EP2906680A1 - Embryo incubator incorporating gas control - Google Patents

Embryo incubator incorporating gas control

Info

Publication number
EP2906680A1
EP2906680A1 EP13776801.6A EP13776801A EP2906680A1 EP 2906680 A1 EP2906680 A1 EP 2906680A1 EP 13776801 A EP13776801 A EP 13776801A EP 2906680 A1 EP2906680 A1 EP 2906680A1
Authority
EP
European Patent Office
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.)
Withdrawn
Application number
EP13776801.6A
Other languages
German (de)
French (fr)
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
Publication of EP2906680A1 publication Critical patent/EP2906680A1/en
Withdrawn legal-status Critical Current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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Abstract

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. In a first aspect the invention 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 CO2 gas sensor and an O2 gas sensor, wherein the gas unitary module is adapted to receive a gas supply of N2 at one of said proportional valves and CO2 at another of said proportional valves, and control the proportional valves based on feedback from the gas sensors such that supply of N2 and CO2 to the incubation chamber is regulated to sustain a predefined level of O2 and/or CO2 in said incubating chamber.

Description

Embryo incubator incorporating gas control
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.
Background of the Invention
Infertility affects more than 80 million people worldwide. It is estimated that 10% of all couples experience primary or secondary infertility. In vitro fertilization (IVF) 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. However, with the present incubators service is in general complicated thereby requiring wasteful offline service time. 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 C02 gas sensor and an 02 gas sensor, wherein the gas unitary module is adapted to receive a gas supply of N2 at one of said proportional valves and C02 at another of said proportional valves, and control the proportional valves based on feedback from the gas sensors such that supply of N2 and C02 to the incubation chamber is regulated to sustain a predefined level of 02 and/or C02 in said incubating chamber. By incorporating proportional valves, gas sensors and gas control many of the key components in the incubation chamber's gas supply is incorporated in a single module. Regulation of the atmosphere in the incubation chamber is thereby upgraded compared to the presently available incubators, and in general serviceability of the incubator is greatly improved.
Description of the drawings
The invention will in the following be described in greater detail with reference to the accompanying drawings:
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, and
Fig.4a-b are pictures of an UV lamp inside a decontamination chamber of a gas unitary module.
Detailed description of the invention
To ensure optimized developmental conditions for embryos cultivated in incubators 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 %. When the incubator is in operation the incubation chamber and the gas unitary module may form a closed (fluid) pipelined system where the gas (i.e. N2 and C02) 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 C02 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 C02 in the incubation chamber. Thus, by having a controlled gas supply of N2 and C02 and by measuring the concentration of 02 and C02, the oxygen concentration in the incubation chamber and pH in the medium can be regulated and controlled. 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.
In a further embodiment of the invention the incubating chamber comprises holding means for at least one embryo, e.g. microscopy slides. The embryos may be human embryos.
In one embodiment of the invention the gas unitary module further comprises a N2 gas sensor to further provide information of the N2 concentration. Further, the gas unitary module may comprise a chamber for accommodating the gas sensors, i.e. a gas sensing chamber.
In further embodiment of the invention the incubator comprises circulation means for recirculating the gas between the incubation chamber and the gas unitary module. Thus, during operation of the incubator 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 C02 or N2 is only supplied to this closed recirculating system when needed to sustain the desired gas concentration. To improve serviceability of the incubator 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.
In a further embodiment of the invention 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. Further, said filtration element may comprise a carbon filter for filtration of volatile organic compounds, such as a VOC filter. In a further embodiment of the invention the gas unitary module further comprises an
UV lamp. In one embodiment of the invention 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. In a further embodiment of the invention the gas unitary module comprises a
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. However, 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. As living organisms are cultivated in the incubation chamber operation of the UV lamp can be helpful to ensure decontamination of the gas entering the incubation chamber. In a further embodiment 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. be mounted in the decontamination chamber. However, as only visual contact is necessary between the UV light sensor and the UV lamp, 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. In a further embodiment of the invention 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.
In a further embodiment of the invention 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.
In a further embodiment of the invention one or more temperature regulators are provided for controlling the temperature in the incubating chamber. Also humidity in the incubation chamber may be controlled.
Detailed description of the drawings
Fig. 1 a shows an example of a gas unitary module V with two proportional valves 2 and pressure regulators 3. An 02 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 C02 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 C02 sensor 7, the 02 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
EmbryoScope™) where the gas unitary module 1 is mounted. The gas outlet 6 from the module 1 is visible. C02 and N2 are supplied via the tube 14 which connects the two proportional valves 2 with the gas outlet 6. Before entering the incubation chamber 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. If 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 02 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
decontamination chamber 1 1. 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.
In some example implementations 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. For example, 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. For example, in some implementations it may be helpful to provide pre-heating of gas before the gas enters into the incubation chamber, and this may, in accordance with some embodiments, be performed by heating the gas in the gas unitary module. 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. Rather than heating each of these elements individually together with the gas stream, 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. For example, 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. In accordance with conventional temperature control techniques, 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.
In one specific example implementation 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) may be provided to cover the heating element to help further improve the uniformity of heat from across the surface(s) of the gas unitary module. 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. Thus, the single replaceable service unit comprising the gas unitary module may additionally comprise its own heating control.
As noted above, 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.
Further details of the invention The invention will now be described in further detail with reference to the following items:
1. 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 C02 gas sensor and an 02 gas sensor, wherein the gas unitary module is adapted to:
- receive a gas supply of N2 at one of said proportional valves and C02 at another of said proportional valves, and
- control the proportional valves based on feedback from the gas sensors such that supply of N2 and C02 to the incubation chamber is regulated to sustain a predefined level of 02 and/or C02 in said incubating chamber.
The incubator according to item 1 , wherein the gas unitary module further comprises an UV lamp.
The incubator according to any of the preceding items, wherein the incubating chamber comprises holding means for at least one embryo.
The incubator according to any of the preceding items, wherein the embryos are human embryos.
The incubator according to any of the preceding items, wherein the gas unitary module further comprises a nitrogen gas sensor.
The incubator according to any of the preceding items, wherein 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.
The incubator according to item 7, wherein the circulation means is mounted in the gas unitary module, preferably mounted in the gas sensing chamber of the gas unitary module.
The incubator according to any of the preceding items 7 to 8, wherein circulation means comprises a fan or pump.
10. The incubator according to any of the preceding items, further comprising a filtration element adapted to filter the gas supplied to the incubation chamber. The incubator according to item 10, wherein said filtration element comprises a high efficiency particulate arresting (H EPA) filter.
The incubator according to any of the preceding items 10 to 11 , wherein 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 item 13, wherein said pressure regulators are non-venting.
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 incubator according to any of the preceding items 2 to 16, wherein the UV lamp is adapted to decontaminate gas flowing through the gas unitary module.
The incubator according to any of the preceding items 2 to 17, wherein the gas unitary module comprises a decontamination chamber for accommodating the UV lamp, said decontamination chamber in fluid communication with the sensing chamber.
The incubator according to any of the preceding items 2 to 18, wherein the gas unitary module further comprises an UV light sensor. The incubator according to item 19, wherein the UV light sensor is mounted in the decontamination chamber.
The incubator according to item 19, wherein the UV light sensor is mounted on the outside of the gas unitary module.
The incubator according to item 19, wherein the UV light sensor is mounted on the outside of the gas unitary module adjacent a transparent part of the gas unitary module.
The incubator according to any of the preceding items, wherein the 02 gas sensor is mounted on the outside of the gas unitary module

Claims

Claims
1. 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 and comprising a C02 gas sensor and an 02 gas sensor and a circulation mechanism mounted in the gas unitary module for circulating gas between the incubation chamber and the gas unitary module, wherein the gas unitary module comprises a single module for the incubator.
2. The incubator according to claim 1 , wherein the gas unitary module comprises at least two proportional valves and is adapted to:
receive a gas supply of N2 at one of said proportional valves and C02 at another of said proportional valves, and
control the proportional valves based on feedback from the gas sensors such that supply of N2 and C02 to the incubation chamber is regulated to sustain a predefined level of 02 and/or C02 in said incubating chamber.
3. The incubator according to claim 1 or 2, wherein the gas unitary module further comprises an ultra violet, UV, lamp adapted to decontaminate gas flowing through the gas unitary module.
4. The incubator according to any of the preceding claims, wherein the gas unitary module comprises a gas sensing chamber for accommodating the gas sensors.
5. The incubator according to claim 4 wherein the circulation means is mounted in the gas sensing chamber of the gas unitary module
6. The incubator according to any of the preceding claims, wherein the circulation mechanism comprises a pump or a fan.
7. The incubator according to any of the preceding claims, further comprising a filtration element, such as a volatile organic compound, VOC, filter, adapted to filter the gas supplied to the incubation chamber.
8. The incubator according to claim 2, further comprising pressure regulators for controlling the pressure at the input of the proportional valves.
9. The incubator according to claim 2, further comprising one or more PID regulators for regulating the proportional valves based on the sensor feedback.
10. The incubator according to any of the preceding claims, further comprising one or more temperature regulators for controlling the temperature in the incubating chamber.
1 1. The incubator according to claim 3, wherein the gas unitary module comprises a decontamination chamber for accommodating the UV lamp.
12. The incubator according to claim 3, wherein the gas unitary module further comprises an UV light sensor.
13. The incubator according to any of the preceding claims, wherein the 02 gas sensor is mounted on the outside of the gas unitary module.
14. The incubator according to any of the preceding claims, further comprising an arrangement for adjusting the temperature of the gas unitary module.
15. The incubator according to claim 14, wherein the arrangement for adjusting the temperature of the gas unitary module comprises a heating element.
16. The incubator according to claim 15, further comprising a temperature sensor for measuring a temperature associated with the gas unitary module and a temperature controller arranged to control the heating element in response to measurements from the temperature sensor.
17. The incubator according to any of the preceding claims, further comprising thermal insulation material arranged around at least a part of the gas unitary module.
EP13776801.6A 2012-10-15 2013-10-14 Embryo incubator incorporating gas control Withdrawn EP2906680A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DKPA201270627 2012-10-15
PCT/EP2013/071433 WO2014060360A1 (en) 2012-10-15 2013-10-14 Embryo incubator incorporating gas control

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EP2906680A1 true EP2906680A1 (en) 2015-08-19

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Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3161123A1 (en) * 2014-06-27 2017-05-03 Kivex Biotec A/S Embryo incubator incorporating temperature control
JP2018508234A (en) * 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 Method and apparatus for dynamically culturing biological samples
EP3619292A1 (en) * 2017-05-04 2020-03-11 Doody, M.D., Kevin J. In vitro fertilization fertilized egg incubation system
EP4083183A1 (en) * 2021-04-27 2022-11-02 Eppendorf SE Cell culture incubator

Family Cites Families (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 (en) * 2005-02-08 2006-08-24 Matsushita Electric Ind Co Ltd Culture apparatus
JP2008220235A (en) * 2007-03-12 2008-09-25 Sanyo Electric Co Ltd Culture apparatus
GB2461707B (en) * 2008-07-08 2013-06-26 Ruskinn Life Sciences Ltd Laboratory apparatus for a controlled environment

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2014060360A1 *

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