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WO2014060360A1 - Incubateur d'embryons comportant un contrôle du gaz - Google Patents

Incubateur d'embryons comportant un contrôle du gaz Download PDF

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Publication number
WO2014060360A1
WO2014060360A1 PCT/EP2013/071433 EP2013071433W WO2014060360A1 WO 2014060360 A1 WO2014060360 A1 WO 2014060360A1 EP 2013071433 W EP2013071433 W EP 2013071433W WO 2014060360 A1 WO2014060360 A1 WO 2014060360A1
Authority
WO
WIPO (PCT)
Prior art keywords
gas
unitary module
chamber
incubator according
incubator
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/EP2013/071433
Other languages
English (en)
Inventor
Thomas William PEDERSEN
Holger Søe PLOUGSGAARD
Niels B Ramsing
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Unisense Fertilitech AS
Original Assignee
Unisense Fertilitech AS
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 Unisense Fertilitech AS filed Critical Unisense Fertilitech AS
Priority to EP13776801.6A priority Critical patent/EP2906680A1/fr
Publication of WO2014060360A1 publication Critical patent/WO2014060360A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M21/00Bioreactors or fermenters specially adapted for specific uses
    • C12M21/06Bioreactors or fermenters specially adapted for specific uses for in vitro fertilization
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • C12M41/14Incubators; Climatic chambers
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas

Definitions

  • the invention relates to an incubator having a chamber for cultivating embryos and a gas control system for maintaining a constant atmosphere in the incubating chamber.
  • Infertility affects more than 80 million people worldwide. It is estimated that 10% of all couples experience primary or secondary infertility.
  • In vitro fertilization is an elective medical treatment that may provide a couple who has been otherwise unable to conceive a chance to establish a pregnancy. It is a process in which eggs (oocytes) are taken from a woman's ovaries and then fertilized with sperm in the laboratory. The embryos created in this process are then placed into the uterus for potential implantation. In between fertilization (insemination) and transfer the embryos are typically stored in incubators for 2-6 days wherein the developmental conditions are optimized by emulating the conditions in the uterus. Thus, when incubating embryos it is of utmost importance to be able to maintain a constant and predefined atmosphere in the actual incubation chamber. Summary of the invention
  • the key to maintain a controlled atmosphere in the incubation chamber is the supply of gasses.
  • Presently available gas control systems for embryo incubators have demonstrated sensitivity to dirt in the gas lines and humidity in the gas. This may cause valve irregularities requiring offline service before deteriorating the atmosphere in the incubation chamber.
  • Regular service is in general needed for incubators, because some of the key components require regular replacement.
  • a purpose of the invention is therefore to optimize gas control and serviceability.
  • One aspect of the invention therefore relates to an incubator for incubating embryos, comprising an incubating chamber adapted to contain the embryos, and a gas unitary module in fluid communication with the incubating chamber comprising at least two proportional valves, a C0 2 gas sensor and an 0 2 gas sensor, wherein the gas unitary module is adapted to receive a gas supply of N 2 at one of said proportional valves and C0 2 at another of said proportional valves, and control the proportional valves based on feedback from the gas sensors such that supply of N 2 and C0 2 to the incubation chamber is regulated to sustain a predefined level of 0 2 and/or C0 2 in said incubating chamber.
  • Fig. 1 a is a picture of a gas unitary module
  • Fig. 1 b is a picture of the inside of a gas unitary module
  • Fig. 2a-c are pictures of a gas unitary module mounted inside an incubator
  • Fig. 3a is a picture of a gas unitary module
  • Fig. 3b is a picture of two proportional valves
  • Fig.4a-b are pictures of an UV lamp inside a decontamination chamber of a gas unitary module.
  • the oxygen concentration (or oxygen tension) in the incubation chamber and pH in the medium containing the embryos must be regulated, sustained and controlled.
  • the oxygen concentration inside the incubation chamber can be regulated by adding gas such as oxygen, nitrogen, carbon dioxide, helium or another inert gas, or a mixture of two or more of these gasses. In this case the oxygen concentration is regulated by nitrogen which is the far most practical and cost effective solution.
  • the oxygen concentration in the incubation chamber can typically be regulated between approximately 5% and 21 %.
  • the incubation chamber and the gas unitary module may form a closed (fluid) pipelined system where the gas (i.e. N 2 and C0 2 ) is circulated in between.
  • the desired oxygen concentration also depends on the type of cultivation medium.
  • the pH in the medium is depending on the type of medium and the concentration of C0 2 in the incubation chamber. I.e. by knowing the type of the medium the pH in the medium can be regulated by measuring and controlling the concentration of C0 2 in the incubation chamber.
  • Gas control may be incorporated in the form of one or more PID regulators for regulating the proportional valves based on the gas sensor feedback.
  • the PID regulators may be incorporated in a PCB control board.
  • the proportional valves are typically magnetic proportional valves (or solenoid valves) relying on the principle of integrating a magnetic valve and a "step motor" in a single assembly thereby allowing a gradual regulation of the flow by controlling the applied current.
  • the incubating chamber comprises holding means for at least one embryo, e.g. microscopy slides.
  • the embryos may be human embryos.
  • the gas unitary module further comprises a N 2 gas sensor to further provide information of the N 2 concentration.
  • the gas unitary module may comprise a chamber for accommodating the gas sensors, i.e. a gas sensing chamber.
  • the incubator comprises circulation means for recirculating the gas between the incubation chamber and the gas unitary module.
  • the incubation chamber and the gas unitary module may form a closed fluid pipelined system where the gas is circulated in between.
  • This is a cost effective solution to reduce the consumption of gas during operation where C0 2 or N 2 is only supplied to this closed recirculating system when needed to sustain the desired gas concentration.
  • the circulation means may be mounted in the gas unitary module, e.g. mounted in the sensing chamber of the gas unitary module.
  • the circulation means may e.g. be a fan or a pump.
  • the incubator comprises a filtration element adapted to filter the gas supplied to the incubation chamber.
  • the filtration element may comprise a high efficiency particulate arresting (HEPA) filter.
  • HEPA high efficiency particulate arresting
  • said filtration element may comprise a carbon filter for filtration of volatile organic compounds, such as a VOC filter.
  • the gas unitary module further comprises an
  • the UV lamp is adapted to decontaminate gas by illuminating the gas flowing through the gas unitary module.
  • An UV lamp could be mounted almost anywhere in the gas flow system. However, by incorporating the UV lamp in the gas unitary module the serviceability of the system is improved.
  • the gas unitary module comprises a
  • the decontamination chamber for accommodating the UV lamp.
  • the decontamination chamber is in fluid communication with the gas sensing chamber.
  • the decontamination chamber may be located at a gas inlet of the gas unitary module, such that gas entering the gas unitary module is decontaminated before entering the gas sensing chamber.
  • the decontamination chamber may also be located at a gas outlet of the gas unitary module such that the gas leaving the gas sensing chamber passes through the decontamination chamber before exiting the gas unitary module.
  • the gas unitary module therefore comprises an UV light sensor adapted for controlling whether the UV lamp is in operation.
  • the UV light sensor may e.g.
  • the UV light sensor maybe mounted on the outside of the gas unitary module, e.g. adjacent a transparent part, such as a small window, of the gas unitary module.
  • Oxygen gas sensors e.g. of the MOX sensor type, require regular service or even exchange.
  • the oxygen sensor is therefore mounted on the outside of the gas unitary module, e.g. on the lid or in the bottom of the gas unitary module, with the sensing part of the oxygen sensor is inside the sensing chamber, e.g. penetrating the frame of the gas unitary module. The oxygen sensor can thereby be accessed without disassembling the gas unitary module.
  • the incubator comprises pressure regulators for controlling the pressure at the input of the proportional valves.
  • An incubator is typically not sold with the actual physical supply of nitrogen and carbon dioxide and the gas pressure in the gas supply can therefore vary depending on the type of gas supply.
  • Pressure regulators can therefore ensure that a constant and predefined pressure (typically 0.5 bars) is provided at the proportional valves.
  • the pressure regulators may be of the non-venting type.
  • one or more temperature regulators are provided for controlling the temperature in the incubating chamber. Also humidity in the incubation chamber may be controlled.
  • Fig. 1 a shows an example of a gas unitary module V with two proportional valves 2 and pressure regulators 3.
  • An 0 2 sensor 4 is mounted on the lid of the module 1 ' such that the sensor 4 is accessible without disassembling the module 1 '.
  • a gas unitary module 1 without lid is seen in fig. 1 b where an UV lamp 9 is mounted in a
  • decontamination chamber 1 1 next to the sensing chamber 12 accommodating a C0 2 sensor 4 and circulation means in the form of a fan 8.
  • Gas is entering unitary module 1 through the gas inlet 5, flows through the decontamination chamber 1 1 with the UV lamp 9 before entering the sensing chamber 12 where the C0 2 sensor 7, the 0 2 sensor 4 (through the lid) and the fan 8 is located.
  • the gas exits the module 1 through the gas outlet 6.
  • Figs. 2a, 3b and 2c show pictures from inside an incubator 10 (in this case an
  • EmbryoScopeTM where the gas unitary module 1 is mounted.
  • the gas outlet 6 from the module 1 is visible.
  • C0 2 and N 2 are supplied via the tube 14 which connects the two proportional valves 2 with the gas outlet 6.
  • the gas is filtered in a VOC filter to remove any volatile organic compounds in the gas.
  • the gas provided via the gas supply does not pass through the decontamination chamber, because the gas used is typically medical grade gas. Only the recirculated gas passes through the decontamination chamber.
  • the tube 14 with the gas supply was connected to the inlet 5 of the gas unitary module 1 , the gas concentration measured in the sensing chamber 12 in the module 1 would not provide an accurate measure of the gas atmosphere inside the incubation chamber 1 and the system would be more difficult to stabilize.
  • Fig. 3a shows a picture of the lid of the gas unitary module 1 with a hole 4' for the 0 2 sensor 4.
  • Fig. 3b shows the two magnetic proportional valves.
  • Figs. 4a and 4b show close up pictures of the UV lamp mounted in the
  • the decontamination chamber 11 is isolated from the sensing chamber 12 except for the connection 15 provided opposite the gas inlet 5, such that no non-illuminated gas enters the sensing chamber 12.
  • a gas unitary module in accordance with an embodiment of the invention may comprise an arrangement to adjust the temperature of gas that circulates through the module together with the components contained within the gas unitary module.
  • the gas unitary module may further comprise one or more heating and / or cooling elements to help with seeking to maintain a desired temperature within an associated embryo incubation chamber to which the gas unitary module is coupled.
  • the gas circulated through a system such as described above may pass through / around several elements of the gas unitary module (for example, gas sensor(s), fan(s), UV-decontaminating unit(s), etc.) before entering the incubation chamber.
  • an alternative approach in accordance with some implementations of the present invention is to provide heating, or other temperature control, of the gas unitary module containing these various elements.
  • one or more heating elements such as heat foils or Peltier-effect heat exchangers, could be applied to one or more of the surfaces of the gas unitary module enclosure to heat the module, and hence the elements therein, so that gas circulating through the gas unitary module achieves a desired temperature before entering the incubation chamber.
  • a servo feedback system based on one or more temperature measurements associated with the gas unitary module may be provided to maintain the desired temperature, for example 37°C.
  • a heat foil may be applied to the removable lid of a gas unitary module such as described above.
  • the heat foil (or other heating mechanism) may be controlled using a standard temperature probe (e.g. a PT1000 thermo sensor), so the temperature can be adjusted to the desired level.
  • a metal plate e.g. formed of aluminium
  • the module may be further insulated, for example by cladding in the conventional thermal insulation materials, to help improve efficiency and reduce the required energy expenditure to maintain a desired temperature.
  • the single replaceable service unit comprising the gas unitary module may additionally comprise its own heating control.
  • an ultraviolet decontamination lamp arrangement may be provided in some implementations. It will be appreciated it can be helpful in some cases to provide shielding (e.g. baffles) to help ensure ultraviolet light from a decontamination lamp in the gas unitary module is prevented from entering an associated incubation chamber.
  • shielding e.g. baffles
  • An incubator for incubating embryos comprising an incubating chamber adapted to contain the embryo(s), and a gas unitary module in fluid communication with the incubating chamber comprising at least two proportional valves, a C0 2 gas sensor and an 0 2 gas sensor, wherein the gas unitary module is adapted to:
  • the incubator according to item 1 wherein the gas unitary module further comprises an UV lamp.
  • the incubating chamber comprises holding means for at least one embryo.
  • the gas unitary module further comprises a nitrogen gas sensor.
  • the gas unitary module comprises a gas sensing chamber for accommodating the gas sensors.
  • the incubator according to any of the preceding items, further comprising circulation means for circulating the gas between the incubation chamber and the gas unitary module.
  • circulation means comprises a fan or pump.
  • the incubator according to any of the preceding items further comprising a filtration element adapted to filter the gas supplied to the incubation chamber.
  • said filtration element comprises a high efficiency particulate arresting (H EPA) filter.
  • said filtration element comprises a carbon filter for filtration of volatile organic compounds, such as a VOC filter.
  • the incubator according to any of the preceding items, further comprising pressure regulators for controlling the pressure at the input of the proportional valves.
  • the incubator according to any of the preceding items, further comprising one or more PID regulators for regulating the proportional valves based on the sensor feedback.
  • the incubator according to any of the preceding items, further comprising one or more temperature regulators for controlling the temperature in the incubating chamber.
  • the gas unitary module comprises a decontamination chamber for accommodating the UV lamp, said decontamination chamber in fluid communication with the sensing chamber.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Sustainable Development (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Thermal Sciences (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

La présente invention concerne un incubateur comprenant une chambre permettant de cultiver des embryons et un système de contrôle de gaz permettant de maintenir une atmosphère constante dans la chambre d'incubation. Selon un premier aspect, l'invention concerne un incubateur permettant d'incuber des embryons, comprenant une chambre d'incubation conçue pour contenir les embryons, et un module unitaire de gaz en communication fluidique avec la chambre d'incubation comprenant au moins deux vannes proportionnelles, un capteur de CO2 gazeux et un capteur de O2 gazeux, le module unitaire de gaz étant conçu pour recevoir une alimentation en N2 gazeux au niveau de l'une desdites vannes proportionnelles, et en CO2 au niveau de l'autre desdites vannes proportionnelles, et contrôler les vannes proportionnelles sur la base d'une rétroaction des capteurs de gaz de telle sorte que l'alimentation en N2 et en CO2 vers la chambre d'incubation est régulée de sorte à maintenir un niveau prédéfini d'O2 et/ou de CO2 dans ladite chambre d'incubation.
PCT/EP2013/071433 2012-10-15 2013-10-14 Incubateur d'embryons comportant un contrôle du gaz Ceased WO2014060360A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13776801.6A EP2906680A1 (fr) 2012-10-15 2013-10-14 Incubateur d'embryons comportant un contrôle du gaz

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DKPA201270627 2012-10-15
DKPA201270627 2012-10-15

Publications (1)

Publication Number Publication Date
WO2014060360A1 true WO2014060360A1 (fr) 2014-04-24

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ID=49356433

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PCT/EP2013/071433 Ceased WO2014060360A1 (fr) 2012-10-15 2013-10-14 Incubateur d'embryons comportant un contrôle du gaz

Country Status (2)

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EP (1) EP2906680A1 (fr)
WO (1) WO2014060360A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015197081A1 (fr) * 2014-06-27 2015-12-30 Kivex Biotec A/S Incubateur d'embryons comportant un régulation de température
WO2016131079A1 (fr) * 2015-02-17 2016-08-25 Genea Ip Holdings Pty Limited Procédé et appareil pour la culture dynamique d'un échantillon biologique
WO2018204007A1 (fr) * 2017-05-04 2018-11-08 Doody M D Kevin J Système d'incubation d'ovule fécondé par fécondation in vitro
EP4083183A1 (fr) * 2021-04-27 2022-11-02 Eppendorf SE Incubateur pour cultures cellulaires

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4701415A (en) * 1984-03-02 1987-10-20 Mallinckrodt, Inc. Controlled atmosphere enclosure
US20030092178A1 (en) * 2001-11-15 2003-05-15 Biospherix, Ltd. Cell culture incubator with dynamic oxygen control
JP2006217806A (ja) * 2005-02-08 2006-08-24 Matsushita Electric Ind Co Ltd 培養装置
EP2130901A1 (fr) * 2007-03-12 2009-12-09 Sanyo Electric Co., Ltd. Appareil de culture
WO2010004279A2 (fr) * 2008-07-08 2010-01-14 Ruskinn Life Sciences Limited Appareil de laboratoire pour un environnement contrôlé

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4701415A (en) * 1984-03-02 1987-10-20 Mallinckrodt, Inc. Controlled atmosphere enclosure
US20030092178A1 (en) * 2001-11-15 2003-05-15 Biospherix, Ltd. Cell culture incubator with dynamic oxygen control
JP2006217806A (ja) * 2005-02-08 2006-08-24 Matsushita Electric Ind Co Ltd 培養装置
EP2130901A1 (fr) * 2007-03-12 2009-12-09 Sanyo Electric Co., Ltd. Appareil de culture
WO2010004279A2 (fr) * 2008-07-08 2010-01-14 Ruskinn Life Sciences Limited Appareil de laboratoire pour un environnement contrôlé

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015197081A1 (fr) * 2014-06-27 2015-12-30 Kivex Biotec A/S Incubateur d'embryons comportant un régulation de température
US20170145372A1 (en) * 2014-06-27 2017-05-25 Kivex Biotec A/S Embryo Incubator Incorporating Temperature Control
WO2016131079A1 (fr) * 2015-02-17 2016-08-25 Genea Ip Holdings Pty Limited Procédé et appareil pour la culture dynamique d'un échantillon biologique
JP2018508234A (ja) * 2015-02-17 2018-03-29 ジェネア アイピー ホールディングス ピーティーワイ リミテッド 生物学的試料を動的に培養するための方法および装置
JP2021072814A (ja) * 2015-02-17 2021-05-13 ジェネア アイピー ホールディングス ピーティーワイ リミテッド 生物学的試料を動的に培養するための方法および装置
JP2022188054A (ja) * 2015-02-17 2022-12-20 ジェネア アイピー ホールディングス ピーティーワイ リミテッド 生物学的試料を動的に培養するための方法および装置
WO2018204007A1 (fr) * 2017-05-04 2018-11-08 Doody M D Kevin J Système d'incubation d'ovule fécondé par fécondation in vitro
EP4083183A1 (fr) * 2021-04-27 2022-11-02 Eppendorf SE Incubateur pour cultures cellulaires
WO2022229268A1 (fr) * 2021-04-27 2022-11-03 Eppendorf Se Incubateur pour cultures cellulaires

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