Single-Molecule Detection of Unique Genome Signatures: Applications in Molecular Diagnostics and Homeland Security

Single-molecule detection (SMD) offers an attractive approach for identifying the presence of certain markers that can be used for in vitro molecular diagnostics in a near real-time format. The ability to eliminate sample processing steps afforded by the ultra-high sensitivity associated with SMD yields an increased sampling pipeline. When SMD and microfluidics are used in conjunction with nucleic acid-based assays such as the ligase detection reaction coupled with single-pair fluorescent resonance energy transfer (LDR-spFRET), complete molecular profiling and screening of certain cancers, pathogenic bacteria, and other biomarkers becomes possible at remarkable speeds and sensitivities with high specificity. The merging of these technologies and techniques into two different novel instrument formats has been investigated. (1) The use of a charge-coupled device (CCD) in time-delayed integration (TDI) mode as a means for increasing the throughput of any single molecule measurement by simultaneously tracking and detecting single-molecules in multiple microfluidic channels was demonstrated. The CCD/TDI approach allowed increasing the sample throughput by a factor of 8 compared to a single-assay SMD experiment. A sampling throughput of 276 molecules s-1 per channel and 2208 molecules s-1 for an eight channel microfluidic system was achieved. A cyclic olefin copolymer (COC) waveguide was designed and fabricated in a pre-cast poly(dimethylsiloxane) stencil to increase the SNR by controlling the excitation geometry. The waveguide showed an attenuation of 0.67 dB/cm and the launch angle was optimized to increase the depth of penetration of the evanescent wave. (2) A compact SMD (cSMD) instrument was designed and built for the reporting of molecular signatures associated with bacteria. The optical waveguides were poised within the fluidic chip at orientation of 90° with respect to each other for the interrogation of single-molecule events. Molecular beacons (MB) were designed to probe bacteria for the classification of Gram +. MBs were mixed with bacterial cells and pumped though the cSMD which allowed S. aureus to be classified with 2,000 cells in 1 min. Finally, the integration of the LDR-spFRET assay on the cSMD was explored with the future direction of designing a molecular screening approach for stroke diagnostics

Enhancement factor distribution around a single SERS Hot-spot and its relation to Single Molecule detection

We provide the theoretical framework to understand the phenomenology and statistics of single-molecule (SM) signals arising in Surface-Enhanced Raman Scattering (SERS) under the presence of so-called electromagnetic hot-spots (HS's). We show that most characteristics of the SM-SERS phenomenon can be tracked down to the presence of tail-like (power law) distribution of enhancements and we propose a specific model for it. We analyze, in the light of this, the phenomenology of SM-SERS and show how the different experimental manifestations of the effect reported in the literature can be analyzed and understood under a unified ``universal'' framework with a minimum set of parameters.Comment: 13 pages, 4 figures, submitted to J. Chem. Phy

Constraining f(R) Gravity as a Scalar Tensor Theory

We search for viable f(R) theories of gravity, making use of the equivalence between such theories and scalar-tensor gravity. We find that models can be made consistent with solar system constraints either by giving the scalar a high mass or by exploiting the so-called chameleon effect. However, in both cases, it appears likely that any late-time cosmic acceleration will be observationally indistinguishable from acceleration caused by a cosmological constant. We also explore further observational constraints from, e.g., big bang nucleosynthesis and inflation.Comment: 15 pages, 5 figure

Systematic Effects in Interferometric Observations of the CMB Polarization

The detection of the primordial $B$-mode spectrum of the polarized cosmic microwave background (CMB) signal may provide a probe of inflation. However, observation of such a faint signal requires excellent control of systematic errors. Interferometry proves to be a promising approach for overcoming such a challenge. In this paper we present a complete simulation pipeline of interferometric observations of CMB polarization, including systematic errors. We employ two different methods for obtaining the power spectra from mock data produced by simulated observations: the maximum likelihood method and the method of Gibbs sampling. We show that the results from both methods are consistent with each other, as well as, within a factor of 6, with analytical estimates. Several categories of systematic errors are considered: instrumental errors, consisting of antenna gain and antenna coupling errors, and beam errors, consisting of antenna pointing errors, beam cross-polarization and beam shape (and size) errors. In order to recover the tensor-to-scalar ratio, $r$, within a 10% tolerance level, which ensures the experiment is sensitive enough to detect the $B$-signal at $r=0.01$ in the multipole range $28 < \ell < 384$, we find that, for a QUBIC-like experiment, Gaussian-distributed systematic errors must be controlled with precisions of $|g_{rms}| = 0.1$ for antenna gain, $|\epsilon_{rms}| = 5 \times 10^{-4}$ for antenna coupling, $\delta_{rms} \approx 0.7^\circ$ for pointing, $\zeta_{rms} \approx 0.7^\circ$ for beam shape, and $\mu_{rms} = 5 \times 10^{-4}$ for beam cross-polarization.Comment: 15 pages, 6 figures, submitted to ApJ

Mosaicking with cosmic microwave background interferometers

Measurements of cosmic microwave background (CMB) anisotropies by interferometers offer several advantages over single-dish observations. The formalism for analyzing interferometer CMB data is well developed in the flat-sky approximation, valid for small fields of view. As the area of sky is increased to obtain finer spectral resolution, this approximation needs to be relaxed. We extend the formalism for CMB interferometry, including both temperature and polarization, to mosaics of observations covering arbitrarily large areas of the sky, with each individual pointing lying within the flat-sky approximation. We present a method for computing the correlation between visibilities with arbitrary pointing centers and baselines and illustrate the effects of sky curvature on the l-space resolution that can be obtained from a mosaic.Comment: 9 pages; submitted to Ap

Systematic Errors in Cosmic Microwave Background Interferometry

Cosmic microwave background (CMB) polarization observations will require superb control of systematic errors in order to achieve their full scientific potential, particularly in the case of attempts to detect the B modes that may provide a window on inflation. Interferometry may be a promising way to achieve these goals. This paper presents a formalism for characterizing the effects of a variety of systematic errors on interferometric CMB polarization observations, with particular emphasis on estimates of the B-mode power spectrum. The most severe errors are those that couple the temperature anisotropy signal to polarization; such errors include cross-talk within detectors, misalignment of polarizers, and cross-polarization. In a B mode experiment, the next most serious category of errors are those that mix E and B modes, such as gain fluctuations, pointing errors, and beam shape errors. The paper also indicates which sources of error may cause circular polarization (e.g., from foregrounds) to contaminate the cosmologically interesting linear polarization channels, and conversely whether monitoring of the circular polarization channels may yield useful information about the errors themselves. For all the sources of error considered, estimates of the level of control that will be required for both E and B mode experiments are provided. Both experiments that interfere linear polarizations and those that interfere circular polarizations are considered. The fact that circular experiments simultaneously measure both linear polarization Stokes parameters in each baseline mitigates some sources of error.Comment: 19 pages, 9 figures, submitted to Phys. Rev.

Bayesian Inference of Polarized CMB Power Spectra from Interferometric Data

Detection of B-mode polarization of the cosmic microwave background (CMB) radiation is one of the frontiers of observational cosmology. Because they are an order of magnitude fainter than E-modes, it is quite a challenge to detect B-modes. Having more manageable systematics, interferometers prove to have a substantial advantage over imagers in detecting such faint signals. Here, we present a method for Bayesian inference of power spectra and signal reconstruction from interferometric data of the CMB polarization signal by using the technique of Gibbs sampling. We demonstrate the validity of the method in the flat-sky approximation for a simulation of an interferometric observation on a finite patch with incomplete uv-plane coverage, a finite beam size and a realistic noise model. With a computational complexity of O(n^{3/2}), n being the data size, Gibbs sampling provides an efficient method for analyzing upcoming cosmology observations.Comment: 8 pages, 8 figures, expanded discussion and edited to match ApJS approved version, acknowledgments update

Bayesian semi-blind component separation for foreground removal in interferometric 21-cm observations

We present in this paper a new Bayesian semi-blind approach for foreground removal in observations of the 21-cm signal with interferometers. The technique, which we call HIEMICA (HI Expectation-Maximization Independent Component Analysis), is an extension of the Independent Component Analysis (ICA) technique developed for two-dimensional (2D) CMB maps to three-dimensional (3D) 21-cm cosmological signals measured by interferometers. This technique provides a fully Bayesian inference of power spectra and maps and separates the foregrounds from signal based on the diversity of their power spectra. Only relying on the statistical independence of the components, this approach can jointly estimate the 3D power spectrum of the 21-cm signal and, the 2D angular power spectrum and the frequency dependence of each foreground component, without any prior assumptions about foregrounds. This approach has been tested extensively by applying it to mock data from interferometric 21-cm intensity mapping observations under idealized assumptions of instrumental effects. We also discuss the impact when the noise properties are not known completely. As a first step toward solving the 21 cm power spectrum analysis problem we compare the semi-blind HIEMICA technique with the commonly used Principal Component Analysis (PCA). Under the same idealized circumstances the proposed technique provides significantly improved recovery of the power spectrum. This technique can be applied straightforwardly to all 21-cm interferometric observations, including epoch of reionization measurements, and can be extended to single-dish observations as well.Comment: 18 pages, 7 figures, added some discussions about the impact of noise misspecificatio

Deep Burn Develpment of Transuranic Fuel for High-Temperature Helium-Cooled Reactors - July 2010

The DB Program Quarterly Progress Report for April - June 2010, ORNL/TM/2010/140, was distributed to program participants on August 4. This report discusses the following: (1) TRU (transuranic elements) HTR (high temperature helium-cooled reactor) Fuel Modeling - (a) Thermochemical Modeling, (b) 5.3 Radiation Damage and Properties; (2) TRU HTR Fuel Qualification - (a) TRU Kernel Development, (b) Coating Development, (c) ZrC Properties and Handbook; and (3) HTR Fuel Recycle - (a) Recycle Processes, (b) Graphite Recycle, (c) Pyrochemical Reprocessing - METROX (metal recovery from oxide fuel) Process Development