To form a layer separating two volumes of aqueous solution, there is used an apparatus comprising elements defining a chamber, the elements including a body of non-conductive material having formed therein at least one recess opening into the chamber, the recess containing an electrode. A pre-treatment coating of a hydrophobic fluid is applied to the body across the recess. Aqueous solution, having amphiphilic molecules added thereto, is flowed across the body to cover the recess so that aqueous solution is introduced into the recess from the chamber and a layer of the amphiphilic molecules forms across the recess separating a volume of aqueous solution introduced into the recess from the remaining volume of aqueous solution.
The invention relates to a new method of characterising a target RNA polynucleotide by taking one or more measurements as the target RNA polynucleotide moves with respect to a transmembrane pore. The movement is controlled by a DNA helicase. The invention also relates to a modified RNA construct wherein the RNA polynucleotide has been modified to increase DNA helicase binding thereto.
The invention relates to new methods for synthesising polynucleotide molecules according to a predefined nucleotide sequence. The invention also relates to methods for the assembly of synthetic polynucleotides following synthesis, as well as systems and kits for performing the synthesis and/or assembly methods.
A microfluidic device for analysing a test liquid comprises: a sensor provided in a sensing chamber; a sensing chamber inlet channel and a sensing chamber outlet channel, each connecting to the sensing chamber for respectively passing liquid into and out of the sensing chamber, and a reservoir forming a sample input port to the microfluidic device, the reservoir being in fluid communication with the sensing chamber inlet channel; a liquid collection channel; a barrier between an end of the sensing chamber outlet channel and the liquid collection channel; a first seal, covering the sample input port; a second seal, covering the end of the sensing chamber outlet channel, thereby preventing liquid from flowing from the sensing chamber, over the barrier, into the liquid collection channel; wherein the microfluidic device is filled with a liquid from the first seal at the sample input port to the second seal at the end of the sensing chamber outlet channel, such that the sensor is covered by liquid and unexposed to a gas or gas/liquid interface; and wherein the first and second seals are removable to cause the liquid to flow between the reservoir and the end of the sensing chamber outlet and over the barrier.
There are provided apparatuses for controlling insertion of a membrane channel into a membrane, comprising: a first bath for holding a first liquid in contact with a first surface of the membrane; a second bath for holding a second liquid in contact with a second surface of the membrane, wherein the membrane separates the first and second liquids; a first electrode configured to contact the first liquid; a second electrode configured to contact the second liquid; and a driving circuit configured to apply a potential difference across the membrane via the first and second electrodes to promote insertion of a membrane channel into the membrane from the first liquid or the second liquid. Various configurations of the driving circuit are described that allow effective promotion of membrane channel insertion while reducing the risk of damage to the membrane. Corresponding methods are also described.
The present invention relates to novel protein pores and their uses in analyte detection and characterisation. The invention particularly relates to an isolated pore complex formed by a CsgG-like pore and a modified CsgF peptide, or a homologue or mutant thereof, thereby incorporating an additional channel constriction or reader head in the nanopore. The invention further relates to a transmembrane pore complex and methods for production of the pore complex and for use in molecular sensing and nucleic acid sequencing applications.
Provided is a method of characterising a polynucleotide using a transmembrane pore, wherein the pore is a double pore comprising a first Csg G pore, or a homologue thereof, and second CsgG pore, or a homologue thereof.
Methods and apparatus for forming apertures in a solid state membrane using dielectric breakdown are provided. In one disclosed arrangement a plurality of apertures are formed. The membrane comprises a first surface area portion on one side of the membrane and a second surface area portion on the other side of the membrane. Each of a plurality of target regions comprises a recess or a fluidic passage opening out into the first or second surface area portion. The method comprises contacting all of the first surface area portion of the membrane with a first bath comprising ionic solution and all of the second surface area portion with a second bath comprising ionic solution. A voltage is applied across the membrane via first and second electrodes in respective contact with the first and second baths comprising ionic solutions to form an aperture at each of a plurality of the target regions in the membrane.
B01D 67/00 - Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or propertiesManufacturing processes specially adapted therefor characterised by their properties
An array of membranes comprising amphipathic molecules is formed using an apparatus comprising a support defining an array of compartments. Volumes comprising polar medium are provided within respective compartments and a layer comprising apolar medium is provided extending across the openings with the volumes. Polar medium is flowed across the support to displace apolar medium and form a layer in contact with the volumes, forming membranes comprising amphipathic molecules at the interfaces. In one construction of the apparatus, the support that comprises partitions which comprise inner portions and outer portions. The inner portions define inner recesses without gaps therebetween that are capable of constraining the volumes comprising polar medium contained in neighbouring inner recesses from contacting each other. The outer portions extend outwardly from the inner portions and have gaps allowing the flow of an apolar medium across the substrate.
Apparatus and methods for controlling the insertion of a membrane channel into a membrane are disclosed. In one arrangement a first bath holds a first liquid in contact with a first surface of a membrane. A second bath holds a second liquid in contact with a second surface of the membrane. The membrane separates the first and second liquids. A first electrode contacts the first liquid. A second electrode contacts the second liquid. A driving unit applies a potential difference across the membrane via the first and second electrodes to promote insertion of a membrane channel into the membrane from the first liquid or the second liquid. A membrane voltage reduction unit is connected in series with the membrane. The driving unit applies a driving voltage across the membrane voltage reduction unit and the membrane, the driving voltage providing the potential difference across the membrane. The membrane voltage reduction unit is configured such that a reduction in resistance through the membrane caused by insertion of a membrane channel intrinsically increases a potential difference across the membrane voltage reduction unit thereby lowering the potential difference across the membrane. The lowering of the potential difference across the membrane is sufficient to prevent or reduce promotion of insertion of a further membrane channel.
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Scientific research and laboratory apparatus; scientific,
optical, analytical, measuring, sensing, dosing, checking
and quality control apparatus and instruments, in particular
for use in laboratories for sample preparation; sensing
devices for determining an analyte, in particular for single
molecule sensing or determining a polynucleotide,
polypeptide and polysaccharide; nanopore sensing devices;
analytical apparatus and instruments for scientific,
industrial, agricultural or non-medical use; pipetting
devices and sampling devices, dispensers, motorized syringe
dilutors, pumps and dosing apparatus for laboratory use;
robots for laboratory automation and robots for the
automation of analysis processes; robots for automated
dispensing of a sample to a sensing device, in particular a
nanopore sensing device for single molecule sensing;
laboratory apparatus and instruments used for extraction and
sample preparation; microplate readers, namely light
absorption measuring apparatus and luminescence and
fluorescence measuring apparatus; imaging devices for
scientific use; microplate washers; genomics automation
devices; disposable pipette tips for laboratory use;
disposable containers for reagents and samples in connection
with pipetting devices; microplates; disposable materials
for use in laboratory apparatus; cell counting chambers for
scientific use; extraction plates; extraction columns;
syringes for dilutors; valves for dilutors; software for
controlling laboratory apparatus and for controlling medical
apparatus; software for evaluation of measurement results;
software for controlling a robot for laboratory sample
preparation; software for automated delivery of a sample to
a sensing device for sensing; software for image analysis;
computer software; application software; software
downloadable from computer networks and clouds; software for
use in remote monitoring of laboratory apparatus; software
for remote maintenance of laboratory apparatus; software for
connecting laboratory apparatus; software for use in the
automation of laboratories; training software; downloadable
electronic information and publications; recorded data
files; downloadable course materials for training and
education. Scientific and technological services and research and
design relating thereto; industrial analysis and research
services; scientific research for chemical, biochemical,
industrial, agricultural, biological, bacteriological,
medical or veterinary purposes; biological, chemical,
biochemical, bacteriological, DNA, RNA, protein, polynucleic
acid and molecular analysis services for scientific research
purposes; industrial analysis and research services relating
to robots for laboratory automation, automation of analysis
processes and automated dispensing of a sample to a sensing
device; industrial analysis and research services relating
to an integrated apparatus comprising a robot for automated
sample preparation and dispensing and a sensing device,
small molecules, genomes, DNA, RNA or other nucleic acids,
oligosaccharides, proteins and peptides; scientific research
for medical or veterinary purposes; genome, DNA, RNA and
nucleic acid, oligosaccharide and polynucleic acid
sequencing services; protein sequencing services; design and
development of instruments and apparatus for biological,
chemical, biochemical, DNA, RNA, protein and molecular
analysis; laboratory testing services; DNA and polynucleic
acid testing services; genome sequencing services;
scientific and technological services for the analysis and
evaluation of data, including scientific and medical data;
scientific and technological services related to overseeing,
monitoring and managing scientific and medical experiments
and tests; scientific and technological services related to
overseeing, monitoring and managing the analysis and
evaluation of scientific and medical data; design of
scientific experiments; analysis of data generated by
scientific and medical experiments and tests; biological,
bacteriological, chemical, biochemical, DNA, RNA, protein,
polynucleic acid and molecular analysis and evaluation
services, being scientific and technological services; DNA
and RNA and polynucleic acid and protein sequencing,
analysis and evaluation services, being scientific and
technological services; genome sequencing services and the
analysis and evaluation of data resulting therefrom;
provision of reports relating to scientific and medical
experiments, the results of scientific and medical
experiments and tests, the analysis and evaluation of
scientific and medical data, and data generated by
scientific and medical experiments and tests; scientific and
medical research and development services; technical data
analysis and evaluation services; electronic data storage
services; application service provider (ASP) services for
providing access to computer software applications installed
or downloaded onto data processing apparatus, scientific
apparatus, medical and veterinary apparatus, computers,
mobile phones, tablet computers and handheld mobile digital
electronic devices; information, advisory and consultancy
services relating to the aforesaid.
The invention relates to new methods for synthesising polynucleotide molecules according to a predefined nucleotide sequence. The invention also relates to methods for the assembly of synthetic polynucleotides following synthesis.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
B01J 19/00 - Chemical, physical or physico-chemical processes in generalTheir relevant apparatus
C40B 50/14 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creationParticular methods of cleavage from the solid support
13.
CURRENT MEASUREMENT APPARATUS, MOLECULAR ENTITY SENSING APPARATUS, METHOD OF MEASURING A CURRENT, METHOD OF SENSING A MOLECULAR ENTITY
Methods and apparatus for measuring current are provided. In one arrangement, a first charge amplifier integrates a current to be measured. A processing circuit filters an output from the first charge amplifier using a first low pass filter module and a second low pass filter module. A second charge amplifier integrates a current derived from the filtered output from the first charge amplifier. The apparatus is configured to reset the first charge amplifier at the start of each of a plurality of sensing frames. The processing circuit obtains at least a first sample of the output from the first charge amplifier in each sensing frame. The sampling of the first sample alternates from one sensing frame to the next sensing frame between sampling via the first low pass filter module and sampling via the second low pass filter module.
G01N 27/12 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon absorption of a fluidInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon reaction with a fluid
G01N 33/487 - Physical analysis of biological material of liquid biological material
The invention relates to modified helicases with reduced unbinding from polynucleotides. The helicases can be used to control the movement of polynucleotides and are particularly useful for sequencing polynucleotides.
09 - Scientific and electric apparatus and instruments
Goods & Services
Downloadable software for running an e-commerce platform,
namely, software that allows users to perform electronic
business transaction over the Internet; cloud computing
software for running an e-commerce platform, namely,
software that allows users to perform electronic business
transaction over the Internet; downloadable software for use
in analysing, transmitting and receiving data via a global
communications network; cloud computing software for use in
analysing, transmitting and receiving data via a global
communications network; downloadable software for
developing, running and communicating with software on data
processing apparatus, scientific apparatus, medical and
veterinary apparatus, computers, mobile phones, tablet
computers and handheld mobile digital electronic devices;
computer operating software; computer operating system
software; computer operating system software for data
processing apparatus, scientific apparatus, medical and
veterinary apparatus, computers, mobile phones, tablet
computers and handheld mobile digital electronic devices;
laboratory equipment, namely, micro-array chips; electronic
sensing apparatus for analysing chemical, biochemical,
biological, bacteriological and microbiological test samples
for scientific testing purposes; scientific testing
apparatus and instruments, namely, optical or
electrochemical readers for biological, bacteriological,
chemical, biochemical, DNA, RNA, protein, polynucleic acid
and molecular test samples and the measurement of ions;
portable apparatus and instrument, namely, optical or
electrochemical readers for biological, bacteriological,
chemical, biochemical, DNA, RNA, protein, polynucleic acid
and molecular test samples, and measurement of ions;
scientific instruments, namely, sequencing devices for use
in DNA, RNA, protein and polynucleic acid sequencing;
computer software and optical or electrochemical readers for
the analysis of polynucleic acid sequences; scientific
apparatus and instruments for the analysis of nucleic and
polynucleic acids; scientific apparatus and instruments for
the analysis of proteins; apparatus and instruments for
analysis, not for medical use, of genetic information,
genomic information and proteomic information, namely,
automated instruments for detecting the presence, properties
and identity of analytes, comprising cartridges,
microarrays, silicon chip based arrays, ASICS (application
specific integrated circuits), and networked computer
hardware and software for performing and controlling the
analysis, and for processing, displaying and storing the
information obtained from the analysis; computer programs,
computer hardware and data processing apparatus, all for the
analysis and recordal of scientific data;
electrowetting-on-dielectric (EWOD) devices; scientific
apparatus and instruments for automating the extraction and
preparation of chemical, biochemical, biological,
bacteriological and microbiological test samples; data
processing apparatus, devices and instruments; scientific
apparatus, devices and instruments for identifying,
measuring, analysing, sequencing small molecules, genomes,
DNA, RNA or other nucleic acids, oligosaccharides, proteins
and peptides for scientific research and scientific testing
purposes; portable computer hardware and data processing
apparatus, all for the analysis and recordal of scientific
data; electronic display interfaces for the display of
information obtained from scientific equipment; silicon
chips; DNA chips; biosensor chips for scientific research
and scientific testing use; cartridges namely, cartridges
for test samples and cartridges for use with concentrates
and solutions in solid or liquid form for use in biological,
bacteriological, chemical, biochemical, DNA, RNA, protein,
polynucleic acid and molecular analysis, not for medical
use.
16.
METHOD OF DETERMINING A TARGET POLYMER IN A SAMPLE BY USING A GUIDE POLYMER
The invention relates generally to a method of detecting and/or analysing target polymers, especially target polynucleotides, using a biological pore. The invention also relates to a novel system for carrying out the method. The method has many uses. In particular, the method may be used for diagnosis, detection of polymorphisms and V(D)J repertoire analysis.
Droplet interfaces are formed between droplets in an electro-wetting device comprising an array of actuation electrodes. Actuation signals are applied to selected actuation electrodes to place the droplets into an energised state in which the shape of the droplets is modified compared to a shape of the droplets in a lower energy state and to bring the two droplets into proximity. The actuation signals are then changed to lower the energy of the droplets into the lower energy state so that the droplets relax into the gap and the two droplets contact each other thereby forming a droplet interface. The use of sensing electrodes in the device permit electrical current measurements across the droplet interface. The sensing electrodes can be used for either (i) applying a reference signal during droplet actuation or (ii) recording electrical current measurements. Two or more electrodes are configurable to lyse cells within a droplet positioned over said electrodes.
Methods and apparatus for measuring current are provided. In one arrangement, a first charge amplifier integrates a current to be measured. A processing circuit filters an output from the first charge amplifier using a first low pass filter module and a second low pass filter module. A second charge amplifier integrates a current derived from the filtered output from the first charge amplifier. The apparatus is configured to reset the first charge amplifier at the start of each of a plurality of sensing frames. The processing circuit obtains at least a first sample of the output from the first charge amplifier in each sensing frame. The sampling of the first sample alternates from one sensing frame to the next sensing frame between sampling via the first low pass filter module and sampling via the second low pass filter module.
G01N 27/12 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon absorption of a fluidInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon reaction with a fluid
G01N 33/487 - Physical analysis of biological material of liquid biological material
19.
METHOD AND PRODUCTS FOR CHARACTERIZING A POLYNUCLEOTIDE USING A NANOPORE
Provided herein are methods of characterising a polynucleotide during the translocation of the polynucleotide through a nanopore. Also provided herein are methods of operating a nanopore array. Further provided herein are kits and apparatuses for carrying out such methods.
The invention relates to modified helicases which are capable of controlling the movement of polynucleotides with increased speed. The modified helicases are particularly useful for sequencing polynucleotides.
C07K 14/31 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
A modular instrument (1) for preparing and sensing an analyte in a prepared sample. The modular instrument includes a main body (12), an EWOD sample preparation device (2), and a nanopore sensor device (3) for sensing the analyte. The main body is electrically connectable to and separable from both the EWOD sample preparation device and the nanopore sensor device. The main body, the EWOD sample preparation device and nanopore sensor are physically connectable to and separable from each other.
A series of measurements taken from a polymer during translocation through a nanopore is analysed using a machine learning technique using a recurrent neural network (RNN). The RNN may derive posterior probability matrices each representing, in respect of different respective historical sequences of polymer units corresponding to measurements prior to the respective measurement, posterior probabilities of plural different changes to the respective historical sequence of polymer units giving rise to a new sequence of polymer units. Alternatively, the RNN may output decisions on the identity of successive polymer units of the series of polymer units, wherein the decisions are fed back into the recurrent neural network. The analysis may comprise performing convolutions of groups of consecutive measurements using a trained feature detector such as a convolutional neural network to derive a series of feature vectors, on which the RNN operates.
An apparatus for supporting an array of layers of amphiphilic molecules, the apparatus comprising: a body, formed in a surface of the body, an array of sensor wells capable of supporting a layer of amphiphilic molecules across the sensor wells, the sensor wells each containing an electrode for connection to an electrical circuit, and formed in the surface of the body between the sensor wells, flow control wells capable of smoothing the flow of a fluid across the surface.
The present invention relates to novel actinoporin monomers, actinoporin pores formed from the monomers and their uses in analyte detection and characterisation.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
G01N 33/487 - Physical analysis of biological material of liquid biological material
Medical and veterinary testing and diagnostic apparatus for
biological, chemical, biochemical, DNA, RNA, protein and
molecular analysis; electrowetting devices for medical and
veterinary purposes; apparatus and instruments for
automating the extraction and preparation of test samples
for medical and veterinary purposes; portable medical and
veterinary testing and diagnostic apparatus for biological,
chemical, biochemical, DNA, RNA, protein and molecular
analysis; diagnostic apparatus for medical or veterinary
purposes for pregnancy testing, and for detecting
pathogenic, infectious, psychiatric, oncogenic, metabolic,
genetic, respiratory, genitourinary, digestive,
inflammatory, autoimmune, reproductive, hepatic, central
nervous system, degenerative and cardiovascular diseases or
conditions; portable diagnostic apparatus for medical or
veterinary purposes for pregnancy testing, and for detecting
pathogenic, infectious, psychiatric, oncogenic, metabolic,
genetic, respiratory, genitourinary, digestive,
inflammatory, autoimmune, reproductive, hepatic, central
nervous system, degenerative and cardiovascular diseases or
conditions; testing apparatus for medical or veterinary
purposes for detecting pathogenic, infectious, psychiatric,
oncogenic, metabolic, genetic, respiratory, genitourinary,
digestive, inflammatory, autoimmune, reproductive, hepatic,
central nervous system, degenerative and cardiovascular
diseases or conditions; portable testing apparatus for
medical or veterinary purposes for detecting pathogenic,
infectious, psychiatric, oncogenic, metabolic, genetic,
respiratory, genitourinary, digestive, inflammatory,
autoimmune, reproductive, hepatic, central nervous system,
degenerative and cardiovascular diseases or conditions;
cartridges for test samples, for medical purposes; reaction
units containing chemical reagents, namely, reaction systems
for medical testing purposes; Nanopore sensing devices for
medical and veterinary purposes.
The invention relates to a method of uniquely labelling RNA molecules in a population of cells and kits for use in such methods. The methods and kits of the invention allow the study of the transcriptome in individual cells or populations of cells.
DEUTSCHES KREBSFORSCHUNGSZENTRUM STIFTUNG DES OEFFENTLICHEN RECHTS (Germany)
UNIVERSITAET HEIDELBERG (Germany)
OXFORD NANOPORE TECHNOLOGIES PLC (United Kingdom)
Inventor
Sahm, Felix
Sill, Martin
Von Deimling, Andreas
Pfister, Stefan
Jones, David
Patel, Areeba
Dogan, Helin
Loose, Matt
Payne, Alexander
Abstract
The present disclosure relates to a computer-implemented method for cancer diagnosis, comprising: a) selectively sequencing polymers of a biological sample according to at least one target gene site by translocating the polymers through nanopores of a nanopore sequencing system, including: (i) analyzing an initial nucleotide sequence of a first polymer of the biological sample while the first polymer is translocating through a nanopore of the nanopore sequencing system to determine whether the initial nucleotide sequence corresponds to the at least one target gene site; and (ii) continuing the sequencing of the first polymer to obtain measurement data of the first polymer only if the initial nucleotide sequence of the first polymer corresponds to the at least one target gene site: b) determining, based on the measurement data, a biological state of a nucleotide sequence of the first polymer corresponding to the at least one target gene site; and c) classifying a cancer using a classification algorithm based on the biological state of the nucleotide sequence of the first polymer, wherein the classification algorithm is trained based on the at least one target gene site and biological state data pertaining to cancer types.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 40/10 - Signal processing, e.g. from mass spectrometry [MS] or from PCR
The invention relates to new methods for synthesising polynucleotide molecules according to a predefined nucleotide sequence. The invention also relates to methods for the assembly of synthetic polynucleotides following synthesis, as well as systems and kits for performing the synthesis and/or assembly methods.
The invention relates to a new method of characterizing a target polynucleotide. The method uses a pore and a Hel308 helicase or amolecular motor which is capable of binding to the target polynucleotide at an internal nucleotide. The helicase or molecular motor controls the movement of the target polynucleotide through the pore.
Methods and apparatus for forming apertures in a solid state membrane using dielectric breakdown are provided. In one disclosed arrangement a plurality of apertures are formed. The membrane comprises a first surface area portion on one side of the membrane and a second surface area portion on the other side of the membrane. Each of a plurality of target regions comprises a recess or a fluidic passage opening out into the first or second surface area portion. The method comprises contacting all of the first surface area portion of the membrane with a first bath comprising ionic solution and all of the second surface area portion with a second bath comprising ionic solution. A voltage is applied across the membrane via first and second electrodes in respective contact with the first and second baths comprising ionic solutions to form an aperture at each of a plurality of the target regions in the membrane.
B01D 67/00 - Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or propertiesManufacturing processes specially adapted therefor characterised by their properties
A sensor device (902) for a nanopore sensor, the sensor device (902) comprising: an insulating substrate (903); one or more wells (908) for containing a fluid; wherein the one or more wells (908) are formed on a first side of the substrate (903); a sensor electrode (910) for detecting an ionic current in each of the one or more wells (908); wherein the sensor electrodes (910) are formed on the first side of the substrate (903) at the base of the one or more wells (908); one or more contacts (914) formed on a second side of the substrate (903); and one or more vias (912) extending through the substrate (903); wherein the one or more vias (912) connect the sensor electrodes (910) to the one or more contacts (914); wherein the electrodes (910) comprise a different structure from the one or more contacts (914) and/or the sensor electrodes (910) are made from a different material or materials from the one or more contacts (914).
A sensor device (902) for a nanopore sensor, the sensor device (902) comprising: an insulating substrate (903); one or more wells (908) for containing a fluid; wherein the one or more wells (908) are formed on a first side of the substrate (903); a sensor electrode (910) for detecting an ionic current in each of the one or more wells (908); wherein the sensor electrodes (910) are formed on the first side of the substrate (903) at the base of the one or more wells (910); one or more vias (912) extending through the substrate (903); wherein the one or more vias (912) are connected to sensor electrodes (910); wherein the one or more vias (912) each comprise a conducting cap (950) at one or both ends of the via (912).
A sensor device (902) for a nanopore sensing apparatus (901), the sensor device (902) comprising: an insulating substrate (903); one or more wells (908) for containing a fluid; wherein the one or more wells (908) are formed on a first side of the substrate (903); a sensor electrode (910) for detecting an ionic current in a respective well (908) of the one or more wells (908); wherein the one or more sensor electrodes (910) are formed on the first side of the substrate (903) at the base of the one or more wells (908); and wherein the base of each of the one or more wells (908) extends over a base area on the first side of the substrate (903); and one or more vias (912) extending through the substrate (903); wherein each of the one or more sensor electrodes (910) is connected to a respective via (912) of the one or more vias (912); and wherein each via (912) has a cross-sectional area at the first side of the substrate (903) that at least partially falls outside of the base area of each corresponding well (908).
A sensor device (902) for a nanopore sensor, the sensor device (902) comprising: an insulating substrate (903); one or more wells (908) for containing a fluid; wherein the one or more wells (908) are formed on a first side of the substrate (903); a sensor electrode (910) for detecting an ionic current in each of the one or more wells (908); wherein the sensor electrodes (910) are formed on the first side of the substrate (903) at the base of the one or more wells (908); one or more vias (912) extending through the substrate (903); wherein the one or more vias (912) are connected to the sensor electrodes (910); wherein the one or more vias (912) each comprise: a conductor (946) forming a conductive path through the via (912); and a material (948) arranged to retain the conductor (946) in the via; wherein the material (948) arranged to retain the conductor (946) in the via (912) is different from a material of the conductor (946).
The invention relates to modified Dda helicases which can be used to control the movement of polynucleotides and are particularly useful for sequencing polynucleotides.
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
(1) Scientific research and laboratory apparatus; scientific, optical, analytical, measuring, sensing, dosing, checking and quality control apparatus and instruments, in particular for use in laboratories for sample preparation; sensing devices for determining an analyte, in particular for single molecule sensing or determining a polynucleotide, polypeptide and polysaccharide; nanopore sensing devices; analytical apparatus and instruments for scientific, industrial, agricultural or non-medical use; pipetting devices and sampling devices, dispensers, motorized syringe dilutors, pumps and dosing apparatus for laboratory use; robots for laboratory automation and robots for the automation of analysis processes; robots for automated dispensing of a sample to a sensing device, in particular a nanopore sensing device for single molecule sensing; laboratory apparatus and instruments used for extraction and sample preparation; microplate readers, namely light absorption measuring apparatus and luminescence and fluorescence measuring apparatus; imaging devices for scientific use; microplate washers; genomics automation devices; disposable pipette tips for laboratory use; disposable containers for reagents and samples in connection with pipetting devices; microplates; disposable materials for use in laboratory apparatus; cell counting chambers for scientific use; extraction plates; extraction columns; syringes for dilutors; valves for dilutors; software for controlling laboratory apparatus and for controlling medical apparatus; software for evaluation of measurement results; software for controlling a robot for laboratory sample preparation; software for automated delivery of a sample to a sensing device for sensing; software for image analysis; computer software; application software; software downloadable from computer networks and clouds; software for use in remote monitoring of laboratory apparatus; software for remote maintenance of laboratory apparatus; software for connecting laboratory apparatus; software for use in the automation of laboratories; training software; downloadable electronic information and publications; recorded data files; downloadable course materials for training and education. (1) Scientific and technological services and research and design relating thereto; industrial analysis and research services; scientific research for chemical, biochemical, industrial, agricultural, biological, bacteriological, medical or veterinary purposes; biological, chemical, biochemical, bacteriological, DNA, RNA, protein, polynucleic acid and molecular analysis services for scientific research purposes; industrial analysis and research services relating to robots for laboratory automation, automation of analysis processes and automated dispensing of a sample to a sensing device; industrial analysis and research services relating to an integrated apparatus comprising a robot for automated sample preparation and dispensing and a sensing device, small molecules, genomes, DNA, RNA or other nucleic acids, oligosaccharides, proteins and peptides; scientific research for medical or veterinary purposes; genome, DNA, RNA and nucleic acid, oligosaccharide and polynucleic acid sequencing services; protein sequencing services; design and development of instruments and apparatus for biological, chemical, biochemical, DNA, RNA, protein and molecular analysis; laboratory testing services; DNA and polynucleic acid testing services; genome sequencing services; scientific and technological services for the analysis and evaluation of data, including scientific and medical data; scientific and technological services related to overseeing, monitoring and managing scientific and medical experiments and tests; scientific and technological services related to overseeing, monitoring and managing the analysis and evaluation of scientific and medical data; design of scientific experiments; analysis of data generated by scientific and medical experiments and tests; biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular analysis and evaluation services, being scientific and technological services; DNA and RNA and polynucleic acid and protein sequencing, analysis and evaluation services, being scientific and technological services; genome sequencing services and the analysis and evaluation of data resulting therefrom; provision of reports relating to scientific and medical experiments, the results of scientific and medical experiments and tests, the analysis and evaluation of scientific and medical data, and data generated by scientific and medical experiments and tests; scientific and medical research and development services; technical data analysis and evaluation services; electronic data storage services; application service provider (ASP) services for providing access to computer software applications installed or downloaded onto data processing apparatus, scientific apparatus, medical and veterinary apparatus, computers, mobile phones, tablet computers and handheld mobile digital electronic devices; information, advisory and consultancy services relating to the aforesaid.
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Scientific research and laboratory apparatus; scientific, optical, analytical, measuring, sensing, dosing, checking and quality control apparatus and instruments, in particular for use in laboratories for sample preparation; sensing devices for determining an analyte, in particular for single molecule sensing or determining a polynucleotide, polypeptide and polysaccharide; nanopore sensing devices; analytical apparatus and instruments for scientific, industrial, agricultural or non-medical use; pipetting devices and sampling devices, dispensers, motorized syringe dilutors, pumps and dosing apparatus for laboratory use; robots for laboratory automation and robots for the automation of analysis processes; robots for automated dispensing of a sample to a sensing device, in particular a nanopore sensing device for single molecule sensing; laboratory apparatus and instruments used for extraction and sample preparation; microplate readers, namely light absorption measuring apparatus and luminescence and fluorescence measuring apparatus; imaging devices for scientific use; microplate washers; genomics automation devices; disposable pipette tips for laboratory use; disposable containers for reagents and samples in connection with pipetting devices; microplates; disposable materials for use in laboratory apparatus; cell counting chambers for scientific use; extraction plates; extraction columns; syringes for dilutors; valves for dilutors; software for controlling laboratory apparatus and for controlling medical apparatus; software for evaluation of measurement results; software for controlling a robot for laboratory sample preparation; software for automated delivery of a sample to a sensing device for sensing; software for image analysis; computer software; application software; software downloadable from computer networks and clouds; software for use in remote monitoring of laboratory apparatus; software for remote maintenance of laboratory apparatus; software for connecting laboratory apparatus; software for use in the automation of laboratories; training software; downloadable electronic information and publications; recorded data files; downloadable course materials for training and education. Scientific and technological services and research and design relating thereto; industrial analysis and research services; scientific research for chemical, biochemical, industrial, agricultural, biological, bacteriological, medical or veterinary purposes; biological, chemical, biochemical, bacteriological, DNA, RNA, protein, polynucleic acid and molecular analysis services for scientific research purposes; industrial analysis and research services relating to robots for laboratory automation, automation of analysis processes and automated dispensing of a sample to a sensing device; industrial analysis and research services relating to an integrated apparatus comprising a robot for automated sample preparation and dispensing and a sensing device, small molecules, genomes, DNA, RNA or other nucleic acids, oligosaccharides, proteins and peptides; scientific research for medical or veterinary purposes; genome, DNA, RNA and nucleic acid, oligosaccharide and polynucleic acid sequencing services; protein sequencing services; design and development of instruments and apparatus for biological, chemical, biochemical, DNA, RNA, protein and molecular analysis; laboratory testing services; DNA and polynucleic acid testing services; genome sequencing services; scientific and technological services for the analysis and evaluation of data, including scientific and medical data; scientific and technological services related to overseeing, monitoring and managing scientific and medical experiments and tests; scientific and technological services related to overseeing, monitoring and managing the analysis and evaluation of scientific and medical data; design of scientific experiments; analysis of data generated by scientific and medical experiments and tests; biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular analysis and evaluation services, being scientific and technological services; DNA and RNA and polynucleic acid and protein sequencing, analysis and evaluation services, being scientific and technological services; genome sequencing services and the analysis and evaluation of data resulting therefrom; provision of reports relating to scientific and medical experiments, the results of scientific and medical experiments and tests, the analysis and evaluation of scientific and medical data, and data generated by scientific and medical experiments and tests; scientific and medical research and development services; technical data analysis and evaluation services; electronic data storage services; application service provider (ASP) services for providing access to computer software applications installed or downloaded onto data processing apparatus, scientific apparatus, medical and veterinary apparatus, computers, mobile phones, tablet computers and handheld mobile digital electronic devices; information, advisory and consultancy services relating to the aforesaid.
A time-ordered series of measurements of a polymer made during translocation of the polymer through a Nanopore are analysed. The measurements are dependent on the identity of k-mers in the Nanopore, a k-mer bring k polymer units of the polymer, where k is a positive integer. The method involves deriving, from the series of measurements, a feature vector of time-ordered features representing characteristics of the measurements; and determining similarity between the derived feature vector and at least one other feature vector.
A method of generating a polymer sequence using a nanopore sequencing device, the nanopore array device comprising a nanopore channel, the nanopore channel (35) formed in a membrane (32) separating two ionic solutions (33, 36), the nanopore channel connecting the ionic solutions, the method comprising: translocating a series of polymers through the nanopore channel; generating measurement signals during the translocation of each polymer through the nanopore channel; analysing a set of measurement signals from each polymer taken during the translocation of said polymer through the nanopore channel to determine a scaling factor for each polymer; applying the scaling factor to the measurement signals generated during the translocation of the polymer through the nanopore channel to determine normalised measurement signal values; and generating a polymer sequence for each polymer of the series from the corresponding normalised measurement signal values for each polymer.
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 35/62 - LeechesWorms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
42.
Formation of Array of Membranes and Apparatus Therefor
An array of membranes comprising amphipathic molecules is formed using an apparatus comprising a support defining an array of compartments. Volumes comprising polar medium are provided within respective compartments and a layer comprising apolar medium is provided extending across the openings with the volumes. Polar medium is flowed across the support to displace apolar medium and form a layer in contact with the volumes, forming membranes comprising amphipathic molecules at the interfaces. In one construction of the apparatus, the support that comprises partitions which comprise inner portions and outer portions. The inner portions define inner recesses without gaps therebetween that are capable of constraining the volumes comprising polar medium contained in neighbouring inner recesses from contacting each other. The outer portions extend outwardly from the inner portions and have gaps allowing the flow of an apolar medium across the substrate.
An array of membranes comprising amphipathic molecules is formed using an apparatus comprising a support defining an array of compartments. Volumes comprising polar medium are provided within respective compartments and a layer comprising apolar medium is provided extending across the openings with the volumes. Polar medium is flowed across the support to displace apolar medium and form a layer in contact with the volumes, forming membranes comprising amphipathic molecules at the interfaces. In one construction of the apparatus, the support that comprises partitions which comprise inner portions and outer portions. The inner portions define inner recesses without gaps therebetween that are capable of constraining the volumes comprising polar medium contained in neighbouring inner recesses from contacting each other. The outer portions extend outwardly from the inner portions and have gaps allowing the flow of an apolar medium across the substrate.
An analysis instrument comprises plural modules connected together over a data network, each module comprising an analysis apparatus operable to perform biochemical analysis of a sample. Each module comprises a control unit that controls the operation of the analysis apparatus. The control units are addressable to select an arbitrary number of modules to operate as a cluster for performing a common biochemical analysis. The control units communicate over the data network, repeatedly during the performance of the common biochemical analysis, to determine the operation of the analysis apparatus of each module required to meet the global performance targets, on the basis of measures of performance derived from the output data produced by the modules. The arrangement of the instrument as modules interacting in this manner provides a scalable analysis instrument.
Provided herein is a method of loading a motor protein onto a polynucleotide adapter. Also provided are polynucleotide adapters and kits comprising such adapters. The adapters find use in characterising analytes such as polynucleotides in methods in which the polynucleotide moves in respect of a nanopore.
The invention relates to constructs comprising a transmembrane protein pore subunit and a nucleic acid handling enzyme. The pore subunit is covalently attached to the enzyme such that both the subunit and enzyme retain their activity. The constructs can be used to generate transmembrane protein pores having a nucleic acid handling enzyme attached thereto. Such pores are particularly useful for sequencing nucleic acids. The enzyme handles the nucleic acid in such a way that the pore can detect its component nucleotides by stochastic sensing.
C07K 14/31 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
Aspects of the disclosure relate to compositions and methods for characterizing nucleic acids using a nanopore. The disclosure is based, in part, on methods for increasing follow-on sequencing of nucleic acid strands. In some embodiments, the methods comprise increasing the concentration of a tethering agent. In some embodiments, the methods comprise use of adaptors having a rigid (or stiffened) leader section. Compositions and systems including, e.g., adaptors for attachment to double-stranded poly nucleotides and/or tethering agents, which can be used in the methods are also provided.
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The invention provides a method of detecting a target polynucleotide in a sample comprising: (a) contacting the sample with a guide polynucleotide that binds to a sequence in the target polynucleotide and a polynucleotide-guided effector protein, wherein the guide polynucleotide and polynucleotide-guided effector protein form a complex with any target polynucleotide present in the sample; (b) contacting the sample with a membrane comprising a transmembrane pore: (c) applying a potential to the membrane; and (d) monitoring for the presence or absence of an effect resulting from the interaction of the complex with the transmembrane pore to determine the presence or absence of the complex, thereby detecting the target polynucleotide in the sample.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Reagents for use in automated test systems for non-medical purposes; Reagents for analytical tests for non-medical purposes; Reagents for industrial use, namely, for food testing, soil testing, water testing and air quality testing; Reagents for use in science; Reagents for laboratory use; Reagents for use in molecular biology, biotechnology, microbiology, Reagents for testing water and other liquids; Reagents for testing aqueous solutions; Reagents for biological processing prior to their use with or analysis by scientific apparatus; Reagents for use in nucleic acid characterisation and nucleic acid sequencing for non-medical purposes; Reagents for protein identification and analysis for non-medical purposes; Chemicals for use in tests to detect diseases in plant life; Reagents for formation of amphipathic membranes; Chemicals, namely, buffer solutions for scientific or research use; Nonaqueous media in the nature of solid or liquid non-aqueous solutions for scientific or research use; surfactants for use in analytical tests for scientific or research use; Silicone oils for analytical tests for scientific or research use; Silicone fluids; Enzymes for scientific and research purposes and use in analytical tests; Proteins for use in analytical tests for scientific or research use; Nucleic acid amplification reagents for veterinary, medical, medical research or forensic use; all the aforesaid other than for medical or veterinary purposes Reagents for use in automated test systems for veterinary or medical use; Reagents for use in blood grouping, molecular biology, bacteriological, biotechnology and microbiological analysis, including reagents for formation of amphipathic membranes, buffer solutions, non-aqueous solvents, all for medical or veterinary use; Reagents for medical and veterinary diagnosis; Reagents for laboratory tests for medical or veterinary purposes; Reagents for medical or veterinary use, namely, reagents, for immunoassay analysers; Reagents for medical or veterinary use, namely, reagents for testing aqueous solutions; Medical and veterinary diagnostic reagents for testing for susceptibility to allergies; Reagents for medical or veterinary use, namely, reagents for use in biological processing; Reagents for medical or veterinary use, namely, reagents for use in nucleic acid characterisation and nucleic acid sequencing; Reagents for medical or veterinary use, namely, reagents for protein identification and analysis; Reagents for medical or veterinary use, namely, reagents for formation of amphipathic membranes; buffer solutions for medical and veterinary diagnostic use; Aqueous solvents for use in tests for medical and veterinary purposes; non-aqueous solvents for use in tests for medical and veterinary purposes; Non-aqueous media in the nature of solid or liquid non-aqueous solutions for use in tests for medical and veterinary purposes; Silicone oil reagents for formation of amphipathic membranes for medical and veterinary use; Enzymes for use in tests for medical and veterinary purposes; proteins for use in tests, all for medical or veterinary purposes Apparatus and instruments for biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular analysis, namely, automated instruments for detecting the presence, properties and identity of analytes, comprising cartridges, microarrays, silicon chip based arrays, ASICs (application specific integrated circuits), and networked computer hardware and software for performing and controlling the analysis, and for processing, displaying and storing the information obtained from the analysis for scientific or research purposes; portable apparatus and instruments for biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular analysis, namely, microarrays, and silicon chip based arrays for scientific or research purposes; Apparatus and instruments for use in DNA, RNA, protein and polynucleic acid sequencing, namely, portable electronic sequencing devices for scientific and research use; Apparatus and instruments for the analysis of nucleic and polynucleic acids, namely, microarrays, and silicon chip based arrays for scientific or research purposes; Apparatus and instruments for the analysis of proteins, namely, microarrays, and silicon chip based arrays for scientific or research purposes; Apparatus and instruments for analysis of genetic information, genomic information and proteomic information, namely, portable electronic devices for analysing the results of scientific tests and experiments; Diagnostic and testing apparatus, for testing air quality, food, soil or water, not for medical purposes; Downloadable or pre-recorded software for performing and controlling the analysis, and for processing, displaying and storing the information obtained from the analysis for scientific or research purposes; Computer programs, computer hardware and data processing apparatus, all for the analysis and recordal of scientific data; Portable computer hardware and data processing apparatus, all for the analysis and recordal of scientific data; Computer peripheral devices; Instruments and apparatus for the display of information obtained from scientific equipment, namely, electronic display interfaces; Silicon chips; DNA chips; Microarray chips; Analyte detector chips for scientific or research use; biosensor chips for scientific or research use; Laboratory equipment, namely, empty cartridges for use with concentrates and solutions in solid or liquid form samples for use in biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular analysis; Batteries; Rechargeable batteries; Chargers for batteries; Computer docking stations; Apparatus for connecting and charging portable digital electronic devices; Testing apparatus incorporating chemical or biological reagents for testing air quality, food, soil or water; laboratory equipment, namely, reaction units containing chemical or biological reagents for scientific or research use; Nanopore sensing devices for scientific research and scientific testing use; parts and fittings for all the aforesaid goods Medical and veterinary apparatus for biological, chemical, biochemical, DNA, RNA, protein and molecular analysis; portable medical and veterinary apparatus for biological, chemical, biochemical, DNA, RNA, protein and molecular analysis; blood testing apparatus; diagnostic apparatus for medical or veterinary purposes; portable diagnostic apparatus for medical or veterinary purposes; testing apparatus for medical or veterinary purposes; portable testing apparatus for medical or veterinary purposes; cartridges for test samples, for medical purposes; reaction units containing chemical reagents, for medical purposes; Nanopore sensing devices for medical purposes; parts and fittings for all the aforesaid goods Scientific and technological services and research and design relating thereto, namely, consultation, research and design services relating to automated systems and instruments for direct electrical detection and analysis of molecules for use in the field of genomics, protein analysis, molecular analysis, life sciences, healthcare, security and defense; industrial analysis and research services in the field of genomics, protein analysis, molecular analysis, life sciences, healthcare, security and defense; Scientific research for chemical, biochemical, biological, bacteriological, medical or veterinary purposes; biological, chemical, biochemical, bacteriological, DNA, RNA, protein, polynucleic acid and molecular analysis services, namely, biological, chemical, biochemical, bacteriological DNA, RNA, protein, polynucleic acid and molecular analysis for scientific or research purposes; DNA and RNA and polynucleic acid sequencing services for scientific and research purposes; Protein sequencing services for scientific and research purposes; Product design and development in the fields of instruments and apparatus for biological, chemical, biochemical, DNA, RNA, protein and molecular analysis; Laboratory testing services for chemical, biochemical, biological, bacteriological, molecular analysis, medical or veterinary purposes; DNA and polynucleic acid testing services for chemical, biochemical, biological, bacteriological, molecular analysis, medical or veterinary purposes; Genome sequencing services for scientific testing, scientific research or clinical research purposes; Information and advice regarding all the aforesaid services
A sensor system comprising a sensor device, a hub component, and a tablet computer. The hub component is connectable to the sensor device, such that the hub component provides an interface for powering the sensor device and transferring data from the sensor device. The hub component further comprises a connection to a computer, such that the hub can deliver data collected from the sensor device to the computer. The height profile dimensions of the sensor device and the hub are similar to the height profile dimension of the tablet computer.
To form a layer separating two volumes of aqueous solution, there is used an apparatus comprising elements defining a chamber, the elements including a body of non-conductive material having formed therein at least one recess opening into the chamber, the recess containing an electrode. A pre-treatment coating of a hydrophobic fluid is applied to the body across the recess. Aqueous solution, having amphiphilic molecules added thereto, is flowed across the body to cover the recess so that aqueous solution is introduced into the recess from the chamber and a layer of the amphiphilic molecules forms across the recess separating a volume of aqueous solution introduced into the recess from the remaining volume of aqueous solution.
09 - Scientific and electric apparatus and instruments
Goods & Services
Downloadable software for running an e-commerce platform, namely, software that allows users to perform electronic business transaction over the Internet; cloud computing software for running an e-commerce platform, namely, software that allows users to perform electronic business transaction over the Internet; downloadable software for use in analysing, transmitting and receiving data via a global communications network; cloud computing software for use in analysing, transmitting and receiving data via a global communications network; downloadable software for developing, running and communicating with software on data processing apparatus, scientific apparatus, medical and veterinary apparatus, computers, mobile phones, tablet computers and handheld mobile digital electronic devices; computer operating software; computer operating system software; computer operating system software for data processing apparatus, scientific apparatus, medical and veterinary apparatus, computers, mobile phones, tablet computers and handheld mobile digital electronic devices; laboratory equipment, namely, micro-array chips; electronic sensing apparatus for analysing chemical, biochemical, biological, bacteriological and microbiological test samples for scientific testing purposes; scientific testing apparatus and instruments, namely, optical or electrochemical readers for biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular test samples and the measurement of ions; portable apparatus and instrument, namely, optical or electrochemical readers for biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular test samples, and measurement of ions; scientific instruments, namely, sequencing devices for use in DNA, RNA, protein and polynucleic acid sequencing; computer software and optical or electrochemical readers for the analysis of polynucleic acid sequences; scientific apparatus and instruments for the analysis of nucleic and polynucleic acids; scientific apparatus and instruments for the analysis of proteins; apparatus and instruments for analysis, not for medical use, of genetic information, genomic information and proteomic information, namely, automated instruments for detecting the presence, properties and identity of analytes, comprising cartridges, microarrays, silicon chip based arrays, ASICS (application specific integrated circuits), and networked computer hardware and software for performing and controlling the analysis, and for processing, displaying and storing the information obtained from the analysis; computer programs, computer hardware and data processing apparatus, all for the analysis and recordal of scientific data; electrowetting-on-dielectric (EWOD) devices; scientific apparatus and instruments for automating the extraction and preparation of chemical, biochemical, biological, bacteriological and microbiological test samples; data processing apparatus, devices and instruments; scientific apparatus, devices and instruments for identifying, measuring, analysing, sequencing small molecules, genomes, DNA, RNA or other nucleic acids, oligosaccharides, proteins and peptides for scientific research and scientific testing purposes; portable computer hardware and data processing apparatus, all for the analysis and recordal of scientific data; electronic display interfaces for the display of information obtained from scientific equipment; silicon chips; DNA chips; biosensor chips for scientific research and scientific testing use; cartridges namely, cartridges for test samples and cartridges for use with concentrates and solutions in solid or liquid form for use in biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular analysis, not for medical use.
09 - Scientific and electric apparatus and instruments
Goods & Services
(1) Downloadable software for running an e-commerce platform, namely, software that allows users to perform electronic business transaction over the Internet; cloud computing software for running an e-commerce platform, namely, software that allows users to perform electronic business transaction over the Internet; downloadable software for use in analysing, transmitting and receiving data via a global communications network; cloud computing software for use in analysing, transmitting and receiving data via a global communications network; downloadable software for developing, running and communicating with software on data processing apparatus, scientific apparatus, medical and veterinary apparatus, computers, mobile phones, tablet computers and handheld mobile digital electronic devices; computer operating software; computer operating system software; computer operating system software for data processing apparatus, scientific apparatus, medical and veterinary apparatus, computers, mobile phones, tablet computers and handheld mobile digital electronic devices; laboratory equipment, namely, micro-array chips; electronic sensing apparatus for analysing chemical, biochemical, biological, bacteriological and microbiological test samples for scientific testing purposes; scientific testing apparatus and instruments, namely, optical or electrochemical readers for biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular test samples and the measurement of ions; portable apparatus and instrument, namely, optical or electrochemical readers for biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular test samples, and measurement of ions; scientific instruments, namely, sequencing devices for use in DNA, RNA, protein and polynucleic acid sequencing; computer software and optical or electrochemical readers for the analysis of polynucleic acid sequences; scientific apparatus and instruments for the analysis of nucleic and polynucleic acids; scientific apparatus and instruments for the analysis of proteins; apparatus and instruments for analysis, not for medical use, of genetic information, genomic information and proteomic information, namely, automated instruments for detecting the presence, properties and identity of analytes, comprising cartridges, microarrays, silicon chip based arrays, ASICS (application specific integrated circuits), and networked computer hardware and software for performing and controlling the analysis, and for processing, displaying and storing the information obtained from the analysis; computer programs, computer hardware and data processing apparatus, all for the analysis and recordal of scientific data; electrowetting-on-dielectric (EWOD) devices; scientific apparatus and instruments for automating the extraction and preparation of chemical, biochemical, biological, bacteriological and microbiological test samples; data processing apparatus, devices and instruments; scientific apparatus, devices and instruments for identifying, measuring, analysing, sequencing small molecules, genomes, DNA, RNA or other nucleic acids, oligosaccharides, proteins and peptides for scientific research and scientific testing purposes; portable computer hardware and data processing apparatus, all for the analysis and recordal of scientific data; electronic display interfaces for the display of information obtained from scientific equipment; silicon chips; DNA chips; biosensor chips for scientific research and scientific testing use; cartridges namely, cartridges for test samples and cartridges for use with concentrates and solutions in solid or liquid form for use in biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular analysis, not for medical use.
Medical and veterinary testing and diagnostic apparatus for biological, chemical, biochemical, DNA, RNA, protein and molecular analysis; electrowetting devices for medical and veterinary purposes; apparatus and instruments for automating the extraction and preparation of test samples for medical and veterinary purposes; portable medical and veterinary testing and diagnostic apparatus for biological, chemical, biochemical, DNA, RNA, protein and molecular analysis; diagnostic apparatus for medical or veterinary purposes for pregnancy testing, and for detecting pathogenic, infectious, psychiatric, oncogenic, metabolic, genetic, respiratory, genitourinary, digestive, inflammatory, autoimmune, reproductive, hepatic, central nervous system, degenerative and cardiovascular diseases or conditions; portable diagnostic apparatus for medical or veterinary purposes for pregnancy testing, and for detecting pathogenic, infectious, psychiatric, oncogenic, metabolic, genetic, respiratory, genitourinary, digestive, inflammatory, autoimmune, reproductive, hepatic, central nervous system, degenerative and cardiovascular diseases or conditions; testing apparatus for medical or veterinary purposes for detecting pathogenic, infectious, psychiatric, oncogenic, metabolic, genetic, respiratory, genitourinary, digestive, inflammatory, autoimmune, reproductive, hepatic, central nervous system, degenerative and cardiovascular diseases or conditions; portable testing apparatus for medical or veterinary purposes for detecting pathogenic, infectious, psychiatric, oncogenic, metabolic, genetic, respiratory, genitourinary, digestive, inflammatory, autoimmune, reproductive, hepatic, central nervous system, degenerative and cardiovascular diseases or conditions; cartridges for test samples, for medical purposes; reaction units containing chemical reagents, namely, reaction systems for medical testing purposes; Nanopore sensing devices for medical and veterinary purposes
The invention relates to a new method of determining the presence, absence or characteristics of an analyte. The analyte is coupled to a membrane. The invention also relates to nucleic acid sequencing.
A relationship (30) between a target sequence of polymer units in a target polymer (10) and a reference sequence of polymer units (20) in a reference polymer such as an alignment is determined from a measured target signal (11) comprising signal levels measured by a measurement system from parts of the target polymer (10) ordered along the target sequence. The measured target signal (10) is segmented, and a sequence of target signal symbols (13) is derived, each representing a quantised signal level derived from the signal levels of a respective segment. A sequence of reference signal symbols (23) representing quantised signal levels of a sequence of modelled reference signal levels predicted by a measurement system model to be measured from the reference sequence of the reference polymer (20) by the measurement system is also used. The sequence of target signal symbols (13) is aligned with the sequence of reference signal symbols (23) to derive the relationship (30) between the target sequence and the reference sequence.
The present invention relates to novel pore monomer conjugates comprising pore monomers and functionalised partner molecules, pore complexes formed from the conjugates and their uses in analyte detection and characterisation.
Provided herein are methods of characterising a target polypeptide as it moves with respect to a nanopore. Also provided are related kits, systems and apparatuses for carrying out such methods.
A method of controlling a biochemical analysis system for analysing polymers comprising a sequence of polymer units is provided. The system is operable to take successive measurements of a polymer from a sensor element during translocation of the polymer with respect to a nanopore of the sensor element. The method comprises, when a polymer has partially translocated through the nanopore, analysing the measurements taken from the polymer during the partial translocation thereof to determine modification information in respect of a portion of the sequence of the polymer units. The polymer is classified as belonging to one of a set of classes based on the modification information; and the system is operated to reject the polymer or continue taking measurements from the polymer based on the class to which the polymer unit is classified as belonging.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical diagnostic reagents for scientific and research use; Chemical reagents for use in automated test systems for scientific and research purposes; Chemical reagents for use in analytical tests for scientific and research purposes; Chemical diagnostic reagents for industrial use; Chemical reagents for scientific use in the fields of molecular biology, biotechnology, microbiology, and bacteriology; Chemical reagents for use in nucleic acid amplification for scientific, research, and industrial purposes; Chemical reagents for use in forensic analysis for scientific and research purposes; Chemical reagents for use in blood grouping for scientific and research purposes; Reagents for use in environmental testing and environmental analysis for scientific and research purposes; Reagents for testing water and other liquids for scientific research and industrial purposes; Deoxyribonucleic acid (DNA) for use in scientific laboratory tests and experiments for scientific and research purposes; Ribonucleic acid (RNA) for scientific and research use; Peptide nucleic acids (PNAs) for use in scientific tests and experiments; Locked nucleic acids (LNAs) for use in scientific tests and experiments; Nucleic acids for use in scientific tests and experiments; Nucleic acids in the nature of oligonucleotides for scientific testing and research use; Chemicals in the nature of oligosaccharides for scientific testing and research use; Proteins in raw material form for scientific testing and research use; Peptide substrates for scientific testing and research use; Chemical preparations, enzymes, and reagents for use in genome, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and nucleic acid synthesis for scientific, research, and industrial use; Enzymes in the nature of endonucleases, polymerases, ligases, glycosylases for use in scientific tests and experiments; Chemical and organic compounds in the nature of nucleotides, pyrimidines, purines for use in scientific tests and experiments; Amino acids for use in scientific tests and experiments; Chemicals in the nature of saccharides for use in scientific tests and experiments; Reagents for use in nucleic acid characterization and nucleic acid sequencing for scientific and research purposes; Reagents for protein identification and analysis for use in scientific tests and experiments; Reagents for formation of amphipathic membranes for use in scientific tests and experiments; Buffer solutions for use in scientific tests and experiments; Chemicals in the nature of surfactants as raw materials for use in scientific tests and experiments; Polymer compositions in the nature of silicone oils for use in scientific tests and experiments; Lytic enzymes in the nature of lysozyme, lyticase, and cellulose for use in scientific tests and experiments; Enzymes in the nature of proteases for use in scientific tests and experiments; Enzymes in the nature of nucleases, namely, ribonuclease (RNase), deoxyribonuclease (DNase), and restriction enzymes for use in scientific tests and experiments; Chemical compounds in the nature of chaotropes, namely, guanidine hydrochloride and guanidinium thiocyanate for use in scientific tests and experiments; Proteins in raw form material for use in analytical tests for scientific testing and scientific research purposes; all the aforesaid other than for medical or veterinary purposes Chemical diagnostic reagents for use in automated test systems for medical and veterinary use; Chemical reagents for use in blood grouping, molecular biology, bacteriological, biotechnology and microbiological analysis, including reagents for formation of amphipathic membranes, buffer solutions, non-aqueous solvents, surfactants for medical purposes; Chemical reagents for medical and veterinary purposes; Chemical reagents for medical laboratory tests for medical or veterinary purposes; Nucleic acid amplification reagents for medical or veterinary purposes; Reagents for Immunoassay analyzers for medical and veterinary use; Chemical diagnostic reagents for testing for susceptibility to allergies for medical purposes; Reagents for use in nucleic acid characterization and nucleic acid sequencing for medical and veterinary diagnostic use; Reagents for protein identification and analysis for medical and veterinary diagnostic purposes; Reagents for formation of amphipathic membranes for medical and veterinary diagnostic use; Protein arrays for use in medical tests for medical or veterinary diagnostic purposes Downloadable software for running an e-commerce platform, namely, software that allows users to perform electronic business transaction over the Internet; cloud computing software for running an e-commerce platform, namely, software that allows users to perform electronic business transaction over the Internet; downloadable software for use in analysing, transmitting and receiving data via a global communications network; cloud computing software for use in analysing, transmitting and receiving data via a global communications network; downloadable software for developing, running and communicating with software on data processing apparatus, scientific apparatus, medical and veterinary apparatus, computers, mobile phones, tablet computers and handheld mobile digital electronic devices; computer operating software; computer operating system software; computer operating system software for data processing apparatus, scientific apparatus, medical and veterinary apparatus, computers, mobile phones, tablet computers and handheld mobile digital electronic devices; laboratory equipment, namely, micro-array chips; electronic sensing apparatus for analysing chemical, biochemical, biological, bacteriological and microbiological test samples for scientific testing purposes; scientific testing apparatus and instruments, namely, optical or electrochemical readers for biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular test samples and the measurement of ions; portable apparatus and instrument, namely, optical or electrochemical readers for biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular test samples and measurement of ions; scientific instruments, namely, sequencing devices for use in DNA, RNA, protein and polynucleic acid sequencing; computer software and optical or electrochemical readers for the analysis of polynucleic acid sequences; scientific apparatus and instruments for the analysis of nucleic and polynucleic acids; scientific apparatus and instruments for the analysis of proteins; apparatus and instruments for analysis of genetic information, genomic information and proteomic information, namely, automated instruments for detecting the presence, properties and identity of analytes, comprising cartridges, microarrays, silicon chip based arrays, ASICS (application specific integrated circuits), and networked computer hardware and software for performing and controlling the analysis, and for processing, displaying and storing the information obtained from the analysis; computer programs, computer hardware and data processing apparatus, all for the analysis and recordal of scientific data; scientific apparatus and instruments; electrowetting-on-dielectric (EWOD) devices; scientific apparatus and instruments for automating the extraction and preparation of chemical, biochemical, biological, bacteriological and microbiological test samples test samples; scientific apparatus, devices and instruments for synthesising chemical compounds, small molecules, genomes, DNA, RNA or other nucleic acids, oligosaccharides, proteins and peptides for scientific research and scientific testing purposes; data processing apparatus, devices and instruments; scientific apparatus, devices and instruments for identifying, measuring, analysing, sequencing or synthesising small molecules, genomes, DNA, RNA or other nucleic acids, oligosaccharides, proteins and peptides for scientific research and scientific testing purposes; portable computer hardware and data processing apparatus, all for the analysis and recordal of scientific data; electronic display interfaces for the display of information obtained from scientific equipment; silicon chips; DNA chips; biosensor chips for scientific research and scientific testing use; cartridges namely, cartridges for test samples and cartridges for use with concentrates and solutions in solid or liquid form for use in biological, bacteriological, chemical, biochemical, DNA, RNA, protein, polynucleic acid and molecular analysis Medical and veterinary testing and diagnostic apparatus for analyzing biological, chemical, biochemical, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), protein and molecular samples; Electrowetting devices for the analysis of body fluids for medical and veterinary purposes; Apparatus and instruments for automating the extraction and preparation of test samples for medical, and veterinary purposes; Portable medical and veterinary testing and diagnostic apparatus for analyzing biological, chemical, biochemical, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), protein and molecular samples; Diagnostic apparatus for medical or veterinary purposes for pregnancy testing, and for detecting pathogenic, infectious, psychiatric, oncogenic, metabolic, genetic, respiratory, genitourinary, digestive, inflammatory, autoimmune, reproductive, hepatic, central nervous system, degenerative and cardiovascular diseases or conditions; Portable diagnostic apparatus for medical or veterinary purposes for pregnancy testing, and for detecting pathogenic, infectious, psychiatric, oncogenic, metabolic, genetic, respiratory, genitourinary, digestive, inflammatory, autoimmune, reproductive, hepatic, central nervous system, degenerative and cardiovascular diseases or conditions; 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A nanopore device and a method of controlling a nanopore device for analysing a polymer, the nanopore device comprising at least one sensor element, the sensor element comprising a nanopore and a sensor, the method comprising: translocating a polymer through the nanopore; generating a series of measurements using the sensor as the polymer translocates through the nanopore; comparing the series of measurements to a reference data to determine a measurement of similarity; operating the nanopore device to eject the polymer from the nanopore if the measure of similarity is determined to be below a threshold value; and determining whether the polymer has been successfully ejected from the nanopore by analysing a further set of measurements taken by the sensor.
A method of amplifying a target polynucleotide, comprising: providing a template polynucleotide comprising a 5′ hairpin, a target polynucleotide and a 3′ hairpin, wherein the 5′ hairpin comprises one or more non-canonical nucleotides and contacting the template polynucleotide with a polymerase and canonical nucleotides, wherein the polymerase extends, using the canonical nucleotides, the target polynucleotide from its 3′ end to form a first extended polynucleotide comprising the 5′ hairpin at its 5′ end and the complement of the 5′ hairpin at its 3′ end, wherein the complement of the 5′ hairpin forms a 3′ hairpin; and the polymerase extends the first extended polynucleotide from its 3′ end to form a second extended polynucleotide comprising the 5′ hairpin at its 5′ end and the complement of the 5′ hairpin at its 3′ end, wherein the complement of the 5′ hairpin forms a 3′ hairpin.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligationUse of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
A method for determining the presence, absence or amount of two or more target polynucleotides in a sample comprising additional components, the method comprising:
(i) contacting the sample with a panel of two or more probes under conditions suitable for hybridisation of the target polynucleotides to the probes, wherein:
(a) each probe comprises a non-hybridisation region and a hybridisation region that specifically hybridises to one of the target polynucleotides to form a hybridised probe; and
(b) the hybridisation region of a probe of the panel comprises one or more non-natural nucleotides;
(ii) contacting the sample prepared in step (i) with a transmembrane pore through which a single stranded polynucleotide but not a double stranded polynucleotide can pass and applying a potential difference to the transmembrane pore such that the hybridised probes in the sample interact with the pore;
(iii) measuring current blockades having a duration within a defined window, wherein:
(a) the one or more non-natural nucleotides present in the hybridisation region of the probe increase or decrease the duration of the current blockade due to the probe hybridised to its target polynucleotide such that the proportion of current blockades that occur within the window due to the interaction of the hybridised probes with the pore is increased compared to when the corresponding one or more natural nucleotides are present in the hybridisation region; and
(b) each hybridised probe gives rise to a current blockade indicative of that probe; and
(iv) correlating the measured current blockades with the probes, thereby determining the presence, absence or amount of the two or more target polynucleotides in the sample.
Provided herein is a method of characterising a target polynucleotide as it moves with respect to a nanopore using a motor protein. Also provided are polynucleotide adapters and kits comprising such adapters. The methods, kits and adapters find use in characterising polynucleotides, for example in sequencing.
Devices for improved nanopore sensing are described. An example device has a structure arranged to separate an analyte reservoir and an outlet chamber. An example device has a structure arranged to separate an analyte reservoir and an outlet chamber. The structure can include an array of nanopore structures, each nanopore structure comprising a passage for fluid connection through the structure between the analyte reservoir and outlet chamber. Control terminals can be arranged for applying a control signal to alter the electrical potential difference across that nanopore structure. Some embodiments include an electronic circuit configured to detect a signal from an electrical transduction element at each nanopore structure. Additional structural features and methods of operating and making the devices are described.
G01N 33/487 - Physical analysis of biological material of liquid biological material
G01N 27/12 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon absorption of a fluidInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon reaction with a fluid
71.
METHOD OF DETERMINING THE PRESENCE OR ABSENCE OF A
TARGET ANALYTE COMPRISING USING A REPORTER
POLYNUCLEOTIDE AND A TRANSMEMBRANE PORE
The invention relates to a method of determining the presence or absence of a target analyte in a sample. The method comprises immobilising any target analyte present in the sample on a surface; contacting the surface with: (i) a first detection agent that binds specifically to the target analyte; and (ii) a reporter polynucleotide, wherein the reporter polynucleotide is bound to, or binds to, the first detection agent; and contacting a transmembrane pore with any reporter polynucleotide that has been immobilised on the surface, wherein the reporter polynucleotide is immobilised on the surface by binding of the first agent to the target analyte, and using the transmembrane pore to detect the reporter polynucleotide, thereby determining the presence or absence of the target analyte in the sample.
The invention relates to improving the movement of a target polynucleotide with respect to a transmembrane pore when the movement is controlled by a polynucleotide binding protein. The invention also relates to improved transmembrane pores and polynucleotide binding proteins
The present invention relates to novel pore monomer conjugates, pore complexes formed from the conjugates and their uses in analyte detection and characterisation.
The present invention relates to novel pore monomer conjugates, pore complexes formed from the conjugates and their uses in analyte detection and characterisation.
The present invention relates to novel pore monomer conjugates, pore complexes formed from the conjugates and their uses in analyte detection and characterisation.
Aspects of the disclosure relate to protein pore complexes and their uses in analyte detection and characterisation. The disclosure is based, in part, on nanopore complexes formed by CsgG-like pores and one or more auxiliary proteins, which form one or more channel constrictions in the nanopore complex. In some embodiments, the one or more auxiliary protein is a fusion protein. The disclosure further relates to methods for design of auxiliary proteins and production of the nanopore complexes, and for use in molecular sensing and analyte sequencing applications.
Provided herein are methods of characterising a target polypeptide as it moves with respect to a nanopore. Also provided are related kits, systems and apparatuses for carrying out such methods.
The invention relates to new methods of attaching one or more polynucleotide binding proteins to a target polynucleotide. The invention also related to new methods of characterising target polynucleotides.
The invention relates to a new method of determining in a sample the presence or absence of one or more analyte members of a group of two or more analytes. The invention therefore relates to a multiplex assay for determining the presence or absence of each analyte in a group of multiple analytes. The assay uses aptamers and transmembrane pores.
The invention relates to a method for modifying a template double stranded polynucleotide, especially for characterisation using nanopore sequencing. The method produces from the template a plurality of modified double stranded polynucleotides. These modified polynucleotides can then be characterised.
The invention relates to a new method of determining the presence, absence or one or more characteristics of multiple analytes. The invention concerns coupling a first analyte to a membrane containing a detector and investigating the first analyte using the detector. The invention also concerns coupling a second analyte to the membrane and investigating the second analyte. The first analyte is uncoupled form the membrane prior to investigating the second analyte. The invention also relates to polynucleotide sequencing.
A method of calibrating a nanopore array device is described. The nanopore array device comprises an array of nanopore channels, each nanopore channel formed in a membrane separating two ionic solutions. The nanopore channel connects the ionic solutions and the device further comprises a thermal control component for adjusting the temperature of the array of nanopore channels. The method comprises the steps of measuring signals indicative of ion flow through the nanopore channels; analysing the measurement signals and comparing to a reference value; and adjusting the thermal control component to regulate the temperature of the array of nanopore channels based upon the comparison.
Aspects of the disclosure relate to methods for extracting and/or purifying nucleic acids from biological samples. The disclosure is based, in part, on methods comprising contacting DNA in a sample with a polyhedral, rigid substrate under conditions under which the nucleic acids interact (e.g., adsorb or bind) with the substrate to form aggregates, and eluting isolated or purified DNA from the substrate after washing or other sample processing techniques. In some embodiments, methods described by the disclosure result in less sheared isolated or purified DNA relative to previously employed substrates. The resulting isolated nucleic acids may be used for sequencing, for example ultra-long read DNA sequencing.
A nanopore sensing device comprises a planar structure provided with plural fluidic passages extending between the first and second chambers. The planar structure supports nanopores in membranes across respective passages and sensor electrodes are arranged to sense a fluidic electrical potential in respective passages between the nanopores and the second chamber. The passages comprise planar fluidic resistor portions between the sensor electrode and the second chamber, the planar fluidic resistor portions extending in a planar direction of the planar structure and being configured to form a fluidic resistor.
The present invention relates to modified Dda helicases which can be used to control the movement of analytes such as polynucleotides. The modified Dda helicases are used in analyte detection and characterisation. The present invention also relates to novel protein pores and their uses in analyte detection and characterisation. The invention particularly relates to an isolated pore complex formed by a CsgG-like pore and a modified CsgF peptide, or a homologue or mutant thereof, thereby incorporating an additional channel constriction or reader head in the nanopore.
The disclosure relates to The disclosure relates to methods of attaching a nucleic acid adapter to a target polynucleotide, and methods of preparing a nucleic acid library, using a topoisomerase activated adapter. The disclosure also relates to methods of producing adapted PCR amplicons, and kits for carrying out the methods of the disclosure.
A microfluidic device comprises: a sensor provided in a sensing chamber; a liquid inlet and liquid outlet connecting to the sensor chamber for respectively passing liquid into and out of the sensing chamber and; a sample input port in fluid communication with the liquid inlet; a liquid collection channel downstream of the sensing chamber outlet; a flow path interruption between the liquid outlet and the liquid collection channel, preventing liquid from flowing into the liquid collection channel from upstream; a buffer liquid filling from the sample input port to the sensing chamber, and filling the sensing chamber and filing from the liquid outlet to the flow path interruption; an activation system operable to complete the flow path between the liquid outlet and the liquid collection channel such that the sensor remains unexposed to gas or a gas/liquid interface.
A method of calibrating a nanopore array device. The nanopore array device comprising: a common electrode, an array of sensing elements each comprising a sensing electrode and a nanopore channel, and an ionic solution in contact with the common electrode and the array of sensing electrodes, the ionic solution providing electrical communication between the common electrode and each of the array of sensing electrodes via the corresponding array of nanopore channels. The method comprises the steps of: applying a two or more test signals across the nanopore channels between the common electrode and array of sensing electrode measuring a corresponding current or voltage value associated with each sensing electrode for each test signal, determining an offset value for each sensing electrode from the measured current or voltage signals, and calculating a general offset value from the determined offset values, and applying a calibrated signal between the common electrode and sensing electrodes; wherein the calibrated signal is adjusted by the general offset value.
The invention provides a method of selectively characterising polynucleotides of a desired property, such as length, using a nanopore, based on the translocation of the polynucleotide through or across the nanopore. Kits and systems for use in such methods are also provided. The methods of the invention are particularly suitable for sequencing polynucleotides such as DNA.
The disclosure relates to novel primers, and their use to detect the presence of drug resistance mutations in a sample from a subject with suspected or confirmed Tuberculosis.
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
96.
MODIFIED NANOPORES, COMPOSITIONS COMPRISING THE SAME, AND USES THEREOF
Provided herein relate to modified or mutant forms of secretin and compositions comprising the same. In particular, the modified or mutant forms of secretin permits efficient capture and/or translocation of an analyte through the modified or mutant secretin nanopores. Methods for using unmodified secretin or the modified or mutant forms of secretin and compositions, for example, for characterizing an analyte, e.g., a target polynucleotide, are also provided.
There are provided apparatuses for controlling insertion of a membrane channel into a membrane, comprising: a first bath for holding a first liquid in contact with a first surface of the membrane; a second bath for holding a second liquid in contact with a second surface of the membrane, wherein the membrane separates the first and second liquids; a first electrode configured to contact the first liquid; a second electrode configured to contact the second liquid; and a driving circuit configured to apply a potential difference across the membrane via the first and second electrodes to promote insertion of a membrane channel into the membrane from the first liquid or the second liquid. Various configurations of the driving circuit are described that allow effective promotion of membrane channel insertion while reducing the risk of damage to the membrane. Corresponding methods are also described.
The invention relates to a process for producing a substrate comprising an aperture, which process comprises providing a substrate which comprises a solid-state membrane and a chemical surface modification on a first surface of the solid-state membrane; and forming an aperture through the chemical surface modification and the solid-state membrane. The invention also relates to a substrate comprising a chemical surface membrane and an aperture, a sensor comprising such a substrate and an apparatus comprising such a substrate.
The invention relates to an improved method for characterising a template polynucleotide. The method involves using a polymerase to prepare a modified polynucleotide which makes it easier to characterise than the template polynucleotide.
An analysis instrument comprises plural modules connected together over a data network, each module comprising an analysis apparatus operable to perform biochemical analysis of a sample. Each module comprises a control unit that controls the operation of the analysis apparatus. The control units are addressable to select an arbitrary number of modules to operate as a cluster for performing a common biochemical analysis. The control units communicate over the data network, repeatedly during the performance of the common biochemical analysis, to determine the operation of the analysis apparatus of each module required to meet the global performance targets, on the basis of measures of performance derived from the output data produced by the modules. The arrangement of the instrument as modules interacting in this manner provides a scalable analysis instrument.