Abstract: Composite organic-inorganic nanoclusters (COINs) are provided that produce surface-enhanced Raman signals (SERS) when excited by a laser. The nanoclusters include metal particles and a Raman-active organic compound. The metal required for achieving a suitable SERS signal is inherent in the nanocluster and a wide variety of Raman-active organic compounds and combinations thereof can be incorporated into the nanocluster. In addition, polymeric microspheres containing the nanoclusters and methods of making them are also provided. The nanoclusters and microspheres can be used, for example, in assays for multiplex detection of biological molecules.

Abstract: Methods and apparatus are provided for assaying cell samples, which may be living cells, using probes labeled with composite organic-inorganic nanoparticles (COINs) and microspheres with COINs embedded within a polymer matrix to which the probe moiety is attached. COINs intrinsically produce SERS signals upon laser irradiation, making COIN-labeled probes particularly suitable in a variety of methods for assaying cells, including biological molecules that may be contained on or within cells, most of which are not inherently Raman-active. The invention provides variations of the sandwich immunoassay employing both specific and degenerate binding, methods for reverse phase assay of tissue samples and cell microstructures, in solution displacement and competition assays, and the like. Systems and chips useful for practicing the invention assays are also provided.

Abstract: A nano-electrode or nano-wire may be etched centrally to form a gap between nano-electrode portions. The portions may ultimately constitute a single electron transistor. The source and drain formed from the electrode portions are self-aligned with one another. Using spacer technology, the gap between the electrodes may be made very small.

Abstract: The methods and apparatus 100, disclosed herein are of use for sequencing 150 and/or identifying 160 proteins 230, 310, polypeptides 230, 310 or peptides 230, 310. Proteins 230, 310 containing labeled amino acid residues may be synthesized and passed through nanopores 255, 330. A detector 257, 345 operably coupled to a nanopore 255, 330 may detect labeled amino acid residues as they pass through the nanopore 255, 330. Distance maps 140 for each type of labeled amino acid residue may be compiled. The distance maps 140 may be used to sequence 150 and/or identify 160 the protein 230, 310. In different embodiments of the invention, amino acid residues labeled with luminescent labels 235, 245 or nanoparticles 315 may be detected using photodetectors 257 or electrical detectors 345. Apparatus 100 of use for protein 230, 310 sequencing 150 and/or identification 160 are also disclosed herein.

Abstract: A three-dimensional printer uses inkjet-type printheads to rapidly prototype, or print, a three-dimensional model. A powder feeder includes a conveyor system and a metering system to deliver powder to a build area in measured quantities. The powder feeder also includes a vacuum system for loading powder into a feed reservoir or chamber. The vacuum system can also be used to cleanup excess powder. Other powder control features include powder gutters and magnetic powder plows. During printing, a cleaning system operates to remove powder from the printheads. In the event of a printhead or jet failure, the failure can be detected and corrective measures taken automatically. After printing, the model can be depowdered and infiltrated in an enclosure.

Abstract: Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

Abstract: Provided herein are methods and systems for detecting biomolecular binding events using gigahertz or terahertz radiation. The methods and systems use low-energy spectroscopy to detect biomolecular binding events between molecules in an aqueous solution. The detected biomolecular binding events include, for example, nucleic acid hybridizations, antibody/antigen binding, and receptor/ligand binding.

Abstract: A three-dimensional printer uses inkjet-type printheads to rapidly prototype, or print, a three-dimensional model. A powder feeder includes a conveyor system and a metering system to deliver powder to a build area in measured quantities. The powder feeder also includes a vacuum system for loading powder into a feed reservoir or chamber. The vacuum system can also be used to cleanup excess powder. Other powder control features include powder gutters and magnetic powder plows. During printing, a cleaning system operates to remove powder from the printheads. In the event of a printhead or jet failure, the failure can be detected and corrective measures taken automatically. After printing, the model can be depowdered and infiltrated in an enclosure.

Abstract: A micro-fluidic device containing a micro-fluidic inlet channel to convey a process flow, a plurality of micro-fluidic focusing channels to each convey one of a plurality of focusing flows, a focusing manifold coupled with the inlet channel at an inlet port thereof and with the plurality of focusing channels at a plurality of focusing channel ports thereof to focus the process flow by contacting and hydrodynamically impacting at least three sides of the process flow with the focusing flows, and a micro-fluidic outlet channel coupled with the focusing manifold at an outlet channel port to convey the combined focused process flow and focusing flow from the focusing manifold.

Abstract: In certain embodiments of the invention, a plurality of images of one or more subjects may be captured using different imaging techniques, such as different modalities of scanning probe microscopy. Parameters may be estimated from the plurality of images, using one or more models of known molecular structures to provide a model-based analysis. The estimated parameters may be fused, with further input from physical models of known molecular structures. The fused parameters may be used to characterize the subjects. Such characterization may include the detection and/or identification of specific molecular structures, such as proteins, peptides and/or nucleic acids of known sequence and/or structure. In some embodiments of the invention the structural characterizations may be used to identify previously unknown properties of a subject molecule.

Abstract: In certain embodiments of the invention, a plurality of images of one or more subjects may be captured using different imaging techniques, such as different modalities of scanning probe microscopy. Parameters may be estimated from the plurality of images, using one or more models of known molecular structures to provide a model-based analysis. The estimated parameters may be fused, with further input from physical models of known molecular structures. The fused parameters may be used to characterize the subjects. Such characterization may include the detection and/or identification of specific molecular structures, such as proteins, peptides and/or nucleic acids of known sequence and/or structure. In some embodiments of the invention the structural characterizations may be used to identify previously unknown properties of a subject molecule.

Abstract: The methods, apparatus and systems disclosed herein concern ordered arrays of carbon nanotubes. In particular embodiments of the invention, the nanotube arrays are formed by a method comprising attaching catalyst nanoparticles 140, 230 to polymer 120, 210 molecules, attaching the polymer 120, 210 molecules to a substrate, removing the polymer 120, 210 molecules and producing carbon nanotubes on the catalyst nanoparticles 140, 230. The polymer 120, 210 molecules can be attached to the substrate in ordered patterns, using self-assembly or molecular alignment techniques. The nanotube arrays can be attached to selected areas 110, 310 of the substrate. Within the selected areas 110, 310, the nanotubes are distributed non-randomly. Other embodiments disclosed herein concern apparatus that include ordered arrays of nanotubes attached to a substrate and systems that include ordered arrays of carbon nanotubes attached to a substrate, produced by the claimed methods.

Abstract: The methods, apparatus and systems disclosed herein concern ordered arrays of carbon nanotubes. In particular embodiments of the invention, the nanotube arrays are formed by a method comprising attaching catalyst nanoparticles 140, 230 to polymer 120, 210 molecules, attaching the polymer 120, 210 molecules to a substrate, removing the polymer 120, 210 molecules and producing carbon nanotubes on the catalyst nanoparticles 140, 230. The polymer 120, 210 molecules can be attached to the substrate in ordered patterns, using self-assembly or molecular alignment techniques. The nanotube arrays can be attached to selected areas 110, 310 of the substrate. Within the selected areas 110, 310, the nanotubes are distributed non-randomly. Other embodiments disclosed herein concern apparatus that include ordered arrays of nanotubes attached to a substrate and systems that include ordered arrays of carbon nanotubes attached to a substrate, produced by the claimed methods.

Abstract: Methods, systems, and devices for speech transduction are disclosed. One aspect of the invention involves a computer-implemented method in which a computer receives far-field acoustic data acquired by one or more microphones. The far-field acoustic data are analyzed. The far-field acoustic data are modified to reduce characteristics of the far-field acoustic data that are incompatible with human speech characteristics of near-field acoustic data.

Abstract: A three-dimensional printer uses inkjet-type printheads to rapidly prototype, or print, a three-dimensional model. A powder feeder includes a conveyor system and a metering system to deliver powder to a build area in measured quantities. The powder feeder also includes a vacuum system for loading powder into a feed reservoir or chamber. The vacuum system can also be used to cleanup excess powder. Other powder control features include powder gutters and magnetic powder plows. During printing, a cleaning system operates to remove powder from the printheads. In the event of a printhead or jet failure, the failure can be detected and corrective measures taken automatically. After printing, the model can be depowdered and infiltrated in an enclosure.

Abstract: The methods, compositions and apparatus disclosed herein are of use for nucleic acid sequence determination. The methods involve isolation of one or more nucleic acid template molecules and polymerization of a nascent complementary strand of nucleic acid, using a DNA or RNA polymerase or similar synthetic reagent. As the nascent strand is extended one nucleotide at a time, the disappearance of nucleotide precursors from solution is monitored by Raman spectroscopy or FRET. The nucleic acid sequence of the nascent strand, and the complementary sequence of the template strand, may be determined by tracking the order of incorporation of nucleotide precursors during the polymerization reaction. Certain embodiments concern apparatus comprising a reaction chamber and detection unit, of use in practicing the claimed methods. The methods, compositions and apparatus are of use in sequencing very long nucleic acid templates in a single sequencing reaction.

Abstract: Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

Abstract: The invention relates to apparatus and methods for producing three-dimensional objects and auxiliary systems used in conjunction with the aforementioned apparatus and methods. The apparatus and methods involve 3D printing and servicing of the equipment used in the associated 3D printer.

Abstract: A three-dimensional printer uses inkjet-type printheads to rapidly prototype, or print, a three-dimensional model. A powder feeder includes a conveyor system and a metering system to deliver powder to a build area in measured quantities. The powder feeder also includes a vacuum system for loading powder into a feed reservoir or chamber. The vacuum system can also be used to cleanup excess powder. Other powder control features include powder gutters and magnetic powder plows. During printing, a cleaning system operates to remove powder from the printheads. In the event of a printhead or jet failure, the failure can be detected and corrective measures taken automatically. After printing, the model can be depowdered and infiltrated in an enclosure.

Abstract: The disclosed methods and apparatus concern Raman spectroscopy using metal coated nanocrystalline porous silicon substrates. Porous silicon substrates may be formed by anodic etching in dilute hydrofluoric acid. A thin coating of a Raman active metal, such as gold or silver, may be coated onto the porous silicon by cathodic electromigration or any known technique. In certain alternatives, the metal coated porous silicon substrate comprises a plasma-oxidized, dip and decomposed porous silicon substrate. The metal-coated substrate provides an extensive, metal rich environment for SERS, SERRS, hyper-Raman and/or CARS Raman spectroscopy. In certain alternatives, metal nanoparticles may be added to the metal-coated substrate to further enhance the Raman signals. Raman spectroscopy may be used to detect, identify and/or quantify a wide variety of analytes, using the disclosed methods and apparatus.