Abstract: Hybrid nanopores, comprising a protein pore supported within a solid-state membrane, which combine the robust nature of solid-state membranes with the easily tunable and precise engineering of protein nanopores. In an embodiment, a lipid-free hybrid nanopore comprises a water soluble and stable, modified portal protein of the Thermus thermophilus bacteriophage G20c, electrokinetically inserted into a larger nanopore in a solid-state membrane. The hybrid pore is stable and easy to fabricate, and exhibits low peripheral leakage, allowing sensing and discrimination among different types of biomolecules.

Abstract: An apparatus is provided for sensing a molecule in a sample. The apparatus utilizes an electric field to draw molecules from a first chamber through an aperture, defined by a chemical layer, into a second chamber. The apparatus can detect a DNA molecule with, for example, 4, 5, or 6 unique base pairs. As molecules pass through the aperture, a sensor detects or measures a change in an electric parameter used to generate the electric field, thereafter translating the change in the electric parameter into information about the molecule. A divider element separates the first and second chambers and supports a chemical layer defining the aperture. The apparatus enables detection or measurement of molecules over prolonged time at a higher electric field strength than other nanopores, due to a combination of the shape of the divider, structural elements thereon, and thickness of the chemical layer at the aperture.

Abstract: A method for manufacturing a component and a component are provided for sensing a molecule. The method includes controlling a temperature during a reaction of two gases that react to produce a crystalline film spanning at least a cross-sectional area of a nanoaperture defined by a substrate among an array of nanoapertures aligned with crater structures defined by the substrate. A unique chemical vapor deposition (CVD) method that introduces a first gas and a second gas allows for formation of the crystalline film. When used in a molecule sensor, the component enables a user to record double-stranded DNA (dsDNA) translocations at unprecedented high (e.g., 1 MHz) bandwidths. The method for manufacturing the component enables development of applications requiring single-layer membranes built at- scale and enables high throughput 2-dimensional (2D) nanofluidics and nanopore studies.

Abstract: A porous membrane comprising stacked layers of nanosheets, each nanosheet comprising one to three atomic layers of a 2D material comprising or consisting of one or more transition metal dichalcogenides is provided. The nanosheets have pores and the membrane comprises a network of water permeation pathways including through-pathways formed by the pores, horizontal pathways formed by gaps between the layers, and vertical pathways formed by gaps between adjacent nanosheets and stacking defects between the layers. Also provided is a method for making the membrane.

Abstract: Hybrid nanopores, comprising a protein pore supported within a solid-state membrane, which combine the robust nature of solid-state membranes with the easily tunable and precise engineering of protein nanopores. In an embodiment, a lipid-free hybrid nanopore comprises a water soluble and stable, modified portal protein of the Thermus thermophilus bacteriophage G20c, electrokinetically inserted into a larger nanopore in a solid-state membrane. The hybrid pore is stable and easy to fabricate, and exhibits low peripheral leakage, allowing sensing and discrimination among different types of biomolecules.

Abstract: A method and system to decode information stored on a polymer sequence, such as a DNA strand, is described herein. The method and system use molecular probes to label sections of the polymer sequence. Each molecular probe includes a fluorophore and a quencher. The fluorophore produces light with a color and wavelength corresponding to the information stored on the section of the polymer sequence the molecular probe labels. The quencher inhibits the production of light by an adjacent fluorophore. When adjacent sections of the polymer sequence are labeled with molecular probes, the fluorophore of the leading molecular probe produces light while the trailing molecular probe's light is quenched. The method and system then sequentially unbind the molecular probes from the sections of the polymer sequence within a waveguide, producing a sequence of observable fluorescence signals. The sequence can be used to determine the information stored on a polymer sequence.

Abstract: A system and apparatus are provided for sensing a molecule in a sample for identifying the molecule in the sample. Also provided is a method of manufacturing an apparatus for sensing a molecule in a sample. The system and apparatus may contain a composition of a mixture of a buffer solution and a sample solution containing a sample. The apparatus contains a series of wells. The sample is deposited into the system and a molecule having an electric charge in the sample attaches to a layer in a well of the apparatus, allowing for a sensor connected to the apparatus to identify the molecule.

Abstract: A method and system for performing single molecule proteomics utilizing a nanopore sensor to measure an electronic signature of protein or peptide being transported through the nanopore from a first chamber to a second chamber. The protein's electronic signature is a function of ionic current over time. The method and system utilizing an agent, such as guanidinium chloride, to bind to the nanopore's interior and provide an electroosmotic force within the nanopore. The electroosmotic force, in some embodiments, enables stretching and unfolding of the protein during transport through the nanopore. The agent may also or alternatively induce the unfolding of the protein before transport through the nanopore and/or provide force moving the protein through the nanopore.

Abstract: Hybrid nanopores, comprising a protein pore supported within a solid-state membrane, which combine the robust nature of solid-state membranes with the easily tunable and precise engineering of protein nanopores. In an embodiment, a lipid-free hybrid nanopore comprises a water soluble and stable, modified portal protein of the Thermus thermophilus bacteriophage G20c, electrokinetically inserted into a larger nanopore in a solid-state membrane. The hybrid pore is stable and easy to fabricate, and exhibits low peripheral leakage, allowing sensing and discrimination among different types of biomolecules.

Abstract: A multiplexed digital detection platform embodiment for molecular species in solution is based on a single-molecule immunochemistry, and/or aptamer chemistry, on color-barcoded beads. Beads that capture molecular species from a complex sample using selective binders are exposed to a test sample, and the captured molecular species is tagged using second affinity probes that are linked to photocleavable nucleic acid particles. In the embodiment, the beads are then introduced to a counter system that comprises a microcavity/nanopore device. Once a bead is captured by the micropore, nucleic acid particles, e.g., reporter nucleic acid nanoparticles (rNANPs), are released using photocleavage, and are detected by the nanopore. Each electrical spike that is uniquely produced by the nucleic acid nanoparticle is counted as a single molecular species, and the total count represents the overall number of molecular species in the sample. Various molecular species can be detected at the same time.

Abstract: The present technology provides a nanopore electrode sequencer for the characterization and sequencing of biomolecules. Two or more ultrathin MXene sheets containing nanopores serve as electrodes that bind and store cations which can be released to provide ionic current through the nanopore during sequencing, thereby eliminating access resistance to ions at the entrance to the nanopore from bulk solution. Resolution of ionic current changes caused by biopolymer components within the nanopore is thereby substantially improved, providing more sensitive and robust sequencing of biopolymers.

Abstract: A method for etching a light absorbing material permits directly writing a pattern of etching of silicon nitride and other light absorbing materials, without the need of a lithographic mask, and allows the creation of etched features of less than one micron in size. The method can be used for etching deposited silicon nitride films, freestanding silicon nitride membranes, and other light absorbing materials, with control over the thickness achieved by optical feedback. The etching is promoted by solvents including electron donor species, such as chloride ions. The method provides the ability to etch silicon nitride and other light absorbing materials, with fine spatial and etch rate control, in mild conditions, including in a biocompatible environment. The method can be used to create nanopores and nanopore arrays.

Abstract: Described herein are devices containing freestanding, ultrathin (<10 nm thick) membranes and methods of making such devices. Also described are methods of using devices containing freestanding ultrathin membranes for determining the sequence of a polynucleotide and for desalination of aqueous solutions.

Abstract: Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof. Nanopores are extremely sensitive single-molecule sensors. Recently, electron beams have been used to fabricate synthetic nanopores in thin solid-state membranes with sub-nanometer resolution. A new class of chemically modified nanopore sensors are provided with two approaches for monolayer coating of nanopores by: (1) self-assembly from solution, in which nanopores ?10 nm diameter can be reproducibly coated, and (2) self-assembly under voltage-driven electrolyte flow, in which 5 nm nanopores may be coated. Applications of chemically modified nanopore are provided including: the detection of biopolymers such as DNA and RNA; immobilizing enzymes or other proteins for detection or for generating chemical gradients; and localized pH sensing.

Abstract: A method for etching a light absorbing material permits directly writing a pattern of etching of silicon nitride and other light absorbing materials, without the need of a lithographic mask, and allows the creation of etched features of less than one micron in size. The method can be used for etching deposited silicon nitride films, freestanding silicon nitride membranes, and other light absorbing materials, with control over the thickness achieved by optical feedback. The etching is promoted by solvents including electron donor species, such as chloride ions. The method provides the ability to etch silicon nitride and other light absorbing materials, with fine spatial and etch rate control, in mild conditions, including in a biocompatible environment. The method can be used to create nanopores and nanopore arrays.

Abstract: The invention provides methods for direct growth of low noise, atomically thin freestanding membranes of two-dimensional monocrystalline or polycrystalline materials, such as transition metal chalcogenides including molybdenum disulfide. The freestanding membranes are directly grown over an aperture by reacting two precursors in a chemical vapor deposition process carried out at atmospheric pressure. Membrane growth is preferentially over apertures in a thin sheet of solid state material. The resulting membranes are one or a few atomic layers thick and essentially free of defects. The membranes are useful for sequencing of biopolymers through nanopores.

Abstract: Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof. Nanopores are extremely sensitive single-molecule sensors. Recently, electron beams have been used to fabricate synthetic nanopores in thin solid-state membranes with sub-nanometer resolution. A new class of chemically modified nanopore sensors are provided with two approaches for monolayer coating of nanopores by: (1) self-assembly from solution, in which nanopores ?10 nm diameter can be reproductibly coated, and (2) self-assembly under voltage-driven electrolyte flow, in which 5 nm nanopores may be coated. Applications of chemically modified nanopore are provided including: the detection of biopolymers such as DNA and RNA; immobilizing enzymes or other proteins for detection or for generating chemical gradients; and localized pH sensing.

Abstract: An apparatus is provided for sensing a molecule in a sample. The apparatus utilizes an electric field to draw molecules from a first chamber through an aperture, defined by a chemical layer, into a second chamber. The apparatus can detect a DNA molecule with, for example, 4, 5, or 6 unique base pairs. As molecules pass through the aperture, a sensor detects or measures a change in an electric parameter used to generate the electric field, thereafter translating the change in the electric parameter into information about the molecule. A divider element separates the first and second chambers and supports a chemical layer defining the aperture. The apparatus enables detection or measurement of molecules over prolonged time at a higher electric field strength than other nanopores, due to a combination of the shape of the divider, structural elements thereon, and thickness of the chemical layer at the aperture.

Abstract: An apparatus and a method are provided for selectively and rapidly applying heat to a nanoscale environment in a controlled manner. The technology utilizes laser irradiation of a solid state material to heat a nanoscale point of interest by an optothermal effect. The technology can be used to the tip of an atomic force microscope, a spot on a flat surface, or a nanopore, or molecules in their vicinity. The apparatus and method are capable of rapidly scanning the temperature of a nanoscale object such as a molecule or biomolecular complex and to interrogate properties of the object at high throughput. The methods can be used in nanofabrication processes or to drive single molecule chemistry.

Abstract: Provided is a highly multiplex approach to disease condition diagnostics that combines nanopore sensing and nucleic acid nanoparticle (NANP) design and synthesis to detect multiple biomarkers to diagnose diseases. The system works by taking a sample containing biomarkers that is mixed with a plurality of nucleic acid nanoparticle (NANP) populations, with each population designed and synthesized to be able to detect a particular biomarker. Upon incubation, the mixture is used with nanopore measurements, with recordings of the ionic current through the nanopore. The ionic current recordings are analyzed, which determines the presence and/or concentration of biomarkers in the sample.