Abstract: Systems and methods for detecting the presence of biomolecules in a sample using biosensors that incorporate resonators which have functionalized surfaces for reacting with target biomolecules. In one embodiment, a device includes a piezoelectric resonator having a functionalized surface configured to react with target molecules, thereby changing the mass and/or charge of the resonator which consequently changes the frequency response of the resonator. The resonator's frequency response after exposure to a sample is compared to a reference, such as the frequency response before exposure to the sample, a stored baseline frequency response or a control resonator's frequency response.

Abstract: An embodiment of the invention relates to a device comprising (1) an array of electromagnetic elements comprising coils, metal cores, and metal core heads, and (2) a controller that is adapted to control a current for one or more coils individually, to vary the current for said one or more coils individually, to reverse the current for one or more coils individually, and to generate a specific magnetic flux distribution and gradient across two or more coils; wherein the metal core head is at one end of the coil and the metal core head has a geometry to create a desired magnetic flux, intensity and gradient, in a region of interest between two adjacent coils; further wherein the device is functionally coupled to a fluidic device to concentrate and transport magnetic particles in a fluid without fluidic movement of the fluid.

Abstract: Disclosed herein are a Raman spectroscopy structure comprising a porous material substrate, and a method of performing Raman spectroscopy of a sample disposed adjacent to the structure comprising the porous material substrate. Generally, the substrate includes one or more layers of a porous material such as porous silicon, porous polysilicon, porous ceramics, porous silica, porous alumina, porous silicon-germanium, porous germanium, porous gallium arsenide, porous gallium phosphide, porous zinc oxide, and porous silicon carbide. It has been discovered that such a substrate material, when excited with near-infrared light, does not exhibit undesired background fluorescence characteristic of other known Raman spectroscopy substrates.

Abstract: Systems and methods for detecting the presence of biomolecules in a sample using biosensors that incorporate resonators which have functionalized surfaces for reacting with target biomolecules. In one embodiment, a device includes a piezoelectric resonator having a functionalized surface configured to react with target molecules, thereby changing the mass and/or charge of the resonator which consequently changes the frequency response of the resonator. The resonator's frequency response after exposure to a sample is compared to a reference, such as the frequency response before exposure to the sample, a stored baseline frequency response or a control resonator's frequency response.

Abstract: A microfluidic device and method is disclosed for fractionating and/or trapping selected molecules with a diffusion barrier or porous membrane. The device includes a source fluid flow channel and a target fluid flow channel. The target fluid flow channel and the source fluid flow channel meet at cross-channel area and are in fluid communication with each other. A porous membrane separates the source fluid flow channel from the target fluid flow channel in the cross-channel area. A field-force/gradient mechanism may be positioned proximate the porous membrane with or without detection/state monitoring devices.

Abstract: An embodiment of the invention relates to a device comprising (1) an array of electromagnetic elements comprising coils, metal cores, and metal core heads, and (2) a controller that is adapted to control a current for one or more coils individually, to vary the current for said one or more coils individually, to reverse the current for one or more coils individually, and to generate a specific magnetic flux distribution and gradient across two or more coils; wherein the metal core head is at one end of the coil and the metal core head has a geometry to create a desired magnetic flux, intensity and gradient, in a region of interest between two adjacent coils; further wherein the device is functionally coupled to a fluidic device to concentrate and transport magnetic particles in a fluid without fluidic movement of the fluid.

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: The methods, apparatus and compositions disclosed herein concern the detection, identification and/or sequencing of biomolecules, such as nucleic acids or proteins. In certain embodiments of the invention, coded probes comprising a probe molecule attached to one or more nano-barcodes may be allowed to bind to one or more target molecules. After binding and separation from unbound coded probes, the bound coded probes may be aligned on a surface and analyzed by scanning probe microscopy. Where the probes are oligonucleotides, adjacent coded probes hybridized to a target nucleic acid may be ligated together before alignment and SPM analysis. Compositions comprising coded probes are also disclosed herein. Systems for biomolecule analysis may comprise an SPM instrument and at least one coded probe attached to a surface.

Abstract: Disclosed herein are a Raman spectroscopy structure comprising a porous material substrate, and a method of performing Raman spectroscopy of a sample disposed adjacent to the structure comprising the porous material substrate. Generally, the substrate includes one or more layers of a porous material such as porous silicon, porous polysilicon, porous ceramics, porous silica, porous alumina, porous silicon-germanium, porous germanium, porous gallium arsenide, porous gallium phosphide, porous zinc oxide, and porous silicon carbide. It has been discovered that such a substrate material, when excited with near-infrared light, does not exhibit undesired background fluorescence characteristic of other known Raman spectroscopy substrates.

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: Disclosed herein are a Raman spectroscopy structure comprising a porous material substrate, and a method of performing Raman spectroscopy of a sample disposed adjacent to the structure comprising the porous material substrate. Generally, the substrate includes one or more layers of a porous material such as porous silicon, porous polysilicon, porous ceramics, porous silica, porous alumina, porous silicon-germanium, porous germanium, porous gallium arsenide, porous gallium phosphide, porous zinc oxide, and porous silicon carbide. It has been discovered that such a substrate material, when excited with near-infrared light, does not exhibit undesired background fluorescence characteristic of other known Raman spectroscopy substrates.

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: The methods, apparatus and compositions disclosed herein concern the detection, identification and/or sequencing of biomolecules, such as nucleic acids or proteins. In certain embodiments of the invention, coded probes comprising a probe molecule attached to one or more nanobarcodes may be allowed to bind to one or more target molecules. After binding and separation from unbound coded probes, the bound coded probes may be aligned on a surface and analyzed by scanning probe microscopy. The nanobarcodes may be any molecule or complex that is distinguishable by SPM, such as carbon nanotubes, fullerenes, submicrometer metallic barcodes, nanoparticles or quantum dots. Where the probes are oligonucleotides, adjacent coded probes hybridized to a target nucleic acid may be ligated together before alignment and scanning probe microscopy (SPM) analysis. Compositions comprising coded probes are also disclosed herein.

Abstract: The methods, apparatus and compositions disclosed herein concern the detection, identification and/or sequencing of biomolecules, such as nucleic acids or proteins. In certain embodiments of the invention, coded probes comprising a probe molecule attached to one or more nano-barcodes may be allowed to bind to one or more target molecules. After binding and separation from unbound coded probes, the bound coded probes may be aligned on a surface and analyzed by scanning probe microscopy. The nano-barcodes may be any molecule or complex that is distinguishable by scanning probe microscopy (SPM), such as carbon nanotubes, fullerenes, submicrometer metallic barcodes, nanoparticles or quantum dots. Where the probes are oligonucleotides, adjacent coded probes hybridized to a target nucleic acid may be ligated together before alignment and scanning probe microscopy (SPM) analysis. Compositions comprising coded probes are also disclosed herein.

Abstract: Method and device to collect multiplex data simultaneously in analyte detection and analyze the data by experimentally trained software (machine-learning) is disclosed. Various ways (magnetic particles and microcoils) are disclosed to collect multiple reporter (tag) signals. Multiplex detection can increase the biomolecule analysis efficiency by using small sample size and saving assay reagents and time. Machine learning and data analysis schemes are also disclosed. Multiple affinity binding partners, each labeled by a unique reporter, are contacted with a sample and a single spectrum is taken to detect multiple reporter signals. The spectrum is deconvoluted by experimentally trained software to identify multiple analytes.

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: Method and device to collect multiplex data simultaneously in analyte detection and analyze the data by experimentally trained software (machine-learning) is disclosed. Various ways (magnetic particles and microcoils) are disclosed to collect multiple reporter (tag) signals. Multiplex detection can increase the biomolecule analysis efficiency by using small sample size and saving assay reagents and time. Machine learning and data analysis schemes are also disclosed. Multiple affinity binding partners, each labeled by a unique reporter, are contacted with a sample and a single spectrum is taken to detect multiple reporter signals. The spectrum is deconvoluted by experimentally trained software to identify multiple analytes.

Abstract: Epigenetic events such as DNA methylation play important roles in the regulation of gene expression. DNA methylation patterns have been found to differ between healthy and diseased tissue, such as healthy and cancerous tissue, thereby allowing DNA methylation to serve as a biomarker for disease states. Embodiments of the invention provide methods for detecting methylation patterns in DNA polymers. Methylation patterns are detected, in part, through the use of surface enhanced Raman spectroscopy (SERS). SERS provides a sensitive structure-based technique for chemical analysis.