WO2023163600A1 - Dispositif intraruminal et procédé - Google Patents

Dispositif intraruminal et procédé Download PDF

Info

Publication number
WO2023163600A1
WO2023163600A1 PCT/NZ2023/050019 NZ2023050019W WO2023163600A1 WO 2023163600 A1 WO2023163600 A1 WO 2023163600A1 NZ 2023050019 W NZ2023050019 W NZ 2023050019W WO 2023163600 A1 WO2023163600 A1 WO 2023163600A1
Authority
WO
WIPO (PCT)
Prior art keywords
ruminal
culture
signal
factor
light
Prior art date
Application number
PCT/NZ2023/050019
Other languages
English (en)
Inventor
Stephen John Sowerby
Peter Francis Fennessy
Darcy Marc Schack
Bruce Thomas PARTRIDGE
Original Assignee
Methane Mitigation Ventures Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Methane Mitigation Ventures Limited filed Critical Methane Mitigation Ventures Limited
Publication of WO2023163600A1 publication Critical patent/WO2023163600A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/0624—Apparatus adapted for a specific treatment for eliminating microbes, germs, bacteria on or in the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K11/00—Marking of animals
    • A01K11/006—Automatic identification systems for animals, e.g. electronic devices, transponders for animals
    • A01K11/007—Boluses
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K29/00—Other apparatus for animal husbandry
    • A01K29/005—Monitoring or measuring activity, e.g. detecting heat or mating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/01—Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/07—Endoradiosondes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
    • A61B5/4222—Evaluating particular parts, e.g. particular organs
    • A61B5/4238—Evaluating particular parts, e.g. particular organs stomach
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6861—Capsules, e.g. for swallowing or implanting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D1/00—Surgical instruments for veterinary use
    • A61D1/14—Devices for degassing animals' stomachs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D99/00—Subject matter not provided for in other groups of this subclass
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0068—Rumen, e.g. rumen bolus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • A61N5/0603—Apparatus for use inside the body for treatment of body cavities
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/067—Radiation therapy using light using laser light
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/22—Transparent or translucent parts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M31/00—Means for providing, directing, scattering or concentrating light
    • C12M31/08—Means for providing, directing, scattering or concentrating light by conducting or reflecting elements located inside the reactor or in its structure
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/06—Means for regulation, monitoring, measurement or control, e.g. flow regulation of illumination
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/46—Means for regulation, monitoring, measurement or control, e.g. flow regulation of cellular or enzymatic activity or functionality, e.g. cell viability
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00—Evaluating a particular growth phase or type of persons or animals
    • A61B2503/40—Animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14507—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • A61N5/0603—Apparatus for use inside the body for treatment of body cavities
    • A61N2005/0609—Stomach and/or esophagus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0626—Monitoring, verifying, controlling systems and methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/065—Light sources therefor
    • A61N2005/0651—Diodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0662—Visible light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0662—Visible light
    • A61N2005/0663—Coloured light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0664—Details
    • A61N2005/0667—Filters

Definitions

  • the present invention relates to reducing and monitoring methane emissions from ruminant and pseudo-ruminant animals, particularly farmed ruminant animals.
  • Methanogenic archaebacteria typically present in the foregut organs of ruminant and pseudo-ruminant animals produce methane gas by a process of methanogenesis.
  • the methane is emitted from the animal by eructation (belching), which is difficult to monitor, and has a significant environmental impact as methane is a potent greenhouse gas.
  • Reducing methane emissions and monitoring methane emissions from ruminant and pseudo-ruminant animals can reduce greenhouse gases, as greenhouse gases are known to contribute to climate change.
  • the present disclosure provides devices and methods to reduce and monitor methanogenesis, methanogens, and the emission of methane into the environment.
  • a device comprising a housing incorporating at least one optically transparent portion at least one light source with an illumination wavelength in the range of about 420 nm to about 470 nm means for controlling the intensity of illumination from the light source for at least one interval of time.
  • said device further comprises at least one sensor.
  • said device is selected from a capsule, a bolus, an electronic bolus, a probe, an electronic probe.
  • said housing is less than 200 mm long, less than 150 mm long, less than 100 mm long or less than 50 mm long, and less than 75 mm wide, less than 50 mm wide, and less than 25 mm wide.
  • said optically transparent portion is selected from the group comprising, window, lens, half-ball lens, prism, dove prism,
  • said optically transparent portion is selected from the group comprising glass, silica glass, borosilicate, polymer, polymethylmethacrylate, polycarbonate.
  • said light source is selected from the group comprising, light emitting diode (LED), laser, laser diode, lamp, filter, interference filter, bandpass filter, notch filter, diffraction grating, prism, fibre-optic, light with a wavelength of about 360 nm to 480 nm, light with a wavelength of about 420 nm, light with a wavelength of about 470 nm
  • said sensor is selected from the group comprising, light sensor, photodiode, photo resistor, charge coupled device (CCD), complementary metal oxide silicon (CMOS), ion-sensitive field-effect transistor (ISFET), filter, interference filter, bandpass filter, notch filter, diffraction grating, prism, fibre-optic, temperature sensor, motion sensor, orientation sensor, electrochemical sensor, pH sensor, oxidation reduction sensor, hydrogen sensor, , oxygen sensor, carbon dioxide sensor.
  • a method for inactivating co-factor F420 in a ruminal culture comprising the step of administering a device as described herein to said ruminal culture wherein co-factor F420 is illuminated and photobleached.
  • ruminal culture is selected from the group comprising, the interior and contents of foregut organs of live animals from the suborder Ruminantia (ruminants) including domesticated animals, cattle, goats, sheep, bison, buffalo, yaks, deer, antelope, the interior and contents of the pseudo-rumen of live animals from the suborder Tylopoda (pseudo-ruminants) including camels, alpacas and lamas, the interior and contents of foregut models including, mechanical rumens, artificial rumens, rumen simulation technique (RUSITEC), and bioreactors, microorganisms including archaea, methanogens, bacteria, mycobacterium, fungi, viruses and protozoa, organic and inorganic rumen materials including fluids, liquids and gases, dissolved gas, hydrogen (H), molecular hydrogen (H2), ionic hydrogen (H + ), oxygen (O), molecular oxygen (O2), carbon dioxide (CO2), nitrogen (N
  • a method of reducing methanogenesis in a ruminal culture comprising the step of administering a device as described herein to said ruminal culture wherein co-factor F420 is illuminated and photobleached.
  • a method of reducing methanogens in a ruminal culture comprising the step of administering a device as described herein to said ruminal culture wherein co-factor F420 is illuminated and photobleached.
  • methanogens is organisms selected from the group comprising, archaea, ruminal archaea, the order Methanomicrobiales, the order Methanobacteriales, the order Methanosarcinales, the genus Methanobrevibacter, the genus Methanosphaera, the genus Methanomicrobium, the genus Methanobacterium, the genus Methanosarcina.
  • a method of reducing emitted methane from a ruminal culture comprising the step of administering a device as described herein to said ruminal culture wherein co-factor F420 is illuminated and photobleached.
  • a method of reducing emitted methane from a ruminal culture treated with a methanogen/methanogenesis inhibitor comprising the step of administering a device as described herein to said ruminal culture wherein co-factor F420 is illuminated and photobleached.
  • a method for monitoring co-factor F420 in a ruminal culture comprising the step of administering a device as described herein to said ruminal culture wherein said ruminal culture is illuminated and co-factor F420 detected.
  • said ruminal culture is illuminated by light of wavelength selected from the group comprising, the fluorescence excitation of co-factor F420, the fluorescence excitation of oxidized co-factor F420, about 420 nm, the fluorescence emission of cofactor F420, the fluorescence emission of oxidized co-factor F420, about 470 nm, about 405 nm to about 490 nm.
  • co-factor F420 is detected by detecting a signal from said ruminal culture selected from the group comprising, light signal, fluorescence signal, optical sensor signal, photodiode signal, CCD signal, spectrophotometer signal, optically filtered signal, processed signal, signal from illumination at about 420 nm, signal from illumination at about 470 nm, signal generated by a mathematical operation of the signal from illumination at about 420 nm and the signal from illumination at about 470 nm, signal generated by a mathematical subtraction of the signal from illumination at about 470 nm from the signal from illumination at about 420 nm.
  • a signal from said ruminal culture selected from the group comprising, light signal, fluorescence signal, optical sensor signal, photodiode signal, CCD signal, spectrophotometer signal, optically filtered signal, processed signal, signal from illumination at about 420 nm, signal from illumination at about 470 nm, signal generated by a mathematical operation of the signal from illumination at about 420 nm and the signal from
  • a method for monitoring methanogenesis in a ruminal culture comprising the step of administering a device as described herein to said ruminal culture wherein said ruminal culture is illuminated and co-factor F420 detected.
  • a method for monitoring methanogens in a ruminal culture comprising the step of administering a device as described herein to said ruminal culture wherein said ruminal culture is illuminated and co-factor F420 detected.
  • a method for monitoring emitted methane from a ruminal culture comprising the step of administering a device as described herein to said ruminal culture wherein said ruminal culture is illuminated and co-factor F420 detected.
  • a method for monitoring a ruminal culture treated with a methanogen/methanogenesis inhibitor comprising the step of administering a device as described herein to said ruminal culture wherein said ruminal culture is illuminated and co-factor F420 detected.
  • methanogen/methanogenesis inhibitor is selected from the group comprising, antibiotic, organohalogen, haloform, chloroform, bromoform, iodoform, seaweed, Asparagopsis sp., Asparagopsis extract, Asparagopsis matter, alliin, iso-alliin, allicin, MootralTM, garlic extract, garlic matter, 3-Nitrooxypropanol (3-NOP), BovaerTM, fluid, solid, lozenge, bolus, device, electronic bolus, light, biocidal light, flavin, co-factor F420, photobleaching, 420 nm.
  • a method of validating the treatment of a ruminal culture treated with methanogen and/or methanogenesis inhibitor comprising the step of administering a device as described herein to said ruminal culture wherein said ruminal culture is illuminated and co-factor F420 detected.
  • Figure 1 depicts an overview of one example of a device.
  • Figure 2 depicts an overview of another example of a device.
  • Figure 3 depicts an overview of one example of a device of FIG. 1 administered to an animal.
  • Figure 4 shows an example of an algorithm to use a device of any of FIGS. 1 and 3 administered to an animal.
  • Figure 5 shows one example of a manufactured device.
  • Figure 6 depicts one example of an electronic circuit board of a manufactured device.
  • Figure 7 shows one example of an algorithm to control a device.
  • Figure 8 shows a graph of sensing data from one example of the device of any of FIGS. 1-7.
  • Figure 9 shows a graph of reducing methane from one example of the device of any of FIGS. 1-7.
  • a diverse assemblage of microorganisms including archaea, bacteria, fungi, viruses and protozoa comprises a ruminal culture that ferments feed materials and produces volatile fatty acids (VFAs) for animal growth.
  • VFAs volatile fatty acids
  • An undesirable by-product of the ruminal culture is the synthesis of methane by hydrogenotrophic methanogenic archaea (methanogens) in a process called methanogenesis.
  • methane emissions from ruminant and pseudo-ruminant animals are difficult to monitor and are widely understood to represent lost VFAs and lost animal productivity.
  • methane is a potent greenhouse gas that traps heat in the atmosphere and contributes to climate change and has a significant environmental impact.
  • methanogens produce methane (CF ) from carbon dioxide (CO2) and hydrogen (H2) in enzyme-catalysed biochemical reactions that are dependent on the molecule called co-factor F420 or F420.
  • F420 should be understood as meaning a 5- deazaflavin molecule specifically comprised of the chromophore headgroup 7,8- didemethyl-8-hydroxy-5-deazariboflavin (sometimes called 8-HDF, FO, or FO), which is bonded through its ribityl side chain to an oligo-glutamate via a lactate moiety and a phosphodiester linkage, which is sometimes called "coenzyme F420", or”F420", which exists in protonated and deprotonated forms and functions as a hydride transfer agent in biochemical reactions. See Grinter, R. and Greening, C., 2021. Cofactor F420, an expanded view of its distribution, biosynthesis and roles in bacteria and archaea. FEMS Microbiology Reviews, 45(5), p.fuab021.
  • F420 is a 5-deazaflavin molecule comprised of the chromophore headgroup 7,8- didemethyl-8-hydroxy-5-deazariboflavin (sometimes called 8-HDF, F0, or FO).
  • F420 has optical absorbance maxima at 260 nm and 420 nm, and a fluorescence emission maximum at 470 nm, which is mediated by a n ⁇ n transition upon photon absorption.
  • the reduced form of F420 has an absorbance maximum at 320 nm with a lower molar absorption coefficient and no associated fluorescence.
  • F420 electrochemical and photochemical properties of F420 and the hydride transfer functionality of F420 is entirely dependent on the precise chemical structures of the oxidized and reduced forms of F420.
  • F420 is present in levels of up to 400 mg per kg and the ratio of reduced to oxidized forms is maintained at approximately 1.10. (See Grinter, R. and Greening, C., 2021.
  • Cofactor F420 an expanded view of its distribution, biosynthesis and roles in bacteria and archaea. FEMS Microbiology Reviews, 45(5), p.fuab021.)
  • the present disclosure in broad terms relates to inactivating F420 and monitoring F420 in ruminal cultures as means to reduce methane and monitor methane production in ruminal cultures.
  • the present disclosure is devised for in vivo use in the foregut organs of live ruminant and pseudo-ruminant animals, and in vitro models of the ruminant or pseudo-ruminant foregut, for reducing and monitoring the production of methane, a potent greenhouse gas.
  • rumen should be understood as meaning the foregut organs of ruminant and pseudo-ruminant animals, where the fermentation of consumed feed predominantly occurs.
  • the first and largest stomach chamber or alternatively a combination of the first and second stomach chambers, in the alimentary canal of animals from the suborder Ruminantia (ruminants) including domesticated animals, cattle, goats, sheep, bison, buffalo, yaks, deer, and the first stomach chamber in the alimentary canal of animals from the suborder Tylopoda (pseudo-ruminants) including antelope, camels, alpacas and lamas.
  • Ruminantia Ruminants
  • Tylopoda pseudo-ruminants
  • ruminal culture should be understood as meaning the interior and contents of rumen including, microorganisms for example archaea, methanogens, bacteria, fungi, viruses and protozoa; organic and inorganic materials for example fluids, liquids and gases, dissolved gas, hydrogen (H), molecular hydrogen (H2), ionic hydrogen (H + ), oxygen (O), molecular oxygen (O2), carbon dioxide (CO2), nitrogen (N), molecular nitrogen (N2), hydrogen sulfide (H2S), methane (CH4), water, mineral salts, ions, bicarbonate, buffers; biomolecules for example proteins, nucleic acids, carbohydrates, fatty acids, volatile fatty acids, volatile fatty acid, acetic acid, acetate, propionic acid, propionate, butyric acid, butyrate, isobutyrate, isobutyric acid, valerate, valeric acid, co-factors, flavin co-factors, co-factor F
  • ruminal culture should also be understood as meaning the interior and contents of in vitro models of foregut fermentation devised to investigate various aspects of ruminant and pseudo-ruminant gastrointestinal biology, feed performance, methanogenesis, methanogenesis inhibition, and energy production including for example, mechanical rumens, artificial rumens, rumen simulation technique (RUSITEC), and bioreactors etc.
  • a model of foregut fermentation requires one or more of the contents of live animal rumens, which can be sourced from the group comprising, rumen materials, faecal materials, animals, ruminant animals, pseudo-ruminant animals, live animals, canulated animals, slaughtered animals, cultures, microbial cultures, chemicals, and biochemicals.
  • the administration of contents to the model of foregut fermentation can occur in one or more steps separated by one or more intervals of time.
  • the present disclosure is based on the unexpected finding that illuminating a ruminal culture with specific wavelengths of light to cause F420 fluorescence reduces methanogenesis. Monitoring the fluorescence emissions in an illuminated ruminal culture is indicative of changes in methanogenesis and methane emitted from said ruminal culture.
  • An object of the present disclosure is to inactivate F420 in a ruminal culture by a photochemical mechanism that causes potentially irreversible change to the chemical structure of F420 thereby eliminating or reducing its ability to function as a hydride transfer agent.
  • F420 inactivator should be understood as meaning any device or device component, that provides a photochemical process, that prevents F420 from acting as a hydride transfer agent in biochemical reactions, hereinafter collectively referred to as "F420 inactivator”.
  • F420 monitor should be understood as meaning any device or device component that monitors F420.
  • Figure 1 depicts a schematic of a device 100.
  • the device 100 includes a housing 101 that is configured to be in contact with a ruminal culture 102.
  • the housing 101 incorporates at least one optically transparent portion 103, which has a surface 104 contacting the inside of the device 100, a body of transparent material 105, and an exterior surface 106 contacting the ruminal culture 102.
  • F420 107 In the ruminal culture 102 is depicted F420 107 that is proximal to and in optical communication with the exterior surface of the optically transparent portion 106.
  • At least one light source 108 of light of at least one wavelength Ai schematically depicted as a dashed arrow 109 indicating one general direction, which light source 108 is positioned to illuminate and enter the interior surface of the optically transparent portion 104, transmits through the body of the optically transparent portion 103 and emerges from the exterior surface of the optically transparent portion 106.
  • the light source 108 and optically transparent portion 103 are configured to illuminate the ruminal culture 102 contacting the exterior surface of the of the optically transparent portion 106 and F420 107 present in the ruminal culture 102 that is proximal to the exterior surface of the optically transparent portion 106.
  • the transmission of light can be substantially attenuated by light scattering due to particles, and by light absorption due to chromophores, such that the ruminal culture 102 is effectively opaque thereby limiting conventional optical measurements that rely on transmission. It is a feature of the disclosure to illuminate the layer of ruminal culture 102 proximal the exterior surface of the optically transparent portion 106.
  • the optically transparent portion 103 is schematically depicted as a half-ball lens, also known as a hemispherical lens, and has a planar surface 104 contacting the inside of the device 100, a body of transparent material 105, and a curved exterior surface 106 contacting the ruminal culture 102.
  • the half-ball lens provides a large exterior surface 106 contacting the ruminal culture 102.
  • the optically transparent portion 103 is selected from the group comprising, window, lens, trapezoid lens, dove lens.
  • an optical detector 110 is incorporated inside the housing 101 that is illuminated by light of at least one wavelength A2, schematically depicted as a dashed arrow 111 indicating one general direction, that originates in the ruminal sample 102 in contact with the exterior surface of the optically transparent portion 106, and enters that exterior surface of the optically transparent portion 106, and is transmitted through the body of the optically transparent portion 103, and emerges from the interior surface of the optically transparent portion 104.
  • the optical detector 110 and the optically transparent portion 103 are configured to detect light from the ruminal culture 102 contacting the exterior surface of the optically transparent portion 106.
  • an optical detector 110 is not required for the function of F420 inactivator.
  • wavelengths of light from the light source 108 and its modes of operation are selected to cause F420 107 in the ruminal culture 102 to fluoresce and to photo-bleach and become inactivated.
  • wavelengths of light from the light source 108 and its modes of operation are selected for sensing a F420 107 in the ruminal culture 102 by causing it to fluoresce wherein a portion of the emitted fluorescence is detected by the optical detector 110.
  • the wavelength selected to cause F420 107 to fluoresce is optimally at about the absorption maximum of F420 in its oxidised form which is about 420 nm. It will be appreciated that the absorption maximum is not the only wavelength to cause F420 to fluoresce and any wavelength in the range of about 400 nm to about 460 nm illuminating F420 107 will cause some amount of fluorescence and some amount to photobleaching.
  • the light emitted from the ruminal culture 102 may be caused by fluorescence from the ruminal culture 102 proximal to the exterior surface of the optically transparent portion 106.
  • the fluorescence may be due to excitation of a fluorophore in the ruminal culture 102 by the light source 108, or it may be from Fluorescence Resonance Energy Transfer (FRET), a phenomenon where excitation energy is transferred from one fluorophore to another fluorophore causing fluorescence.
  • FRET Fluorescence Resonance Energy Transfer
  • the ruminal culture 102 may have diverse sources of fluorescence and bioluminescence due to the diversity of microorganisms, the diversity of feed materials, and the diversity of fluorophores in the ruminal culture 102. These diverse sources of fluorescence and bioluminescence may comprise a plurality of wavelengths.
  • the light emitted from F420 107 in the ruminal culture 102 and proximal to the exterior surface of the optically transparent portion 106 and caused to fluoresce, will have wavelengths about the excitation maximum of F420, which is about 470 nm. It is noted that the excitation maximum is not the only wavelength emitted from F420 caused to fluoresce and a plurality of wavelengths in the range of about 430 nm to about 490 nm can be emitted from F420 107 caused to fluoresce.
  • the device 100 depicted in Figure 1 may include at least one additional light source 112 of at least one wavelength As, schematically depicted as a dashed arrow 113 indicating one general direction, that can be of the same wavelength as the light source 108 or a different wavelength.
  • the wavelength of the additional light source 112 can be about 470 nm, which is the same wavelength as the fluorescence emitted by F420 107 and can be used to provide a reference for comparison with the fluorescence emission of F420 107.
  • any ultraviolet, visible, or infra-red wavelength may be selected to illuminate the ruminal culture 102.
  • dashed arrow 109 representing the illumination of the ruminal culture 102 from the light source 108
  • dashed arrow 111 representing the illumination of the optical sensor 110 from the ruminal culture 102
  • the light source 108 and the additional light source 112 are light emitting diodes (LEDs), which have the advantage that they are physically robust, have long lifetimes, and are available in many different shapes and emission wavelengths.
  • the light source 108 and the additional light source 112 are selected from the group comprising, lamp, laser, laser diode.
  • the light source 108 and the additional light source 112 are external to the housing and piped into the housing by a light conduit such as a fibre optic or fibre optic bundle.
  • the light source 108 and/or the additional light source 112 emits a plurality of wavelengths of light. In some examples a relatively pure light source is desirable and so the light source 108 and the additional light source 112 can be adjusted to produce a narrow bandwidth of light using optical elements from the group comprising, filter, bandpass filter, diffraction grating, prism.
  • the device 100 further includes (or is in operative communication with) control circuitry 114 that is used to control the operation of the of the light source 108, the additional light source 112, the optical sensor 110 and any other component and power circuitry 115 that provides power to the device 100.
  • control circuitry 114 and/or power circuity 115 can include and/or utilise power supplies; batteries; energy harvesters, inductors, cables; electronic circuits; optoelectronic circuits; fibre optics, integrated circuits; microcircuits; microprocessors; electronic memory; electronic components; telecommunications; global positioning system; Bluetooth; wireless; software; firmware; internet connectivity; software; firmware; code; operating system; applications; protocols; and/or internet protocols.
  • illumination from the light source 108 at certain frequencies and certain intensities causes the fluorescence and photobleaching of F420 107 in the ruminal culture 102 proximal to the exterior surface of the optically transparent portion 106.
  • the light source 108 and the additional light source 112 emit light continuously or in pulses.
  • the pulses of light from the light source 108 and the additional light source 112 are emitted with a pulse width selected from the group comprising about, 1 ms, 10 ms, 100 ms, 1 s, 10 s, 100s.
  • the pulses of light from the light source 108 and the additional light source 112 are emitted with a pulse frequency selected from the group comprising about, 1 pHz, 10 pHz, 100 pHz, 1 mHz, 10 mHz, 100 mHz, 1 Hz, 10 Hz, 100 Hz, 1 kHz and 10 kHz.
  • the pulses of light from the light source 108 and the additional light source 112 are emitted with a pulse intensity selected from the group comprising, 1 pWm’ 2 , 10 pWnr 2 , 100 pWnr 2 , 1 m Wm’ 2 , 10 Wnr 2 , 100 WOT 2 .
  • the device 100 is introduced into a ruminal culture 102 and used to illuminate F420 107 proximal to the exterior surface of the optically transparent portion 106 and cause the illuminated F420 107 to fluoresce and photo-bleach and so be inactivated.
  • the continuous movement of the device 100 within the ruminal culture 102 will cause the ruminal culture 102 contacting the exterior surface of the optically transparent portion 106 to be under a state of flux and with sufficient time, the volume of ruminal culture 102 exposed to the illuminated exterior surface of the optically transparent portion 106 causes sufficient fluorescence and photo-bleaching to inactivate F420 107 in the ruminal culture 102 to reduce methanogenesis and to reduce methane emissions.
  • the light source 108, additional light source 112, optical detector 110, control circuitry 114, and the power circuitry 115 are physically located and functionally connected inside the housing 101 of the device. This configuration provides the utility that the device 100 is self-contained and suited for autonomous operation and for installation in the ruminal culture 102 of a live animal.
  • the device 100 is only used to emit 420 nm light to photo bleach or otherwise deactivate F420 requiring only a subset of the elements depicted Figure 1 comprising a housing 101 with at least one optically transparent portion 103, at least one light source 108 of least one wavelength of about 420 nm positioned to illuminate and enter the interior surface of the optically transparent portion 104, control circuitry 114, and power circuitry 115.
  • Figure 2 depicts a device 200 wherein the light source 208, additional light source 212, optical detector 210, control circuitry 214, and the power circuitry 215 are physically located outside the housing 201 in a base unit 216 and connected via a tether 217.
  • the tether 217 provides a conduit to maintain functional connectivity between the housing 201 and the base unit 216 using cables selected from the group comprising, wire, data, power, and may include wireless communication.
  • This configuration of device 200 provides the utility that the light source 208, additional light source 212, optical detector 210, control circuitry 214, and the power circuitry 215 can be easily adjusted without the need to remove the housing 201 of the device from the ruminal culture 202.
  • the optical data can be conveniently analysed externally using methods selected from the group comprising, spectrometry, and fluorimetry.
  • the device 200 includes a housing 201 that is configured to be in contact with a ruminal culture 202.
  • the housing 201 incorporates at least one optically transparent portion 203, which has a surface 204 contacting the inside of the device 201, a body of transparent material 205, and an exterior surface 206 contacting the ruminal culture 202.
  • F420 207 that is proximal to and in optical communication with the exterior surface of the optically transparent portion 206.
  • At least one light source 208 of light of at least one wavelength is inside the base unit 216 , schematically depicted as a dashed arrow 209 indicating one general direction, which source of light 208 is positioned to illuminate though the tether 217 and enter the interior surface of the optically transparent portion 204, transmits through the body of the optically transparent portion 203 and emerges from the exterior surface of the optically transparent portion 206.
  • the light source 208 and optically transparent portion 203 are configured to illuminate the ruminal culture 202 contacting the exterior surface of the of the optically transparent portion 206 and F420 207 present in the ruminal culture 202 that is proximal to the exterior surface of the optically transparent portion 206.
  • the device 200 depicted in Figure 2 includes at least one additional light source 212 of at least one wavelength schematically depicted as a dashed arrow 213 indicating one general direction, that can be of the same wavelength as the light source 208 or a different wavelength.
  • Figure 3 depicts an overview of one example of a device 300 administered to a ruminant animal 301, wherein the device 300 has located in a ruminal culture 302 inside the rumen 303 of a cow 301.
  • Administration of the device 300 into the animal 301 can be via the oral route comprising the mouth 304 and the oesophagus 305.
  • the device 300 may be administered using an applicator of the type routinely used for administering a bolus wherein the device 300 is configured with the applicator and then inserted to the open mouth 304 of the cow 301 and pushed into the oesophagus 303 wherein the device is detached from the applicator and the applicator withdrawn.
  • the device 300 enters the reticulum 306 of ruminant foregut and can remain and function in the reticulum 306 or can locate and remain and function in the rumen 303.
  • the device 300 is fabricated to have a specific gravity of about 1.5 or about 2 so that the device 300 substantially contacts the liquor fraction of the ruminal culture 302 rather the headspace 307 of the rumen 303, otherwise called the gas cap.
  • the device 300 is intended to remain permanently in the animal 301 from the time of administration.
  • the device 300 may be recovered from the dead animal 301 at slaughter by autopsy of the foregut organs for example the rumen 304 of a cow 301.
  • the device 300 may be recovered from the live animal 301 by using a retrieval apparatus that is inserted into the open mouth of the animal 304 down the oesophagus 305 and into the foregut organ 303 and the ruminal culture 302 wherein the the retrieval apparatus attaches to the device 300 by an attachment means selected from the group comprising magnet, hook, and loop, wherein the attached device 300 is extracted via the oral route.
  • the device 300 is powered by a battery.
  • the device 300 includes energy harvesting means to augment or replace a battery to permit the device 300 to function for times exceeding the storage capacity of a battery and include energy harvesting means selected from the group comprising inductive, piezoelectric, electro-mechanical, thermoelectric, and electrochemical energy harvesting means.
  • Figure 4 shows an example of an algorithm 400 to use a device of any of Figs. 1 and 3 administered to an animal.
  • the step START 401 of the algorithm 400 comprises having possession of a suitable device Fig. 1 100 and ruminant animal Fig. 3 300 for administration of the device into the ruminal culture 302.
  • the step ACTIVATION 402 comprises turning the device on to an active state if it was in an off or inactive state.
  • the step ACTIVATION 402 comprises establishing that the power circuitry and the control circuitry are functional and may include and adjusting or otherwise calibrating the device Fig. 1 100 in preparation for administration to an animal Fig. 3 300.
  • the step ACTIVATION 402 includes linking appropriate animal and device identification codes and establishing communication channels with wireless interfaces to ensure that data reporting from the device is functional.
  • the step ADMINISTRATION 403 comprises preparing the animal and the device for placement of the device in the ruminal culture of a ruminant animal foregut.
  • the step ADMINISTRATION 403 comprises using an applicator of the type routinely used for administering a bolus wherein the device is configured with the applicator and then inserted to the open mouth of the ruminant animal and pushed into the oesophagus wherein the device is detached from the applicator and the applicator withdrawn.
  • the device enters the reticulum of ruminant foregut and can remain and function in the reticulum or can locate and remain and function in the rumen. In some examples the device will start to operate automatically or alternatively the device may be triggered remotely via wireless communications. In some examples the step 420 nm CONTROL 404 will cause the emission of 420 nm light from the device. In some examples the dose of 420 nm light has been predetermined. In some examples the step 420 nm CONTROL 404 is adjusted based on feedback from a F420 sensor configured to detect the fluorescence emission of excited F420.
  • the step READ 470 nm 405 determines the value of fluorescence and may in some examples record, transmit, or store a value in a step called REPORT 406.
  • a decision step F420 THRESHOLD 407 is employed to compare the value of the fluorescence to a value for fluorescence stored in the memory of the control circuitry. In some examples if the value of the fluorescence measured is higher than the recorded value, then the dose of the 420 nm light may be adjusted or increased by the control circuitry in the step 420 mm DOSE 408. In some examples if the value of the fluorescence measured is lower than the recorded value, then the dose of the 420 nm light may be adjusted or decreased by the control circuitry in the step 420 mm DOSE 408. By adjusting the dose of 420 nm light based on the value of fluorescence has clear advantages in energy efficiency and device utility.
  • the step REPORT 406 may send records of the value of fluorescence via wireless communications.
  • the device use is only to emit 420 nm light to photo bleach or otherwise deactivate F420 requiring only a subset of the elements depicted Figure 1 comprising a housing Fig. 1 101 with at least one optically transparent portion Fig. 1 103, at least one light source Fig. 1 108 of least one wavelength of about 420 nm positioned to illuminate and enter the interior surface of the optically transparent portion Fig. 1 104, control circuitry Fig. 1 114, and power circuitry Fig. 1 115.
  • the algorithm 400 the utilises only a subset of steps comprising START 401, ACTIVATION 402, and 420 CONTROL 403 and the only function of the device is to emit 420 nm light at a predetermined level of intensity specified for example by the current draw on an LED such as about 10 mA and for a predetermined period of continuous time, or semicontinuous times, or for an undefined period of time until the algorithm is terminated either manually, the electrical energy on the device has been exhausted, or the device has been recovered from the animal.
  • a predetermined level of intensity specified for example by the current draw on an LED such as about 10 mA and for a predetermined period of continuous time, or semicontinuous times, or for an undefined period of time until the algorithm is terminated either manually, the electrical energy on the device has been exhausted, or the device has been recovered from the animal.
  • F420 sensors of the present disclosure include, for example, measuring photons at selected wavelengths emitted due to the fluorescence of F420 including wavelengths selected from the group comprising, fluorescent; auto-fluorescent; oxidized F420; at about 470 nm.
  • Sensors to monitor F420 in the rumen of ruminant animals include, for example, devices or device components selected from the group comprising, absorbance, fluorescence, autofluorescence, light sensor; photodiode, charge coupled device (CCD), camera; optical filter, diffraction grating, fibre optic; power source, battery, rechargeable battery, energy harvesting, power generator, inductor, capacitor; supercapacitor; electronic circuit; integrated circuit; logic circuit; microprocessor; memory circuit; code; firmware; software.
  • F420 is indicative for monitoring methanogenesis, and indicative for monitoring methanogens, and indicative for monitoring emitted methane.
  • the methods of the present disclosure utilize devices that when administered to the ruminal culture, emit photons which when said photons are absorbed by F420 cause F420 to both fluoresce and become photobleached, which permits the inactivation of F420 and the monitoring of F420.
  • the inactivation and the monitoring of F420 can be performed separately and independently from each other, or they can be performed together.
  • the devices required to perform the methods of the present disclosure are intraruminal electronic devices that preferably radiate photons at wavelengths which can be optimally absorbed by F420 and that preferably detect photons from the fluorescence of F420.
  • Such devices include a light emitter, a light detector, a controller module, a communication module, and a power module.
  • Electronic intraruminal devices have been disclosed that radiate photons, detect photons, are controlled, receive and transmit communications and use various forms of power such as for example:
  • a light emitter preferably emitting light with a wavelength of about 420 nm, for example a light emitting diode
  • a light detector preferably detecting F420 fluorescence at a wavelength of about 470 nm, for example a photodiode
  • a controller module to specify the illumination pulse width, frequency and power, and to report photodiode current for example, integrated logic, memory, and communication circuits
  • a power module to power the electronic components of the device for example a battery and/or an energy harvesting apparatus.
  • the dosages of radiation to cause sufficient F420 inactivation in the ruminal culture can be selected by monitoring F420.
  • F420 can be contemporaneously measured and photobleached.
  • the inventors have recognized that by increasing the inactivation of F420 by measuring F420 has surprising efficiencies for selecting dosages of radiation and the power requirements for radiation.
  • the methods described herein may be for uses, for example, including, to inactivate F420 in a ruminal culture; to reduce methanogenesis in a ruminal culture by the inactivation of F420 in said ruminal culture; to reduce methanogens in a ruminal culture by the inactivation of F420 in said ruminal culture; to reduce methane emissions from a ruminal culture by the inactivation of F420 in said ruminal culture.
  • Methane is a greenhouse gas with a global warming potential (GWPioo) 28 times that of carbon dioxide.
  • enteric methane is a by-product of ruminant digestion and is produced by a complex community of microorganisms, the rumen microbiome, which includes archaea, bacteria, ciliate protozoa, and anaerobic fungi.
  • Methanogenic archaebacteria (methanogens) synthesize methane by a cofactor F420- dependent biochemical process called methanogenesis.
  • the foregut organs of some ruminant and pseudo-ruminant animals are relatively rich in methanogens such as, for example, adult animals, whereas the foregut organs of some animals are relatively poor in methanogens such as, for example, in neonate animals, or adult animals that have had their foregut organ modified by treatments that include, antibiotics; ionophores; methanogen inhibitors, methanogenesis inhibitors; organohalogen compounds; organohalogen-rich marine macroalgae; organosulfur compounds; organosulfur-rich plants; polyphenol compounds; and polyphenol-rich plants; organo-halogens; bromoform; red seaweeds; asparagopsis species extracts; asparagopsis matter; allicin; MootralTM; garlic extracts; garlic matter; 3-Nitrooxypropanol (3-NOP); BovaerTM.
  • the methods of the present disclosure cause inactivation of F420 by photo bleaching, which prevents the function of F420 as a hydride transfer agent and reduces methanogenesis.
  • the methods can be used to reduce methanogenesis in the rumen and to reduce emitted methane from ruminant and pseudo-ruminant animals.
  • the methods of the present disclosure can be used to monitor the presence and growth of methanogens in the rumen of a ruminant animal, and to also monitor treatments administered to ruminant animals to reduce methanogenesis and/or methanogens and/or methane emissions and also to validate the administration of treatments to ruminant animals.
  • Figure 5 depicts a manufactured device 500 comprising a housing 501 made from PVC pipe (25 mm internal diameter x 200 mm) sealed at one end with an optically transparent portion 503 comprising a 25 mm diameter borosilicate (K9) half-ball lens from YV Optoelectronics Co. Ltd with the hemispherical surface 506 of the lens faced outwards, and the backplane of the lens 504 located inside the pipe.
  • a 25 mm diameter disk of electronic circuit board 505 was positioned inside the housing 501, adjacent and co-linear to the back plane of the lens 504 and populated with optoelectronic assembly comprising,
  • a centrally-located photodiode 310 (Hamamatsu pin-photo-diode S5973-02 with enhanced 470nm sensitivity of 0.35 A/W), which had an outer diameter 5.4 mm and an internal sensor surface of 2.54 mm diameter was centrally configured to enable its sensor surface to be illuminated by light entering the hemispherical surface of the lens 506 and passing through the backplane of the lens 504.
  • a light source comprising three LEDs 508 with an emission maximum of 417 nm (OSA OCU-400 UE415) and a flat rectangular form factor (2 mm x 3 mm x 1 mm) arranged to encircle the photodiode 510 with 120-degree separation and configured to project their light through the back plane of the lens 504 to illuminate the hemispherical surface of the lens 506.
  • An additional light source comprising three LEDs 512 with an emission maximum of 470 nm (KPTR-3216) and a flat rectangular form factor (2 mm x 3 mm x 1 mm) arranged to encircle the photodiode 510 with 120-degree separation and configured to project their light through the back plane of the lens 504 to illuminate the hemispherical surface of the lens 506.
  • a 470 nm ⁇ 15 nm bandpass interference filter (5 mm x 5 mm x 1 mm, not shown) placed between the photodiode 510 and the backplane of the lens 504.
  • the light source LEDs 508 and the additional light source LEDs 512 were positioned as close as practicable to the photodiode 510 and arranged in an alternating fashion according to their wavelength.
  • the LEDs 508/512 were bonded to the backplane of the lens with optical adhesive (Loctite Hysol E -30CL) for refractive index matching and to minimise reflections.
  • the photodiode 510, light source LEDs 508, and the additional light source LEDs 512 were fixed to the disk of electrical circuit board 505 by standard soldering techniques common in the assembly of devices from electronic components.
  • the optoelectronic assembly was mounted in the housing 501 using a sealing adhesive.
  • Figure 6 depicts the electronic circuit schematic 600 of a manufactured device depicted in Figure 5.
  • This second electronic circuit board was connected by cables which exited the device housing through a sealed terminus at the end opposite the ball lens.
  • the cables connected the circuitry inside the housing with power circuitry and additional control circuitry comprising a Raspberry Pi computer with a quad core ARM processor running Debian Linux.
  • Control of the device light source was achieved using MOSFET 14N05L switches operated by GPIO lines from the Raspberry Pi. These FETs were chosen for their low gate turn-on voltage and can be operated directly from the I/O signals. LED intensity is regulated by TIP31 transistors which are adjusted by trim-pots on the end of the device. Optical signals are captured by a 16-bit A/D convertor ADS1115 controlled by I2C bus. The ADS1115 provides programmable reference voltage and can perform at speeds up to 860 samples/sec.
  • a high gain amplifier (Burr Brown PGA204) configured in a bespoke electronic circuit was linked directly to the photodiode. Key considerations were noise rejection and drift.
  • the PGA204 had a manually set programable gain of xl, xlO, xlOO & X1000 in some examples.
  • Input offset was adjusted once at setup, then in operation the output offset was adjusted automatically by software operating two digital potentiometers connected to the controller by the SPI bus. One was for coarse adjustment and the other was for fine adjustment.
  • a temperature sensor (Dallas DS1822) was mounted near the optical head and connected to the Raspberry Pi by a "one wire" bus on the general purpose input output (GPIO) interface.
  • Power circuitry provided a positive and a negative voltage regulated by LM7805 and LM7905 voltage regulators, respectively. These integrated circuits were fed by a 12VDC plug pack with voltage inversion for the negative regulator. A 5VDC regulator was provided for the LED circuit which must be separated from the amplifier to avoid inducing noise into the optical signal. Shielding was provided for the amplifier circuit by enclosing it in a metal envelope. Digital gain selection lines from the Raspberry pi provided a digital ground for the amplifier. The Raspberry Pi was provided with a plug pack supply.
  • Figure 7 depicts one example of an algorithm to control a device.
  • a bespoke software application written in Python3 provided a script-based interface for device parameter setup, operation, and the acquisition of data from the device.
  • the software and/or control circuitry specified attributes selected from the group comprising, sample identifier, the time interval of LED illumination (pulse width), the intensity of LED illumination (power), the time interval between LED pulses, the LED wavelengths selected for illumination, the photodiode integration time, and dark (no illumination) readings.
  • Data from the photodiode in response to the illumination, and the temperature from the temperature sensor were acquired and printed to the terminal, written to a datafile, and written to a USB drive.
  • the device response to stepwise addition of fluorescent microspheres.
  • the emitted methane response of a ruminal culture to the device configured to inactivate F420.
  • Figure 8 shows a panel 800 of time-course graphs of the recorded signals from the device shown in Figure 5 contacting a body of water with stepwise additions of a synthetic fluorescent microparticle (Blue Fluorescent Polymer Microspheres 1.3g/cc - 1-5 pm from Cospheric, Santa Barbara, California).
  • the spectral characteristics of the microspheres from Cospheric show the excitation curve has a maxima at about 407 nm and the emission curve has maxima at about 445 nm. It is noted that the excitation curve is only shown from 250 nm to 450 nm and there appears to be increasing adsorption from 440 nm.
  • the spectral characteristics of the microspheres suggest that they will be excited into a fluorescent state by the 420 nm LED and emit light with an emission maximum at about 445 nm.
  • Panel 801 shows photodiode signals due to the 420 nm LEDs with pulse width of about 0.5 seconds and an interval between pulses of about 10 seconds.
  • Panel 802 shows photodiode signals due to the 470 nm LEDs with pulse width of about 0.5 seconds and an interval between pulses of about 10 seconds.
  • Each timepoint in panel 801 is lagged (about 0.1 seconds) by a matching timepoint in panel 802 such that there are two photodiode signals from about the same timepoint, the first photodiode signal is due to the 420 nm LEDs, and the second lagging photodiode signal due to the 470 nm LEDs.
  • Panel 803 shows the difference signal in mV created at each timepoint by subtracting the photodiode signal generated from the 470 nm LEDs, from the photodiode signal from a pulse of light from the 420 nm LEDs.
  • Panel 804 shows the temperature signal in °C from a temperature sensor placed inside the device proximal to the LEDs.
  • the device of Figure 5 was placed in a light proof container and left to thermally equilibrate for 45 minutes at room temperature (about 20 °C) with the photodiode and temperature sensor recording consecutive pulsing of the 420 nm and 470 nm LEDs.
  • the photodiode signal from the 420 nm LEDs 601 shows a staircase of stepwise increases in reported signal 807 caused by fluorescence from the microspheres proximal to the surface of the half-ball lens when illuminated by the 420 nm LEDs. Subsequently, the system was flushed with clean water wherein the photodiode signal reduced to a baseline level 808. The stepwise addition of Cospheric fluorescent blue microparticles was repeated to generate a second characteristic staircase 809. Subsequently, the system was flushed with clean water wherein the photodiode signal reduced to a baseline level 810.
  • an additional light source comprising the 470 nm LEDs was selected to pass any reflected through the 470 nm bandpass filter that was installed in the device in front of the photodiode.
  • Panel 806 also shows a staircase of photodiode responses at 470 nm to the stepwise addition of Cospheric fluorescent blue microparticles. This response is also likely due to fluorescence signal due to spectral overlap between LED emission and the Cospheric fluorescent blue microparticles excitation wavelengths.
  • Experiments (not shown) using an additional light source comprising 530 nm LEDs and removing the 470 nm bandpass filter from the photodiode showed no staircase response to the addition of Cospheric fluorescent blue microparticles, contrary to the 420 nm LEDs and the 470 nm LEDs.
  • the emission characteristics of the 530 nm LEDs shows no spectral overlap with the Cospheric fluorescent blue microparticles, which indicates about no contribution to the photodiode signal from reflectance.
  • Figure 9 shows of time-course graph of measured methane in parts per million (ppm) 900 recorded from a bioreactor containing a ruminal culture and the device shown in Figure 5 500.
  • the applicant applied varying levels of 420 nm LED illumination from the device of Figure 5 500 to the ruminal culture and monitored the methane emitted from the ruminal culture comprising,
  • a bioreactor comprising,
  • a reactor chamber of internal dimensions 60 mm x 152 mm x 230 mm was fabricated from acrylic sheet (polymethylmethacrylate, 10 mm) and bonded with a solvent cement (dichloromethane) to provide an enclosed volume of about 2 L, that when in use typically contained a ruminal culture liquor volume of about 1.5 L and a headspace volume of about 0.5 L. Included in the chamber was, a removable lid to open and close the chamber; a gas outlet to vent emitted gases from the chamber headspace; and a siphon tube (20 mm inner diameter) that entered the chamber below the ruminal culture liquor level and extended above the top of ruminal culture liquor level. When in use the chamber contents were periodically mixed by mechanical agitation.
  • a chamber heater comprised of two silicon heater mats (30 W, 150 x 200mm, 12 V de) attached to the two of the opposing external surfaces of the chamber and insulated with polystyrene foam (12 mm).
  • the chamber temperature was adjusted using a programmable temperature controller with a temperature probe centrally located in the chamber and when in use was immersed in ruminal culture liquor. When in use the temperature of the ruminal culture was maintained at about 39 °C.
  • a methane gas sensor gas emitted from the ruminal culture into the chamber headspace and vented through that gas outlet was monitored using an infra-red electronic methane sensor (INIR Mel00%, from SGX Sensortech) controlled by a computer and a bespoke software application according to the manufacturer's instructions.
  • a headspace gas analysis tube (5 mm inner diameter) connected to the gas outlet of the chamber for processing and analysis comprised, in-line gas scrubbers to remove, water vapor via a clay filled polymethylmethacrylate pipe, 180 mm x 15 mm inner diameter); and hydrogen sulfide (H2S) (gas tight PVC tube packed with steel wool, 600 mm x 5 mm inner diameter).
  • the scrubbed gas was directly piped to the methane gas sensor installed in an inline flow-through gas hood (JAS769638AA from SGX Sensortech) that was in turn connected to gas storage reservoir comprising a PVC tube (3 m x 5 mm inner diameter) and terminated by fermentation airlock filled with about 2 mL of water.
  • inline flow-through gas hood Java769638AA from SGX Sensortech
  • gas storage reservoir comprising a PVC tube (3 m x 5 mm inner diameter) and terminated by fermentation airlock filled with about 2 mL of water.
  • a ruminal culture comprising,
  • McDougall's buffer comprised rainwater containing NazHPC (26 mM); NaHCCh (111.0 mM); NH4CHO3 (6.0 mM); NaCI (8.0 mM), KCI (8.0 mM); MgCI 2 (0.3 mM); CaCI 2 (0.2 mM). Rumen contents from a freshly slaughtered cow were extracted and strained through a stainless-steel sieve with a 1 mm mesh to yield a rumen liquor with a pH of about 6.4.
  • a sample of about 0.7 L of liquor was combined with about 20 g of dried lucerne fines to create an inoculation slurry with a total volume of about 0.75 L, which was immediately transferred to the chamber containing about 0.75 L of 0.5X McDougall's buffer pre-heated to about 39°C.
  • the extraction of ruminal culture from the chamber comprised tilting the chamber forward to a desired angle until the ruminal culture began to decant from the opening of the siphon tube for a desired interval of time, until the desired volume of ruminal culture had been decanted, and then tilting the chamber backward to a desired angle to stop the decanting.
  • the administration of materials (feeding) to the ruminal culture comprised tilting the chamber backward to a desired angle, administering a material into the chamber via the siphon tube.
  • the hydraulic retention time of reactor was set to about 3 days by the daily extraction of ruminal culture of about 0.5 L and replacement with an equivalent volume of feed materials during feeding.
  • the pH of the extracted ruminal culture was measured ex situ at daily feeding using a calibrated pH meter and maintained in the range 6.0 to 6.5 by the co-administration of McDougall's Buffer during feeding.
  • the feeding material comprised adding dried lucerne fines (20 g) to water and/or McDougall's buffer to form a fresh slurry a volume of about 0.5 L.
  • the methane emitted from the ruminal culture was monitored Figure 9 with the device Fig. 5 500 installed in the bioreactor and contacting the ruminal culture and specifying the parameters of the device operation including, LEDs to be illuminated, LED intensity (the current draw in mA), LED pulse width (the length of time the LED is on per pulse), and the interval width (the length of time between pulses).
  • Figure 9 shows a graph 900 of the methane level traces 901 in Parts Per Million (ppm) 902 of two separate events 903 and 904 respectively, each recorded over a time course of about 11 hours 905. The first event was recorded 903 and then after about 12 hours the second event was recorded 904 and the two traces overlaid in the graph 900 to permit convenient comparison of the trace of event 1 903 with the trace of event 2 904.
  • ppm Parts Per Million
  • Event 1 and Event 2 were both initiated by providing the ruminal culture with feed as described and the methane traces 903 and 904 respectively, show an abrupt step change 906 due to the removal of 0.5 L of the ruminal culture and the replacement with 0.5 L of the feed material.
  • the methane trace decreases for a short period of about 30 minutes until it reaches a point of inflection 907 and then rapidly increases over about two hours until a second point of inflection 908.
  • the trace 403 then declines gradually.
  • Event 1 reflects a pattern of methane sensor responses due to feed events with no LED illumination from the device Fig. 5 500 and reflects a typical baseline methane emission characteristics of the ruminal culture after feeding.
  • the device LEDs Fig 5 508 were switched on at a selected time 909 to illuminate the ruminal culture.
  • the LED illumination comprised the three 420 nm LEDs Fig. 5 508 adjusted to draw about 10 mA each, all switched on simultaneously for a pulse width of about 0.5 seconds, with an interval between pulses of about 2 seconds.
  • the methane trace 904 showed decreased methane production due to the 420 nm light as indicated by the change in the methane level traces 903 and 904 respectively from about 168000 ppm in the trace of Event 1 403 to about 130000 ppm in the trace of Event 2 405 to yield a difference of about 38000 ppm 910 or about 23%.
  • the effect of the 420 nm light with the parameters described can be characterised as a reduction of methane emission from the ruminal culture of about 23 %.
  • devices that can deliver illumination to ruminal cultures to excite, fluoresce, detect, photo-bleach, and inactivate co-factor F420, a flavin molecule manufactured by methanogenic archaea in the ruminal culture to produce methane.
  • the devices are comparatively inexpensive to manufacture to enable their widespread availability.
  • Some examples of devices may be used inactivate F420 in the ruminal cultures of ruminant animals, particularly farmed ruminant animals, and reduce their methane emissions. Some examples of devices can be used excite F420 in the ruminal cultures of ruminant animals, particularly farmed ruminant animals, and detect their methane emissions.
  • the use of a device may to reduce methane emissions and monitor methane emissions from ruminant animals, particularly farmed ruminant animals.

Abstract

La présente invention concerne des dispositifs et des procédés pour réduire et surveiller les émissions de méthane provenant d'animaux ruminants et pseudoruminants. En particulier, l'invention concerne un dispositif intraruminal comprenant une source de lumière ayant une longueur d'onde d'éclairage d'environ 420 nm à environ 470 nm. La source de lumière peut inactiver le cofacteur 420, qui est essentiel pour la production de méthane chez les animaux ruminants, de façon à réduire le méthane émis. Le dispositif peut en outre incorporer des capteurs comprenant des capteurs configurés pour détecter l'émission de fluorescence de F420 excité.
PCT/NZ2023/050019 2022-02-22 2023-02-21 Dispositif intraruminal et procédé WO2023163600A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NZ785405 2022-02-22
NZ78540522 2022-02-22

Publications (1)

Publication Number Publication Date
WO2023163600A1 true WO2023163600A1 (fr) 2023-08-31

Family

ID=87766516

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/NZ2023/050019 WO2023163600A1 (fr) 2022-02-22 2023-02-21 Dispositif intraruminal et procédé

Country Status (1)

Country Link
WO (1) WO2023163600A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62288569A (ja) * 1986-06-06 1987-12-15 Mitsubishi Electric Corp 微生物活性計測装置
CN102512766A (zh) * 2011-12-23 2012-06-27 代劲 一种可用于杀灭幽门螺杆菌的蓝光发光胶囊
US20140005758A1 (en) * 2010-03-17 2014-01-02 Photopill Medical Ltd. Capsule phototherapy
US20210196972A1 (en) * 2019-12-29 2021-07-01 Brian Michael Coyle Light Capsule

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62288569A (ja) * 1986-06-06 1987-12-15 Mitsubishi Electric Corp 微生物活性計測装置
US20140005758A1 (en) * 2010-03-17 2014-01-02 Photopill Medical Ltd. Capsule phototherapy
CN102512766A (zh) * 2011-12-23 2012-06-27 代劲 一种可用于杀灭幽门螺杆菌的蓝光发光胶囊
US20210196972A1 (en) * 2019-12-29 2021-07-01 Brian Michael Coyle Light Capsule

Similar Documents

Publication Publication Date Title
WO2007110867A8 (fr) Capteur implantable
US10016133B2 (en) Remotely powered sensor with antenna location independent of sensing site
JP2009502360A (ja) 埋め込み型組織虚血センサ
WO2003096028A3 (fr) Procedes et appareil permettant d'identifier des oeufs vivants par detection de la frequence cardiaque et/ou d'un mouvement d'un embryon
ATE535184T1 (de) Integriertes pulsoximeter
WO2007048039A3 (fr) Procédé et appareil d’oxymétrie reposant sur la spectrophotométrie
EP1618834A4 (fr) Endoscope a capsule et systeme d'endoscope a capsule
EP1929930A4 (fr) Dispositif endoscope
ES2730730T3 (es) Procedimiento de tratamiento de aguas para reducir el efecto disruptor endocrino utilizando un organismo vivo
WO2002061405A2 (fr) Procédé et dispositif portable de détection de fluorescence
ES2564398T3 (es) Instrumento y método para el análisis en línea, a tiempo real para la cuantificación del total de especies de ácidos haloacéticos y de trihalometanos en suministros de agua potable
YU44402A (sh) Fluorescentno kontrastno sredstvo u bliskoj infracrvenoj oblasti i fluorescentno snimanje
CN101352343A (zh) 消化道智能释药胶囊系统及方法
CN109269997A (zh) 分布式排泄物潜血检测装置及其方法
ATE395094T1 (de) Verwendung einer brustpumpe
FR2934949B1 (fr) Capsule autonome de detection destinee a etre introduite dans un conduit d'un corps humain ou animal
WO2023163600A1 (fr) Dispositif intraruminal et procédé
CN109073455A (zh) 用于多参数水质测量的光学硝酸盐传感器
US9232885B2 (en) Method and device for detecting tumorous tissue in the gastrointestinal tract with the aid of an endocapsule
US10761015B1 (en) Handheld hemoglobin detecting device
TW202037899A (zh) 血紅素感測器及其血紅素感測方法
WO2005062716A3 (fr) Appareil, systeme et procede d'indication d'un emplacement d'un dispositif in vivo
EP2347708A4 (fr) Dispositif de surveillance pour un corps vivant
Egly et al. A compact multi-channel fluorescence sensor with ambient light suppression
WO2014186727A1 (fr) Polymère greffé à opacité constante pour capteur optique

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23760456

Country of ref document: EP

Kind code of ref document: A1