Patents by Inventor Barnaby Balmforth
Barnaby Balmforth 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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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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Patent number: 10227638Abstract: A method for characterising a DNA analyte comprised of one or more polynucleotide types characteristic of a site of nucleotide polymorphism each of which includes a target region having the formula -X-Y-Z- wherein X and Z are respectively first and second characteristic flanking oligonucleotide regions and Y is one of the variants constituting the site is provided.Type: GrantFiled: June 2, 2015Date of Patent: March 12, 2019Assignee: BASE4 INNOVATION LTD.Inventor: Barnaby Balmforth
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Publication number: 20190062816Abstract: A method of sequencing a nucleic acid comprising the steps of (1) generating a stream of single nucleotides by progressive pyrophosphorolysis; (2) producing at least one substantially double-stranded oligonucleotide used probe comprising (a) a first single-stranded oligonucleotide labelled with first and second regions of detectable element types and (b) second and third single-stranded oligonucleotides capable of hybridising to complementary regions on the first oligonucleotide; (2a) either (i) treating the used probe with a restriction endonuclease to cut the first oligonucleotide strand at the recognition site or (ii) treating the used probe with restriction endonuclease to cut the first oligonucleotide strand at the recognition site; (3) digesting the first oligonucleotide strand of the used probe with an enzyme ide; (4) reacting the fourth oligonucleotide with another first oligonucleotide to produce a substantially double-stranded oligonucleotide product corresponding to the used probe; (5) repeating thType: ApplicationFiled: February 24, 2017Publication date: February 28, 2019Applicant: BASE4 INNOVATION LIMITEDInventor: Barnaby BALMFORTH
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Patent number: 10144958Abstract: A method of determining whether a given single nucleotide is methylated or not methylated characterized by the steps of (a) contacting the single nucleotide with one or more hybridization probe types each of which in its unused form; (b) for the relevant probe type causing (i) the single nucleotide to bind to the region resistant to exonucleolytic degradation and the single-stranded region and (ii) the second oligonucleotide to bind to the single nucleotide and the single-stranded nucleotide region; (c) treating the used probe with a methylation-dependent restriction or a methylation-sensitive restriction endonuclease to cleave adjacent the region resistant to exonucleolytic degradation; and thereafter (d) treating the product of step (c) with an exonuclease or a polymerase exhibiting exonuclease activity to liberate either only first or both first and second detectable elements in a detectable state to determine if the single nucleotide is methylated or not.Type: GrantFiled: February 13, 2015Date of Patent: December 4, 2018Assignee: BASE4 INNOVATION LTD.Inventors: Barnaby Balmforth, Ana Luisa Bras dos Santos Ribeiro da Silva-Weatherley
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Patent number: 10000802Abstract: Disclosed is a method for determining the sequence of nucleotide bases in a polynucleotide analyte characterised by the steps of: a. generating a stream of droplets at least some of which contain a single nucleotide and wherein the order of single nucleotides in the droplet stream corresponds to the sequence of nucleotides in the analyte; b. introducing into each droplet a plurality of biological probe types each type (i) comprising a different detectable element in an undetectable state and (ii) being adapted to capture a different complimentary single nucleotide from which the analyte is constituted; c. causing the single nucleotide contained in the droplet to bind to its complimentary probe to create a used probe; and d. causing the detectable element to be released from the used probe in a detectable state.Type: GrantFiled: April 9, 2015Date of Patent: June 19, 2018Assignee: BASE4 INNOVATION LTDInventors: Cameron Alexander Frayling, Barnaby Balmforth, Bruno Flavio Nogueira de Sousa Soares, Thomas Henry Isaac, Boris Breiner, Alessandra Natale, Michele Amasio
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Publication number: 20180080074Abstract: A method of sequencing a nucleic acid such as DNA or RNA is provided.Type: ApplicationFiled: November 20, 2017Publication date: March 22, 2018Applicant: BASE4 INNOVATION LTDInventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING
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Publication number: 20180057872Abstract: A method of sequencing a nucleic acid such as DNA or RNA is provided.Type: ApplicationFiled: November 9, 2017Publication date: March 1, 2018Applicant: BASE4 INNOVATION LTDInventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING
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Publication number: 20180044729Abstract: 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: ApplicationFiled: October 5, 2017Publication date: February 15, 2018Applicants: BASE4 INNOVATION LTD, MEDICAL RESEARCH COUNCILInventors: 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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Publication number: 20180044728Abstract: 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: ApplicationFiled: October 5, 2017Publication date: February 15, 2018Applicants: BASE4 INNOVATION LTD, MEDICAL RESEARCH COUNCILInventors: 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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Publication number: 20180044721Abstract: A method for characterising a DNA analyte comprised of one or more polynucleotide types characteristic of a site of nucleotide polymorphism each of which includes a target region having the formula -X-Y-Z- wherein X and Z are respectively first and second characteristic flanking oligonucleotide regions and Y is one of the variants constituting the site is provided.Type: ApplicationFiled: June 2, 2015Publication date: February 15, 2018Applicant: BASE4 INNOVATION LTDInventor: Barnaby BALMFORTH
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Publication number: 20180008985Abstract: An apparatus for sequencing a polynucleotide analyte is provided and comprises; •a first zone in which a stream of single nucleotides is generated by progressive digestion of a molecule of the analyte attached to a particle located therein and exposed to a flowing aqueous medium; •a second zone in which a corresponding stream of aqueous droplets is generated from the aqueous medium and the nucleotide stream and wherein at least some of the droplets contain a single nucleotide and •a third zone in which each droplet is stored and/or interrogated to reveal a property characteristic of the single nucleotide it may contain; characterised in that the first zone comprises a microfluidic channel through which the aqueous medium flows and the location comprises a hollow seating in a wall thereof to which suction can be applied and into which the particle can be close-fitted.Type: ApplicationFiled: January 21, 2016Publication date: January 11, 2018Applicant: BASE4 INNOVATION LTDInventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING, Thomas Henry ISAAC
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Patent number: 9856528Abstract: A method of sequencing a nucleic acid involves (1) generating single nucleoside triphosphates by progressive pyrophosphorolysis of the nucleic acid; (2) producing a substantially double-stranded oligonucleotide used probe by reacting one of the single nucleoside triphosphates with a corresponding probe system comprising (a) a first single-stranded oligonucleotide labelled with characteristic detectable elements in an undetectable state and (b) second and third single-stranded oligonucleotides capable of hybridising to complementary regions on the first oligonucleotide; (3) 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 complement of the first oligonucleotide; (4) reacting the fourth oligonucleotide with another first oligonucleotide to produce a substantially double-stranded oligonucleotide product corresponding to the used probe; (5) repeatiType: GrantFiled: July 22, 2015Date of Patent: January 2, 2018Assignee: BASE4 INNOVATION LTDInventors: Barnaby Balmforth, Cameron Alexander Frayling
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Patent number: 9828631Abstract: A method for determining the sequence of nucleotide bases in a polynucleotide analyte is provided. It is characterized 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: April 9, 2014Date of Patent: November 28, 2017Assignees: BASE4 INNOVATION LTD, MEDICAL RESEARCH COUNCILInventors: 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: 9771615Abstract: Disclosed is a method for sequencing a polynucleotide analyte comprising: •a. generating a stream of droplets containing a single nucleotide wherein the order of single nucleotides in the droplet stream corresponds to the sequence of nucleotides in the analyte; •b. introducing into each droplet a plurality of biological probe types each type comprising a different label in an undetectable state and being adapted to capture a different single nucleotide; •c. causing the single nucleotide contained in the droplet to bind to its complementary probe and •d. causing the label to be released from the probe that has bound the nucleotide in a detectable state. The probe is a dumbbell shaped probe comprising fluorescent donor and quencher labels and a single nucleotide gap. After gap repair by a polymerase and a ligase, a restriction enzyme recognition site is cleaved by a restriction enzyme, followed by exonuclease digestion to release the labels.Type: GrantFiled: October 4, 2013Date of Patent: September 26, 2017Assignee: BASE4 INNOVATION LTDInventors: Cameron Alexander Frayling, Barnaby Balmforth, Bruno Flavio Nogueira de Sousa Soares, Thomas Henry Isaac, Boris Breiner, Alessandra Natale, Michele Amasio
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Publication number: 20170058331Abstract: A method of determining whether a given single nucleotide is methylated or not methylated characterised by the steps of (a) contacting the single nucleotide with one or more hybridisation probe types each of which in its unused form comprises (1) a first oligonucleotide to which is attached one or more first detectable elements in an essentially undetectable state and which further comprises (i) double- and single-stranded regions and (ii) a region resistant to exonucleolytic degradation attached to the end of the double-stranded region adjacent the single-stranded region and (2) a second single-stranded oligonucleotide to which is attached one or more second detectable elements also in an essentially undetectable state and which is adapted to be at least in part the nucleotide sequence compliment of the single-stranded region of the first oligonucleotide; (b) for the relevant probe type causing (i) the single nucleotide to bind to the region resistant to exonucleolytic degradation and the single-stranded regType: ApplicationFiled: February 13, 2015Publication date: March 2, 2017Applicant: BASE4 INNOVATION LTDInventors: Barnaby BALMFORTH, Ana Luisa Bras dos Santos Ribeiro da SILVA-WEATHERLEY
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Patent number: 9546996Abstract: The present invention provides an apparatus for analyzing the sequence of nucleotides in a nucleic acid sample, said apparatus comprising a substrate and a plurality of nanopores provided therein suitable for the passage of nucleic acid molecules therethrough; at least one sample holding chamber disposed upstream of the inlet of said nanopores, at least one detection window juxtaposed within or downstream of the outlet of each nanopore adapted to detect a property characteristic of one or more detectable elements associated with the nucleic acid as each nucleic acid molecule passes therethrough and a detector adapted to generate a data stream characteristic of the various detection events occurring in the detection window characterized in that the apparatus further comprises a means located within the sample holding chamber adapted to increase the local concentration of the nucleic acid sample adjacent the inlet of the nanopores relative to the bulk concentration thereof.Type: GrantFiled: July 9, 2013Date of Patent: January 17, 2017Assignee: BASE4 INNOVATION LTD.Inventors: Bruno Flavio Nogueira de Sousa Soares, Cameron Alexander Frayling, Barnaby Balmforth, Michele Amasio
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Publication number: 20160040223Abstract: 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: ApplicationFiled: April 9, 2014Publication date: February 11, 2016Applicants: MEDICAL RESEARCH COUNCIL, BASE4 INNOVATION LTDInventors: 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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Publication number: 20160040224Abstract: 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: ApplicationFiled: April 9, 2014Publication date: February 11, 2016Applicants: MEDICAL RESEARCH COUNCIL, BASE4 INNOVATION LTDInventors: 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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Publication number: 20150275293Abstract: Disclosed is a biological probe characterised in that it comprises a single-stranded nucleotide region the ends of which are attached to two different oligonucleotide regions wherein at least one of the oligonucleotide regions comprises detectable elements having a characteristic detection property and wherein the detectable elements are so arranged on the oligonucleotide region that the detectable property is less detectable than when the same number detectable elements are bound to a corresponding number of single nucleotides. The biological probe is especially useful for capturing single nucleotides or single-stranded nucleotides to create a used probe which can be degraded by means of a restriction enzyme and an exonuclease to generate single nucleotides carrying a detectable element in a form which can be detected.Type: ApplicationFiled: October 4, 2013Publication date: October 1, 2015Applicant: BASE4 INNOVATION LTDInventors: Cameron Alexander Frayling, Barnaby Balmforth, Bruno Flavio Nogueira de Sousa Soares, Thomas Henry Isaac, Boris Breiner, Alessandra Natale, Michele Amasio