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 device (and methods of using and manufacturing the device) that utilize a plurality of photomultipliers (PMT)s or a photodiodes coupled with a set of filters to collect Raman signal from samples. Also a method of detecting Raman signals includes receiving Raman signals from a sample utilizing a plurality of photomultiplier tubes (PMT)s or photodiodes, wherein at least one PMT or photodiode provides a different Raman signal than at least one other PMT or photodiode.

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: The embodiments of the invention are directed to improved SERS and SECARS devices and method of manufacturing and using the same. In one embodiment of the invention, a device having at least one laser, a sample stage and a detector, wherein the sample stage is moveable and has as SERS active material is disclosed. In another embodiment of the invention, the device has at least one laser, a scanning mirror, a sample stage having a SERS active material and a detector, wherein the scanning mirror is adapted to steer a laser beam across a surface of the sample stage.

Abstract: In embodiments of the present invention, the electric field of a focused laser beam induces a dipole in a single-walled carbon nanotube. The single-walled carbon nanotube has one or more resonant frequencies. When the frequency of the laser beam is less than a resonance frequency of the single-walled carbon nanotube, the single-walled carbon nanotube may be trapped and the laser beam may move the single-walled carbon nanotube from a first microfluidic laminar flow to a second microfluidic laminar flow. When the frequency of the laser beam is higher than a resonant frequency of the single-walled carbon nanotube, the single-walled carbon nanotube may be repelled and the laser beam may not move the single-walled carbon nanotube.

Abstract: Embodiments of the invention relate to determining the number concentration and size distribution of particles using dark-field microscopy. These embodiments are especially useful for the simultaneous determination of particle number concentration and size distribution of particles with dimensions below 4 microns.

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: The invention provides methods used to analyze the contents of a biological sample, such as blood serum, with cascade Raman sensing. A fluorescence producing nanoporous biosensor having probes that bind specifically to known analytes is contacted with a biological sample and one or more bound complexes coupled to the porous semiconductor structure are formed. The bound complexes are contacted with a Raman-active probe that binds specifically to the bound complexes and the biosensor is illuminated to generate fluorescent emissions from the biosensor. These fluorescent emissions generate Raman signals from the bound complexes. The Raman signals produced by the bound complexes are detected and the Raman signal associated with a bound protein-containing analyte is indicative of the presence of the protein-containing compound in the sample. The invention methods are useful to provide a protein profile of a patient sample. The invention also provides detection systems useful to practice the invention methods.

Abstract: The application relates to a method, system and device for performing biological assays. The method, system and device allow more accurate and specific detections of biomolecules in multiplex assays, such as immunoassays and DNA microarray assays. More specifically, the embodiments of the invention allow the detection of labels after their detachment or disassociation from a binding situation wherein interference from other labels or the background may reduce the accuracy of specificity of the detection. The embodiments of the invention further allow detection of individual labels.

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: Embodiments of the present invention provide a miniaturized spectroscopy system comprising a light source fabricated from porous silicon. Porous silicon light emitting devices can provide tunable, narrow, and directional luminescence. Advantageously, a porous silicon light source can be integrated into a silicon wafer based device thus simplifying the manufacture of a miniaturized spectros copy system and lab-on-a-chip type devices employing spectroscopic detection.

Abstract: Embodiments of the invention relate to integrated chemiluminescence devices and methods for monitoring molecular binding utilizing these devices and methods. These devices and methods can be used, for example, to identify antigen binding to antibodies. The devices include both a chemiluminescence material and a detector integrated together.

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: An instrument having (a) an illumination source configured to illuminate a field of illumination on a surface of a substrate that is configured to hold a sample, the field of illumination having a diameter greater than 1 micron or an area greater than that of at least one pad of an array, (b) an interferometer; and (c) a detector, wherein the instrument id configured to perform Fourier transform imaging without single spot scanning or without line scanning is disclosed. The instrument could include an illumination light source, an array detector and spectral processing electronics. A method of collecting Fourier transform (FT) data is also disclosed.

Abstract: The present methods and apparatus concern nucleic acid sequencing by incorporation of nucleotides into nucleic acid strands. The incorporation of nucleotides is detected by changes in the mass and/or surface stress of the structure. In some embodiments of the invention, the structure comprises one or more nanoscale or microscale cantilevers. In certain embodiments of the invention, each different type of nucleotide is distinguishably labeled with a bulky group and each incorporated nucleotide is identified by the changes in mass and/or surface stress of the structure upon incorporation of the nucleotide. In alternative embodiments of the invention only one type of nucleotide is exposed at a time to the nucleic acids. Changes in the properties of the structure may be detected by a variety of methods, such as piezoelectric detection, shifts in resonant frequency of the structure, and/or position sensitive photodetection.

Abstract: The present disclosure concerns methods for producing and/or using molecular barcodes. In certain embodiments of the invention, the barcodes comprise polymer backbones that may contain one or more branch structures. Tags may be attached to the backbone and/or branch structures. The barcode may also comprise a probe that can bind to a target, such as proteins, nucleic acids and other biomolecules or aggregates. Different barcodes may be distinguished by the type and location of the tags. In other embodiments, barcodes may be produced by hybridization of one or more tagged oligonucleotides to a template, comprising a container section and a probe section. The tagged oligonucleotides may be designed as modular code sections, to form different barcodes specific for different targets. In alternative embodiments, barcodes may be prepared by polymerization of monomeric units. Bound barcodes may be detected by various imaging modalities, such as, surface plasmon resonance, fluorescent or Raman spectroscopy.

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 green spectrum is taken to detect multiple reporter signals. The spectrum is deconvoluted by experimentally trained software to identify multiple analytes.

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: 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: 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.