1458 results about "Nanopore" patented technology

The invention relates to devices and methods for nanopore sequencing. The invention includes arrays of nanopores having incorporated electronic circuits, for example, in CMOS. In some cases, the arrays of nanopores comprise resistive openings for isolating the electronic signals for improved sequencing. Methods for controlling translocation of through the nanopore are disclosed.

Single-channel thin film devices and methods for using the same are provided. The subject devices comprise cis and trans chambers connected by an electrical communication means. At the cis end of the electrical communication means is a horizontal conical aperture sealed with a thin film that includes a single nanopore or channel. The devices further include a means for applying an electric field between the cis and trans chambers. The subject devices find use in applications in which the ionic current through a nanopore or channel is monitored where such applications include the characterization of naturally occurring ion channels, the characterization of polymeric compounds, and the like.

A method of employing a nanopore structure in a manner that allows the detection of the positions (relative and / or absolute) of nucleic acid probes that are hybridized onto a single-stranded nucleic acid molecule. In accordance with the method the strand of interest is hybridized with a probe having a known sequence. The strand and hybridized probes are translocated through a nanopore. The fluctuations in current measured across the nanopore will vary as a function of time corresponding to the passing of a probe attachment point along the strand. These fluctuations in current are then used to determine the attachment positions of the probes along the strand of interest. This probe position data is then fed into a computer algorithm that returns the sequence of the strand of interest.

The present invention provides an apparatus and method for making an apparatus for sensing and / or characterizing a biopolymer translocating a nanopore. The apparatus of the present invention provides a first electrode, a first insulator, a second electrode, a optional insulator, a voltage source for applying a time varying potential difference between the electrodes, and a means of measuring the resulting current between the two electrodes. A method for making the apparatus is also disclosed.

The methods and apparatus 100 disclosed herein are of use for sequencing and / or identifying nucleic acids 230, 310. Nucleic acids 230, 310 containing labeled nucleotides 235, 245, 315 may be synthesized and passed through nanopores 255, 310. Detectors 257, 345 operably coupled to the nanopores 255, 310 may detect the labeled nucleotides 235, 245, 315. By determining the time intervals at which labeled nucleotides 235, 245, 315 are detected, distance maps 140 for each type of labeled nucleotide 235, 245, 315 may be compiled. The distance maps 140 in turn may be used to sequence 150 and / or identify 160 the nucleic acid 230, 310. In different embodiments of the invention, luminescent nucleotides 235, 245 or nanoparticles 315 may be detected using photodetectors 257 or electrical detectors 310. Apparatus 100 and sub-devices 200, 300 of use for nucleic acid 230, 310 sequencing 150 and / or identification 160 are also disclosed herein.

Methods for determining the presence of double stranded nucleic acids in a sample are provided. In the subject methods, nucleic acids present in a fluid sample are translocated through a nanopore, e.g. by application of an electric field to the fluid sample. The current amplitude through the nanopore is monitored during the translocation process and changes in the amplitude are related to the passage of single- or double-stranded molecules through the nanopore. The subject methods find use in a variety of applications in which the detection of the presence of double-stranded nucleic acids in a sample is desired, e.g. in hybridization assays, such as Northern blot assays, Southern blot assays, array based hybridization assays, etc.

The invention provides articles of manufacture comprising biocompatible nanostructures comprising nanotubes and nanopores for, e.g., organ, tissue and / or cell growth, e.g., for bone, kidney or liver growth, and uses thereof, e.g., for in vitro testing, in vivo implants, including their use in making and using artificial organs, and related therapeutics. The invention provides lock-in nanostructures comprising a plurality of nanopores or nanotubes, wherein the nanopore or nanotube entrance has a smaller diameter or size than the rest (the interior) of the nanopore or nanotube. The invention also provides dual structured biomaterial comprising micro- or macro-pores and nanopores. The invention provides biomaterials having a surface comprising a plurality of enlarged diameter nanopores and / or nanotubes.

The invention herein disclosed provides for devices and methods that can detect and control an individual polymer in a mixture is acted upon by another compound, for example, an enzyme, in a nanopore in the absence of requiring a terminating nucleotide. The devices and methods are also used to determine rapidly (˜>50 Hz) the nucleotide base sequence of a polynucleotide under feedback control or using signals generated by the interactions between the polynucleotide and the nanopore. The invention is of particular use in the fields of drug discovery, molecular biology, structural biology, cell biology, molecular switches, molecular circuits, and molecular computational devices, and the manufacture thereof.

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.

The present invention provides a device having at least one constriction that is sized to permit translocation of only a single copy of the molecule. The device has a pair of spaced apart sensing electrodes that border the constriction, which may be a nanopore. The first electrode is connected to a first affinity element and the second electrode is connected to a second affinity element. The first and second affinity elements are configured to temporarily form hydrogen bonds with first and second portions of the target molecule as the latter passes through the constriction.

This invention provides a process for sequencing single-stranded DNA by employing a nanopore and modified nucleotides.

Novel nanowell microarrays are disclosed in optical contact with polymer waveguides wherein evanescent field associated with lightwaves propagated in the waveguide excite target substances in the nanowells either by a common waveguide or by individual waveguides. Fluid samples are conveyed to the nanowells by means of microfluidics. The presence of the target substances in fluid samples is detected by sensing fluorescent radiation generated by fluorescent tag bound to the target substances. The fluorescent tags generate fluorescent radiation as a result of their excitation by the evanescent field. One or more PMT detectors or a CCD detector are located at the side of the waveguide opposite to the nanowells. Fluorescent radiation is detected due to its coupling with the waveguide or its emission through the waveguide.

This invention provides a process for sequencing single-stranded DNA by employing a nanopore and modified nucleotides.

Provided are devices comprising one or more nanoscale pores for use in, inter alia, analyzing various biological molecules. Also provided are methods for the fabrication of nanoscale pores in solid-state substrates, methods for functionalizing nanopores in solid-state substrates, and methods for sequencing polymers using devices containing nanoscale pores.

The invention features methods for evaluating the conformation of a polymer, for example, for determining the conformational distribution of a plurality of polymers and to detect binding or denaturation events. The methods employ a nanopore which the polymer, e.g., a nucleic acid, traverses. As the polymer traverses the nanopore, measurements of transport properties of the nanopore yield data on the conformation of the polymer.

Methods and devices are provided for characterizing a duplex nucleic acid, e.g., a duplex DNA molecule. In the subject methods, a fluid conducting medium that includes a duplex nucleic acid molecule is contacted with a nanopore under the influence of an applied electric field and the resulting changes in current through the nanopore caused by the duplex nucleic acid molecule are monitored. The observed changes in current through the nanopore are then employed as a set of data values to characterize the duplex nucleic acid, where the set of data values may be employed in raw form or manipulated, e.g., into a current blockade profile. Also provided are nanopore devices for practicing the subject methods, where the subject nanopore devices are characterized by the presence of an algorithm which directs a processing means to employ monitored changes in current through a nanopore to characterize a duplex nucleic acid molecule responsible for the current changes. The subject methods and devices find use in a variety of applications, including, among other applications, the identification of an analyte duplex DNA molecule in a sample, the specific base sequence at a single nulceotide polymorphism (SNP), and the sequencing of duplex DNA molecules.

Techniques for characterizing a molecule are described herein. In one example, a portion of the molecule is trapped in a nanopore, a variable voltage is applied across the nanopore until the trapped portion of molecule is moved within the nanopore, and the molecule is characterized based on the electrical stimulus required to affect movement of at least a portion of the trapped portion of the molecule within the nanopore.

The invention relates to devices and methods for nanopore sequencing. The invention includes compositions and methods of nucleic acid sequencing using a single polymerase enzyme complex comprising a polymerase enzyme and a template nucleic acid attached proximal to a nanopore, and nucleotide analogs in solution comprising charge blockade label that are attached to the polyphosphate portion of the nucleotide analog such that the charge blockade labels are cleaved when the nucleotide analog is incorporated into a growing nucleic acid and the charge blockade label is detected by the nanopore to determine the presence and identity of the incorporated nucleotide and thereby determine the sequence of a template nucleic acid.

Methods and apparatus are provided for analysis and correlation of phenotypic and genotypic information for a high throughput sample on a cell by cell basis. Cells are isolated and sequentially analyzed for phenotypic information and genotypic information which is then correlated. Methods for correlating the phenotype-genotype information of a sample population can be performed on a continuous flow sample within a microfluidic channel network or alternatively on a sample preloaded into a nano-well array chip. The methods for performing the phenotype-genotype analysis and correlation are scalable for samples numbering in the hundreds of cells to thousands of cells up to the tens and hundreds of thousand cells.

Featured are devices and systems embodying one or more electrically-addressable-solid-state nanopores useful for sensing and / or characterizing single macromolecules as well as sequencing DNA or RNA. In one aspect of the present invention, there is featured a linear or 2-D electrically-addressable array of nanopores, where the nanopores are located at points of intersections between V-shaped grooves formed in an upper surface of the insulating member and a V-shaped groove formed in a lower surface of the insulating member. In another aspect of the present invention the solid-state nanopore of the present invention the width and / or length of the nanopore is defined or established by sharp edges of cleaved crystals that are maintained in fixed relation during the formation of the insulating member including the nanopore.

Resonant tunneling devices and methods of using and fabricating the same are provided. The subject devices include a first and second fluid containment members separated by a fluid barrier having a single nanopore therein providing fluid communication between the first and second fluid containment members, wherein the nanopore has a top inner diameter that is smaller than a bottom inner diameter and includes first and second perimeter electrodes separated by an insulator element, and a proteinaceous channel positioned in the nanopore. Also provided are methods of fabricating such a device and methods of using such a device for improved detection and characterization of a sample.

An apparatus and method for making a nanopore chip exhibiting low capacitance. The apparatus provides a thin diaphragm on a rigid semiconductor frame suitable for nanopore fabrication, the diaphragm having associated thicker insulator regions to reduce capacitance. Also disclosed is a method of making the apparatus.

Disclosed herein are controlled release drug delivery systems. The systems comprise a medical device at least one nonoporous surface, at least one bioactive agent and optionally a biodegradable polymer. The nanoporous surfaces of the medical devices contain nanopores capable of acting as reservoirs for drugs that are controllably released.

The present invention provides an apparatus for detecting a nanoscale moiety and a method for sensing a nanoscale moiety. The apparatus includes a substrate having a nanopore, at least one excitable molecule attached to the substrate adjacent to the nanopore, and a light source for exciting the excitable molecule attached to the substrate adjacent to the nanopore wherein the excitable molecule is quenched by the quencher molecule on the nanoscale moiety as it passes by the excitable molecule. The invention also includes a method for detecting the presence or identity of the nanoscale moiety.

There is provided a substantially bare, self-supported single-layer graphene membrane including a nanopore extending through a thickness of the graphene membrane from a first to a second membrane surface opposite the first graphene membrane surface. A connection from the first graphene membrane surface to a first reservoir provides, at the first graphene membrane surface, a species in an ionic solution to the nanopore, and a connection from the second graphene membrane surface to a second reservoir is provided to collect the species and ionic solution after translocation of the species and ionic solution through the nanopore from the first graphene membrane surface to the second graphene membrane surface. An electrical circuit is connected on opposite sides of the nanopore to measure flow of ionic current through the nanopore in the graphene membrane.

The invention relates to devices and methods for nanopore sequencing. The invention includes compositions and methods of nucleic acid sequencing using a single polymerase enzyme complex comprising a polymerase enzyme and a template nucleic acid attached proximal to a nanopore, and nucleotide analogs in solution comprising charge blockade label that are attached to the polyphosphate portion of the nucleotide analog such that the charge blockade labels are cleaved when the nucleotide analog is incorporated into a growing nucleic acid and the charge blockade label is detected by the nanopore to determine the presence and identity of the incorporated nucleotide and thereby determine the sequence of a template nucleic acid.

A method of using a sensor comprising a field effect transistor (FET) embedded in a nanopore includes placing the sensor in an electrolyte comprising at least one of biomolecules and deoxyribonucleic acid (DNA); placing an electrode in the electrolyte; applying a gate voltage in the sub-threshold regime to the electrode; applying a drain voltage to a drain of the FET; applying a source voltage to a source of the FET; detecting a change in a drain current in the sensor in response to the at least one of biomolecules and DNA passing through the nanopore.

Methods, compositions, and systems are provided for characterization of modified nucleic acids. Nanopore sequencing is performed using a processive enzyme to control the rate of translation of a single strand of a nucleic acid through a nanopore. The presence and identity of a modified base can be determined by monitoring the kinetics of translation through the pore even though the events that lead to the kinetic changes are separated in time and space from the translation of the modified base or it's compliment through the nanopore. The invention also comprises the use of hemi-genomic DNA in nanopore sequencing.

Compounds which are otherwise difficult to solubilize, such as, for example, pharmaceutical actives difficult for the body to absorb, are solubilized into a composition using a solvent system that is a structured fluid. The structured fluid is a reversed cubic phase or reversed hexagonal phase material, or a combination thereof, which includes a polar solvent, a surfactant and a non-paraffinic liquid with a high octanol-water partition coefficient which does not qualify as a surfactant. The compositions thus formed are able to enhance absorption of drugs by the induction of local, transient nanopores in biomembrane absorption barriers and particularly those in which efflux mechanisms, such as those associated with P-glycoprotein and / or cytochrome 3A4, are active. The compositions and methods that are used for solubilizing pharmaceutical actives in structured fluids can simultaneously accomplish solubilization of difficultly soluble drugs and enhancement of absorption.