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Electron Transport in Silicon Nanocrystal Devices: From Memory Applications to Silicon Photonics
Get PDFThe push to integrate the realms of microelectronics and photonics on the silicon platform is currently lacking an efficient, electrically pumped silicon light source. One promising material system for photonics on the silicon platform is erbium-doped silicon nanoclusters (Er:Si-nc), which uses silicon nanoclusters to sensitize erbium ions in a SiO2 matrix. This medium can be pumped electrically, and this thesis focuses primarily on the electrical properties of Er:Si-nc films and their possible development as a silicon light source in the erbium emission band around 1.5 micrometers.
Silicon nanocrystals can also be used as the floating gate in a flash memory device, and work is also presented examining charge transport in novel systems for flash memory applications. To explore silicon nanocrystals as a potential replacement for metallic floating gates in flash memory, the charging dynamics in silicon nanocrystal films are first studied using UHV-AFM. This approach uses a non-contact AFM tip to locally charge a layer of nanocrystals. Subsequent imaging allows the injected charge to be observed in real time as it moves through the layer. Simulation of this interaction allows the quantication of the charge in the layer, where we find that each nanocrystal is only singly charged after injection, while holes are retained in the film for hours.
Work towards developing a dielectric stack with a voltage-tunable barrier is presented, with applications for flash memory and hyperspectral imaging. For hyperspectral imaging applications, film stacks containing various dielectrics are studied using I-V, TEM, and internal photoemission, with barrier tunability demonstrated in the Sc2O3/SiO2 system.
To study Er:Si-nc as a potential lasing medium for silicon photonics, a theoretical approach is presented where Er:Si-nc is the gain medium in a silicon slot waveguide. By accounting for the local density of optical states effect on the emitters, and carrier absorption due to electrical pumping, it is shown that a pulsed excitation method is needed to achieve gain in this system. A gain of up to 2 db/cm is predicted for an electrically pumped gain medium 50 nm thick. To test these predictions Er:Si-nc LEDs were fabricated and studied. Reactive oxygen sputtering is found to produce more robust films, and the electrical excitation cross section found is two orders of magnitude larger than the optical cross section. The fabricated devices exhibited low lifetimes and low current densities which prevent observation of gain, and the modeling is used to predict how the films must be improved to achieve gain and lasing in this system.</p
Recognition of Nucleic Acid Mismatches by Luminescent Ruthenium Complexes
Get PDFDeficiencies in DNA mismatch repair (MMR) have been implicated in the development of several forms of cancers, and MMR-deficient cells tend to be resistant to commonly employed cancer therapeutics such as cisplatin. Mismatch-targeting metalloinsertors developed in our laboratory have shown great promise as therapeutic and diagnostic agents for MMR-deficient cancers. In this work, we examine fundamental aspects of binding interactions of octahedral rhodium and ruthenium complexes to DNA mismatches, and strive to develop a luminescent sensor for mismatches inside cells.
We first demonstrate that the mismatch binding affinity of rhodium metalloinsertors directly correlates with their antiproliferative effect against MMR-deficient colorectal carcinoma cells. Smaller ancillary ligands on the rhodium center facilitate binding to mismatches via metalloinsertion from the narrow minor groove of DNA. Complexes with higher mismatch binding affinity in turn selectively inhibit the growth of MMR-deficient cells compared to MMR-proficient ones. This correlation suggests that DNA mismatches are indeed the biological target of rhodium metalloinsertors inside cells.
Besides rhodium metalloinsertors, luminescent ruthenium complexes are found to bind DNA mismatches as well. Mismatch binding is accompanied by enhanced luminescence intensity. We determined two crystal structures of Δ-Ru(bpy)2dppz2+ bound to oligonucleotide duplexes. For an oligonucleotide containing AA mismatches, the atomic-resolution structure revealed that the ruthenium complex binds to DNA mismatches also through metalloinsertion: the complex inserts a planar ligand into the mismatched site from the minor groove, ejecting the mismatched bases out of the helix. Several binding geometries of the complex intercalated between well-matched DNA were also observed.
To improve the mismatch selectivity of luminescent ruthenium complexes, we tethered the complexes to organic dye molecules in an effort to amplify mismatch-associated luminescence signal through resonance energy transfer. We also modified the structure of the inserting ligand in an attempt to improve the binding affinity to mismatches over well-matched DNA. Coupling mismatch binding to luminescence response has proved most challenging in these endeavors.
Finally, we venture into the realm of RNA. Unlike their nonspecific binding to DNA, ruthenium complexes bind poorly to well-matched RNA but quite avidly to RNA mismatches. As a result, mismatched RNA produces a higher luminescence signal from bound ruthenium. We subsequently applied the ruthenium complex to image RNA mismatches inside live HeLa cells using fluorescence microscopy.</p
Statistical Models of the Protein Fitness Landscape: Applications to Protein Evolution and Engineering
Get PDFUnderstanding the protein fitness landscape is important for describing how natural proteins evolve and for engineering new proteins with useful properties. This mapping from protein sequence to protein function involves an extraordinarily complex balance of numerous physical interactions, many of which are still not well understood. Directed evolution circumvents our ignorance of how a protein’s sequence encodes its function by using iterative rounds of random mutation and artificial selection. The selection criteria is based on experimental measurements, which permits the optimization of protein sequence properties that are not understood. While directed evolution has been useful for exploring protein fitness landscapes, these searches have been relatively local in comparison to the vast space of possible protein sequences. Here, we present several classes of statistical models that map protein sequence space on a larger scale. We use these simple models to interpret data from SCHEMA recombination libraries, understand the evolutionary benefit of intragenic recombination, and design optimized protein sequences. By training on directly on experimental data, these models implicitly capture the numerous and possibly unknown factors that shape the protein fitness landscape. This provides an unrivaled quantitative accuracy across a massive number of protein sequences.</p
The Role of Transport Phenomena in Whispering Gallery Mode Optical Biosensor Performance
Get PDFWhispering gallery mode (WGM) optical resonator sensors have emerged as promising tools for label-free detection of biomolecules in solution. These devices have even demonstrated single-molecule limits of detection in complex biological uids. This extraordinary sensitivity makes them ideal for low-concentration analytical and diagnostic measurements, but a great deal of work must be done toward understanding and optimizing their performance before they are capable of reliable quantitative measurents. The present work explores the physical processes behind this extreme sensitivity and how to best take advantage of them for practical applications of this technology.
I begin by examining the nature of the interaction between the intense electromagnetic elds that build up in the optical biosensor and the biomolecules that bind to its surface. This work addresses the need for a coherent and thorough physical model that can be used to predict sensor behavior for a range of experimental parameters. While this knowledge will prove critical for the development of this technology, it has also shone a light on nonlinear thermo-optical and optical phenomena that these devices are uniquely suited to probing. The surprisingly rapid transient response of toroidal WGM biosensors despite sub-femtomolar analyte concentrations is also addressed. The development of asymmetric boundary layers around these devices under ow is revealed to enhance the capture rate of proteins from solution compared to the spherical sensors used previously. These lessons will guide the design of ow systems to minimize measurement time and consumption of precious sample, a key factor in any medically relevant assay.
Finally, experimental results suggesting that WGM biosensors could be used to improve the quantitative detection of small-molecule biomarkers in exhaled breath condensate demonstrate how their exceptional sensitivity and transient response can enable the use of this noninvasive method to probe respiratory distress. WGM bioensors are unlike any other analytical tool, and the work presented here focuses on answering engineering questions surrounding their performance and potential.</p
Genetically Restricted Metabolic Labeling in Danio rerio, a Simple Vertebrate Capable of Protein Synthesis-Dependent Memory Formation
Get PDFDetermining which neural circuits and proteins are involved in encoding memories is a central goal in neuroscience. Protein expression in the nervous system is known to undergo regulated changes in response to changes in behavioral states, in particular long-term memory formation. In this study we developed tools to investigate protein synthesis in an intact organism, the larval zebrafish, capable of simple learning behavior. Methods have recently been developed (BONCAT and FUNCAT), which introduce noncanonical amino acids bearing small bioorthogonal functional groups into proteins using the cells’ own translational machinery. Using the selective ‘click reaction’, this allows for the identification and visualization of newly synthesized proteins in vitro.
Here we demonstrate that noncanonical amino acid labeling can be achieved in vivo in the larval zebrafish. We show that azidohomoalanine is metabolically incorporated into newly synthesized proteins, in a time- and concentration-dependent manner, but has no apparent toxic effect and does not influence simple behaviors such as spontaneous swimming and escape responses. This enables fluorescent labeling of newly synthesized proteins in whole mount larval zebrafish. Furthermore, we demonstrate that genetically restricted expression of a mutant methionyl-tRNA synthetase permits cell-specific metabolic labeling with the larger noncanonical amino acid, azidonorleucine, both in vitro and in vivo. Finally, we present an associative conditioning paradigm for larval zebrafish. During a three-hour training period, 6-8dpf larvae learn to associate the social reward of visual access to a group of conspecifics with a dark environment. The memory formed during this place-conditioning paradigm undergoes rapid extinction, but is extremely stable, lasting for up to 36h. Furthermore, memory formation is both protein synthesis- and partially NMDAR-dependent. Together, the techniques developed in this study will enable the investigation of protein synthesis during long-term memory formation in the larval zebrafish.</p
Silicon Nanostructure Photovoltaics
Get PDFPhotovoltaic devices consisting of highly periodic, ultradense, silicon nanowire arrays and nanohole arrays have been fabricated with nominal nanowire widths of 20 nm, nanohole sizes of 12 nm, and lattice pitches of 32 nm, deep in the subwavelength regime for visible light. We have developed a set of surface passivation protocols that provide the extremely low surface recombination velocities typical of thick, high-quality, furnace-grown thermal silicon dioxide, but within an ultrathin layer on the order of 5 – 10 nm thick. With this high quality oxide passivation, these devices exhibit good photovoltaic performance that rivals or exceeds all comparable devices reported in the literature. Using a collection of characterization techniques, including optical microscopy, scanning electron microscopy, cross-sectional transmission electron microscopy, and spectroscopic ellipsometry, we characterize the structure and morphology of these nanostructure arrays. The high perfection of the arrays enables absorptance calculations to be performed using rigorous coupled-wave analysis, which solves Maxwell’s equations for periodic structures. The calculations show that these deep subwavelength nanostructures behave as homogeneous optical materials with effective refractive indices determined by the structural parameters. We solve approximate models to estimate their refractive indices. When the spectral responses of these devices were measured, their external quantum efficiencies track the calculated absorptances, except for a small multiplicative offset at shorter wavelengths due to a greater than unity internal quantum efficiency, which we estimate by dividing the absorptance into the external quantum efficiency
The Quantum Electron Dynamics of Materials Subjected to Extreme Environments
Get PDFQuantum wavepacket molecular dynamics simulations are used to study the effects of extreme environments on materials. The electron forcefield (eFF) method provides energies and forces from which wavepackets can be propagated in time under conditions ranging from standard temperature and pressure to tens of thousands of Kelvin and hundreds of GPa of pressure with strain rates as high as 1 km per second. Using this technique nanometer scale systems with hundreds of thousands of particles can be simulated for up to hundreds of picoseconds.
High strain rate fracture in solids is accompanied by the emission of electrons and photons, though atomistic simulations have thus far been unable to capture such processes. The eFF method for nonadiabatic dynamics accounts for electron emission and large potential differences consistent with the experiments, providing the first atomistic description of the origin of these effects. The effects that we explain are (1) loading of a crack leads to a sudden onset of crack propagation at 7 GPa followed by uniform velocity of the crack at 2500 km/sec after initiation, and (2) voltage fluctuations in the 10–400 mV range, charge creation (up to 1011 carriers/cm2), and current production (up to 1.3 mA). The development of an effective core potential for eFF enabled this large scale study.
Using the eFF wavepacket molecular dynamics method, simulations of the single shock Hugoniot are reported for crystalline polyethylene (PE). The eFF results are in good agreement with previous DFT theories and experimental data which is available up to 80 GPa. We predict shock Hugoniots for PE up to 350 GPa. In addition, we analyze the phase transformations that occur due to heating. Our analysis includes ionization fraction, molecular decomposition, and electrical conductivity during isotropic compression. We find that above a compression of 2.4 g/cc the PE structure transforms into a Lennard-Jones fluid, leading to a sharp increase in electron ionization and a significant increase in system conductivity. eFF accurately reproduces shock pressures and temperatures for PE along the single shock Hugoniot.</p
Characterization of an Unusual Collection of Olfactory Neurons in the Nose
Get PDFWe have used a combination of histochemical, electrophysiological, and behavioral approaches to study signal transduction, membrane biophysics, and chemosensory function in the neurons of the mouse Grueneberg ganglion (GG) olfactory subsystem. The GG is a recently appreciated collection of ~1,000 clustered primary olfactory neurons located at the anterior tip of the mammalian nasal cavity. Despite their far-forward position, GG neurons are fully trapped beneath a keratinized epithelium and are wrapped by glial cells. This raises the question of how they contribute to the sense of smell. We found that GG neurons have key components of cGMP signal transduction pathway and are molecularly similar to GC-D neurons, which project to the enigmatic necklace glomeruli in the olfactory bulb. In electrophysiological analyses, individual GG neurons spontaneously discharged action potentials in one of three distinct temporal patterns that were stable for >20 min. An auxiliary fast-inactivating Na+ current accounted for the various discharge patterns in computer simulations of the neuronal ionic currents. Despite differences in baseline activity, the majority of GG neurons responded to specific mammalian pheromones. In behavioral experiments, we found that the weaning of adolescent mice induced GG activity; however, the effects did not depend on ambient temperature or the presence of other animals. Because GG neurons reside on a dense vascular bed, have specialized access to serum contents, and directly responded to pressure ejections of serum, their activity can likely be modulated by internally circulating hormones or proteins associated with specific physiological states such as stress. Taken together, our results demonstrate unusual molecular and functional aspects of a morphologically and anatomically atypical olfactory nerve
DNA Mechanics and Transcriptional Regulation in the E. coli lac Operon
Get PDFMany gene regulatory motifs in both prokaryotes and eukaryotes involve physical manipulations of the genetic material, often on length scales short enough that the mechanical properties of the DNA significantly impact gene expression. One class of such manipulations, called “action at a distance”, includes transcription factor-mediated DNA looping, in which a binding site some distance away on the DNA is brought into close proximity with the transcription machinery at the promoter. DNA looping is a key component of several important regulatory systems in bacteria, and is crucial to the combinatorial control that is common at eukaryotic promoters regulated by more transcription factors than can physically bind adjacent to the promoter. Here we use a prototypical DNA looping protein, the Lac repressor from E. coli, to explore questions regarding the role of DNA mechanics in DNA looping and combinatorial control, particularly concerning the role of sequence flexibility in short-length-scale looping. We combine a statistical mechanical model of looping by the Lac repressor with a single-molecule technique called tethered particle motion that allows us to quantify this looping, and the systematic tuning of four biologically relevant and experimentally tractable parameters: loop length, loop sequence, repressor-DNA affinity, and repressor concentration. We show that this combination is a powerful approach to measuring repressor-DNA binding affinities and sequence-dependent DNA flexibilities in a way that is orthogonal, and therefore complementary, to conventional ensemble assays. Our results show that the sequence dependence to looping is more complicated than has been observed in other contexts, suggesting that “sequence flexibility” as a general term is misleading, and, we argue, that the measurement of sequence flexibilities depend more strongly than previously appreciated on the shape of the deformation used to make the measurement. Finally, we present preliminary results with a more complicated system that is a case study for broader issues in combinatorial control, and a new hidden Markov model approach, based on variational Bayesian inference, to analyze these more complicated systems, which we hope will allow more precise dissections of, and more robust extraction of kinetic parameters from, tethered particle motion assays
Large-Eddy Simulation of the Flat-Plate Turbulent Boundary Layer at High Reynolds Numbers
Get PDFThe near-wall, subgrid-scale (SGS) model [Chung and Pullin, "Large-eddy simulation and wall-modeling of turbulent channel flow", J. Fluid Mech. 631, 281--309 (2009)] is used to perform large-eddy simulations (LES) of the incompressible developing, smooth-wall, flat-plate turbulent boundary layer. In this model, the stretched-vortex, SGS closure is utilized in conjunction with a tailored, near-wall model designed to incorporate anisotropic vorticity scales in the presence of the wall. The composite SGS-wall model is presently incorporated into a computer code suitable for the LES of developing flat-plate boundary layers. This is then used to study several aspects of zero- and adverse-pressure gradient turbulent boundary layers.
First, LES of the zero-pressure gradient turbulent boundary layer are performed at Reynolds numbers Reθ based on the free-stream velocity and the momentum thickness in the range Reθ = 103 - 1012. Results include the inverse skin friction coefficient, √2/Cf, velocity profiles, the shape factor H, the Karman "constant", and the Coles wake factor as functions of Reθ. Comparisons with some direct numerical simulation (DNS) and experiment are made, including turbulent intensity data from atmospheric-layer measurements at Reθ = O(106. At extremely large Reθ, the empirical Coles-Fernholz relation for skin-friction coefficient provides a reasonable representation of the LES predictions. While the present LES methodology cannot of itself probe the structure of the near-wall region, the present results show turbulence intensities that scale on the wall-friction velocity and on the Clauser length scale over almost all of the outer boundary layer. It is argued that the LES is suggestive of the asymptotic, infinite Reynolds-number limit for the smooth-wall turbulent boundary layer and different ways in which this limit can be approached are discussed. The maximum Reθ of the present simulations appears to be limited by machine precision and it is speculated, but not demonstrated, that even larger Reθ could be achieved with quad- or higher-precision arithmetic.
Second, the time series velocity signals obtained from LES within the logarithmic region of the zero-pressure gradient turbulent boundary layer are used in combination with an empirical, predictive inner--outer wall model [Marusic et al., "Predictive model for wall-bounded turbulent flow", Science 329, 193 (2010)] to calculate the statistics of the fluctuating streamwise velocity in the inner region of the zero-pressure gradient turbulent boundary layer. Results, including spectra and moments up to fourth order, are compared with equivalent predictions using experimental time series, as well as with direct experimental measurements at Reynolds numbers Reτ based on the friction velocity and the boundary layer thickness, Reτ =7,300, 13,600 and 19,000. LES combined with the wall model are then used to extend the inner-layer predictions to Reynolds numbers Reτ =62,000, 100,000 and 200,000 that lie within a gap in log(Reτ) space between laboratory measurements and surface-layer, atmospheric experiments. The present results support a log-like increase in the near-wall peak of the streamwise turbulence intensities with Reτ and also provide a means of extending LES results at large Reynolds numbers to the near-wall region of wall-bounded turbulent flows.
Finally, we apply the wall model to LES of a turbulent boundary layer subject to an adverse pressure gradient. Computed statistics are found to be consistent with recent experiments and some Reynolds number similarity is observed over a range of two orders of magnitude.</p