including printed circuit boards, plastics and glass. We show that plain borosilicate glass is effective for templated bottom-up fabrication, with comparable performance to expensive silicon based nanostructured microelectrodes. Current state-of-the-art readout of many biomarkers is hampered by serially addressing arrays of low cost biosensors, without the use of high cost active electronics. Here we have developed a new concept, solution-based electrochemical circuits, which makes highly multiplexed sensing feasible on the surface of low-cost, glass chips. This method utilizes the idea that physical separation of liquid on an insulator can result in electrochemical isolation. Using this we can reduce the number of outputs to 2√n, where n would be the number of serially connected sensors. We use urinary tract infections as a model system and prove that we can accurately detect species and antimicrobial resistance in multiplexed formats at clinically relevant concentrations.

Humidity sensors are one of the most widely used sensors in commercial and industrial applications for environmental monitoring and controlling. Although related technology have been studied intensively, humidity sensing in harsh environments still remains a challenge. The inability of current humidity sensors to operate in high temperature environments is generally due to the degradation of the sensing films caused by high temperature, high humidity level, and/or contamination. Our goal is the design and fabrication of a humidity sensor that is capable of working under high temperatures and in a condensing environment. The targeted application of this sensor is in the polymer electrolyte membrane (PEM) fuel cell, where humidity control is crucial for performance optimization. In this work, ordered macroporous silicon is thoroughly studied as a humidity sensing layer. In addition to the advantages of traditional porous silicon for gas sensing (high resistance to high temperature and good compatibility with current IC fabrication process), the ordered macroporous silicon used in these experiment has uniform pore size, pore shape and distribution. All the vertical aligned pores can be opened to the environment at both ends, which can significantly increase the efficiency of gas diffusion and adsorption. Moreover, this special structure opens the door to uniform surface modifications for sensing enhancement. Both ordered macroporous silicon based heterostructure and self-supporting membrane are fabricated and investigated as a humidity sensor. Heterostructure sensors with different thin film surface coatings including bare Si, thermally grown SiO2, atom layer deposited ZnO, HfO2, and Ta2O5 are characterized. Post micro-fabrication is achieved on this ordered porous structure without affecting the material and its sensing properties. It has been proven that the ordered macroporous silicon with Ta2O5 surface coating shows the best sensing property due to its ultra-hydrophilic surface. The sensor shows high sensitivity, fast response times, small hysteresis, and extraordinary stability and repeatability under high temperatures and in condensing environment. It demonstrates great potential and advantages over existing commercial humidity sensors in the fuel cell application field. In addition to ordered macroporous silicon, well aligned 1D ZnO nanorods/nanowires -another widely used nanostructure in gas sensing- is also investigated as humidity sensing materials. Both vertically and laterally aligned nanorods/nanowires are fabricated and tested against humidity changes. The sensors shows increasing resistance to increasing relative humidity, which is contrary to most published works so far. Possible mechanisms have been proposed in this thesis and future work has been suggested for further study. To the best of our knowledge, this work is the first to use ordered macroporous silicon and well aligned 1D ZnO nanorods/nanowires for humidity sensing.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non-transport permissive and intact BBB, we also assessed the role of magnetic resonance imaging (MRI) guided focused ultrasound (MRgFUS) disruption of the BBB in enhancing permeation of AuNPs across the intact BBB and tumor BBB in vivo. MRgFUS is a novel technique that can transiently increase BBB permeability thereby allowing delivery of therapeutics into the CNS. We demonstrated enhanced delivery of AuNPs with therapeutic potential into the CNS via MRgFUS. Our study was the first to establish a definitive role for MRgFUS in delivering AuNPs into the CNS. In summary, this thesis describes results from a series of research projects that have contributed to our understanding of the influence of design features on AuNP permeation through the BBB and also the potential role of MRgFUS in AuNP permeation across the BBB.

This thesis presents investigations into the design and synthesis of nanomaterials in supercritical carbon dioxide (sc-CO₂) as well as novel experimental design methodologies. First, the process-structure-property relationships are studied for the deposition of materials from organometallic precursors in sc-CO₂. The materials that were investigated in these studies were: (1) the semiconductor material copper zinc tin sulfide (Cu₂ZnSnS₄, or CZTS), which has application in solar energy capture; (2) zinc sulfide nanoparticles deposited onto carbon nanotubes, which have application in optoelectronics; and (3) silver nanoparticles deposited on silicon and glass wafer surfaces, which find application as biosensors via surface enhanced Raman spectroscopy. Next, two novel experimental design methodologies were implemented. The first is termed layers of experiment with adaptive combined design (LoE/ACD), which efficiently optimizes a process that is expensive and time consuming to study by zooming in on the process optimum through successive layers. The mean silver nanoparticle size was optimized as a function of temperature in the sc-CO₂ system using the LoE/ACD approach. The second experimental design methodology is called initial experimental design (IED). The IED methodology was developed to choose the first round of experiments for a system that is expensive to study (in terms of time and money), poorly understood, and possesses a related, non-identical system that is well-studied. The IED approach was used to optimize the mean iridium nanoparticle size as a function of temperature given expert opinion, prior data, and an engineering model for silver nanoparticles synthesized in sc-CO₂.

<p> A laboratory scale plating cell was built that provided reproducible bottom-up fill results for the electrochemical deposition of copper in damascene features. Several techniques used in the full wafer plating tool were incorporated into the setup to accurately control the process conditions. These techniques included but were not limited to a voltage controlled `hot-entry' step, a custom coupon holder to allow sample rotation, a secondary thief electrode and an automatic entry system. The results of qualification experiments are presented to demonstrate that precise control was realized along with repeatable partial fill plating results. The qualified setup was then used to perform time-evolved partial fill plating experiments using several different structural configurations of open-source suppressors to investigate their affect on the gap-fill characteristics. </p><p> Common open-source suppressors used for copper filling of damascene interconnects include polyethylene glycol (PEG), polypropylene glycol (PPG), or a copolymer structure of both. Differences in the configuration and structure of these suppressors generate variations in polarization strength, surface adsorption rate, and SPS displacement rate. These properties were measured by electrochemical transient analysis and coupled with the results of time-evolved partial fill plating experiments to determine the effect of electrochemical property variations on the gap-fill characteristics. The high polarization strength of PPG, along with its greater dependence on concentration was found to greatly increase the bottom-up growth rate during copper filling, while the improved resistance to accelerator displacement of PEG resulted in better sidewall protection. Both these gap-fill characteristics were evident when PEG and PPG were combined together as a mixture of separate homopolymers or in copolymer structures, although the overall influence was dependent on the size and configuration of each component. These data sets provided a more fundamental understanding of PEG, PPG and their different configurations role in the metallization of damascene interconnects. These data can also be used to infer the relative gap-fill performance to screen new suppressor candidates and reduce the quantity of plating experiments by comparison of the electrochemical properties.</p>

An important research area in medicine is molecular diagnostics of cancers and infectious diseases, which can be diagnosed, managed and treated more effectively with genetic information. We have developed an integrated sample to answer bacterial detection platform combining a simple, universal bacterial lysis approach and sensitive nanomaterial electrochemical biosensors. Lysis is rapid and effective at releasing intercellular nucleic acid targets. The platform was directly challenged with unpurified lysates and successful at determining the presence of clinically relevant concentrations within 30min from sample to answer. Another important aspect of biosensor development is the development of cheap and efficient methods for manufacturing nanostructured microelectrodes. Previously, we have used costly silicon wafers for fabrication. Here we explored alternate inexpensive materials for fabrication including printed circuit boards, plastics and glass. We show that plain borosilicate glass is effective for templated bottom-up fabrication, with comparable performance to expensive silicon based nanostructured microelectrodes. Current state-of-the-art readout of many biomarkers is hampered by serially addressing arrays of low cost biosensors, without the use of high cost active electronics. Here we have developed a new concept, solution-based electrochemical circuits, which makes highly multiplexed sensing feasible on the surface of low-cost, glass chips. This method utilizes the idea that physical separation of liquid on an insulator can result in electrochemical isolation. Using this we can reduce the number of outputs to 2&radic;n, where n would be the number of serially connected sensors. We use urinary tract infections as a model system and prove that we can accurately detect species and antimicrobial resistance in multiplexed formats at clinically relevant concentrations.