Digital microarrays: single-molecule readout with interferometric detection of plasmonic nanorod labels

DNA and protein microarrays are a high-throughput technology that allow the simultaneous quantification of tens of thousands of different biomolecular species. The mediocre sensitivity and limited dynamic range of traditional fluorescence microarrays compared to other detection techniques have been the technology’s Achilles’ heel and prevented their adoption for many biomedical and clinical diagnostic applications. Previous work to enhance the sensitivity of microarray readout to the single-molecule (“digital”) regime have either required signal amplifying chemistry or sacrificed throughput, nixing the platform’s primary advantages. Here, we report the development of a digital microarray which extends both the sensitivity and dynamic range of microarrays by about 3 orders of magnitude. This technique uses functionalized gold nanorods as single-molecule labels and an interferometric scanner which can rapidly enumerate individual nanorods by imaging them with a 10× objective lens. This approach does not require any chemical signal enhancement such as silver deposition and scans arrays with a throughput similar to commercial fluorescence scanners. By combining single-nanoparticle enumeration and ensemble measurements of spots when the particles are very dense, this system achieves a dynamic range of about 6 orders of magnitude directly from a single scan. As a proof-of-concept digital protein microarray assay, we demonstrated detection of hepatitis B virus surface antigen in buffer with a limit of detection of 3.2 pg/mL. More broadly, the technique’s simplicity and high-throughput nature make digital microarrays a flexible platform technology with a wide range of potential applications in biomedical research and clinical diagnostics.The authors wish to thank Oguzhan Avci and Jacob Trueb for thoughtful comments and suggestions regarding numerical optimization of the optical system. This work was funded in part by a research contract with ASELSAN, Inc. and the Wallace H. Coulter Foundation 2010 Coulter Translational Award. (ASELSAN, Inc.; Wallace H. Coulter Foundation Coulter Translational Award)Accepted manuscrip

Interactive Sketching of Mannequin Poses

It can be easy and even fun to sketch humans in different poses. In contrast, creating those same poses on a 3D graphics 'mannequin' is comparatively tedious. Yet 3D body poses are necessary for various downstream applications. We seek to preserve the convenience of 2D sketching while giving users of different skill levels the flexibility to accurately and more quickly pose/refine a 3D mannequin. At the core of the interactive system, we propose a machine-learning model for inferring the 3D pose of a CG mannequin from sketches of humans drawn in a cylinder-person style. Training such a model is challenging because of artist variability, a lack of sketch training data with corresponding ground truth 3D poses, and the high dimensionality of human pose-space. Our unique approach to synthesizing vector graphics training data underpins our integrated ML-and-kinematics system. We validate the system by tightly coupling it with a user interface, and by performing a user study, in addition to quantitative comparisons

Chirality dependence of the radial breathing phonon mode density in single wall carbon nanotubes

A mass and spring model is used to calculate the phonon mode dispersion for single wall carbon nanotubes (SWNTs) of arbitrary chirality. The calculated dispersions are used to determine the chirality dependence of the radial breathing phonon mode (RBM) density. Van Hove singularities, usually discussed in the context of the single particle electronic excitation spectrum, are found in the RBM density of states with distinct qualitative differences for zig zag, armchair and chiral SWNTs. The influence the phonon mode density has on the two phonon resonant Raman scattering cross-section is discussed.Comment: 6 pages, 2 figures, submitted to Phys. Rev.

Tunable Resonant Raman Scattering from Singly Resonant Single Wall Carbon Nanotubes

We perform tunable resonant Raman scattering on 17 semiconducting and 7 metallic singly resonant single wall carbon nanotubes. The measured scattering cross-section as a function laser energy provides information about a tube's electronic structure, the lifetime of intermediate states involved in the scattering process and also energies of zone center optical phonons. Recording the scattered Raman signal as a function of tube location in the microscope focal plane allows us to construct two-dimensional spatial maps of singly resonant tubes. We also describe a spectral nanoscale artifact we have coined the "nano-slit effect"

High-speed GaAs-based resonant-cavity-enhanced 1.3 μm photodetector

Cataloged from PDF version of article.We report GaAs-based high-speed, resonant-cavity-enhanced, Schottky barrier internal photoemissionphotodiodes operating at 1.3 μm. The devices were fabricated by using a microwave-compatible fabrication process. Resonance of the cavity was tuned to 1.3 μm and a nine-fold enhancement was achieved in quantum efficiency. The photodiode had an experimental setup limited temporal response of 16 ps, corresponding to a 3 dB bandwidth of 20 GHz. © 2000 American Institute of Physic

Presentations and word problem for strong semilattices of semigroups

Let I be a semilattice, and Si (i ∈ I) be a family of disjoint semigroups. Then we prove that the strong semilattice S = S[I, Si , φj,i] of semigroups Si with homomorphisms φj,i : Sj → Si (j ≥ i) is finitely presented if and only if I is finite and each Si (i ∈ I) is finitely presented. Moreover, for a finite semilattice I, S has a soluble word problem if and only if each Si (i ∈ I) has a soluble word problem. Finally, we give an example of nonautomatic semigroup which has a soluble word problem

Digital detection of exosomes by interferometric imaging

Exosomes, which are membranous nanovesicles, are actively released by cells and have been attributed to roles in cell-cell communication, cancer metastasis, and early disease diagnostics. The small size (30–100 nm) along with low refractive index contrast of exosomes makes direct characterization and phenotypical classification very difficult. In this work we present a method based on Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) that allows multiplexed phenotyping and digital counting of various populations of individual exosomes (>50 nm) captured on a microarray-based solid phase chip. We demonstrate these characterization concepts using purified exosomes from a HEK 293 cell culture. As a demonstration of clinical utility, we characterize exosomes directly from human cerebrospinal fluid (hCSF). Our interferometric imaging method could capture, from a very small hCSF volume (20 uL), nanoparticles that have a size compatible with exosomes, using antibodies directed against tetraspanins. With this unprecedented capability, we foresee revolutionary implications in the clinical field with improvements in diagnosis and stratification of patients affected by different disorders.This work was supported by Regione Lombardia and Fondazione Cariplo through POR-FESR, project MINER (ID 46875467); Italian Ministry of Health, Ricerca Corrente. This work was partially supported by The Scientific and Technological Research Council of Turkey (grant #113E643). (Regione Lombardia; 46875467 - Fondazione Cariplo through POR-FESR, project MINER; Italian Ministry of Health, Ricerca Corrente; 113E643 - Scientific and Technological Research Council of Turkey)Published versio

High-Speed High Effiency Large Area Resonant Cavity Enhanced p-I-n Photodiodes for Multimode Fiber Communications

Cataloged from PDF version of article.In this letter, we report AlGaAs–GaAs p-i-n photodiodes with a 3-dB bandwidth in excess of 10 GHz for devices as large as 60- m diameter. Resonant cavity enhanced photodetection is employed to improve quantum efficiency, resulting in more than 90% peak quantum efficiency at 850 nm

Robust Entanglement in Atomic Systems via Lambda-Type Processes

It is shown that the system of two three-level atoms in $\Lambda$ configuration in a cavity can evolve to a long-lived maximum entangled state if the Stokes photons vanish from the cavity by means of either leakage or damping. The difference in evolution picture corresponding to the general model and effective model with two-photon process in two-level system is discussed.Comment: 10 pages, 3 figure