Patents by Inventor Cameron Alexander Frayling
Cameron Alexander Frayling has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 11920192Abstract: A method of sequencing a nucleic acid comprising (1) generating a stream of single nucleoside triphosphates by progressive enzymatic digestion of the nucleic acid; (2) producing at least one oligonucleotide used probe by reacting, in the presence of a polymerase, at least one of the single nucleoside triphosphates with a corresponding biological probe comprising (a) a first single-stranded oligonucleotide including an exonuclease blocking-site, a restriction endonuclease recognition-site located on the 5? side of the blocking-site and including a single nucleotide capture-site e, and at least one fluorophore region and (b) a second and optionally a third single-stranded oligonucleotide each separate from the first oligonucleotide; (3) cleaving the first oligonucleotide strand of the used probe at the recognition-site with a restriction endonuclease; (4) digesting the first oligonucleotide component with an enzyme to yield fluorophores in a detectable state and (5) detecting the fluorophores released in step (Type: GrantFiled: May 15, 2018Date of Patent: March 5, 2024Assignee: LIGHTCAST DISCOVERY LTDInventors: Barnaby Balmforth, Cameron Alexander Frayling, Mark Dethlefsen
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Publication number: 20230201836Abstract: A method for manipulating a microdroplet of a reaction medium in an immiscible carrier medium with a target molecule bound to a solid support for the purposes of effecting a chemical transformation is provided. It is characterised by the steps of (a) bringing the microdroplet into contact with the solid support under conditions where the microdroplet and solid support are caused to combine, (b) allowing the reaction medium to react with the target molecule and (c) thereafter exerting a force to induce the reaction medium to become detached from the solid support and reform a microdroplet in the carrier fluid. In one embodiment the solid support is a particle, bead or the like.Type: ApplicationFiled: March 2, 2023Publication date: June 29, 2023Applicant: LIGHTCAST DISCOVERY LTDInventors: Cameron Alexander FRAYLING, Pedro CUNHA, Thomas Henry ISAAC
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Publication number: 20230129793Abstract: Provided herein are kits and devices which may be used for improved polynucleotide detection.Type: ApplicationFiled: December 23, 2020Publication date: April 27, 2023Applicant: Biofidelity LtdInventors: Cameron Alexander FRAYLING, Magdalena STOLAREK-JANUSZKIEWICZ, Barnaby William BALMFORTH
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Publication number: 20210146364Abstract: A method for manipulating a microdroplet of a reaction medium in an immiscible carrier medium with a target molecule bound to a solid support for the purposes of effecting a chemical transformation is provided. It is characterised by the steps of (a) bringing the microdroplet into contact with the solid support under conditions where the microdroplet and solid support are caused to combine, (b) allowing the reaction medium to react with the target molecule and (c) thereafter exerting a force to induce the reaction medium to become detached from the solid support and reform a microdroplet in the carrier fluid. In one embodiment the solid support is a particle, bead or the like.Type: ApplicationFiled: June 21, 2018Publication date: May 20, 2021Applicant: BASE4 INNOVATION LTDInventors: Cameron Alexander FRAYLING, Pedro CUNHA, Thomas Henry ISAAC
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Publication number: 20200283832Abstract: A method of detecting whether the nucleobase of a given nucleoside triphosphate molecule in an analyte includes a given chemical or structural modification comprising (1) reacting the analyte in the presence of a polymerase with a biological probe comprised of (a) a pair of single-stranded first oligonucleotides each comprising an exonuclease blocking-site; a restriction endonuclease recognition-site; a single nucleotide capture-site and respectively first and second fluorophore(s) in a substantially undetectable state, and (b) at least one second single-stranded oligonucleotide to create a used-probe duplex; (2) reacting the duplex with a restriction endonuclease system comprised of at least one restriction endonuclease; (3) creating another used-probe duplex; (4) digesting the first oligonucleotide elements with an enzyme having 5?-3? exonucleolytic activity to produce fluorophore(s) in a detectable state; and (5) detecting the fluorophore(s) released.Type: ApplicationFiled: October 23, 2018Publication date: September 10, 2020Applicant: BASE4 INNOVATION LTDInventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING
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Publication number: 20200277668Abstract: A first apparatus for sequencing a polynucleotide analyte is provided an apparatus for sequencing a polynucleotide analyte comprising: (a) a first zone for generating a flowing stream of single nucleotides by progressive pyrophosphorolysis of a molecule of the analyte attached to a particle and exposed to a flowing aqueous medium; (b) a second zone for generating a corresponding stream of aqueous droplets from the aqueous medium and the nucleotide stream and wherein at least some of the droplets contain a single nucleotide; and (c) a third zone for storing and/or for interrogating each droplet to reveal a property characteristic of the single nucleotide it may contain; wherein in that the first zone includes at least one chemically-modified substrate adapted to bind temporarily to a particle having at least two different regions adapted to bind respectively to the substrate and to the analyte.Type: ApplicationFiled: February 17, 2017Publication date: September 3, 2020Applicant: BASE4 INNOVATION LIMITEDInventors: Cameron Alexander FRAYLING, Thomas ISAAC, Maciej SOSNA
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Publication number: 20200216883Abstract: A method of sequencing a nucleic acid comprising the steps of (1) generating a stream of single nucleoside triphosphates; (2) producing at least one substantially double-stranded primary oligonucleotide used probe by reacting with a corresponding primary probe comprising (a) a first single-stranded oligonucleotide including a restriction endonuclease nicking-site, a single nucleotide capture site, and oligonucleotide flanking regions.Type: ApplicationFiled: September 6, 2017Publication date: July 9, 2020Applicant: Base4 Innovation LimitedInventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING
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Publication number: 20200208210Abstract: A method of sequencing a nucleic acid comprising (1) generating a stream of single nucleoside triphosphates by progressive enzymatic digestion of the nucleic acid; (2) producing at least one oligonucleotide used probe by reacting, in the presence of a polymerase, at least one of the single nucleoside triphosphates with a corresponding biological probe comprising (a) a first single-stranded oligonucleotide including an exonuclease blocking-site, a restriction endonuclease recognition-site located on the 5? side of the blocking-site and including a single nucleotide capture-site e, and at least one fluorophore region and (b) a second and optionally a third single-stranded oligonucleotide each separate from the first oligonucleotide; (3) cleaving the first oligonucleotide strand of the used probe at the recognition-site with a restriction endonuclease; (4) digesting the first oligonucleotide component with an enzyme to yield fluorophores in a detectable state and (5) detecting the fluorophores released in step (Type: ApplicationFiled: May 15, 2018Publication date: July 2, 2020Applicant: BASE4 INNOVATION LTDInventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING, Mark DETHLEFSEN
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Patent number: 10690689Abstract: A microfluidic sequencing device in which a stream of microdroplets at least some of which contain a single nucleotide base are made to undergo reaction with a capture system to capture and detect an ordered sequence of single nucleotide bases generated by progressive pyrophosphorolysis.Type: GrantFiled: October 5, 2017Date of Patent: June 23, 2020Assignees: BASE4 INNOVATION LTD, UNITED KINGDOM RESEARCH AND INNOVATIONInventors: Cameron Alexander Frayling, Barnaby Balmforth, Bruno Flavio Nogueira de Sousa Soares, Thomas Henry Isaac, Boris Breiner, Alessandra Natale, Michele Amasio, Paul Dear
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Patent number: 10551399Abstract: A method for determining the sequence of nucleotide bases in a polynucleotide analyte is provided. It is characterised by the steps of (1) generating a stream of single nucleotide bases from the analyte by pyrophosphorolysis; (2) producing captured molecules by reacting each single nucleotide base with a capture system labelled with detectable elements in an undetectable state; (3) releasing the detectable elements from each captured molecule in a detectable state and (4) detecting the detectable elements so released and determining the sequence of nucleotide bases therefrom. The method can be used advantageously in sequencers involving the use of microdroplets.Type: GrantFiled: October 5, 2017Date of Patent: February 4, 2020Assignees: BASE4 INNOVATION LTD, UNITED KINGDOM RESEARCH AND INNOVATIONInventors: Cameron Alexander Frayling, Barnaby Balmforth, Bruno Flavio Nogueira de Sousa Soares, Thomas Henry Isaac, Boris Breiner, Alessandra Natale, Michele Amasio, Paul Dear
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Patent number: 10525459Abstract: An apparatus for sequencing a nucleic acid by printing droplets at least some of which contain single nucleotides derived from the nucleic acid is provided.Type: GrantFiled: July 6, 2016Date of Patent: January 7, 2020Assignee: BASE4 INNOVATION LTDInventors: Cameron Alexander Frayling, Thomas Henry Isaac
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Patent number: 10519497Abstract: A method of analysing a single nucleoside triphosphate comprising: (1) producing at least one substantially double-stranded oligonucleotide used probe by reacting in the presence of a polymerase and a ligase the single nucleoside triphosphate with a corresponding probe system comprising (a) a first single-stranded oligonucleotide labelled with detectable elements in an undetectable state and (b) second and third single-stranded oligonucleotides capable of hybridising to complementary regions on the first oligonucleotide; (2) digesting the used probe with an enzyme having double-stranded exonucleolytic activity to yield the detectable elements in a detectable state and a single-stranded fourth oligonucleotide which is at least in part the sequence complement of the first oligonucleotide; (3) reacting the fourth oligonucleotide with another first oligonucleotide to produce a substantially double-stranded oligonucleotide product corresponding to the used probe; (4) repeating steps (2) and (3) in a cycle and (5)Type: GrantFiled: November 20, 2017Date of Patent: December 31, 2019Assignee: BASE4 INNOVATION LTDInventors: Barnaby Balmforth, Cameron Alexander Frayling
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Patent number: 10501795Abstract: A probe system comprising (a) a first single-stranded oligonucleotide labelled with detectable elements in an undetectable state, and (b) second and third single-stranded oligonucleotides capable of hybridising to complementary regions on the first oligonucleotide.Type: GrantFiled: November 9, 2017Date of Patent: December 10, 2019Assignee: BASE4 INNOVATION LTDInventors: Barnaby Balmforth, Cameron Alexander Frayling
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Patent number: 10480024Abstract: A method for determining the sequence of nucleotide bases in a polynucleotide analyte is provided. It is characterised by the steps of (1) generating a stream of single nucleotide bases from the analyte; (2) producing captured molecules by reacting each single nucleotide base with a capture system; (3) amplifying at least part of the captured molecule to produce a plurality of amplicons characteristic of the single nucleotide base; (4) labelling the amplicons with a corresponding probe having a characteristic detectable element and (5) detecting a property characteristic of the detectable element.Type: GrantFiled: April 9, 2014Date of Patent: November 19, 2019Assignees: BASE4 INNOVATION LTD, UNITED KINGDOM RESEARCH AND INNOVATIONInventors: Cameron Alexander Frayling, Barnaby Balmforth, Bruno Flavio Nogueira de Sousa Soares, Thomas Henry Isaac, Boris Breiner, Alessandra Natale, Michele Amasio, Paul Dear
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Patent number: 10369569Abstract: Disclosed is a method of identifying the contents of individual droplets in a droplet stream each droplet containing fluorophores in an initial non-fluorescing state characterized by the steps of introducing the droplets one-by-one into at least one open-ended tube to create a stack of droplets therein; activating the fluorophores within the droplets to cause them to fluoresce; releasing each droplet in the droplet stack in turn from the tube and detecting along the major axis of the tube fluorescence associated with each droplet as it emerges.Type: GrantFiled: July 14, 2017Date of Patent: August 6, 2019Assignee: BASE4 INNOVATION LTDInventors: Cameron Alexander Frayling, Thomas Henry Isaac
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Publication number: 20190226014Abstract: A method of sequencing a nucleic acid such as DNA or RNA comprising (1) generating a stream of single nucleoside triphosphates; (2) producing at least one substantially double-stranded oligonucleotide used probe by reacting the single nucleoside triphosphates with a corresponding biological probe comprising (a) a first single-stranded oligonucleotide including a restriction endonuclease nicking-site, a single nucleotide capture site and oligonucleotide regions juxtaposed either side of the nicking-site having at least one fluorophore and at least one quencher and (b) second and third single-stranded oligonucleotides; (3) nicking the first oligonucleotide strand of the used probe at the nicking-site; (4) separating the first oligonucleotide components generated in step (3) from the complementary strand of the used probe and (5) detecting the fluorophores. New biological probes and probe systems for use with the method are also described.Type: ApplicationFiled: September 4, 2017Publication date: July 25, 2019Applicant: Base4 Innovation LimitedInventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING
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Publication number: 20190203273Abstract: A method of sequencing a nucleic acid comprising the steps of (1) generating a stream of single nucleoside triphosphates; (2) producing at least one substantially double-stranded primary oligonucleotide used probe comprising (a) a first single-stranded oligonucleotide including a first restriction endonuclease nicking-site, a single nucleotide capture site, and oligonucleotide flanking regions juxtaposed either side of the capture site and (b) second and third single-stranded oligonucleotides; (3) nicking the first oligonucleotide strand of the used primary probe; (4) separating the first oligonucleotide components; (5) producing at least one substantially double-stranded secondary used probe by reacting with a corresponding secondary probe comprising (c) a complementary fourth oligonucleotide and optionally (d) a single-stranded fifth oligonucleotide; (6) nicking the fourth oligonucleotide strand of the used secondary probe to create separate fourth oligonucleotide components having fluorophores and a singleType: ApplicationFiled: September 20, 2017Publication date: July 4, 2019Applicant: Base4 Innovation LimitedInventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING
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Publication number: 20180353949Abstract: An apparatus for sequencing a nucleic acid by printing droplets at least some of which contain single nucleotides derived from the nucleic acid is provided.Type: ApplicationFiled: July 6, 2016Publication date: December 13, 2018Applicant: BASE4 INNOVATION LTDInventors: Cameron Alexander FRAYLING, Thomas Henry ISAAC
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Publication number: 20180264475Abstract: Disclosed is a method of identifying the contents of individual droplets in a droplet stream each droplet containing fluorophores in an initial non-fluorescing state characterised by the steps of introducing the droplets one-by-one into at least one open-ended tube to create a stack of droplets therein; activating the fluorophores within the droplets to cause them to fluoresce; releasing each droplet in the droplet stack in turn from the tube and detecting along the major axis of the tube fluorescence associated with each droplet as it emerges.Type: ApplicationFiled: July 14, 2017Publication date: September 20, 2018Applicant: BASE4 INNOVATION LTDInventors: Cameron Alexander FRAYLING, Thomas Henry ISAAC
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Patent number: 10000794Abstract: A method of storing a stream of droplets at least some of which comprise one or more single nucleotides and/or oligonucleotides, and a droplet fluid is provided. It is characterized by the step of introducing each droplet sequentially onto a surface of a substrate at a corresponding unique location and further characterized in that the stream of droplets is prepared by a process which includes the steps of generating an ordered stream of nucleotides from the analyte by progressive pyrophosphorolysis or exo nucleolysis and capturing each nucleotide in a corresponding droplet. The method can advantageously be used in association with microdroplet droplet sequencers and an analysis unit in which the sequence of nucleotides in a precursor polynucleotide analyte is determined using fluorescence spectroscopy. A device for carrying out the method is also described.Type: GrantFiled: June 13, 2014Date of Patent: June 19, 2018Assignee: BASE4 INNOVATION LTDInventor: Cameron Alexander Frayling