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).

  • Patent number: 12365938
    Abstract: A method of detecting a target polynucleotide sequence in a given nucleic acid analyte characterised by the steps of: a. annealing the analyte to a single-stranded probe oligonucleotide A0 to create a first intermediate product which is at least partially double-stranded and in which the 3? end of A0 forms a double-stranded complex with the analyte target sequence; b. pyrophosphorolysing the first intermediate product with a pyrophosphorolysing enzyme in the 3?-5? direction from the 3? end of A0 to create partially digested strand A1 and the analyte; c. (i) annealing A1 to a single-stranded trigger oligonucleotide B and extending the A1 strand in the 5?-3? direction against B; or (ii) circularising A1 through ligation of its 3? and 5? ends; or (iii) ligating the 3? end of A1 to the 5? end of a ligation probe oligonucleotide C; in each case to create an oligonucleotide A2; d. priming A2 with at least one single-stranded primer oligonucleotide and creating multiple copies of A2, or a region of A2; and e.
    Type: Grant
    Filed: April 29, 2024
    Date of Patent: July 22, 2025
    Assignee: BIOFIDELITY LTD
    Inventors: Barnaby Balmforth, Cameron Frayling, Ana Luisa Bras dos Santos Ribeiro da Silva Weatherley, Magdalena Stolarek-Januszkiewicz
  • Publication number: 20250108378
    Abstract: A method of causing the cellular proliferation of one or more cell types contained within a microdroplet having an average volume in the range 4 femtolitres to 10 nanolitres and comprised of an aqueous buffer is provided. It is characterised by the step of incubating the cell(s) inside the droplets in suitable environmental conditions and thereafter detecting the number of cells inside each droplet, characterised in that the microdroplets are suspended in an immiscible carrier fluid further comprising secondary droplets having an average volume less than 25% of the average volume of the microdroplets up to and including a maximum of 4 femtolitres and wherein the volume ratio of carrier fluid to total volume of microdroplets per unit volume of the total is greater than 2:1. The method may be employed for example with microdroplets containing biological cells or with microdroplets containing single nucleoside phosphate such as are prepared in a droplet-based nucleic acid sequencer.
    Type: Application
    Filed: October 3, 2024
    Publication date: April 3, 2025
    Applicant: LIGHTCAST DISCOVERY LTD
    Inventors: Tom ISAAC, Barnaby BALMFORTH, Jasmin CONTERIO, Kerr Francis JOHNSON, Maciej SOSNA, Richard INGHAM, Gareth PODD
  • Publication number: 20240392361
    Abstract: A method of detecting a target polynucleotide sequence in a given nucleic acid analyte characterised by the steps of: a. annealing the analyte to a single-stranded probe oligonucleotide A0 to create a first intermediate product which is at least partially double-stranded and in which the 3? end of A0 forms a double-stranded complex with the analyte target sequence; b. pyrophosphorolysing the first intermediate product with a pyrophosphorolysing enzyme in the 3?-5? direction from the 3? end of A0 to create partially digested strand A1 and the analyte; c. (i) annealing A1 to a single-stranded trigger oligonucleotide B and extending the A1 strand in the 5?-3? direction against B; or (ii) circularising A1 through ligation of its 3? and 5? ends; or (iii) ligating the 3? end of A1 to the 5? end of a ligation probe oligonucleotide C; in each case to create an oligonucleotide A2; d. priming A2 with at least one single-stranded primer oligonucleotide and creating multiple copies of A2, or a region of A2; and e.
    Type: Application
    Filed: April 29, 2024
    Publication date: November 28, 2024
    Applicant: BIOFIDELITY LTD
    Inventors: Barnaby BALMFORTH, Cameron FRAYLING, Ana SILVA-WEATHERLEY, Magdalena STOLAREK-JANUSZKIEWICZ
  • Patent number: 12134098
    Abstract: A method of manipulating microdroplets having an average volume in the range 0.5 femtolitres to 10 nanolitres comprised of at least one biological component and a first aqueous medium having a water activity of aw1 of less than 1 is provided. It is characterised by the step of maintaining the microdroplets in a water-immiscible carrier fluid which further includes secondary droplets having an average volume less than 25% of the average volume of the microdroplets up to and including a maximum of 4 femtolitres and wherein the volume ratio of carrier fluid to total volume of microdroplets per unit volume of the total is greater than 2:1. The method may be employed for example with microdroplets containing biological cells or with microdroplets containing single nucleoside phosphate such as are prepared in a droplet-based nucleic acid sequencer.
    Type: Grant
    Filed: October 25, 2022
    Date of Patent: November 5, 2024
    Assignee: LIGHTCAST DISCOVERY LTD
    Inventors: Tom Isaac, Barnaby Balmforth, Jasmin Conterio, Kerr Francis Johnson, Maciej Sosna, Richard Ingham, Gareth Podd
  • Publication number: 20240271200
    Abstract: 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: Application
    Filed: January 10, 2024
    Publication date: August 15, 2024
    Applicant: LIGHTCAST DISCOVERY LTD
    Inventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING, Mark DETHLEFSEN
  • Patent number: 11999996
    Abstract: A method of detecting a target polynucleotide sequence in a given nucleic acid analyte characterised by the steps of: a. annealing the analyte to a single-stranded probe oligonucleotide A0 to create a first intermediate product which is at least partially double-stranded and in which the 3? end of A0 forms a double-stranded complex with the analyte target sequence; b. pyrophosphorolysing the first intermediate product with a pyrophosphorolysing enzyme in the 3?-5? direction from the 3? end of A0 to create partially digested strand A1 and the analyte; c. (i) annealing A1 to a single-stranded trigger oligonucleotide B and extending the A1 strand in the 5?-3? direction against B; or (ii) circularising A1 through ligation of its 3? and 5? ends; or (iii) ligating the 3? end of A1 to the 5? end of a ligation probe oligonucleotide C; in each case to create an oligonucleotide A2; d. priming A2 with at least one single-stranded primer oligonucleotide and creating multiple copies of A2, or a region of A2; and e.
    Type: Grant
    Filed: February 22, 2021
    Date of Patent: June 4, 2024
    Assignee: BIOFIDELITY LTD
    Inventors: Barnaby Balmforth, Cameron Frayling, Ana Silva-Weatherley, Magdalena Stolarek-Januszkiewicz
  • Patent number: 11920192
    Abstract: 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: Grant
    Filed: May 15, 2018
    Date of Patent: March 5, 2024
    Assignee: LIGHTCAST DISCOVERY LTD
    Inventors: Barnaby Balmforth, Cameron Alexander Frayling, Mark Dethlefsen
  • Publication number: 20240002912
    Abstract: Disclosed is a hybridisation capture method based on the pyrophosphorolysis reaction. According to the present invention, there is provided a method for increasing the ratio of a first nucleic acid sequence to second nucleic acid sequence in a sample.
    Type: Application
    Filed: March 10, 2023
    Publication date: January 4, 2024
    Inventors: Robert Osborne, Magdalena Stolarek-Januszkiewicz, Barnaby Balmforth
  • Patent number: 11634754
    Abstract: Disclosed is a hybridisation capture method based on the pyrophosphorolysis reaction. According to the present invention, there is provided a method for increasing the ratio of a first nucleic add sequence to second nucleic add sequence in a sample.
    Type: Grant
    Filed: April 15, 2022
    Date of Patent: April 25, 2023
    Inventors: Robert Osborne, Magdalena Stolarek-Januszkiewicz, Barnaby Balmforth
  • Publication number: 20230042115
    Abstract: A method of manipulating microdroplets having an average volume in the range 0.5 femtolitres to 10 nanolitres comprised of at least one biological component and a first aqueous medium having a water activity of aw1 of less than 1 is provided. It is characterised by the step of maintaining the microdroplets in a water-immiscible carrier fluid which further includes secondary droplets having an average volume less than 25% of the average volume of the microdroplets up to and including a maximum of 4 femtolitres and wherein the volume ratio of carrier fluid to total volume of microdroplets per unit volume of the total is greater than 2:1. The method may be employed for example with microdroplets containing biological cells or with microdroplets containing single nucleoside phosphate such as are prepared in a droplet-based nucleic acid sequencer.
    Type: Application
    Filed: October 25, 2022
    Publication date: February 9, 2023
    Applicant: Lightcast Discovery Ltd
    Inventors: Tom ISAAC, Barnaby BALMFORTH, Jasmin CONTERIO, Kerr Francis JOHNSON, Maciej SOSNA, Richard INGHAM, Gareth PODD
  • Patent number: 11504715
    Abstract: A method of manipulating microdroplets having an average volume in the range 0.5 femtolitres to 10 nanolitres comprised of at least one biological component and a first aqueous medium having a water activity of aw1 of less than 1 is provided. It is characterised by the step of maintaining the microdroplets in a water-immiscible carrier fluid which further includes secondary droplets having an average volume less than 25% of the average volume of the microdroplets up to and including a maximum of 4 femtolitres and wherein the volume ratio of carrier fluid to total volume of microdroplets per unit volume of the total is greater than 2:1. The method may be employed for example with microdroplets containing biological cells or with microdroplets containing single nucleoside phosphate such as are prepared in a droplet-based nucleic acid sequencer.
    Type: Grant
    Filed: February 7, 2020
    Date of Patent: November 22, 2022
    Assignee: LIGHTCAST DISCOVERY LTD
    Inventors: Tom Isaac, Barnaby Balmforth, Jasmin Conterio, Kerr Francis Johnson, Maciej Sosna, Richard Ingham, Gareth Podd
  • Publication number: 20220340957
    Abstract: Disclosed is a hybridisation capture method based on the pyrophosphorolysis reaction. According to the present invention, there is provided a method for increasing the ratio of a first nucleic acid sequence to second nucleic acid sequence in a sample.
    Type: Application
    Filed: April 15, 2022
    Publication date: October 27, 2022
    Inventors: Robert Osborne, Magdalena Stolarek-Januszkiewicz, Barnaby Balmforth
  • Patent number: 11332780
    Abstract: Methods of detecting target polynucleotide sequences may include introducing one or more nucleic acid analytes to a first reaction mixture comprising a single-stranded probe oligonucleotide A0, a pyrophosphorolysing enzyme, and a ligase. The analyte may anneal to the single-stranded probe oligonucleotide A0 to create a first intermediate product which is at least partially double-stranded, where the 3? end of A0 forms a double-stranded complex with the analyte and where A0 is pyrophosphorylsed in the 3?-5? direction from the 3? end to create at least a partially digested strand A1. A1 may undergo ligation to form oligonucleotide A2. The methods may also include detecting a signal derived from the formed oligonucleotides, and inferring therefrom the presence or absence of the target polynucleotide sequence in the analyte.
    Type: Grant
    Filed: June 25, 2020
    Date of Patent: May 17, 2022
    Assignee: BIOFIDELITY LTD
    Inventors: Barnaby Balmforth, Magdalena Stolarek-Januszkiewicz, Ana Silva-Weatherley, Paulina Powalowska
  • Publication number: 20220088606
    Abstract: A method of manipulating microdroplets having an average volume in the range 0.5 femtolitres to 10 nanolitres comprised of at least one biological component and a first aqueous medium having a water activity of aw1 of less than 1 is provided. It is characterised by the step of maintaining the microdroplets in a water-immiscible carrier fluid which further includes secondary droplets having an average volume less than 25% of the average volume of the microdroplets up to and including a maximum of 4 femtolitres and wherein the volume ratio of carrier fluid to total volume of microdroplets per unit volume of the total is greater than 2:1. The method may be employed for example with microdroplets containing biological cells or with microdroplets containing single nucleoside phosphate such as are prepared in a droplet-based nucleic acid sequencer.
    Type: Application
    Filed: February 7, 2020
    Publication date: March 24, 2022
    Applicant: Lightcast Discovery Ltd
    Inventors: Tom ISAAC, Barnaby BALMFORTH, Jasmin CONTERIO, Kerr Francis JOHNSON, Maciej SOSNA, Richard INGHAM, Gareth PODD
  • Publication number: 20210189478
    Abstract: Methods of detecting target polynucleotide sequences may include introducing one or more nucleic acid analytes to a first reaction mixture comprising a single-stranded probe oligonucleotide A0, a pyrophosphorolysing enzyme, and a ligase. The analyte may anneal to the single-stranded probe oligonucleotide A0 to create a first intermediate product which is at least partially double-stranded, where the 3? end of A0 forms a double-stranded complex with the analyte and where A0 is pyrophosphorylsed in the 3?-5? direction from the 3? end to create at least a partially digested strand A1. A1 may undergo ligation to form oligonucleotide A2. The methods may also include detecting a signal derived from the formed oligonucleotides, and inferring therefrom the presence or absence of the target polynucleotide sequence in the analyte.
    Type: Application
    Filed: June 25, 2020
    Publication date: June 24, 2021
    Applicant: BIOFIDELITY LTD
    Inventors: Barnaby BALMFORTH, Magdalena STOLAREK-JANUSZKIEWICZ, Ana SILVA-WEATHERLEY, Paulina POWALOWSKA
  • Publication number: 20210180122
    Abstract: A method of detecting a target polynucleotide sequence in a given nucleic acid analyte characterised by the steps of: a. annealing the analyte to a single-stranded probe oligonucleotide A0 to create a first intermediate product which is at least partially double-stranded and in which the 3? end of A0 forms a double-stranded complex with the analyte target sequence; b. pyrophosphorolysing the first intermediate product with a pyrophosphorolysing enzyme in the 3?-5? direction from the 3? end of A0 to create partially digested strand A1 and the analyte; c. (i) annealing A1 to a single-stranded trigger oligonucleotide B and extending the A1 strand in the 5?-3? direction against B; or (ii) circularising A1 through ligation of its 3? and 5? ends; or (iii) ligating the 3? end of A1 to the 5? end of a ligation probe oligonucleotide C; in each case to create an oligonucleotide A2; d. priming A2 with at least one single-stranded primer oligonucleotide and creating multiple copies of A2, or a region of A2; and e.
    Type: Application
    Filed: February 22, 2021
    Publication date: June 17, 2021
    Applicant: BIOFIDELITY LTD
    Inventors: Barnaby BALMFORTH, Cameron FRAYLING, Ana SILVA-WEATHERLEY, Magdalena STOLAREK-JANUSZKIEWICZ
  • Patent number: 10961569
    Abstract: A method of detecting a target polynucleotide sequence in a given nucleic acid analyte characterised by the steps of: a. annealing the analyte to a single-stranded probe oligonucleotide A0 to create a first intermediate product which is at least partially double-stranded and in which the 3? end of A0 forms a double-stranded complex with the analyte target sequence; b. pyrophosphorolysing the first intermediate product with a pyrophosphorolysing enzyme in the 3?-5? direction from the 3? end of A0 to create partially digested strand A1 and the analyte; c. (i) annealing A1 to a single-stranded trigger oligonucleotide B and extending the A1 strand in the 5?-3? direction against B; or (ii) circularising A1 through ligation of its 3? and 5? ends; or (iii) ligating the 3? end of A1 to the 5? end of a ligation probe oligonucleotide C; in each case to create an oligonucleotide A2; d. priming A2 with at least one single-stranded primer oligonucleotide and creating multiple copies of A2, or a region of A2; and e.
    Type: Grant
    Filed: June 16, 2020
    Date of Patent: March 30, 2021
    Assignee: BIOFIDELITY LTD
    Inventors: Barnaby Balmforth, Cameron Frayling, Ana Silva-Weatherley, Magdalena Stolarek-Januszkiewicz
  • Publication number: 20200354786
    Abstract: A method of detecting a target polynucleotide sequence in a given nucleic acid analyte characterised by the steps of: a. annealing the analyte to a single-stranded probe oligonucleotide A0 to create a first intermediate product which is at least partially double-stranded and in which the 3? end of A0 forms a double-stranded complex with the analyte target sequence; b. pyrophosphorolysing the first intermediate product with a pyrophosphorolysing enzyme in the 3?-5? direction from the 3? end of A0 to create partially digested strand A1 and the analyte; c. (i) annealing A1 to a single-stranded trigger oligonucleotide B and extending the A1 strand in the 5?-3? direction against B; or (ii) circularising A1 through ligation of its 3? and 5? ends; or (iii) ligating the 3? end of A1 to the 5? end of a ligation probe oligonucleotide C; in each case to create an oligonucleotide A2; d. priming A2 with at least one single-stranded primer oligonucleotide and creating multiple copies of A2, or a region of A2; and e.
    Type: Application
    Filed: June 16, 2020
    Publication date: November 12, 2020
    Inventors: Barnaby BALMFORTH, Cameron Frayling, Ana SILVA-WEATHERLEY, Magdalena STOLAREK-JANUSZKIEWICZ
  • Publication number: 20200283832
    Abstract: 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: Application
    Filed: October 23, 2018
    Publication date: September 10, 2020
    Applicant: BASE4 INNOVATION LTD
    Inventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING
  • Publication number: 20200216883
    Abstract: 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: Application
    Filed: September 6, 2017
    Publication date: July 9, 2020
    Applicant: Base4 Innovation Limited
    Inventors: Barnaby BALMFORTH, Cameron Alexander FRAYLING