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.

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 method for determining a nucleotide sequence of a nucleic acid is provided that includes contacting the nucleic acid with a series of labeled oligonucleotides for binding to the nucleic acid, wherein each labeled oligonucleotide includes a known nucleotide sequence and a molecular nanocode. The nanocode of an isolated labeled oligonucleotides that binds to the nucleic acid is then detected using SPM. Nanocodes of the present invention in certain aspects include detectable features beyond the arrangement of tags that encode information about the barcoded object, which assist in detecting the tags that encode information about the barcoded object. The detectable features include structures of a nanocode or associated with a nanocode, referred to herein as detectable feature tags, for error checking/error-correction, encryption, and data reduction/compression.

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, 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: One embodiment relates to an analyzer having an interferometer, a detector and a microprocessor, wherein the analyzer does not contain a spectrometer having a dispersive grating, the interferometer is to create a phase shift in an original spectrum of electromagnetic radiation emitted from a sample and Fourier transform the original spectrum to a Fourier transform spectrum, the detector is to detect a characteristic of the Fourier transform spectrum, and the microprocessor comprises software or a hardware to inverse transform the Fourier transform spectrum and reproduce the original spectrum. Another embodiment relates to a Raman analyzer having an interferometer, wherein the Raman analyzer contains no dispersive grating or moving parts and has an ability to analyze a Raman signal. The embodiments of the invention could be used for analyzing a sample by striking a laser to the sample and examining the spectrum of the emitted electromagnetic radiation from the sample.

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 continuously printing radially about a circular and/or rotating build table using multiple printheads. The apparatus and methods also include optionally using multiple build tables. The auxiliary systems relate to build material supply, printhead cleaning, diagnostics, and monitoring operation of the apparatus.

Abstract: The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation into a nucleic acid. In other embodiments, unlabeled nucleic acids are used. Exonuclease treatment of the nucleic acid results in the release of labeled or unlabeled nucleotides that are detected by Raman spectroscopy. In alternative embodiments of the invention, nucleotides released from a nucleic acid by exonuclease treatment are covalently cross-linked to nanoparticles and detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus for nucleic acid sequencing.

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: A surface analysis device is disclosed for identifying molecules by simultaneously scanning nanocodes on a surface of a substrate. The device includes a scanning array that is capable of simultaneously scanning the nanocodes on the surface of the substrate and an analyzer that is coupled with the scanning array. The analyzer is capable of receiving simultaneously scanned information from the scanning array and identifying molecules associated with the nanocodes.

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 continuously printing radially about a circular and/or rotating build table using multiple printheads. The apparatus and methods also include optionally using multiple build tables. The auxiliary systems relate to build material supply printhead cleaning diagnostics, and monitoring operation of the apparatus.

Abstract: The present methods and apparatus concern the detection and/or identification of target analytes using probe molecules. In various embodiments of the invention, the probes or analytes are attached to one or more cantilevers. Binding of a probe to an analyte results in deflection of the cantilever, detected by a detection unit. A counterbalancing force may be applied to restore the cantilever to its original position. The counterbalancing force may be magnetic, electrical or radiative. The detection unit and the mechanism generating the counterbalancing force may be operably coupled to an information processing and control unit, such as a computer. The computer may regulate a feedback loop that maintains the cantilever in a fixed position by balancing the deflecting force and the counterbalancing force. The concentration of analytes in a sample may be determined from the magnitude of the counterbalancing force required to maintain the cantilever in a fixed position.

Abstract: Microfluidic devices with porous membranes for molecular sieving, metering, and separation of analyte fluids. In one aspect, a microfluidic device includes a substrate having input and output microfluidic channel sections separated by a porous membrane formed integral to the substrate. In another aspect, the porous membrane may comprise a thin membrane that is sandwiched between upper and lower substrate members. The microfluidic device may include one or a plurality of porous membranes. In one embodiment, a plurality of porous membranes having increasingly smaller pores are disposed along portions of a microfluidic channel. In another embodiment, a cascading series of upper and lower channels are employed, wherein each upper/lower channel interface is separated by a respective porous membrane. In another aspect, a porous membrane is rotatably coupled to a substrate within a microfluidic channel via a MEMS actuator to enable the porous membrane to be positioned in filtering and pass-through positions.

Abstract: A method and apparatus for forming a polymer array on a substrate suitable for synthesizing polymer sequences. This includes forming an array, each location of the array having at least one strand end, forming photosensitive protection on the strand ends, and selectively scanning and modulating at least one energy beam to expose a pattern on the photosensitive protection. In some embodiments, the method further includes removing a protective group from selected strand ends based on the exposed pattern. The method then includes adding a predetermined one or more polymeric subunits to the deprotected strand ends. In some embodiments the photosensitive protection includes a layer of photoresist to cover the strand ends. Some embodiments use an ultra-violet laser.

Abstract: The present methods and apparatus concern the detection and/or identification of target analytes using probe molecules. In various embodiments of the invention, the probes or analytes are attached to one or more cantilevers. Binding of a probe to an analyte results in deflection of the cantilever, detected by a detection unit. A counterbalancing force may be applied to restore the cantilever to its original position. The counterbalancing force may be magnetic, electrical or radiative. The detection unit and the mechanism generating the counterbalancing force may be operably coupled to an information processing and control unit, such as a computer. The computer may regulate a feedback loop that maintains the cantilever in a fixed position by balancing the deflecting force and the counterbalancing force. The concentration of analytes in a sample may be determined from the magnitude of the counterbalancing force required to maintain the cantilever in a fixed position.

Abstract: Embedded in a transport assembly are arrays of microelectromechanical sensors and actuators for detecting and propelling an object. A controller having defined therein local computational agents and a global controller controls the array of sensors and actuators. The global controller provides global operating constraints to the local computational agents. The global operating constraints are developed using an approximate specification of system behavior based on simplified assumptions of an idealized system as well as limited sensor information aggregated from the array of sensors. The local computational agents compute a desired local actuator response using sensor information from a localized grouping of sensor units. To improve the accuracy of the global operating constraints, the local computational agents reduce differences between a global actuator response, computed using the global operating constraints, and the desired local actuator response.

Abstract: Embodiments of the present invention provide methods for determining the degenerate binding capabilities of antibodies. The methods provide information about degenerate binding capabilities without the use of involved procedures. Optionally, a molecule toward which an antibody exhibits degenerate binding ability may be identified through the use of a reporter, such as, a composite organic inorganic nanocluster (COIN). COINs are sensitive SERS (surface enhanced Raman spectroscopy) reporters capable of multiplex analysis of analytes.

Abstract: The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, nucleotides are covalently attached to Raman labels before incorporation into a nucleic acid. In other embodiments, unlabeled nucleic acids are used. Exonuclease treatment of the nucleic acid results in the release of labeled or unlabeled nucleotides that are detected by Raman spectroscopy. In alternative embodiments of the invention, nucleotides released from a nucleic acid by exonuclease treatment are covalently cross-linked to nanoparticles and detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Other embodiments of the invention concern apparatus for nucleic acid sequencing.

Abstract: An apparatus and system, as well as fabrication methods therefor, may include a thermal interface material comprised of an array of carbon nanotubes and a buffer layer disposed between the thermal interface material and one of a die or a heat spreader. In some embodiments the carbon nanotubes may be formed above a buffer layer formed above a surface of the head spreader.

Abstract: The methods and apparatus disclosed herein are useful for detecting nucleotides, nucleosides, and bases and for nucleic acid sequence determination. The methods involve detection of a nucleotide, nucleoside, or base using surface enhanced Raman spectroscopy (SERS). The detection can be part of a nucleic acid sequencing reaction to detect uptake of a deoxynucleotide triphosphate during a nucleic acid polymerization reaction, such as a nucleic acid sequencing reaction. The nucleic acid sequence of a synthesized nascent strand, and the complementary sequence of the template strand, can be determined by tracking the order of incorporation of nucleotides during the polymerization reaction.