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Silicon-Based Terahertz Circuits and Systems
Get PDFThe Terahertz frequency range, often referred to as the `Terahertz' gap, lies wedged between microwave at the lower end and infrared at the higher end of the spectrum, occupying frequencies between 0.3-3.0 THz. For a long time, applications in THz frequencies had been limited to astronomy and chemical sciences, but with advancement in THz technology in recent years, it has shown great promise in a wide range of applications ranging from disease diagnostics, non-invasive early skin cancer detection, label-free DNA sequencing to security screening for concealed weapons and contraband detection, global environmental monitoring, nondestructive quality control and ultra-fast wireless communication. Up until recently, the terahertz frequency range has been mostly addressed by high mobility compound III-V processes, expensive nonlinear optics, or cryogenically cooled quantum cascade lasers. A low cost, room temperature alternative can enable the development of such a wide array of applications, not currently accessible due to cost and size limitations. In this thesis, we will discuss our approach towards development of integrated terahertz technology in silicon-based processes. In the spirit of academic research, we will address frequencies close to 0.3 THz as 'Terahertz'.
In this thesis, we address both fronts of integrated THz systems in silicon: THz power generation, radiation and transmitter systems, and THz signal detection and receiver systems. THz power generation in silicon-based integrated circuit technology is challenging due to lower carrier mobility, lower cut-o frequencies compared to compound III-V processes, lower breakdown voltages and lossy passives. Radiation from silicon chip is also challenging due to lossy substrates and high dielectric constant of silicon. In this work, we propose novel ways of combining circuit and electromagnetic techniques in a holistic design approach, which can overcome limitations of conventional block-by-block or partitioned design methodology, in order to generate high-frequency signals above the classical definition of cut-off frequencies (ƒt/ƒmax). We demonstrate this design philosophy in an active electromagnetic structure, which we call Distributed Active Radiator. It is inspired by an Inverse
Maxwellian approach, where instead of using classical circuit and electromagnetic blocks to generate and radiate THz frequencies, we formulate surface (metal) currents in silicon chip for a desired THz field prole and develop active means of controlling different harmonic
currents to perform signal generation, frequency multiplication, radiation and lossless filtering, simultaneously in a compact footprint. By removing the articial boundaries between circuits, electromagnetics and antenna, we open ourselves to a broader design space. This
enabled us to demonstrate the rst 1 mW Eective-isotropic-radiated-power(EIRP) THz (0.29 THz) source in CMOS with total radiated power being three orders of magnitude more than previously demonstrated. We also proposed a near-field synchronization mechanism, which is a scalable method of realizing large arrays of synchronized autonomous radiating sources in silicon. We also demonstrate the first THz CMOS array with digitally controlled beam-scanning in 2D space with radiated output EIRP of nearly 10 mW at 0.28 THz.
On the receiver side, we use a similar electronics and electromagnetics co-design approach to realize a 4x4 pixel integrated silicon Terahertz camera demonstrating to the best of our knowledge, the most sensitive silicon THz detector array without using post-processing,
silicon lens or high-resistivity substrate options (NEP < 10 pW √ Hz at 0.26 THz). We put the 16 pixel silicon THz camera together with the CMOS DAR THz power generation arrays and demonstrated, for the first time, an all silicon THz imaging system with a CMOS source.</p
Cavity Optomechanics with High Stress Silicon Nitride Films
Get PDFThere has been a barrage of interest in recent years to marry the fields of nanomechanics and quantum optics. Mechanical systems provide sensitive and scalable architectures for sensing applications ranging from atomic force microscopy to gravity wave interferometry. Optical resonators driven by low noise lasers provide a quiet and well-understood means to read-out and manipulate mechanical motion, by way of the radiation pressure force. Taken to an extreme, a device consisting of a high-Q nanomechanical oscillator coupled to a high-finesse optical cavity may enable ground-state preparation of the mechanical element, thus paving the way for a new class of quantum technology based on chip-scale phononic devices coupled to optical photons. By way of mutual coupling to the optical field, this architecture may enable coupling of single phonons to real or artificial atoms, an enticing prospect because of the vast "quantum optics toolbox" already developed for cavity quantum electrodynamics.
The first step towards these goals --- ground-state cooling of the mechanical element in a "cavity optomechanical" system --- has very recently been realized in a cryogenic setup. The work presented in this thesis describes an effort to extend this capability to a room temperature apparatus, so that the usual panoply of table-top optical/atomic physics tools can be brought to bear. This requires a mechanical oscillator with exceptionally low dissipation, as well as careful attention to extraneous sources of noise in both the optical and mechanical componentry. Our particular system is based on a high-Q, high-stress silicon nitride membrane coupled to a high-finesse Fabry-Perot cavity. The purpose of this thesis is to record in detail the procedure for characterizing/modeling the physical properties of the membrane resonator, the optical cavity, and their mutual interaction, as well as extraneous sources of noise related to multimode thermal motion of the oscillator, thermal motion of the cavity apparatus, optical absorption, and laser phase fluctuations. Our principle experimental result is the radiation pressure-based cooling of a high order, 4.8 MHz drum mode of the membrane from room temperature to ~ 100 mK (~ 500 phonons). Secondary results include an investigation of the Q-factor of membrane oscillators with various geometries, some of which exhibit state-of-the-art Q x frequency products of 3 x 10^13 Hz, and a novel technique to suppress extraneous radiation pressure noise using electro-optic feedback.</p
Clustering Affine Subspaces: Algorithms and Hardness
Get PDFWe study a generalization of the famous k-center problem where each object is an affine subspace of dimension Δ, and give either the first or significantly improved algorithms and hardness results for many combinations of parameters. This generalization from points (Δ=0) is motivated by the analysis of incomplete data, a pervasive challenge in statistics: incomplete data objects in Rd can be modeled as affine subspaces. We give three algorithmic results for different values of k, under the assumption that all subspaces are axis-parallel, the main case of interest because of the correspondence to missing entries in data tables.
1) k=1: Two polynomial time approximation schemes which runs in poly(Δ, 1/ε)nd.
2) k=2: O(Δ1/4)-approximation algorithm which runs in poly(n,d,Δ)
3) General k: Polynomial time approximation scheme which runs in 2O(Δk log k(1+1/ε2))nd
We also prove nearly matching hardness results; in both the general (not necessarily axis-parallel) case (for k ≥ 2) and in the axis-parallel case (for k ≥ 3), the running time of an approximation algorithm with any approximation ratio cannot be polynomial in even one of k and Δ, unless P = NP. Furthermore, assuming that the 3-SAT problem cannot be solved subexponentially, the dependence on both k and Δ must be exponential in the general case (in the axis-parallel case, only the dependence on k drops to 2Ω√k)). The simplicity of the first and the third algorithm suggests that they might be actually used in statistical applications. The second algorithm, which demonstrates a theoretical gap between the axis-parallel and general case for k=2, displays a strong connection between geometric clustering and classical coloring problems on graphs and hypergraphs, via a new Helly-type theorem.</p
High-Throughput Strategies for the Scalable Generation of RNA Component Functions
Get PDFEngineered biological systems hold great promise in providing solutions to many global challenges, including environmental remediation, sustainability, scalable manufacturing, and health and medicine. Synthetic biology is an emerging research field with a primary goal of making the engineering of biology more streamlined and reliable. Recent advances in synthetic RNA biology have led to design of RNA-based gene-regulatory devices from assembly of functional RNA components that encode more basic functions, including sensing, information transmission, and actuation functions. These synthetic RNA control devices allow access and control information on cellular state, thereby advancing our ability to interact with and program biology.
A modular ribozyme device platform was recently described to link an aptamer (sensor) to a hammerhead ribozyme (actuator) through a distinct sequence (information transmitter) capable of a strand-displacement event. The utilization of ribozyme as the actuator in the platform, whose mechanism of action is independent of cell-specific machinery, allows transport of the resultant devices to in vitro or different cellular environments. The broad implementation of these devices requires enabling technologies to support efficient generation of new functional RNA components and quantitative tailoring of device regulatory performance for specific cellular applications. Current component generation and device tailoring strategies are limited in their throughputs and efficiencies, and thus have hampered our ability to generate new ribozyme devices for cellular engineering applications.
To support scalable generation and tailoring of ribozyme devices, we have described high-throughput in vitro selection and in vivo screening strategies based on the modular ribozyme device platform. We proposed a high-throughput solution-based in vitro selection strategy to generate new sensing functions within the device platform. A high-throughput and quantitative two-color FACS-based screening strategy was developed to complement the in vitro selection strategy by allowing efficient tailoring of device regulatory activities in the cellular environments. We further developed quantitative assays based on the surface plasmon resonance (SPR) technology to allow rapid measurements of the device and component activities. Together, these enabling strategies will offer a scalable and integrated process for the construction and programming of RNA control devices for broad cellular engineering applications, thus laying an important foundation for engineering more complex biological systems.</p
Dorsal-Ventral Patterning and Gene Regulation in the Early Embryo of Drosophila melanogaster
Get PDFIn order for an embryo to develop and form properly, the anterior-posterior and dorsal-ventral axes must be specified. This is accomplished by controlled regulation of gene expression that allows for the activation and repression of tissue specific genes. Patterning of the Drosophila dorsal-ventral axis is an excellent model for understanding how axis specification is controlled. The dorsal-ventral axis is patterned by a nuclear gradient of Dorsal that is highest in ventral regions of the embryo. Dorsal activates genes in a concentration dependent manner to establish early patterning of the embryo. The patterns are refined by interactions between Dorsal and other activators as well as repressors in both dorsal and ventral regions of the embryo. Until recently there was only evidence for repressors acting in ventral regions of the embryo but our studies and other recent studies have provided evidence to suggest that several repressors act in dorsal regions of the embryo to refine Dorsal target genes. Here we show that an element, the A-box, previously identified in the cis-regulatory module (CRM) of the gene intermediate neuroblast defective (ind), is necessary and sufficient to mediate dorsal repression and is also involved in activation of ind. We conducted an affinity chromatography assay and identified factors that bound the A-box element. One of the factors that bound to this element, Grh, activates ind. We also identified several chromatin-remodeling factors that may function to silence ind in dorsal regions of the embryo. Our results also indicate that a second tier of repression that is independent of the A-box element, mediates repression of ind via Dpp-signaling. We extended our studies to the CRMs of ventral neuroblast defective (vnd) and short gastrulation (sog). Using a chimeric CRM repression assay, we found that strong and weak dorsal repression are also mediated by the vnd and sog CRMs, respectively. This suggests that limiting amounts of Dorsal are not sufficient to establish the dorsal borders of dorsal-ventral patterning genes as was previously believed, and rather, repressors are used to establish these borders
Frequency-Stabilized Cavity Ring-Down Spectroscopy of O₂ and CO₂ to Support Atmospheric Remote Sensing
Get PDFRecent remote-sensing satellite missions have aimed to measure global greenhouse gas concentrations with precisions as demanding as 0.25%. These high-resolution measurements should allow for the quantification of carbon sources and sinks, thus, allowing for a considerable reduction in present carbon cycle uncertainties. To achieve these unprecedented measurement goals will require the most precise body of spectroscopic reference data (i.e., laboratory measurements) ever assembled. In order to aid these missions, we have measured ultraprecise spectroscopic parameters for the (30012) ←(00001) CO2 band at 1.57 µm and the O2 A-band at 0.76 µm. These near-infrared transitions are utilized in recent greenhouse gas monitoring missions, with the A-band being employed to derive pressure and temperature profiles. In these investigations we have employed frequency-stabilized cavity ring-down spectroscopy (FS-CRDS), a novel ultrasensitive spectroscopic technique. In the O2 A-band we have measured magnetic dipole line parameters for 16O2 as well as each of the rare isotopologues and have produced calculated, HITRAN-style line lists. Due to the clear presence of collisional narrowing in the spectra, we have utilized the Galatry line profile in these studies and have reported narrowing parameters under self- and air-broadened conditions. We anticipate that the use of these spectral parameters will greatly reduce the uncertainties of atmospheric remote-sensing retrievals. In addition, the spectral fidelity of FS-CRDS allowed us to observe and quantify unresolved hyperfine structure for the 17O-containing isotopologues. Furthermore, the high sensitivity of FS-CRDS enabled measurements of ultraweak (S~10−30 cm molec.−1) electric quadrupole transitions in the A-band, many of which had not previously been observed. Recently we have begun a series of studies of the near-infrared CO2 transitions. Measurements at low pressures (<40 kPa) have revealed the simultaneous presence of Dicke narrowing and speed dependence of collisional broadening and shifting. In addition, we have demonstrated that the use of the simple Voigt profile (which neglects these effects) in the pressure range will lead to several percent biases in the retrieved Lorentzian width and spectral area
Structure-Function Studies of Nicotinic Acetylcholine Receptors Using Unnatural Amino Acids
Get PDFThis dissertation primarily describes structure-function studies of the nicotinic acetylcholine receptors (nAChRs). These studies use a combination of unnatural amino acid mutagenesis and electrophysiology to determine the specific molecular interactions required for neurotransmitter binding to nAChRs. Chapter 2 examines the mode of agonist activation for the α4β2 nAChR, the receptor responsible for nicotine addiction. This study investigates the molecular interactions that differentiate the α4β2 receptor from other receptor subtypes and endow it with the ability to mediate nicotine addiction. We report that the high affinity for nicotine at the α4β2 receptor is a result of a strong cation-π interaction and a strengthened backbone hydrogen bond to a conserved tryptophan (TrpB) of this receptor. We also establish that a point mutation just four residues away from TrpB appears to influence the shape of the agonist binding site, such that it can differentiate the agonist binding mode of the α4β2 and muscle-type receptors. Chapter 3 extends studies of the point mutation near TrpB, termed the “loop B glycine.” We examine the muscle-type, α4β2, and α7 subtypes and show that the identity of this residue strongly correlates with agonist potency. Low-potency receptor subtypes have a glycine at the loop B site, while high-potency receptors have a lysine at this site. We establish that mutation of this residue can to convert a low-potency receptor to a high-potency receptor and vice versa. Chapter 4 investigates the agonist binding mechanism of the α4β4 receptor. We show both ACh and nicotine make a strong cation-π interaction to TrpB, and nicotine makes a strong hydrogen bond to the backbone carbonyl of TrpB. Additionally, chimeric β subunits are used to examine the influence of the complementary binding component on receptor pharmacology for the α4β2 and α4β4 receptors. Last, chapter 5 is a methodology-based project focused on optimizing the incorporation of unnatural amino acids into mammalian cells. Using HEK293T cells, we successfully suppressed an amber stop codon using HSAS, an in vivo aminoacylated tRNA. Additional studies will pursue the viability of in vitro aminoacylated tRNAs for nonsense suppression in mammalian cells
Dynamics of Magnetically Driven Plasma Jets: An Instability of an Instability, Gas Cloud Impacts, Shocks, and Other Deformations
Get PDFThe Caltech experiment described here produces plasmas relevant to both astrophysical and fusion energy studies. A disk-shaped set of electrodes mounted on the inside of a meter-scale vacuum chamber provides the energy to break a neutral gas, provided at the electrodes only, down into a plasma. The plasma starts as eight loops, and then self-organizes into a single magnetically driven collimated plasma jet. This thesis explores the dynamic evolution of that plasma jet and how changes made to the jet power source or environment alter the evolution. The most significant finding is the discovery that a series of instabilities can lead to magnetic reconnection. The jet undergoes a first, primary instability, called the kink instability. The exponential growth of kink amplitude provides an acceleration that drives a smaller scale, secondary instability, called the Rayleigh–Taylor instability. The Rayleigh–Taylor instability can drop the diameter of the plasma to a small enough scale to allow magnetic reconnection. A second set of experiments explores the range of collision interactions between the plasma jet and a cloud of neutral gas in its path. A final set of experiments shows the dependence of jet radius on a time-changing current. A new power supply that led to the observation of some of these new dynamics is also described
Parylene as a New Membrane Material for Biomems Applications
Get PDFThe work in this thesis aims to use MEMS and microfabrication technologies to develop two types of parylene membrane devices for biomedical applications. The first device is the parylene membrane filter for cancer detection. The presence of circulating tumor cells (CTC) in patient blood is an important sign of cancer metastasis. However, currently there are two big challenges for CTC detection. First, CTCs are extremely rare, especially at the early stage of cancer metastasis. Secondly, CTCs are very fragile, and are very likely to be damaged during the capturing process. By using size-based membrane filtration through the specially designed parylene filters, together with a constant-pressure filtration system, we are able to capture the CTCs from patient blood with high capture efficiency, high viability, moderate enrichment, and high throughput. Both immunofluorescence enumeration and telomerase activity detection have been used to detect and differentiate the captured CTCs. The feasibility of further cell culture of the captured CTCs has also been demonstrated, which could be a useful way to increase the number of CTCs for future studies. Models of the time-dependent cell membrane damage are developed to predict and prevent CTC damage during this detection process. The results of clinical trials further demonstrate that the parylene membrane filter is a promising device for cancer detection.
The second device is the parylene artificial Bruch’s membrane for age-related macular degeneration (AMD). AMD is usually characterized by an impaired Bruch’s membrane with much lowered permeability, which impedes the transportation of nutrients from choroid vessels to nourish the retinal pigment epithelial (RPE) cells and photoreceptors. Parylene is selected as a substitute material because of its good mechanical properties, transparency, biocompatibility, and machinability. More importantly, it is found that the permeability of submicron parylene is very similar to that of healthy human Bruch’s membrane. A mesh-supported submicron parylene membrane structure has been designed and its feasibility as an artificial Bruch’s membrane has been demonstrated by diffusion experiments, cell perfusion culture, and pressure deflection tests. RPE cells are able to adhere, proliferate and develop into normal in vivo-like morphology and functions. Currently this artificial membrane is under clinical trials.</p
Multi-Scale Dynamics and Rheology of Mantle Convection with Plates
Get PDFFundamental issues in our understanding of plate and mantle dynamics remain unresolved, including the rheology and state of stress of plates and slabs; the coupling between plates, slabs and mantle; the small-scale dynamics in subduction zones; the flow around slabs; and the cause of rapid changes in plate motions. To address these questions, models of global mantle flow with plates are computed using adaptive finite elements, and compared to a variety of observational constraints. These dynamically consistent instantaneous models include a composite rheology with yielding, and incorporate details of the thermal buoyancy field. Around plate boundaries, the local mesh size is 1 km, which allows us to study highly detailed features in a globally consistent framework. Models that best fit plateness criteria and plate motion data have strong slabs with high viscosities around 1024 Pa s, and stresses of ~100 MPa. We find a strong dependence of global plate motions, trench rollback, net rotation, plateness, and strain rate on the stress exponent in the nonlinear viscosity; the yield stress is found to be important only if it is smaller than the ambient convective stress. Due to strong coupling between plates, slabs, and the surrounding mantle, the presence of lower mantle anomalies affect plate motions. The flow in and around slabs, microplate motion, and trench rollback are intimately linked to the amount of yielding in the subducting slab hinge, slab morphology, and the presence of high viscosity structures in the lower mantle beneath the slab. The lateral flow around slabs is generally trench-perpendicular, induced by the strongly coupled downward motion of the subducting slabs, and therefore our models do not account for the trench-parallel flow inferred from shear-wave splitting analysis. Flow models before and after the plate reorganization around 50 Ma are not able to reproduce the rapid change in Pacific plate motion from northwest to west that is associated with the bend in the Hawaiian-Emperor chain, despite a nonlinear rheology and the incorporation of detailed reconstructed paleo plate boundaries and age grids. In these models at 55 and 45 Ma, slab age is an impor- tant factor in the slab pull, determining the coupling between plates and slabs and between upper and lower mantle sections of slabs. The overall dynamics appear to be dominated by the characteristics of slab remnants in the lower mantle. Subducting slabs affect lateral flow in the upper mantle on a much smaller scale, and therefore we conclude that it is unlikely that the slabs in the western Pacific are responsible for the slowing of sub-Pacific flow after the initiation of their subduction around 50 Ma