published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Mechanical Engineering / Master / Master of Philosophy

published_or_final_version / abstract / Surgery / Doctoral / Doctor of Philosophy

It is widely recognized that device and interconnect fabrics at the nanoscale will be characterized by a higher density of permanent defects and increased susceptibility to transient faults. This appears to be intrinsic to nanoscale regimes and fundamentally limits the eventual benefits of the increased device density, i.e., the overheads associated with achieving fault-tolerance may counter the benefits of increased device density -- density-reliability tradeoff. At the same time, as devices scale down one can expect a higher proportion of area to be associated with interconnection, i.e., area is wire dominated. In this work we theoretically explore density-reliability tradeoffs in wire dominated integrated systems. We derive an area scaling model based on simple assumptions capturing the salient features of hierarchical design for high performance systems, along with first order assumptions on reliability, wire area, and wire length across hierarchical levels. We then evaluate overheads associated with using basic fault-tolerance techniques at different levels of the design hierarchy. This, albeit simplified model, allows us to tackle several interesting theoretical questions: (1) When does it make sense to use smaller less reliable devices? (2) At what scale of the design hierarchy should fault tolerance be applied in high performance integrated systems? In the second part of this thesis we explore perturbation-based computational models as a promising choice for implementing next generation ubiquitous information technology on unreliable nanotechnologies. We show the inherent robustness of such computational models to high defect densities and performance uncertainty which, when combined with low manufacturing precision requirements, makes them particularly suitable for emerging nanoelectronics. We propose a hybrid eNano-CMOS perturbation-based computing platform relying on a new style of configurability that exploits the computational model's unique form of unstructured redundancy. We consider the practicality and scalability of perturbation-based computational models by developing and assessing initial foundations for engineering such systems. Specifically, new design and decomposition principles exploiting task specific contextual and temporal scales are proposed and shown to substantially reduce complexity for several benchmark tasks. Our results provide strong evidence for the relevance and potential of this class of computational models when targeted at emerging unreliable nanoelectronics. / text

Manufactured nanomaterials (MNMs) from the rapidly increasing number of consumer products that contain MNMs are being discharged into waste streams. Increasing evidence suggests that several classes of MNMs may accumulate in sludge derived from wastewater treatment and ultimately in soil following land application as biosolids. Little research has been conducted to evaluate the impact of MNMs on terrestrial ecosystems, despite the fact that land application of biosolids from wastewater treatment will be a major pathway for the introduction of MNMs to the environment. To begin addressing this knowledge gap, we have conducted a series of experiments designed to test how bioavailable MNMs are to terrestrial ecoreceptors when exposed through a variety of pathways. First, we used the model organisms Nicotiana tabacum L. cv Xanthi (tobacco) and Triticum aestivum (wheat) to investigate plant uptake of 10, 30 and 50 nm diameter gold (Au) MNMs coated with either tannate (T-MNMs) or citrate (C-MNMs). Both C-MNMs and T-MNMs of each size treatment bioaccumulated in tobacco, but no bioaccumulation of MNMs was observed for any treatment in wheat. In a second exposure, we investigated the potential for bioaccumulation of MNMs from contaminated plant surfaces by a terrestrial secondary consumer, tobacco hornworm (Manduca sexta). We found that hornworms bioaccumulate Au MNMs, but that the assimilation efficiency of bioaccumulation was low. Hornworms eliminate ingested Au MNMs rapidly from 0-24 h, but very slowly from 1 d to 7 d. Finally, we used the model organisms tobacco and tobacco hornworm to investigate the potential for trophic transfer of Au MNMs. Biomagnification of Au MNMs was observed in the hornworms. We have demonstrated that MNMs of a wide range of size and with different surface chemistries are bioavailable to plants, that MNMs resuspended by wind, rain, biota, and mechanical disturbance from soil onto plant surfaces are bioavailable to terrestrial consumers, and that trophic transfer and biomagnification of plant accumulated MNMs can occur. These results have important implications for risks associated with nanotechnology, including the potential for human exposure.

This thesis presents the development and optimization of a high-throughput fluorescence microbead based approach for multiplexed, large scale medical diagnostics of biological fluids. Specifically, different sizes of semiconductor nanocrystals, called quantum dots, are infused into polystyrene microspheres, yielding a set of spectrally unique optical barcodes. The surface of these barcodes are then used for sandwich assays with target molecules and fluorophore-conjugated detection antibodies, changing the optical spectra of beads that have associated with (or captured) biomolecular targets. These assayed microbeads are analyzed at a single bead level in a high-throughput manner using an electrokinetic microfluidic system and laser induced fluorescence. Optical signals collected by solid state photodetectors are then processed using novel signal processing algorithms. This document will discuss developments made in each area of the platform as well as optimization of the platform for improved future performance.

The objectives of this thesis were to optimize the synthesis and surface coating of metallic and semiconductor nanoparticles, to understand how these materials interact with cells and physiological systems and to investigate how they can be used to deliver thermal therapy for medical applications. Reproducible high-yield synthesis of gold nanorods and surface coating with a variety of polymers and silica was optimized. Using gold nanorods as a model system, the relationship between particle surface chemistry, surface charge and cellular uptake was studied, as well as the toxicity of nanoparticles of different surface chemistry. Low toxicity in vitro was encouraging and was confirmed in vivo by intravenously injecting Sprague-Dawley rats with semiconductor quantum dots of various surface coatings. Low toxicity was found during biochemical, haematological and pathological assessment, and these results indicate that applications of nanoparticles should be further investigated. One such application is the use of near infrared absorbing gold nanorods in remotely activated hyperthermia. It was shown that gold nanorods act synergistically with the chemotherapeutic cisplatin to improve cytotoxicity, and reduce the required cytotoxic drug dose to 33% of the unheated amount. Due to the success of hyperthermia treatment in vitro, continuing and future work involves the use of gold nanorods ex vivo on excised human corneas in a novel application to weld corneal tissue for improved wound closure following cataract surgery.

Mantle cell lymphoma (MCL) is an extremely difficult to treat subtype of non-Hodgkin lymphoma (NHL) with a low patient survival rate compared to most common cancers. Recently, nanoparticle delivery systems have received a great deal of interest for treating NHL. One of the more promising cargo options for these systems is short interfering RNA (siRNA). siRNA is a 18-23 nucleotide long double stranded RNA that is used to inhibit the protein expression of target mRNAs in a sequence specific manner. MCLs have several commonly overexpressed genes compared to normal cells making it an ideal candidate for siRNA therapies. For RNA interference to occur, A delivery vehicle is needed for the siRNA to reach the cytoplasm of the cell. In this thesis, ionizable lipid-like materials termed lipidoids are formulated into lipid nanoparticles (LNPs) to deliver siRNA. A new library of lipidoids is constructed to gain a better understanding of how the lipidoid tail-structure affects the silencing ability of LNPs. A novel tail precursor is identified as conferring potency to LNPs. Then, LNPs are used to silence genes within difficult to transfect MCL cells. LNPs targeting the anti-apoptotic protein Mcl-1 exhibit potent gene silencing and cause an increase in the fraction of cells undergoing apoptosis. This is important because there is no therapeutic that is FDA approved that targets this commonly overexpressed protein. Because of this LNP’s potency, siRNAs targeting multiple genes can be encapsulated into LNPs without causing unwanted toxicity. LNPs targeting several genes in multiple pathways cause a larger fraction of MCL cells to undergo apoptosis compared to cells treated with LNPs targeting only one gene. A major issue in cancer therapeutics is that the majority of nanoparticles accumulate in the liver. In an effort to improve the delivery of LNPs to target cells, changes to their formulations and administration methods are investigated as a means to improve LNP circulation time, biodistribution, and silencing ability. Overall, this work identifies lipidoid nanoparticles as potent siRNA delivery systems to treat MCL and investigates key properties for further improvement in LNP siRNA delivery to target cells.

Molecular fluorophores and semiconductor quantum dots (QDs) have been used as cellular imaging agents for biomedical research, but each class has challenges associated with their use, including poor photostability or toxicity. Silicon is a semiconductor material that is inexpensive and relatively environmental benign in comparison to heavy metal-containing quantum dots. Thus, red-emitting silicon nanoparticles (Si NPs) are desirable to prepare for cellular imaging application to be used in place of more toxic QDs. However, Si NPs currently suffer poorly understood photoinstability, and furthermore, the origin of the PL remains under debate. This dissertation first describes the use of diatomaceous earth as a new precursor for the synthesis of photoluminescent Si NPs. Second, the stabilization of red PL from Si NPs in aqueous solution via micellar encapsulation is reported. Thirdly, red to blue PL conversion of decane-terminated Si NPs in alcohol dispersions is described and the origins (i.e., color centers) of the emission events were studied with a comprehensive characterization suite including FT-IR, UV-vis, photoluminescence excitation, and time-resolved photoluminescence spectroscopies in order to determine size or chemical changes underlying the PL color change. In this study, the red and blue PL was determined to result from intrinsic and surface states, respectively. Lastly, we determined that the blue emission band assigned to a surface state can be introduced by base addition in originally red-emitting silicon nanoparticles, and that red PL can be restored by subsequent acid addition. This experimentally demonstrates blue PL is surface state related and can overcome the intrinsic state related excitonic recombination pathway in red PL event. Based on all the data collected and analyzed, we present a simple energy level diagram detailing the multiple origins of Si NP PL, which are related to both size and surface chemistry.

Nanotechnology is more and more present in our world today and different fields are taking advantage of its possibilities. Among others, microscopists have been interested in using nanoparticles in combination with available techniques, one of which is fluorescence microscopy. Lanthanide-doped nanoparticles for example have been studied for many years now for their interesting luminescence and upconversion characteristics. This research presents the development of upconverting biolabels operating in the near-infrared (NIR) to eventually allow scientists to probe deeper into tissues using fluorescence microscopy. Two distinct types of nanoparticles were fabricated using the lanthanide ions Yb3+ and Tm3+ for their upconversion capabilities (from 980 to 800 nm) within the biological window (700 to 1000 nm). The first one, an annealed silica-coated LaF3:Yb,Tm nanoparticle, could not be used as a biolabel due to its lack of dispersibility in aqueous environment. However, the second type, a silica-coated NaYF4:Yb,Tm nanoparticles proved to be very promising. Two surface modifications of these particles were successfully performed. The first introduced NH2 groups while the second incorporated polyethyleneglycol (PEG). The latter was achieved using two distinct methods: one through a reaction with the amino groups and one through a second silica coating involving PEGsilanes. Stable dispersions of these PEGylated nanoparticles were obtained and imaging of ovarian cancer cells grown in their presence showed that they interact with the cells although the nature of this interaction is still to be determined.