WO2024099600A1 - A modular incubator system providing improved illumination for image capture of an incubated biological material - Google Patents

A modular incubator system providing improved illumination for image capture of an incubated biological material Download PDF

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Publication number
WO2024099600A1
WO2024099600A1 PCT/EP2023/067017 EP2023067017W WO2024099600A1 WO 2024099600 A1 WO2024099600 A1 WO 2024099600A1 EP 2023067017 W EP2023067017 W EP 2023067017W WO 2024099600 A1 WO2024099600 A1 WO 2024099600A1
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WIPO (PCT)
Prior art keywords
modular incubator
gas
modular
chamber
docking
Prior art date
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PCT/EP2023/067017
Other languages
French (fr)
Inventor
Ricky Lindgaard Nielsen
Kestutis PLATKUNAS
Dainius BALKAUSKAS
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Esco Medical Technologies, Uab
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Application filed by Esco Medical Technologies, Uab filed Critical Esco Medical Technologies, Uab
Publication of WO2024099600A1 publication Critical patent/WO2024099600A1/en

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    • 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/24Gas permeable parts
    • 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/40Manifolds; Distribution pieces
    • 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/44Multiple separable units; Modules
    • 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
    • C12M31/00Means for providing, directing, scattering or concentrating light
    • C12M31/08Means for providing, directing, scattering or concentrating light by conducting or reflecting elements located inside the reactor or in its structure
    • 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
    • C12M41/36Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements

Definitions

  • a modular incubator system providing improved illumination for image capture of an incubated biological material
  • the present invention relates in general to the field of incubators for incubating a viable biological material.
  • the present invention relates in a first aspect to a modular incubator system comprising one or more modular incubator chambers in combination with a docking station for incubating a viable biological material.
  • the present invention relates to a modular incubator chamber for incubating a viable biological material.
  • the present invention relates to a docking station for incubating a viable biological material.
  • the present invention relates to a use of the modular incubator system according to the first aspect for incubating a viable biological material.
  • the present invention relates to a use of the modular incubator chamber according to the second aspect for incubating a viable biological material.
  • the present invention relates to a use of the docking station according to the third aspect for incubating a viable biological material.
  • the present invention relates to a method for incubating a viable biological material.
  • IVF in vitro fertilization
  • In vitro fertilization involves capturing a ripened egg from a female ovary, fertilizing the ovary with a spermatozoon, incubating the fertilized egg under a controlled environment and subsequently inserting the fertilized and incubated egg in a female’s uterus.
  • in vitro fertilization is most commonly used by females or couples which notoriously are having problems in getting pregnant the natural way, thus implying some degree of reduced fertility by the male or female counterpart of the couple, or both, and as in vitro fertilization techniques involves quite expensive procedures, these in vitro fertilization techniques are usually performed in a way that seek to optimize efficiency, especially in view of the fact that frequently more than one insertion of a fertilized egg into the female’ uterus will be necessary in order to encounter a successful pregnancy.
  • an IVF mediated pregnancy may be advantageous.
  • the female is typically provided with a hormone treatment prior to harvesting eggs from her ovary.
  • hormone treatment will make the female ovary ovulate not only one egg, but a multitude of eggs at the same time.
  • Prior art incubators include a compartment which allows for accommodating more than one culture dish comprising the fertilized eggs.
  • Some prior art incubators comprise a housing having one or more doors for providing access to the interior of the incubator.
  • the interior of the incubator holds one or more culture dishes accommodating the embryos to be cultured.
  • Such incubators may be provided with various regulation means for controlling humidity, temperature and gas composition of the interior of the incubator.
  • modular incubators are configured to be stored in a docking station which may provide the controlling of physical and chemical parameters to be imposed to the embryos being accommodated therein. Once any manual manipulation steps in respect of the embryo is needed, the modular incubator may be removed from the docking station and arranged on a laboratory bench for easy access to the embryo.
  • image capturing means are provided in the prior art incubator and these image capturing means may be equipped with microscopic optics which allow for capturing close-up images of each fertilized egg with the view to only select those embryos that exhibit a normal or healthy development and to only insert those embryos into the female’s uterus.
  • Time lapse imaging provides for visual study of the visible physical development, such as time of division of cells at different stages, overall speed of division of cells etc.
  • the prior art use of microscopic optics in studying morphological quality of an embryo with the view to select the healthiest oocyte(s) typically involves direction of light to the oocyte from one side thereof (such as from above or from below) and studying the morphological quality of the oocyte by use of microscopic optics arranged at an opposite thereof (such as from below or from above the oocyte).
  • the present invention relates in a first aspect to a modular incubator system for incubating a viable biological material, said modular incubator system comprising:
  • said modular incubator chamber comprises a housing; wherein said housing comprises a lid, wherein said lid is being configured to be able to shift between an open configuration allowing access to the interior of said modular incubator chamber and a closed configuration, sealing off access to the interior of said modular incubator chamber; wherein said modular incubator chamber, at said interior thereof, comprises a culture dish support for positioning a culture dish with the view to accommodate one or more biological materials within the housing of said modular incubator chamber; wherein said housing of said modular incubator chamber comprises a transparent window for enabling capturing of images of a biological material being accommodated in the interior thereof, through said transparent window; wherein said housing comprises a light directing element for directing light to an area of said culture dish support in a light aiming direction A; wherein said docking station comprises one or more docking ports for receiving a housing of an incubator chamber; wherein in respect of one or more docking ports of said docking station, said docking port comprises an image capturing device for
  • the present invention relates in a second aspect to a modular incubator chamber, wherein said modular incubator chamber is comprising features as defined in respect of the modular incubator chamber of the modular incubator system of the first aspect of the present invention.
  • the present invention relates in a third aspect to a docking station, wherein said docking station is comprising features as defined in respect of the docking station of the modular incubator system of the first aspect of the present invention.
  • the present invention provides a use of a modular incubator system according to the first aspect of the present invention for incubating a viable biological material.
  • the present invention provides a use of a modular incubator chamber according to the second aspect of the present invention for incubating a viable biological material.
  • the present invention provides a use of a docking station according to the third aspect of the present invention for incubating a viable biological material.
  • the present invention provides a method of incubating a viable biological material M, wherein said method comprises: i) providing a modular incubator system according to the first aspect of the present invention; ii) providing a viable biological material; iii) arranging said viable biological material in a culture dish and subsequently arranging said culture dish on the culture dish support in the interior of said modular incubator chamber of said modular incubator system; iv) docking said modular incubator chamber in a docking port of said docking station of said incubator system; v) allowing said viable biological material to be incubated in said modular incubator chamber; vi) while performing step v) enabling said light directing element of said modular incubator chamber to direct light to an area of said culture dish support in said light aiming direction A; vii) while performing step v) and vi) making said image capturing device capture image(s) of said viable biological material M in the interior of said modular incubator chamber, at a focus direction B; wherein said focus direction A of light propagating from said light directing element of said modular incubator chamber is being
  • the present invention in its various aspects provides improved contrasting effects in capturing images of a viable biological material being incubated in an incubator.
  • Fig. 1 is a perspective view illustrating the general concept of providing an incubator as a modular incubator system comprising a plurality of modular incubator chambers in combination with a docking station.
  • Fig. 2a is a perspective view of the modular incubator chamber of the modular incubator system illustrated in Fig. 1 as seen from above.
  • Fig. 2b is a plan view of a modular incubator chamber of the modular docking system of fig. 1.
  • Fig. 2c is a plan view of the modular incubator chamber illustrated in Fig. 2 as seen from a rear end.
  • Fig. 3 is a cross-sectional view of the modular incubator chamber of the modular incubator system illustrated in Fig. 1.
  • Fig. 4 is a diagram illustrating the principle of the concept of the present invention.
  • Fig. 5 is a diagram illustrating the concept of a light aiming direction as employed in the present application.
  • Fig. 6 is diagrammatic representation of an embodiment illustrating in more details the principle of the present invention.
  • Fig. 7 is a diagrammatic representation of another embodiment illustrating in more details the principle of the present invention.
  • Fig. 8 is diagrammatic representation of yet another embodiment illustrating in more details the principle of the present invention.
  • Fig. 9 is a diagrammatic representation of a still other embodiment illustrating in more details the principle of the present invention.
  • Fig. 10 is diagrammatic representation of a yet still other embodiment illustrating in more details the principle of the present invention.
  • Fig. 11 is diagrammatic representation of an embodiment alternative to the one illustrated in Fig. 10, illustrating in more details the principle of the present invention.
  • Fig. 12 is a diagram illustrating the principle of including an inclination angle adjustment element for adjusting the inclination angle a
  • Fig. 13a, 13b and 12c are diagrams illustrating the principle of including a shadowing element in the docking ports 402 of the docking station.
  • Fig. 14a and 14b are drawings illustrating the working modes of valves of a valve system to be used with the modular incubator chamber and the associated docking port of the docking station of the docking system of the present invention.
  • Fig. 15 is a diagram illustrating one embodiment of a design of a gas supply system comprising a gas source and a gas distribution system to be used with the docking station of the modular incubator system of the present invention.
  • Fig. 16 is a diagram illustrating the concept of gas source which may be incorporated in the docking station of the modular incubator system of the present invention.
  • Fig. 17 is a diagram illustrating the working mode of the controlling of the modular incubator system according to the invention.
  • Fig. 18a - 18c are microscopic photographs illustrating the effect of providing an inclined light, relative to a focus direction, when capturing images of a viable biological material.
  • the present invention relates to a modular incubator system 500 for incubating a viable biological material M, said modular incubator system comprising:
  • said modular incubator chamber 300 comprises a housing 302; wherein said housing 302 comprises a lid 304, wherein said lid is being configured to be able to shift between an open configuration allowing access to the interior 306 of said modular incubator chamber and a closed configuration, sealing off access to the interior of said modular incubator chamber; wherein said modular incubator chamber, at said interior 306 thereof, comprises a culture dish support 308 for positioning a culture dish 310 with the view to accommodate one or more biological materials M within the housing 302 of said modular incubator chamber 300; wherein said housing 302 of said modular incubator chamber 300 comprises a transparent window 316 for enabling capturing of images of a biological material M being accommodated in the interior thereof, through said transparent window; wherein said housing comprises a light directing element 350 for directing light to an area of said culture dish support 308 in a light aiming direction A; wherein said docking station 400 comprises one or more docking ports 402 for receiving a housing 302;
  • the modular incubator system of the first aspect of the present invention is for monitoring the development of a viable biological material during incubation thereof.
  • the monitoring is performed by the image capturing device 408 which is arranged at or in a docking port 402 of the docking station 400 of the modular incubator system 500.
  • the light aiming direction A of the light provided in the interior 306 of the modular incubator chamber by the light directing element 350 is being inclined relative to said focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is 0°.
  • module incubator system shall be construed to mean a system comprising a docking station in combination with one or more incubator chambers, wherein the one or more incubator chambers is/are configured to be docked in respective docking ports of that docking station.
  • the modular incubator system is intended for incubation or cultivation of a viable biological material.
  • the incubator system comprising the docking station and one or more incubator chamber(s) in general is configured for providing some kind of interaction between the docking station and the incubator chambers being docked therein.
  • Such interactions may be one or more of the following: providing a gas having a desired composition to the incubator chamber(s); providing electricity to the incubator chamber(s) for powering hearing elements thereof and/or for powering a light source in the incubator chamber(s); allowing monitoring of the viable biological material being present in the incubator chamber(s), such as by means of an image capturing device which is located in the docking station.
  • module incubator system shall be construed in such a way that the incubator chambers are configured to be used for incubation of a viable biological material, irrespective of whether the individual incubator chamber is being docked in a docking port of the docking station, or whether that incubator chamber is removed from the docking port of the docking station.
  • cultivation or incubation of a viable biological material of the individual incubator chambers may take place and/or be continued even after that incubator chamber has been removed from its docking station and placed e.g. on a laboratory bench.
  • manual manipulation operations such as shift or control of culture or growth media, manual inspection by use of a laboratory microscope or the like can take place.
  • Such operation are preferably carried out under a hood providing a desired gas atmosphere.
  • the incubation chamber when the individual incubation chamber has been removed from a docking port, the incubation chamber is configured in a way that enables support on a planar, horizontal support surface. This may be attained by providing the bottom part of the incubator chamber with one or more supports or simply by making the bottom part of the incubator chamber comprise a flat surface.
  • the incubation chamber in the orientation intended during use for incubation, is having its maximum dimension in a horizontal direction.
  • the dimension of the incubation chamber in a horizontal direction is greater than the dimension in a vertical direction.
  • adequate stability is attended when the incubator chamber is used for incubation at a location outside a docking port of the docking station.
  • the individual incubator chambers may in embodiments comprise a display, such as an electronic display, for providing information relating to the identity of the viable biological material being accommodated in the incubator chamber.
  • a display such as an electronic display
  • the present invention does not relate to methods or uses which involve treatment of the human or animal body by surgery or diagnostic methods practiced on the human or animal body.
  • the present invention may relate to methods or uses which involve treatment of the human or animal body by surgery or diagnostic methods practiced on the human or animal body.
  • the inclination angle a is selected from the ranges of 0.5 - 25°, such as 1 - 24°, for example 2 - 23°, e.g. 3 - 22°, such as 4 - 21°, for example 5 - 20°, such as 6 - 19°, for example 7 - 18°, such as 8 - 17°, for example 9 - 16°, such as 10 - 15°, e.g. 11 - 14° or 12 - 13°.
  • said light directing element 350 is being positioned in the interior 306 of said modular incubator chamber 300 at a position which is displaced relative to the focus direction B of said image capturing device 408 of said docking port 402, in a direction perpendicular to said focus direction B, thereby providing said inclination angle a between said light aiming direction A and said focus direction B.
  • Arranging the light directing element 350 in a position in the interior 306 of the modular incubator chamber 300 which is displaced relative to the focus direction B of the image capturing device 408 is a simple way of providing the desired inclination angle between the light aiming direction A and said focus direction B.
  • said culture dish support 308 is defining a planar support surface P for supporting said culture dish 310.
  • said focus direction B of said image capturing device 408 of said docking port 402 is being essentially perpendicular to said planar support surface P of said culture dish support 308 of said modular incubator chamber 300, and said light aiming direction A of said light directing element 350 of said modular incubator chamber 300 is not being perpendicular to said planar support surface P of said culture dish support 308.
  • the culture dish 310 on a support 308 in the modular incubator chamber 300 in such a way that focus direction B of the image capturing device 408 of the docking port 402 is being essentially perpendicular to a planar support surface P of the culture dish support 308.
  • said light directing element 350 is being attached to said lid 304 of the housing 306 of said modular incubator chamber 300, at an inner side thereof.
  • said light directing element 350 comprises a diffuser, such as a diffuser lens.
  • the light of the light directing element can be softened.
  • said transparent window 316 of said modular incubator chamber 300 is located at a bottom part 330 of said housing 302 of said chamber.
  • the transparent window 316 of the modular incubator chamber 300 is conveniently arranged at a bottom part 330 of the housing 302 of said modular incubator chamber 300.
  • the light directing element 350 is geometrically configured to make said light propagate at a maximum spreading angle of propagation of 1 - 65°, such as 5 - 60°, e.g. 10 - 55°, such as 15 - 50°, for example 20 - 45°, e.g. 25 - 40° or 30 - 35°.
  • the light directing element 350 ensures minimizing any undesired reflections of light within the interior 306 of the modular incubator chamber 300.
  • said light aiming direction A is directed towards said transparent window 316 in said housing 302 of said modular incubator 300.
  • said modular incubator chamber 300 comprises inclination angle adjustment element 332 for adjusting the inclination angle a between said light aiming direction A and said focus direction B, wherein said inclination angle adjustment element 332 is configured to enable adjustment of said inclination angle a so that this inclination angle a may attain an angle selected from the ranges 0.5 - 25°, such as 1 - 24°, for example 2 - 23°, e.g.
  • 3 - 22° such as 4 - 21°, for example 5 - 20°, such as 6 - 19°, for example 7 - 18°, such as 8 - 17°, for example 9 - 16°, such as 10 - 15°, e.g. 11 - 14° or 12 - 13°.
  • the degree or magnitude of the inclination angle may be adjusted during incubation and monitoring of the viable biological material.
  • inclination angle adjustment element 332 comprises a rotational adjustment element 334 which is being configured, upon being adjusted, to enable changing the light aiming direction A of light direction propagation from said light directing element 350 by changing the spatial orientation of said light directing element 350; and/or wherein said inclination angle adjustment element 332 comprises a displacement adjustment element 336 which is being configured, upon being adjusted, to enable changing a position of said light directing element 350.
  • a rotational adjustment element 334 which is being configured, upon being adjusted, to enable changing the light aiming direction A of light direction propagation from said light directing element 350 by changing the spatial orientation of said light directing element 350
  • said inclination angle adjustment element 332 comprises a displacement adjustment element 336 which is being configured, upon being adjusted, to enable changing a position of said light directing element 350.
  • the rotational adjustment element 334 and/or said displacement adjustment element 336 is/are electrically controlled by electric actuators which provides for changing the light aiming direction A of light direction propagation from said light directing element 350 and/or for changing the position of said light directing element 350 upon being supplied by an electric signal thereto.
  • said docking port 402 comprises a shadowing element 450 which is configured to enable blocking part of the light being propagated towards the optics of said image capturing device 408.
  • a shadowing element will enable further control of the contrasting effects necessary for proper monitoring of the degree of cell divisions which have taken place in the viable biological material.
  • the shadowing element 450 comprises a shadowing plate 452 comprising a through-going hole 454 having a fixed geometry and/or size, such as a round hole, such as a circular hole; or a rectangular hole, wherein said shadowing plate 452 is being arranged relative to said image capturing device 408 so that the focus direction B of said image capturing device 408 passes through that hole 452.
  • This embodiment is a very simple way of providing such additional contrasting effects.
  • the shadowing element 450 comprises an iris diaphragm 458 having a plurality of iris lamellas 460 which are movable in relation to each other and thereby are configured, upon being subjected to an external force, to vary the size of a through-going hole 462 formed in the centre of said iris diaphragm; wherein said iris diaphragm 458 is being arranged relative to said image capturing device 408 so that the focus direction B of said image capturing device 408 passes through that hole 462.
  • the iris diaphragm 458 comprises an actuator 464, such as a remote-controlled electric actuator which is mechanically connected to said iris lamellas 460 and which is configured to enable movement of said iris lamellas in concert so as to vary the size of said through-going hole 462.
  • an actuator 464 such as a remote- controlled electric actuator which is mechanically connected to said iris lamellas 460 and which is configured to enable movement of said iris lamellas in concert so as to vary the size of said through-going hole 462.
  • the degree of the shadowing or contrasting effect can be remotely controlled while monitoring and incubating the viable biological material.
  • the shadowing element 450 is coupled to an X- stage or XY-stage 456 in a way enabling said shadowing element 450 to be independently displaced in one or two displacement directions D1,D2 which each optionally is/are being essentially perpendicular to the focus direction B of said image capturing device 408.
  • the X-stage or XY-stage comprises an electric actuator 466, wherein said electric actuator 466 configured to electrically control the displacement of said shadowing element 450 in one or two of said displacement directions D1,D2 upon being supplied by an electric signal thereto.
  • the shadowing element 450 is being arranged outside the optics of said image capturing device 408.
  • said shadowing element 450 is being arranged inside the optics of said image capturing device 408.
  • said light directing element 350 is an active light source 352 being arranged in the interior 306 of the modular incubating chamber 300, wherein said active light source 352 is configured for propagating light in said light aiming direction A, by being supplied with electric power.
  • the light directing element 350 may either be an active light source 352 which is configured to emit light upon being provided with electric power, or the light directing element 350 may be a passive light direction element which directs incoming light, such as by reflection, into the light aiming direction A.
  • the above embodiment is very simple in that an active light source 352 being arranged in the interior 306 of the modular incubating chamber 300 for providing light in the light aiming direction A.
  • said light directing element 350 is a passive light directing element in the form of a light conveyor 354 being arranged in the interior 306 of the modular incubating chamber 300, wherein said light conveyor 354 is configured for directing incoming light, in said light aiming direction A, such as by reflecting said incoming light.
  • said housing 302 of said modular incubator chamber 300 comprises a light transmission element 356 for providing light to said light conveyor 354,350 from a position outside said chamber 300; and wherein in respect of one or more of said one or more docking ports 402 of said docking station 400, said docking port 402 comprises an active light source 352; wherein the position of said light transmission element 356 of said housing 302 of said modular incubator chamber 300 and the position of said active light source 352 of said docking port 402 are adapted to each other in such a way that once being docked in said docking port 402 of said docking station 400, light emitted from said active light source 352 of said docking port 402 will be able to transmit said light transmission element 356 of said housing 302 of said modular incubator chamber 300 and propagate to said light conveyor 354,350 in the interior of said housing 302.
  • said light transmission element 356 of said housing 302 of said modular incubator chamber 300 is being arranged at a top of said housing 302, such as at the lid 304 of said housing 302 and is being the same entity as said light conveyor 350,354.
  • said light transmission element 356 of said housing 302 of said modular incubator chamber 300 is being arranged at a side of said housing 302.
  • the light conveyor 354 is being a light deflector, such as an optical prism or lens.
  • said light transmission element 356 of said housing 302 of said modular incubator chamber 300 is being arranged at a bottom 330 of said housing 302, wherein said housing 302 in the interior thereof comprises a light reflector 358, wherein said light reflector 358 is being configured to reflect upwardly propagating light into an essentially horizontally propagating light, propagating towards said light conveyor 350,354; and wherein said light conveyor 350,354 is configured to reflect said essentially horizontally propagating light into said light aiming direction A.
  • light emitted from an active light source 352 arranged in or at the docking port 402 is directed into the interior 306 of the modular incubator chamber 300, where it is deflected by the reflector 358, whereafter the light hits the light conveyor 354.
  • the light conveyor 350,354 is being a light reflector, such as a mirror.
  • said active light source 352 is arranged in said docking port 402 at a position so as to be configured to direct emitted light in a direction essentially parallel to said focus direction B of said image capturing device 408, and wherein in respect of one or more of said one or more modular incubator chambers 300, said light conveyor 350,354 is configured to direct said emitted light in said light aiming direction A.
  • the light conveyor 350,354 is being a light reflector, such as a mirror.
  • the active light source 352 is being arranged adjacent to said image capturing device 408.
  • the active light source 352 is being arranged within the optics of said capturing device 408.
  • said active light source 352 is being selected from the group of one or more LEDs, one or more laser diodes, one or more incandescent light bulbs.
  • said transparent window 316 and/or said light transmission element 356 is made of glass or plastic.
  • said image capturing device(s) 408 comprise(s) microscopic optics so as to enable capturing of microscope images.
  • magnified images may be captured which improves study of the morphological nature of the biological materials being incubated.
  • said housing 302 of said modular incubator chamber 300 is being provided with electric connectors 322 for providing electric power and/or electric signals to said modular incubator chamber; and wherein in respect of one or more docking ports 402 of said docking station 400, said docking port is being provided with electric connectors 410, thereby allowing providing electric power and/or electric signals between said docking port 402 of said docking station 400 and a modular incubator chamber 300 being docked therein.
  • 410 control instructions can be send to a modular incubator chamber 300 via its corresponding docking port 402 and its electric connectors 410 of the docking station 400.
  • said lid 304 is being a hinged lid which is being connected to said housing of said modular incubator chamber 302 via a hinge.
  • said housing 302 of said modular incubator chamber 300 comprises a display 324 which is being configured to display information relating to an operational status of the incubation taking place in said modular incubator chamber.
  • said modular incubator chamber 300 comprises a chamber inlet opening for gas 312, wherein said chamber inlet opening for gas 312 is being in fluid connection with the interior 306 of said modular incubator chamber; and wherein said modular incubator chamber 300 furthermore comprises a chamber outlet opening for gas 314, wherein said chamber outlet opening for gas 314 is being in fluid connection with the interior 306 of said modular incubator chamber; and wherein in respect of one or more docking ports 402 of said docking station 400, said docking port 402 comprises a docking port outlet opening for gas 404 and a docking port inlet opening for gas 406; thereby enabling transfer of gas from said docking port 402 of said docking station 400 to the interior 306 of said modular incubator chamber 300 via said docking port outlet opening for gas 404 and said chamber inlet opening for gas 312; and thereby enabling transfer of gas from the interior 306 of said modular incubator chamber 300 to said docking port
  • the position of said chamber inlet opening for gas 312 of said housing 302 of said modular incubator chamber 300 and the position of said docking port outlet opening for gas 404 of said docking port 402 are adapted to each other in such a way that once docking said modular incubator chamber 300 in said docking port 402, said chamber inlet opening for gas 312 of said housing 302 of said modular incubator chamber 300 and said docking port outlet opening for gas 404 of said docking port 402 will be in fluid connection, thereby enabling transfer of gas from said docking port 402 to said modular incubator chamber 300; and wherein the position of said chamber outlet opening for gas 314 of said housing 302 of said modular incubator chamber 300 and the position of said docking port inlet opening for gas 406 of said docking port 402 are adapted to each other in such a way that
  • gas having a desired composition can be delivered from a gas source 202 via a gas distribution system 204 to the interior 306 of the modular incubator chamber 300 via the docking port outlet opening for gas 404 and the chamber inlet opening for gas 312, and gas from the interior 306 of the modular incubator chamber 300 can be returned to the gas source 202 via the chamber outlet opening for gas 314 and the docking port inlet opening for gas 406.
  • the docking port outlet opening for gas 404 of said docking port 402 comprises a valve 4 and said chamber inlet opening for gas 312 of said housing 302 comprises a valve 2; and said chamber outlet opening for gas 314 comprises a valve 2 and said docking port inlet opening for gas 406 of said docking port 402 comprises a valve 4.
  • said valve 2 of said chamber inlet opening for gas 312 and said valve 2 of said chamber outlet opening for gas 314 each comprises a valve body 6 having a front end 10, a rear end 12 and a through-going channel 14 therein, and a spring-loaded displaceable valve element 8, wherein said displaceable valve element 8 is being arranged in said through-going channel 14; wherein said displaceable valve element 8 is being configured to be displaceable in said through-going channel 14 of said valve body 6 in such a way, that when not acted upon by an external force, said spring-loaded displaceable valve element 8 is not being displaced in said through-going channel 14 of said valve body 6, thereby making said valve attain a closed configuration blocking passage of gas through said through-going channel 14, and in such a way, that when acted upon by an external force, said spring-loaded displaceable valve element 8 is being displaced in said through-going channel
  • each of the two valves 2,4 will be able to change configuration between an open and a closed configuration by displacement of the respective valve element 8,18 in the associated valve body 6,16.
  • valves 2,4 are having dimensions and geometries in such a way that once docking said modular incubator chamber 300 in said docking port 402 of said docking station 400, said displaceable valve element 8 of said valve 2 and said displaceable valve element 18 of said valve 4 will displace each other into their respective valve bodies 6,16, thereby opening said valves 2,4 of said docking port outlet opening for gas 404 and said chamber inlet opening for gas 312; and thereby opening said valves 2,4 of said chamber outlet opening for gas 314 and said docking port inlet opening for gas 406.
  • each of the two valves 2,4 will open the other valve 4,2 once being brought into contact with each other by making their respective front ends 10,20 meet.
  • said docking port outlet opening for gas 404 comprises a flow restrictor for restricting the magnitude of flow of gas flowing into said docking port 402.
  • the flow restrictor may comprises a tube through which the gas is conveyed to said docking port 402, wherein said tube optionally is having a cross-sectional area selected from the ranges of 0.2 - 8 mm 2 , such as 0.5 - 7 mm 2 , for example 1 - 6 mm 2 , such as 2 - 5 mm 2 or 3 - 4 mm 2 ; and/or the length of said tube is optionally selected from the ranges of 5 - 30 mm, such as 8 -25 mm, for example 10 - 22 mm, e.g. 15 - 20 mm.
  • Such a flow restrictor aids in balancing the flow of gas through the docking ports 402 comprising a modular incubator chamber 300 with the capacity of the gas supply system 200 and thereby also aids in making the flow of gas through the different docking ports 402 equal to each other.
  • the docking station 400 comprises a gas distribution system 204 for supplying gas to and from one or more of said one or more docking ports 402, wherein said gas distribution system 204 comprises a main gas supply line 210 and a main gas return line 212, wherein in respect of one or more of said docking ports 402, said docking port inlet opening for gas 404 is being fluidly connected to said main gas supply line 210, and said docking port outlet opening for gas 406 is being fluidly connected to said main gas return line 212.
  • said gas distribution system 204 comprises a number of manifold pairs 214, wherein each manifold pair comprises an inlet manifold 216 and an outlet manifold 218, wherein said inlet manifold 216 is being fluidly connected to said main gas supply line 210 and wherein said outlet manifold 218 is being fluidly connected to said main gas return line 212; wherein each manifold pair 214 is connected to one or more docking ports 402 of said docking station 400 in such a way that in respect of a specific manifold pair 214, and in respect of said one or more docking ports 402 being connected thereto, said docking port outlet opening for gas 404 of said docking port 402 is being fluidly connected to said inlet manifold 216, and said docking port inlet opening for gas 406 of said docking port 402 is being fluidly connected to said outlet manifold 218.
  • said docking station 400 comprises a gas supply system 200, wherein said gas supply system 200 comprises a gas source 202 and said gas distribution system 204, wherein said gas source comprises a supply gas outlet 206 and a return gas inlet 208, wherein said supply gas outlet 206 of said gas source 202 is being fluidly connected to said main gas supply line 210 of said gas distribution system 204, and wherein said return gas inlet 208 of said gas source 202 is being fluidly connected to said main gas return line 212 of said gas distribution system 204.
  • a gas distribution system 204 it is possible to supply gas from a gas source 202 to the docking ports 402 via the main gas supply line 210 and to return gas from the docking ports to the gas source 202 via the main gas return line 212.
  • the gas source 202 of said gas supply system 200 comprises a gas mixing box 242 fluidly connected to said supply gas outlet 206 and said return gas inlet 208 of said gas source, wherein said main gas supply line 210 of said gas distribution system 204 is being fluidly connected to said supply gas outlet 206, and wherein said main gas return line 212 of said gas distribution system 204 is being fluidly connected to said return gas inlet 208 of said gas source 202, thereby forming a flow loop 244 comprising said gas distribution system 204 and said gas mixing box 242; wherein said flow loop comprises a pump 246.
  • the purpose of the gas source is to provide and deliver a desired gas composition to the gas distribution system 204 including the various docking ports 402 of the docking station 400.
  • the pump 246 is being arranged downstream in relation to said main gas return line 212.
  • the flow loop 244 comprises a pump oscillation damper 247, wherein said pump oscillation damper optionally is being arranged immediately downstream in relation to said pump 246.
  • the flow loop 244 comprises a pressure sensor, such as a differential pressure sensor 248 for sensing the pressure of gas supplied to said main gas supply line 210 of said gas distribution system 204, wherein said pressure senor 248 optionally is being arranged immediately upstream in relation to said main gas supply line 210 of said gas distribution system 204.
  • a pressure sensor such as a differential pressure sensor 248 for sensing the pressure of gas supplied to said main gas supply line 210 of said gas distribution system 204, wherein said pressure senor 248 optionally is being arranged immediately upstream in relation to said main gas supply line 210 of said gas distribution system 204.
  • the pressure sensor 248 allows for regulating the pump 246 in order to maintain a desired pressure in the flow loop 244 by feedback.
  • the pressure sensor 248 is being a differential pressure sensor, sensing a pressure relative to the pressure of the return gas inlet 208.
  • the flow loop 244 comprises a release valve 249 for enabling pressure relief in said flow loop, wherein said release valve optionally is being arranged immediately downstream in relation to said main gas return line 212 of said gas distribution system 402.
  • the pressure release valve 249 enables improved control of the pressure in the flow loop 344.
  • the gas mixing box 242 comprises an inlet for N2 gas 250; and an inlet for CO2 gas 251, wherein said inlet for N2 gas 250 is fluidly connected to an N2 valve 252 for regulating the inflow of N2, and an N2 mass flow sensor 253 arranged downstream of said N2 valve 252 for sensing the amount of N2 flowing into said gas mixing box 242; and wherein said inlet for CO2 gas 251 is fluidly connected to a CO2 valve 254 for regulating the inflow of CO2, and an CO2 mass flow sensor 255 arranged downstream of said CO2 valve 254 for sensing the amount of CO2 flowing into said gas mixing box 242.
  • the flow loop 244 comprises a mass flow sensor 256 arranged at an upstream position in relation to said gas mixing box 242 for sensing the amount of return gas entering said gas mixing box.
  • Information relating to the amount of return gas entering said gas mixing box is used for determining the total amount of N2 gas and CO2 gas which needs to be introduced into the gas mixing box 242.
  • the gas source 202 comprises an O2 sensor 258 for sensing the concentration of O2 exiting said gas distribution system 204; and wherein said gas source 202 comprises a CO2 sensor 260 for sensing the concentration of CO2 exiting said gas distribution system 204, wherein said O2 sensor and/or said CO2 sensor optionally is/are being arranged downstream in relation to said pump 246.
  • the gas source 202 comprises a temperature sensor 262 for sensing the temperature of gas circulating in said flow loop 244, wherein said temperature sensor optionally is being arranged downstream in relation to said pump 246, preferably at a position corresponding to the position of said O2 sensor 258.
  • the gas source 202 comprises a pressure sensor 264 for sensing the absolute pressure in said flow loop 244 wherein said pressure sensor optionally is being arranged downstream in relation to said pump 246, preferably at a position corresponding to the position of said CO2 sensor 260.
  • the temperature sensor 262 and pressure sensor 264 are useful for performing compensation of the readings of the O2 sensor 258 due to temperature sensitivity thereof and the readings of the CO2 sensor 260 due to sensitivity thereof towards pressure.
  • the flow loop 244 comprises a UV sanitizer 266 for sanitizing gas flowing in said flow loop 244 via electromagnetic radiation in the UV range, wherein said UV sanitizer optionally being arranged immediately downstream in relation to said main gas return line 212.
  • the gas source 202 comprises one or more filters 268, such as HEPA and/or VOCs filters, wherein such a filter is being arranged immediately upstream in relation to said main gas supply line 210, and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for N2gas 250 into said gas mixing box 242; and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for CO2 gas 251 into said gas mixing box 242.
  • filters 268 such as HEPA and/or VOCs filters
  • the gas source 202 comprises a gas mixing control system 270, wherein said gas mixing control system is electrically connected to one or more of the following sensors for receiving sensing signals therefrom: said N2 mass flow sensor 253 for sensing the amount of N2 flowing into said gas mixing box; said CO2 mass flow sensor 255 for sensing the amount of CO2 flowing into said gas mixing box; said mass flow sensor 256 for sensing the amount of return gas entering said gas mixing box; said O2 sensor 258 for sensing the concentration of O2 exiting said main gas return line 212 of said gas distribution system 204; said CO2 sensor 260 for sensing the concentration of CO2 exiting said main gas return line 212 of said gas distribution system 204; said temperature sensor 262 for sensing the temperature circulating in said flow loop 244; said pressure sensor 264 for sensing an absolute pressure in said flow loop 244, said pressure sensor 248 for sensing the pressure of gas supplied to said gas main gas supply line 210 of said distribution system 204.
  • said N2 mass flow sensor 253 for sensing the amount of N2 flowing
  • This embodiment enables gaining information of various parameters which are to be used in providing a feed back when controlling the operation of the gas source 202.
  • the gas mixing control system 270 is electrically connected to one or more of the following elements for control thereof: said N2 valve 252 for regulating the inflow of N2 into said gas mixing box 242; said CO2 valve 254 for regulating the inflow of CO2 to said gas mixing box 242; said pump 246 for circulating gas in said flow loop 244; said release valve 249.
  • This embodiment enables providing a feed back when controlling the operation of the gas source 202.
  • the gas mixing control system 270 is being configured to receive input from said pressure sensor 248 and on the basis thereof control said pump 246, optionally also to activate said release valve 249 in order to maintain a desired and predetermined pressure of gas supplied to said main gas supply line 210 of said gas distribution system 204.
  • the gas mixing control system 270 is being configured to receive input from said mass flow sensor 256, and on the basis on said input to determine the total amount of CO2 gas and N2 gas needed to be supplied via said inlet for CO2 gas 251 and via said inlet for N2 gas 250 according to desired and predetermined criteria.
  • the gas mixing control system 270 is being configured to receive input from said CO2 sensor 260 and said O2 sensor 258, and on the basis of the CO2 concentration sensed, is configured to control said CO2 valve 254, by transmitting a control signal thereto, and thereby regulating the inflow of CO2 gas in order to reach a desired and predetermined CO2 concentration, and wherein subsequently, said gas mixing control system 270 on the basis of the O2 concentration sensed, is configured to control said N2 valve 252, by transmitting a control signal thereto, and thereby regulating the inflow of N2 gas in order to reach a desired and predetermined O2 concentration.
  • the gas mixing control system 270 is configured to use the input from said temperature sensor 262 for compensating the temperature sensitivity of said O2 sensor 258.
  • the gas mixing control system 270 is configured the maintain a CO2 concentration of gas entering said main gas supply line 210 of said gas distribution system 204 in the range of 5 - 10%, such as 6 - 9 % or 7 - 8 %; and/or an O2 concentration of gas entering said main gas supply line 210 of said gas distribution system 204 in the range of 5 - 10%, such as 6 - 9 % or 7 - 8 %.
  • the gas mixing control system 270 is configured to use the input from said pressure sensor 264 for compensating the pressure sensitivity of said CO2 sensor 260.
  • the gas mixing control system 270 is being configured to maintain a pressure of gas supplied to said main gas supply line 210 of said gas distribution system 204, relative to the ambient atmospheric pressure, of 3 - 20 mbar, such as 5 - 18 mbar, such as 10 - 15 mbar above that ambient atmospheric pressure.
  • the number of modular incubator chambers 300 of said modular incubator system 500 is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
  • the number of docking ports 402 in said docking station 400 of said modular incubator system 500 is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
  • said docking station 400 comprises said docking ports 402 in an arrangement of one or more shelves of adjacently positioned docking ports 402, wherein in case said docking station comprises two or more shelves, said shelves are being arranged above each other.
  • said modular incubator chamber comprises an incubation chamber engagement means 326 and wherein in respect of one or more docking ports 402 of said docking station 400, said docking port comprises a docking port engagement means 414, wherein said incubation chamber engagement means 326 is being configured to enter into engagement with said docking port engagement means 414.
  • the modular incubator system 500 comprises an image processing unit 660 for image processing of images captured by said image capturing device 408, wherein said modular incubator system 400 furthermore comprises a data storage 658 for storing images captured by said image capturing units 408 and/or for storing images processed by said image processing unit.
  • An image processing unit is beneficial for manipulating the images captured, such as for adjusting contrast, for filtering and for generating time-lapse series of images.
  • one or more of said image capturing devices 408 of said docking ports 402 of said docking station is/are being coupled to said image processing unit 660.
  • said specific docking port comprises its own dedicated image capturing device 408 which is configured to only capture images relating to a modular incubator chamber 300 which is being docked in said specific docking port 402.
  • said adjacently arranged docking ports 402 share a common image capturing device 408 in the sense that one and only one image capturing device is responsible for capturing images relating to a modular incubator chamber 300 which is being docked in one of said N adjacently arranged docking ports 402 s wherein said docking station comprises a displacement device 482 for enabling displacement of said common image capturing device 408 in relation to said N adjacently arranged docking ports 402 of said docking station 400, such as being provided with an electric signal thereto.
  • one image capturing device is responsible for the capturing of images of biological materials being accommodated in different modular incubator chambers which are being docked in different docking port 402 of the docking station 400 on/at the same shelf.
  • the number N is being an integer selected in the ranges of 2 - 25 or more, such as 4 - 22, for example 6 - 20, such as 8 - 18, such as 10 - 16 or 12 - 14.
  • one or more image capturing devices 408, preferably all image capturing devices 408 of the docking station 400 may comprise or be coupled to a displacement device 482, such as an electrically driven and remotely controlled displacement device 482 for enabling displacement of said common image capturing device 408 in a direction transversal to the longitudinal direction X of a modular incubator chamber 300 being docked in a docking port 402 with the view to enable such capturing device 408 to focus on more than one culture well in a culture dish 310 being accommodated in the interior of the modular incubator chamber 300, wherein such culture wells are arranged in such direction transversal to the longitudinal direction X.
  • a displacement device 482 such as an electrically driven and remotely controlled displacement device 482 for enabling displacement of said common image capturing device 408 in a direction transversal to the longitudinal direction X of a modular incubator chamber 300 being docked in a docking port 402 with the view to enable such capturing device 408 to focus on more than one culture well in a culture dish 310 being accommodated in the interior of
  • said modular incubator chamber comprises in its interior 306 an electric heating element 318 for heating the interior of said modular incubator chamber, and wherein said modular incubator chamber comprises a power source 320 for providing power to said heating element 318, wherein said electric heating element 318 is being electrically connected to said power source 320.
  • said power source 320 is being an electric power source, such as a battery, for example a rechargeable battery.
  • said heating element 318 is being thermally connected to a heat distribution element for distributing heat dissipated in said heating element; wherein said heat distribution element is being arranged, at least partly, in the interior 306 of said modular incubator chamber 300.
  • said chamber comprises a thermostat 374 and an electric thermostatic circuit 376, wherein said electric heating element 318, said power source 320 and said thermostat 374 are being electrically connected in said electric thermostatic circuit 376 so as to enable thermostatic control of the temperature inside said modular incubator chamber 300.
  • the above embodiments provide for upholding a desirable and predetermined and optionally also optimum temperature in the interior 306 of the modular incubator chamber 300 in a situation where the modular incubator chamber is removed from its associated docking port 402 with the view to perform visual inspection and manual replenishing, removal, or exchange of growth medium to the biological materials being incubated.
  • said modular incubator system 500 comprises a control unit 650 for controlling the operation of said modular incubator system 500.
  • control unit 650 is being coupled to an input device 652, such as an alphanumerical input device for allowing a user to provide settings input relating to a desired operational protocol of said modular incubator system.
  • control unit 650 is being coupled to a display unit 654 for displaying, to a user, information relating to settings and/or operational status of said modular incubator system 300.
  • control unit 650 is being configured for independently controlling one or more of the following: temperature in the interior 306 of said modular incubator chamber 300 by controlling said electric heating element 318, said thermostat 374 or said thermostatic circuit 376, providing power to said electric power source 320; providing signals to said display 324 of said modular incubator chamber 300, said inclination angle adjustment element 332, said rotational adjustment element 334 of said inclination angle adjustment element 332, said displacement adjustment element 336 of said inclination angle adjustment element 332, switching on and off of said active light source 352, or adjusting light intensity emitted therefrom, said image capturing device 408 of a docking station 408, said displacement device 482 for displacing said image capturing device 408, said actuator of said X-stage or XY-stage 466, said actuator of said iris diaphragm 464 ,said gas mixing control system 270; said gas mixing control system 660
  • control unit 650 is being coupled to a data processing unit 656 and optionally also to a data storage 658 for aiding in handling information during controlling of said modular incubator system.
  • control unit 650 is being configured for conducting automatic operation of said modular incubator system 500 by configuring said control unit 650 to independently control one or more of the following: temperature in the interior 306 of said modular incubator chamber 300 by controlling said electric heating element 318, said thermostat 374 or said thermostatic circuit 376, providing power to said electric power source 320; providing signals to said display 324 a modular incubator chamber 300, said inclination angle adjustment element 332, said rotational adjustment element 334 of said inclination angle adjustment element 332, said displacement adjustment element 336 of said inclination angle adjustment element 332, switching on and off of said active light source 352, or adjusting light intensity emitted therefrom, said image capturing device 408 of said docking station 408, said displacement device 482 for displacing said image capturing device 408, said actuator of said X-stage or XY-stage 466, said actuator of said iris diaphragm 464, said gas mixing control system 270.
  • control unit 650 is being configured for enabling time lapse capturing of images by said image capturing devices 408.
  • the operation of the modular docking system 500 can easily be controlled centrally.
  • the present invention relates in a second aspect to a modular incubator chamber 300, wherein said modular incubator chamber 300 is comprising features as defined in respect of the modular incubator chamber 300 of the modular incubator system 500 of the first aspect of the present invention.
  • the present invention relates in a third aspect to a docking station 400, wherein said docking station is comprising features as defined in respect of the docking station 400 of the modular incubator system 500 of the first aspect of the present invention.
  • the present invention provides a use of a modular incubator system 500 according to the first aspect of the present invention for incubating a viable biological material M.
  • said biological material is being an oocyte or an embryo, such as a human oocyte or a human embryo.
  • the present invention provides a use of a modular incubator chamber 300 according to the second aspect of the present invention for incubating a viable biological material M.
  • said biological material is being an oocyte or an embryo, such as a human oocyte or a human embryo.
  • the present invention provides a use of a docking station 400 according to the third aspect of the present invention for incubating a viable biological material M.
  • said biological material is being an oocyte or an embryo, such as a human oocyte or a human embryo.
  • the present invention provides a method of incubating a viable biological material M, wherein said method comprises: i) providing a modular incubator system 500 according to the first aspect of the present invention; ii) providing a viable biological material M; iii) arranging said viable biological material M in a culture dish 310 and subsequently arranging said culture dish on the culture dish support 308 in the interior 306 of said modular incubator chamber 300 of said modular incubator system 400; iv) docking said modular incubator chamber 300 in a docking port 402 of said docking station 400 of said incubator system 500; v) allowing said viable biological material M to be incubated in said modular incubator chamber 300; vi) while performing step v) enabling said light directing element 350 of said modular incubator chamber 300 to direct light to an area of said culture dish support 308 in said light aiming direction A; vii) while performing step v) and vi) making said image capturing device 408 capture image(s) of said viable biological material M in the interior 306 of said modular incubator chamber 300, at a
  • the method further comprising the step of: viii) removing said incubator chamber 300 from said docking port 402 of said docking station 400, when desired, in order to manually inspect the viable biological material M, and optionally also to remove, add or exchange growth medium/media in said culture dish 310.
  • FIG. 1 is a perspective view illustrating the general concept of providing an incubator as a modular incubator system comprising a plurality of modular incubator chambers in combination with a docking station comprising a plurality of docking ports.
  • Fig. 1 shows the modular incubator system 500 for incubating a viable biological material.
  • the modular incubator system 500 comprises a docking station 400 in combination with a number of modular incubator chambers 300.
  • the docking station 400 comprises a plurality of docking ports 402.
  • Each docking port 402 is configured for receiving and holding a modular incubator chamber 300.
  • Each docking port 402 comprises docking port engagement means 414 which is configured to enter into engagement with a corresponding incubation chamber engagement means 326 arranged underneath each modular incubation chamber 300.
  • the docking station 400 of the incubator system 500 comprises three shelves arranged above each other and each comprising six docking ports 402. Three of these docking ports 402 have been occupied by a modular incubator chamber 300 and a fourth modular incubation chamber is on its way to be docked in a docking port 402.
  • an incubator for IVF procedures as an incubator system 500 comprising a plurality of modular incubator chambers 300 in combination with a docking station 400 allows for having, in a single apparatus, a relative huge number of incubations taking place under individual incubations environments, such as under an individual chemical environment in relation to e.g. gaseous atmosphere and composition of growth medium, and under an individual physical environment in relation to e.g. temperature.
  • modular incubator chamber 300 is simple removed from its respective docking port 402 of the docking station 400 and transferred to a laboratory bench where such manual procedures can be conducted.
  • the modular incubator chamber will be docked in a docking port 402 of the docking station 400.
  • Image capturing device(s) 408 is/are provided in respect of one or more of the docking ports 402 of the docking station 400.
  • the image capturing device(s) 408 of the docking station 400 provide(s) for monitoring the morphological changes taking place during incubation.
  • the image capturing device comprises microscope optics for capturing close-up images.
  • the image capturing device(s) 408 may be configured for automatically capturing of images of the biological material being incubated in a modular incubator chamber 300.
  • the docking ports 402 comprises an electric connector 410 for supplying electric power from the docking port to a modular incubator chamber 300 being docked into that docking port, or for transferring electric signals between a modular incubator chamber 300 and a docking port 402.
  • Such transmittal of light through the housing of the modular incubator chamber is attained by providing the housing of the modular incubator chamber 300 with a transparent window which allows for an image capturing device, located outside the interior of the chamber 300, to capture images of a viable biological material being accommodated in the interior of that incubator chamber 300 as further described below.
  • Fig. 2a is a perspective view showing a modular incubator chamber of the docking system of Fig. 1.
  • Fig. 2a shows the modular incubator chamber 300 for incubating a viable biological material.
  • the modular incubator chamber comprises a housing 302 and the housing comprises a lid 304 which is being configured to be able to shift between an open configuration allowing access to the interior 306 of the modular incubator chamber and a closed configuration, sealing off access to the interior 306 of said modular incubator chamber.
  • the chamber is having a first end 340 and a second end 342.
  • Fig. 2a also shows that the housing 302 of the modular incubator chamber 300 comprises a display 324 which is being configured to display information relating to details of the incubation taking place in said modular incubator chamber and that the housing 302 at a first end 340 thereof, is being provided with electric connectors 322 for providing electric power to the modular incubator chamber or for conveying electric signals between the modular incubator chamber 300 and the corresponding docking port 402.
  • a display 324 which is being configured to display information relating to details of the incubation taking place in said modular incubator chamber and that the housing 302 at a first end 340 thereof, is being provided with electric connectors 322 for providing electric power to the modular incubator chamber or for conveying electric signals between the modular incubator chamber 300 and the corresponding docking port 402.
  • Fig. 2b is a plan top view of the modular incubator chamber 300 illustrated in Fig. 2a.
  • Fig. 2c is a plan rear view of the modular incubator chamber 300 illustrated in Fig. 2a and 2b as seen from its first end.
  • Fig. 2c shows that the modular incubator chamber 300 comprises a chamber engagement means 326. These first engagement means 326 are configured to enter into engagement with a docking port engagement means 414 in a docking port 402 of the docking station 400.
  • Fig. 3 is a cross-sectional view of the modular incubator chamber 300 illustrated in Fig. 2.
  • Fig. 3 shows that the housing 302 of the modular incubator chamber 300 comprises a transparent window 316 for allowing capturing of images of a biological material being accommodated in the interior thereof, through said transparent window.
  • the window is arranged at the bottom 330 of the housing 302 of the modular incubator chamber 300.
  • the modular incubator chamber 300 also comprises, in its interior 306, an electric heating element 318 for heating the interior of said modular incubator chamber.
  • the modular incubator chamber also comprises a power source 320 in the form of a rechargeable battery for providing power to said heating element 318 which is being electrically connected to the power source 320.
  • a light directing element 350 in the form of an active light source 352 is attached to an inner side of the lid 304 of the modular incubator chamber 300.
  • the interior 306 of the modular incubator chamber 300 comprises a culture dish support 308 for positioning a culture dish 310.
  • a culture dish support 308 for positioning a culture dish 310.
  • one or more biological materials can be accommodated and incubated within the housing 302 of the modular incubator chamber 300.
  • FIG. 3 Also seen in Fig. 3 is the engagement means 326 which is being adapted to engage with engagement means 414 of the docking port into which the modular incubator chamber 300 is to be docked.
  • Fig. 4 illustrates the principle of the present invention.
  • Fig. 4 is a diagram illustrating the relative orientations of a light aiming direction A of light emitted from a light source 352,350 and the focus direction B of an image capturing device.
  • Fig. 4 shows a viable biological material M being accommodated in a culture dish 310.
  • An image capturing device 408 is arranged below the culture dish 310 and the image capturing device 408 is focusing in a focus direction B.
  • a light providing element 350 in the form of a light source 352 is providing light for illuminating the biological material M during image capturing.
  • the light emitted from the light source 352 is propagating in a light aiming direction A.
  • the light aiming direction A of the light propagating from the light source 352 is being inclined relative to the focus direction B of the image capturing device 408 at an inclination angle a which is 0°.
  • Fig. 5 illustrates the concept of the term “light aiming direction” as this term may be used in the present application.
  • Fig. 5 shows the active light source 352 with its centre.
  • the active light source 352 propagates light in a downward direction.
  • An imaginary plane IP is visualized at a distance D from the light source 352 and the light emitted from the light source 352 will be projected on that imaginary plane IP and will form the projection PR having the projection boundary PRB on the imaginary plane IP.
  • the light aiming direction A as the direction from a centre of the light source 352 to the centre CP of the projection PR.
  • the centre CP of the projection PR may be calculated from the shape of the projection boundary PRB in the same way that one calculates the centre of mass of an object.
  • the object in this case being the two-dimensional geometrical shape PR within the projection boundary PRB.
  • Fig. 6 is a diagram illustrating in more details the principle of the present invention.
  • contrast can be provided by selecting the angle of incoming light onto the biological materiel in relation to the direction of focus of the image capturing device.
  • Fig. 6 shows part of a modular incubator system 500 comprising a modular incubator chamber 300 which is being docked in a docking port 402 of a docking station 400.
  • the modular incubator chamber 300 comprises a housing 302 having a lid 304, a culture dish support 308 for positioning the culture dish 310 containing the viable biological material M.
  • the housing 302 of the modular incubator chamber comprises a transparent window 316 at the bottom 330 of the housing.
  • the transparent window 316 enables capturing of images of the biological material M through that transparent window 316 by the image capturing device 408 which is arranged at the docking port 402 of the docking station 400 when that image capturing device 408 is focusing in the focus direction B.
  • the housing 302 of the modular incubator chamber 300 comprises a light directing element 350 in the form of an active light source 352 for directing light to the area of the culture dish support 308 in a light aiming direction A, so as to direct light towards the viable biological material M.
  • the light aiming direction A of light propagating from the light directing element 350,352 of the modular incubator chambers 300 is being inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a.
  • the inclination angle a is seen to be clearly 0°.
  • Fig 7 is similar to fig. 6 except that the light direction element 350 in the form of an active light source 352 is now arranged outside the interior 306 of the housing 302 of the modular incubator chamber 300.
  • the active light source 352 may be part of the docking port 402 of the docking station 400.
  • the lid 304 has been provided with a light conveyor 354 which allows transmission of light into the interior 306 of the modular incubating chamber. In this way the transmissive light conveyor 354 acts as the light directing element 350.
  • the light aiming direction A of light propagating from the light directing element 350,354 of the modular incubator chambers 300 is inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is clearly 0°.
  • Fig. 8 illustrates another embodiment of the incubator system 500 according to the first aspect of the present invention, wherein the active light source 352 is being arranged outside of the interior 306 of the housing 302 of the modular incubator chamber.
  • a light transmission element 356 is being arranged at a side of the housing 302 of the modular incubating chamber 300 and that an active light source 352 is being arranged so as to direct light through that light transmission element 356 into the interior 306 of the housing 302.
  • a light directing element 350 in the form of a light conveyor 354 is being arranged in the interior 306 of the modular incubating chamber 300, and the light conveyor 354 is configured for directing incoming light, in said light aiming direction A, such as by reflecting said incoming light.
  • the light conveyor 354 is a light reflector 358, such as a mirror.
  • light propagating in the light aiming direction A is directed from the light directing element 350,354,358 of the modular incubator chamber 300 and is being inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is clearly 0°.
  • Fig. 9 illustrates yet another embodiment of the incubator system 500 according to the first aspect of the present invention, wherein the active light source 352 is being arranged outside the interior of the housing of the modular incubator chamber.
  • Fig. 9 shows an embodiment wherein the optical transmission element 356 of the housing 302 of the modular incubator chamber 300 is being arranged at a bottom 330 of the housing 302.
  • An active light source 352 is being arranged in the docking port 402 below the modular incubator chamber 300, thereby allowing transmission of light through the optical transmission element 356 into the interior 306 of the housing 302.
  • the housing 302 of the modular incubator chamber comprises in the interior 306 thereof a light reflector 358.
  • the light reflector 358 is being configured to reflect upwardly propagating light into an essentially horizontally propagating light, propagating towards the light conveyor 350 which is being in the form of a passive light conveyor 354.
  • the light conveyor 354 is configured to reflect the essentially horizontally propagating light into the light aiming direction A.
  • the light conveyor 354 is a light reflector 358, such as a mirror.
  • the light aiming direction A of light propagating from the light directing element 350, in the form of the light conveyor 354 of the modular incubator chamber 300, is inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is clearly 0°.
  • Fig. 10 illustrates yet another embodiment of the incubator system 500 according to the first aspect of the present invention, wherein the active light source 352 is being arranged outside the interior of the housing of the modular incubator chamber.
  • Fig. 10 shows that the active light source 352 is arranged in the docking port 402 so as to direct emitted light in a direction essentially parallel to the focus direction B of the image capturing device 408 and through the transparent window 316.
  • a light conveyor 354 is directing the emitted light propagating from the active light source 352 into the light aiming direction A.
  • the light conveyor 354 is a light reflector 358, such as a mirror.
  • the culture dish 310 is being made from a transparent material.
  • the light aiming direction A of light propagating from the light directing element 350 in the form of the light conveyor 354 of the modular incubator chambers 300 is inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is clearly 0°.
  • the active light source 352 may also be arranged within the optics of the image capturing device 408.
  • Fig. 12 is a diagram illustrating the principle of including an inclination angle adjustment element for adjusting the inclination angle a between the light aiming direction A and the focus direction B of the image capturing device.
  • Fig. 12 shows an inclination angle adjustment element 332.
  • a light directing element 350 in the form of an active light source 352 is suspended on a displacement adjustment element 336.
  • the displacement adjustment element 336 is connected to a support 338.
  • the displacement adjustment element 336 is configured to be displaceable, via an electric actuator, included therein, relative to the support 338 upon being supplied with an electric signal thereto as indicated by the linear arrows in Fig. 12.
  • the active light source 352 is attached to a rotational adjustment element 334.
  • the rotational adjustment element 334 is being configured, via an electric actuator, included therein, to change the light aiming direction A of light propagating from the light directing element 350 by rotation of the light direction element 350 as indicated by the curved arrows.
  • the rotational adjustment element 334 and the displacement adjustment element 336 are electrically controlled by the electric actuators which provide for changing the light aiming direction A of light direction propagation from said light directing element 350 and/or for changing the position of said light directing element 350 upon being supplied by an electric signal thereto.
  • the displacement adjustment element 336 and the rotational adjustment element 334 will both, upon activation of the corresponding and included actuator, effect a change in the inclination angle between the light aiming direction A of light direction propagation from said light directing element 350 and the focus direction B of the image capturing device 408 in a situation where a modular incubating chamber 300 is comprising the inclination angle adjustment element 332 and is being docked in a docking port 402 of a docking station 400.
  • Fig. 13a, 13b and 13c are diagrams illustrating the principle of including a shadowing element in the docking ports 402 of the docking station.
  • Fig. 13a is a partly cross-sectional view showing the image capturing device 408 focusing in the focus direction B. Above the image capturing device 408 is arranged a shadowing element 450.
  • the shadowing element 450 comprises a plate 452 which comprises a hole 454.
  • the shadowing plate 452 is being arranged relative to the image capturing device 408 so that the focus direction B passes or may pass through that hole 452.
  • the plate 452 is resting on an XY-stage 456.
  • the XY-stage is configured to enable displacing the plate 456 independently in one or two displacement directions D1,D2 which is/are essentially perpendicular to the focus direction B of said image capturing device 408.
  • the displacement direction DI defines movement of the plate 452 in a left-right direction
  • the displacement direction D2 defines movement of the plate 452 in and out of the paper.
  • the XY-stage is electrically controlled by an electric actuator 466 which provides for displacement of said shadowing plate 452 in the one or two displacement directions D1,D2 upon being supplied by an electric signal thereto.
  • Fig. 13b is a top view of the shadowing element 450 seen in Fig. 13a.
  • Fig. 13b shows the plate 452 resting on the XY-stage 456.
  • the plate comprises a hole 454. Beneath the plate 452 and through the hole 454 thereof the image capturing device 408 is seen.
  • the image capturing device is focusing in the focus direction B up through the hole 454.
  • an X-stage may also be used.
  • Fig. 13 c is a photograph showing a commercially available shadowing element in the form of an iris diaphragm 458.
  • theshadowing element 450 is in the form of an iris diaphragm 458 is comprising a plurality of iris lamellas 460.
  • the iris lamellas are movable in relation to each other and are thereby configured, upon being subjected to an external force, to vary the size of the through- going hole 462 formed in the centre of the iris diaphragm.
  • the iris diaphragm 458 is being arranged relative to the image capturing device 408 so that the focus direction B of the image capturing device 408 passes or may pass through that hole 462.
  • the iris diaphragm 458 comprises an actuator 464 in the form of a remote-controlled electric actuator which is mechanically connected to the iris lamellas 460 and which is configured to enable movement of these iris lamellas in concert so as to vary the size of the through-going hole 462 upon being supplied with an electric signal thereto.
  • the iris diaphragm may be used in conjunction with the XY-atsage or the X-stage.
  • the shadowing element is arranged outside the optics of the image capturing device 408.
  • a similar arrangement can be arranged inside the optics of the image capturing device 408 for providing the shadowing effect.
  • the docking ports 402 comprises a docking port outlet opening for gas 404 and a docking port inlet opening for gas 406, and that a valve 4 is arranged in each of these openings.
  • Fig. 2c shows the modular incubator chamber 300 comprises a chamber inlet opening for gas 312 which is in fluid connection with the interior 306 of the modular incubator chamber
  • the chamber inlet opening for gas comprises a valve 2.
  • the housing 302 of said modular incubator chamber 300 furthermore comprises a chamber outlet opening for gas 314, which is being in fluid connection with the interior 306 of the modular incubator chamber 300, thereby allowing conveying gas out of the chamber 300 via the chamber outlet opening for gas 314.
  • the chamber outlet opening for gas comprises a valve 2.
  • the housing 302 of the modular incubator chamber 300 with a chamber inlet opening for gas 312 and optionally also an associated valve 2 and by providing the modular incubator chamber 300 with a chamber outlet opening for gas 314 and optionally also an associated valve 2 it is possible to convey a gas having a suitable and desired gas composition into the interior of the modular incubator chamber 300 from a docking port 402 of the docking station 400, as will be further explained below, and further it will be possible to make the gas in the interior 306 of the modular incubator chamber 300 exit the interior of the chamber through the chamber outlet opening for gas 314 and associated valve 2 and return to the docking station.
  • the relative position of the two electric connectors 410 and 322 of the docking port and the modular incubator chamber, respectively, will match so as to first to allow electric connection between the connectors 410 and 322.
  • the gas openings 312,404 and 314,406 will match pairwise so that passage of gas from the docking port outlet opening for gas 404 into the interior 306 of the modular incubator chamber 300 via the modular incubator chamber inlet opening for gas 312 and the optional valves 2,4 is enabled, and so that passage of gas from the interior 306 of the modular incubator chamber 300 is possible via the modular incubator chamber outlet opening for gas 314 and into the docking port inlet opening for gas 406 and via the optional valves 2,4 is enabled.
  • the modular docking system 500 of the present invention allows for continuously providing gas into the interior 306 of the modular incubator chamber 300 from a gas source 412.
  • Fig. 14a and 14b illustrate the working modes of valves of a valve system to be used with the modular incubator chamber and the associated docking port of the docking station of the docking system of the present invention.
  • Fig. 14a is diagrammatic drawing illustrating a valve system 100 to be used with the modular incubator system of the present invention, where the two valves 2,4 of the valve system 100 are not engaged with each other, thereby attaining a closed configuration.
  • Fig. 14b is diagrammatic drawing illustrating the valve system 100 seen in Fig. 14a in which the two valves 2,4 of the valve system 100 are engaged with each other, thereby attaining an open configuration.
  • the valve 2 comprises a valve body 6 having a front end 10 and a rear end 12.
  • a through- going channel 14 is arranged in the valve body 6 and a valve element 8 is being arranged in the through-going channel 14.
  • the valve element 6 is spring-loaded by a spring 26.
  • the displaceable valve element 8 is being configured to be displaceable in the through-going channel 14 of the valve body 6 by the spring 26 in such a way, that when not acted upon by an external force, the spring-loaded displaceable valve element 8 is being displaced in the through-going channel 14 of said valve body 6 by the spring 26 towards the front end 10 of the valve body 6. Thereby the valve 2 attains a closed configuration blocking passage of gas through the through-going channel 14.
  • Fig. 14a shows that the valve 4 comprises a valve body 16 having a front end 20 and a rear end 22.
  • a through-going channel 24 is arranged in the valve body 16 and a valve element 18 is being arranged in the through-going channel 24.
  • the valve element 18 is spring-loaded by a spring 28.
  • the displaceable valve element 18 is being configured to be displaceable in the through-going channel 24 of the valve body 16 by the spring 28 in such a way, that when not acted upon by an external force, the spring-loaded displaceable valve element 18 is being displaced in the through-going channel 24 of said valve body 16 by the spring 28 towards the first end 20 of the valve body 16. Thereby the valve 4 attains a closed configuration blocking passage of gas through the through-going channel 24. This situation is illustrated in Fig. 14a.
  • valves 2 of the modular incubator chamber 300 and the valves 4 of the docking port 402 of the docking station are having dimensions and geometries in such a way that once docking the modular incubator chamber 300 in the docking port 402 of said docking station 400, the displaceable valve element 8 of the valve 2 and the displaceable valve element 18 of the valve 4 will displace each other into their respective valve bodies 6,16, thereby opening the valves 2,4 of said docking port outlet opening for gas 404 and said chamber inlet opening for gas 312; and also opening the valves 2,4 of the chamber outlet opening for gas 314 and the docking port inlet opening for gas 406.
  • valves 2,4 for the modular incubator chamber 300 and for the docking ports 402 of the docking station will automatically provide for opening the valves 2 of the modular incubator chamber 300 and the valves 4 of docking port 402, once that modular incubator chamber 300 is being docked in that docking port 402, thereby allowing passage of gas through the interior 306 of the modular incubator chamber 300, when being docking in the docking port 402 and also shutting off supply of gas into the docking port 402 and out of the modular incubator chamber 300, when that modular incubator chamber 300 is removed from the docking port.
  • a modular incubator system 500 comprising a docking station 400 with a plurality of docking ports 402 for receiving, by docking, a modular incubator chamber 300 has been described.
  • focus will be directed to features of supplying gas to the docking ports 402 of the docking station 400.
  • Fig. 15 is a diagram illustrating the concept of the gas supply system which may be incorporated in the docking station of the modular incubator system of the present invention.
  • Fig. 15 shows a gas supply system 200 to be used with a modular incubator system 500 according to the present invention.
  • the gas supply system 200 comprises a gas source 202 and a gas distribution system 204.
  • the gas distribution system 204 comprises a plurality of docking ports 402 each having a docking port outlet opening for gas 404 and a docking port inlet opening for gas 406.
  • the docking port outlet openings for gas 404 are in fluid connection with an inlet manifold 216 and the docking port inlet openings for gas 406 are in fluid connection with an outlet manifold 218.
  • a main gas supply line 210 supplies gas from a supply gas outlet 206 of the gas source 202 to the inlet manifolds 216, and a main gas return line 212 returns gas from the outlet manifolds 218 to a return gas inlet 208 of the gas source 202.
  • gas can be circulated from the gas source 202 via the gas distribution system 204 to the docking ports 402 and back to the gas source 202.
  • the gas source is provided with specific features as disclosed with reference to figure 16.
  • Fig. 16 is a diagram illustrating one embodiment of a design of a gas supply system comprising a gas source to be used with the docking station of the modular incubator system of the present invention.
  • solid lines represent flow lines for gas, whereas dashed lines represent signal lines for conveying electric signals or electric power.
  • Fig. 16 shows the gas distribution system 204 comprising its main gas supply line 210 and its main gas return line 212 (illustrated with the rectangle in upper left corner).
  • the main gas supply line 210 and the main gas return line 212 of the gas distribution system 204 is fluidly connected to a gas source 202 as described below.
  • the gas source 202 of said gas supply system 200 comprises a gas mixing box 242 connected to the supply gas outlet 206 and the return gas inlet 208 of the gas source.
  • the main gas supply line 210 of the gas distribution system 204 is being fluidly connected to the supply gas outlet 206, and the main gas return line 212 of the gas distribution system 204 is being fluidly connected to the return gas inlet 208 of the gas source 202.
  • a flow loop 244 comprising the gas distribution system 204 and the gas mixing box 242 is formed.
  • the flow loop 244 comprises a pump 246 for circulating gas in that loop.
  • the pump 246 is being arranged downstream in relation to the main gas return line 212. Also seen in Fig. 16 is that the flow loop 244 comprises a pump oscillation damper 247, which is being arranged immediately downstream in relation to the pump 246.
  • the flow loop 244 comprises a pressure sensor 248 in the form of a differential pressure sensor for sensing the pressure of gas supplied to the main gas supply line 210 of the gas distribution system 204.
  • the pressure senor 248 is being arranged immediately upstream in relation to the main gas supply line 210 of the gas distribution system 204.
  • the flow loop 244 further comprises a release valve 248 for enabling pressure relief in the flow loop.
  • the release valve is arranged immediately downstream in relation to the main gas return line 212 of the gas distribution system 402.
  • the gas mixing box 242 comprises an inlet for N2 gas 250; and an inlet for CO2 gas 251.
  • the inlet for N2 gas 250 is fluidly connected to an N2 valve 252 for regulating the inflow of N2, and an N2 mass flow sensor 253 arranged downstream of the N2 valve 252 for sensing the amount of N2 flowing into said gas mixing box 242.
  • the inlet for CO2 gas 251 is fluidly connected to a CO2 valve 254 for regulating the inflow of CO2, and an CO2 mass flow sensor 255 arranged downstream of the CO2 valve 254 for sensing the amount of CO2 flowing into the gas mixing box 242.
  • the flow loop 244 also comprises a mass flow sensor 256 arranged at an upstream position in relation to the gas mixing box 242 for sensing the amount of return gas entering the gas mixing box.
  • the gas source 202 comprises an O2 sensor 258 for sensing the concentration of O2 exiting the gas distribution system 204; and that the gas source 202 comprises a CO2 sensor 260 for sensing the concentration of CO2 exiting the gas distribution system 204.
  • the O2 sensor and the CO2 sensor is arranged downstream in relation to the pump 246.
  • a temperature sensor 262 for sensing the temperature of gas circulating in said flow loop 244 is included in the gas source 202.
  • the temperature sensor is arranged downstream in relation to the pump 246 at a position corresponding to the position of the O2 sensor 258.
  • a pressure sensor 264 for sensing the absolute pressure in the flow loop 244 is included in the gas source 202. This pressure sensor is arranged downstream in relation to the pump 246, at a position corresponding to the position of the CO2 sensor 260.
  • the flow loop 244 comprises a UV sanitizer 266 for sanitizing gas flowing in the flow loop 244 via electromagnetic radiation in the UV range.
  • the UV sanitizer is arranged immediately downstream in relation to the main gas return line 212.
  • the gas source 202 comprises filters 268 in the form of HEPA/V OCs filters.
  • filters 268 in the form of HEPA/V OCs filters.
  • One such a filter is arranged immediately upstream in relation to the main gas supply line 210.
  • Another such a filter is arranged immediately upstream in relation to the inlet for N2 gas 250 into the gas mixing box 242; and a third such a filter is being arranged immediately upstream in relation to the inlet for CO2 gas 251 into the gas mixing box 242.
  • the gas source 202 comprises a gas mixing control system 270.
  • the gas mixing control system 270 is electrically connected to one or more of the following sensors for receiving sensing signals therefrom: the N2 mass flow sensor 253 for sensing the amount of N2 flowing into the gas mixing box; the CO2 mass flow sensor 255 for sensing the amount of CO2 flowing into the gas mixing box; the mass flow sensor 256 for sensing the amount of return gas entering the gas mixing box; the O2 sensor 258 for sensing the concentration of O2 exiting the main gas return line 212 of the gas distribution system 204; the CO2 sensor 260 for sensing the concentration of CO2 exiting the main gas return line 212 of the gas distribution system 204; the temperature sensor 262 for sensing the temperature circulating in the flow loop 244; the pressure sensor 264 for sensing an absolute pressure in the flow loop 244, the pressure sensor 248 for sensing the pressure of gas supplied to the gas main gas supply line 210 of the distribution system 204.
  • the N2 mass flow sensor 253 for sensing the amount of N2 flowing into the gas mixing box
  • the CO2 mass flow sensor 255
  • the gas mixing control system 270 is electrically connected to one or more of the following elements for control thereof: the N2 valve 252 for regulating the inflow of N2 into the gas mixing box 242; the CO2 valve 254 for regulating the inflow of CO2 to the gas mixing box 242; the pump 246 for circulating gas in the flow loop 244; the release valve 249.
  • the control of the gas source by the gas mixing control system 270 is performed in accordance with two control regimes.
  • the first control regime relates to controlling the pressure of gas exiting the supply gas outlet 206
  • the second control regime relates to controlling the concentration of CO2 and O2 of gas exiting the supply gas outlet 206.
  • the two control regimes are conducted concurrently. This is further explained below.
  • the gas mixing control system 270 is being configured to receive input from the pressure sensor 248 and on the basis thereof control the pump 246 and optionally also activate the release valve 249 in order to maintain a desired and predetermined pressure of gas supplied to the main gas supply line 210 of the gas distribution system 204.
  • the gas mixing control system 270 is further configured to receive input from the mass flow sensor 256, and on the basis on this input to determine the total amount of CO2 gas and N2 gas needed to be supplied via the inlet for CO2 gas 251 and via the inlet for N2 gas 250 according to desired and predetermined criteria.
  • the gas mixing control system 270 will be able to determine the mutual proportion of the CO2 gas and N2 gas to be supplied to the gas mixing box 242.
  • the gas mixing control system 270 will control the CO2 valve 254, by transmitting a control signal thereto, and thereby regulate the inflow of CO2 gas in order to reach a desired and predetermined CO2 concentration.
  • the gas mixing control system 270 will on the basis of the O2 concentration sensed, control the N2 valve 252, by transmitting a control signal thereto, and thereby regulate the inflow of N2 gas in order to reach a desired and predetermined O2 concentration.
  • a constant circulation of gas will be supplied to one or more modular incubator chamber 300 being docked in a respective docking port 402 of the docking station 400.
  • an optimum and predetermined gas composition can be maintained.
  • upstream position when reference is made to an upstream position relative to another position, that upstream position is construed to mean a position still within the gas source 202 and preferably not so much upstream that it passes the gas mixing box 242 or the gas distribution system 204.
  • downstream position when reference is made to a downstream position relative to another position, that downstream position is construed to mean a position still within the gas source 202 and preferably not so much downstream that it passes the gas mixing box 242 or the gas distribution system 204.
  • Fig. 17 is a diagram illustrating the working mode of the controlling of the modular incubator system according to the invention.
  • Fig. 17 shows the control unit 650 for controlling the operation of the modular incubator system 500.
  • the control unit is coupled to an input device 652 in the form of an alphanumerical input device for allowing a user to provide settings input relating to a desired operational protocol of said modular incubator system.
  • a display unit 654 for displaying, to a user, information relating to settings and/or operational status of one or more of the modular incubator chambers 300 which via a docking port 402 is coupled to the control unit 650.
  • control unit 650 is coupled to a electric connectors 410 of the docking ports 402 of the docking station 400. Thereby electrical power and electric signals can be provided to one or more modular incubator chambers 300 which is/are being docked into a docking port 402 of the docking station 400 of the modular incubator system 500 via the associated connector 322 of the modular incubator chamber 300.
  • the control unit 650 may comprises a CPU or other data processor 656 for processing the information involved in controlling the operation of the modular incubator system 500, e.g. by involving a computer program for handing the information involved in the controlling of the operation and the control unit 650 may also comprise a data storage 658.
  • control unit 650 may inter alia independently control the temperature, the gas composition, the switching on and off of the light source 372, and the image capturing unit 408 of one or more of the modular incubator chambers.
  • viable biological materials can be incubated in one or more modular incubators 300 which are being docked in docking ports 402 of the docking station 400, and at the same time visual monitoring of the biological material can be conducted via the image capturing device 408.
  • a desired gas composition can be maintained in the interior 306 of each modular incubator chamber 300.
  • the modular incubator chambers comprises valves 2,4 in the respective inlet opening for gas 312 and outlet opening for gas 314, the gas atmosphere will be maintained and not disturbed by the outside atmosphere (relative to the interior 306 of the modular incubator chamber 300), even when the modular incubator chamber is removed from its respective docking port 402 of the docking station 400 of the modular incubator system 500.
  • the power source 320 and the electric heating element 318 will enable upholding the temperature in the interior 306 of the modular incubator chamber 300.
  • the present invention thereby allows for incubation of a biological material in the modular incubator chamber 300 and at the same time allows for visual monitoring of the morphological development of the biological material, while minimizing the detrimental effects involved in deviating from an optimized and desired gaseous atmosphere in the interior of the modular incubator chamber.
  • these adjacently arranged docking ports 402 may share a common image capturing device 408 in the sense that one and only one image capturing device is responsible for capturing images relating to a modular incubator chamber 300 which is being docked in one of these N adjacently arranged docking ports 402.
  • a displacement device 482 in the form of an electrically motorized suspension of the image capturing device 408 is being configured to be displaced, upon receiving a signal thereto, along a displacement track extending below these N number of adjacent docking ports 402 for enabling displacement of that common image capturing device 408 in relation to the N adjacently arranged docking ports 402 of the docking station 400.
  • the common image capturing device 408 will be able to capture images of a biological material being accommodated in the interior 306 of a modular incubator chamber 300 being docked in any of said N docking ports 402 of the docking station 400.
  • valves 2,4 letting gas into the chamber 300 and in respect of valves 2,4 letting gas out the chamber, or both.
  • Fig. 18a - 18c are microscopic photographs illustrating the effect of providing an inclined light, relative to a focus direction, when capturing images of a viable biological material.
  • Fig. 18a - 18c show microscope images captured of an incubated mouse embryo under three different inclination angles a between a light aiming direction A of a light directing element (active light source) and a focus direction B of an image capturing device and captured at different times.
  • Fig. 18a - 18c The three different inclination angles a between the light aiming direction A of a light directing element and the focus direction B illustrated in Fig. 18a - 18c were 0°, i.e. no inclination (Fig. 18a); 9° (Fig. 18b) and 16.7° (Fig. 18c).
  • the modular incubator system of the present invention improves assessment and reliability in the assessment of the stage (such as the various PN stages) of development of a viable biological material, for example an embryo or an oocyte being incubated in that modular incubator system.
  • a modular incubator system (500) for incubating a viable biological material M comprising:
  • said modular incubator chamber (300) comprises a housing (302); wherein said housing (302) comprises a lid (304), wherein said lid is being configured to be able to shift between an open configuration allowing access to the interior (306) of said modular incubator chamber and a closed configuration, sealing off access to the interior of said modular incubator chamber; wherein said modular incubator chamber, at said interior (306) thereof, comprises a culture dish support (308) for positioning a culture dish (310) with the view to accommodate one or more biological materials M within the housing (302) of said modular incubator chamber (300); wherein said housing (302) of said modular incubator chamber (300) comprises a transparent window (316) for enabling capturing of images of a biological material M being accommodated in the interior thereof, through said transparent window; wherein said housing comprises a light directing element (350) for directing light to an area of said culture dish support (308) in a light aiming direction (A); wherein said docking station (400) comprises one
  • a modular incubator system (500) according to clause 1 or 2, wherein in respect of one or more of said one or more modular incubator chambers (300) and in respect of one or more of said one or more docking ports (402) of said docking station (400), once being docked in said docking port (402) of said docking station, said light directing element (350) is being positioned in the interior (306) of said modular incubator chamber (300) at a position which is displaced relative to the focus direction (B) of said image capturing device (408) of said docking port (402), in a direction perpendicular to said focus direction (B), thereby providing said inclination angle a between said light aiming direction (A) and said focus direction (B).
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said culture dish support (308) is defining a planar support surface P for supporting said culture dish (310).
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is being attached to said lid (304) of the housing (306) of said modular incubator chamber (300), at an inner side thereof.
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350), comprises a diffuser, such as a diffuser lens.
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said transparent window (316) of said modular incubator chamber (300) is located at a bottom part (330) of said housing (302) of said chamber (300).
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is geometrically configured to make said light propagate at a maximum spreading angle of propagation of 1 - 65°, such as 5 - 60°, e.g. 10 - 55°, such as 15 - 50°, for example 20 - 45°, e.g. 25 - 40° or 30 - 35°.
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300) said light aiming direction (A) is directed towards said transparent window (316) in said housing (302) of said modular incubator (300).
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber (300) comprises inclination angle adjustment element (332) for adjusting the inclination angle a between said light aiming direction (A) and said focus direction (B), wherein said inclination angle adjustment element (332) is configured to enable adjustment of said inclination angle a so that this inclination angle a may attain an angle selected from the ranges 0.5 - 25°, such as 1 - 24°, for example 2 - 23°, e.g.
  • 3 - 22° such as 4 - 21°, for example 5 - 20°, such as 6 - 19°, for example 7 - 18°, such as 8 - 17°, for example 9 - 16°, such as 10 - 15°, e.g. 11 - 14° or 12 - 13°.
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), said docking port (402) comprises a shadowing element (450) which is configured to enable blocking part of the light being propagated towards the optics of said image capturing device (408).
  • said shadowing element (450) comprises a shadowing plate (452) comprising a through-going hole (454) having a fixed geometry and/or size, such as a round hole, such as a circular hole; or a rectangular hole, wherein said shadowing plate (452) is being arranged relative to said image capturing device (408) so that the focus direction B of said image capturing device (408) passes through that hole (452).
  • an actuator (464) such as a remote-controlled electric actuator which is mechanically connected to said iris lamellas (460) and which is configured to enable movement of said iris lamellas in concert so as to vary the size of said through-going hole (462).
  • a modular incubator system (500) according to any of the clauses 14 - 17, wherein said shadowing element (450) is coupled to an X- stage or XY-stage (456) in a way enabling said shadowing element (450) to be independently displaced in one or two displacement directions (D1,D2) which each optionally is/are being essentially perpendicular to the focus direction (B) of said image capturing device (408).
  • said shadowing element (450) is coupled to an X- stage or XY-stage (456) in a way enabling said shadowing element (450) to be independently displaced in one or two displacement directions (D1,D2) which each optionally is/are being essentially perpendicular to the focus direction (B) of said image capturing device (408).
  • a modular incubator system (500) according to any of the clauses 14 - 19, wherein said shadowing element (450) is being arranged outside the optics of said image capturing device (408); or wherein said shadowing element (450) is being arranged inside the optics of said image capturing device (408).
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is an active light source (352) being arranged in the interior (306) of the modular incubating chamber (300), wherein said active light source (352) is configured for propagating light in said light aiming direction (A), by being supplied with electric power.
  • said light directing element (350) is an active light source (352) being arranged in the interior (306) of the modular incubating chamber (300), wherein said active light source (352) is configured for propagating light in said light aiming direction (A), by being supplied with electric power.
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is a passive light directing element in the form of a light conveyor (354) being arranged in the interior (306) of the modular incubating chamber (300), wherein said light conveyor (354) is configured for directing incoming light, in said light aiming direction (A), such as by reflecting said incoming light.
  • said light conveyor (350,354) is being a light reflector, such as a mirror.
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said housing (302) of said modular incubator chamber (300), such as at an outer portion thereof, is being provided with electric connectors (322) for providing electric power and/or electric signals to said modular incubator chamber; and wherein in respect of one or more docking ports (402) of said docking station (400), said docking port is being provided with electric connectors (410), thereby allowing providing electric power and/or electric signals between said docking port (402) of said docking station (400) and a modular incubator chamber (300) being docked therein.
  • a modular incubator system (500) according to any of the clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber (300) comprises a chamber inlet opening for gas (312), wherein said chamber inlet opening for gas (312) is being in fluid connection with the interior (306) of said modular incubator chamber; and wherein said modular incubator chamber (300) furthermore comprises a chamber outlet opening for gas (314), wherein said chamber outlet opening for gas (314) is being in fluid connection with the interior (306) of said modular incubator chamber; and wherein in respect of one or more docking ports (402) of said docking station (400), said docking port (402) comprises a docking port outlet opening for gas (404) and a docking port inlet opening for gas (406); thereby enabling transfer of gas from said docking port (402) of said docking station (400) to the interior (306) of said modular incubator chamber (300) via said docking port outlet opening for gas (404) and said chamber inlet opening for gas (312); and thereby
  • a modular incubator system (500) according to any of the clauses 40 or 41, wherein said docking port outlet opening for gas (404) of said docking port (402) comprises a valve (4) and wherein said chamber inlet opening for gas (312) of said housing (302) comprises a valve (2); and wherein said chamber outlet opening for gas (314) comprises a valve (2) and wherein said docking port inlet opening for gas (406) of said docking port (402) comprises a valve (4).
  • a modular incubator system (500) according to any of the clauses 40 - 42; wherein in respect of one or more of said one or more modular incubator chambers (300), said valve (2) of said chamber inlet opening for gas (312) and said valve (2) of said chamber outlet opening for gas (314) each comprises a valve body (6) having a front end (10), a rear end (12) and a through-going channel (14) therein, and a spring-loaded displaceable valve element (8), wherein said displaceable valve element (8) is being arranged in said through-going channel (14); wherein said displaceable valve element (8) is being configured to be displaceable in said through-going channel (14) of said valve body (6) in such a way, that when not acted upon by an external force, said spring-loaded displaceable valve element (8) is not being displaced in said through-going channel (14) of said valve body (6), thereby making said valve attain a closed configuration blocking passage of gas through said through-going channel (14), and in such a way, that when acted
  • a modular incubator system (500) according to any of the clauses 40 - 43, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), and in respect of one or more of said one or more modular incubator chambers (300) said valves (2,4) are having dimensions and geometries in such a way that once docking said modular incubator chamber (300) in said docking port (402) of said docking station (400), said displaceable valve element (8) of said valve (2) and said displaceable valve element (18) of said valve (4) will displace each other into their respective valve bodies (6,16), thereby opening said valves (2,4) of said docking port outlet opening for gas (404) and said chamber inlet opening for gas (312); and thereby opening said valves (2,4) of said chamber outlet opening for gas (314) and said docking port inlet opening for gas (406).
  • a modular incubator system (500) according according to any of the clauses 1 - 44, wherein in respect of one or more of said docking ports (402) of said docking station (400) of said modular incubator system (500), preferably in respect of all said docking ports (402), said docking port outlet opening for gas (404) comprises a flow restrictor for restricting the magnitude of flow of gas flowing into said docking port (402).
  • a modular incubator system (500) according to any of the clauses 40 - 46, wherein said docking station (400) comprises a gas distribution system (204) for supplying gas to and from one or more of said one or more docking ports (402), wherein said gas distribution system (204) comprises a main gas supply line (210) and a main gas return line (212), wherein in respect of one or more of said docking ports (402), said docking port inlet opening for gas (404) is being fluidly connected to said main gas supply line (210), and said docking port outlet opening for gas (406) is being fluidly connected to said main gas return line (212).
  • a modular incubator system (500) according to clause 47 wherein said gas distribution system (204) comprises a number of manifold pairs (214), wherein each manifold pair comprises an inlet manifold (216) and an outlet manifold (218), wherein said inlet manifold (216) is being fluidly connected to said main gas supply line (210) and wherein said outlet manifold (218) is being fluidly connected to said main gas return line (212); wherein each manifold pair (214) is connected to one or more docking ports (402) of said docking station (400) in such a way that in respect of a specific manifold pair (214), and in respect of said one or more docking ports (402) being connected thereto, said docking port outlet opening for gas (404) of said docking port (402) is being fluidly connected to said inlet manifold (216), and said docking port inlet opening for gas (406) of said docking port (402) is being fluidly connected to said outlet manifold (218).
  • a modular incubator system (500) according to clause 47 or 48, wherein said docking station (400) comprises a gas supply system (200), wherein said gas supply system (200) comprises a gas source (202) and said gas distribution system (204), wherein said gas source comprises a supply gas outlet (206) and a return gas inlet (208), wherein said supply gas outlet (206) of said gas source (202) is being fluidly connected to said main gas supply line (210) of said gas distribution system (204), and wherein said return gas inlet (208) of said gas source (202) is being fluidly connected to said main gas return line (212) of said gas distribution system (204).
  • a modular incubator system (500) according to any of the clauses 47 - 49, wherein said gas source (202) of said gas supply system (200) comprises a gas mixing box (242) comprising said supply gas outlet (206) and said return gas inlet (208) of said gas source, wherein said main gas supply line (210) of said gas distribution system (204) is being fluidly connected to said supply gas outlet (206), and wherein said main gas return line (212) of said gas distribution system (204) is being fluidly connected to said return gas inlet (208) of said gas source (202), thereby forming a flow loop (244) comprising said gas distribution system (204) and said gas mixing box (242); wherein said flow loop comprises a pump (246) for circulating gas in said loop.
  • a modular incubator system (500) according to any of the clauses 50 - 52, wherein said flow loop (244) comprises a pressure sensor, such as a differential pressure sensor (248) for sensing the pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204), wherein said pressure senor (248) optionally is being arranged immediately upstream in relation to said main gas supply line (210) of said gas distribution system (204).
  • a pressure sensor such as a differential pressure sensor (248) for sensing the pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204)
  • said pressure senor (248) optionally is being arranged immediately upstream in relation to said main gas supply line (210) of said gas distribution system (204).
  • a modular incubator system (500) according to any of the clauses 50 -54, wherein said flow loop (244) comprises a release valve (249) for enabling pressure relief in said flow loop, wherein said release valve optionally is being arranged immediately downstream in relation to said main gas return line (212) of said gas distribution system (402).
  • a modular incubator system (500) according to any of the clauses 50 -55, wherein said gas mixing box (242) comprises an inlet for N2 gas (250); and an inlet for CO2 gas (251), wherein said inlet for N2 gas (250) is fluidly connected to an N2 valve (252) for regulating the inflow of N2, and an N2 mass flow sensor (253) arranged downstream of said N2 valve (252) for sensing the amount of N2 flowing into said gas mixing box (242); and wherein said inlet for CO2 gas (251) is fluidly connected to a CO2 valve (254) for regulating the inflow of CO2, and an CO2 mass flow sensor (255) arranged downstream of said CO2 valve (254) for sensing the amount of CO2 flowing into said gas mixing box (242).
  • said gas mixing box (242) comprises an inlet for N2 gas (250); and an inlet for CO2 gas (251), wherein said inlet for N2 gas (250) is fluidly connected to an N2 valve (252) for regulating the in
  • a modular incubator system (500) according to any of the clauses 50 -56, wherein said flow loop (244) comprises a mass flow sensor (256) arranged at an upstream position in relation to said gas mixing box (242) for sensing the amount of return gas entering said gas mixing box.
  • Clause 58 A modular incubator system (500) according to any of the clauses 50 -57, wherein said gas source (202) comprises an O2 sensor (258) for sensing the concentration of O2 exiting said gas distribution system (204); and wherein said gas source (202) comprises a CO2 sensor (260) for sensing the concentration of CO2 exiting said gas distribution system (204), wherein said O2 sensor and/or said CO2 sensor optionally is/are being arranged downstream in relation to said pump (246).
  • said gas source (202) comprises an O2 sensor (258) for sensing the concentration of O2 exiting said gas distribution system (204); and wherein said gas source (202) comprises a CO2 sensor (260) for sensing the concentration of CO2 exiting said gas distribution system (204), wherein said O2 sensor and/or said CO2 sensor optionally is/are being arranged downstream in relation to said pump (246).
  • a modular incubator system (500) according to any of the clauses 50 - 58, wherein said gas source (202) comprises a temperature sensor (262) for sensing the temperature of gas circulating in said flow loop (244), wherein said temperature sensor optionally is being arranged downstream in relation to said pump (246), preferably at a position corresponding to the position of said O2 sensor (258).
  • a modular incubator system (500) according to any of the clauses 50 - 59, wherein said gas source (202) comprises a pressure sensor (264) for sensing the absolute pressure in said flow loop (244) wherein said pressure sensor optionally is being arranged downstream in relation to said pump (246), preferably at a position corresponding to the position of said CO2 sensor (260).
  • a modular incubator system (500) according to any of the clauses 50 - 60, wherein said flow loop (244) comprises a UV sanitizer (266) for sanitizing gas flowing in said flow loop (244) via electromagnetic radiation in the UV range, wherein said UV sanitizer optionally being arranged immediately downstream in relation to said main gas return line (212).
  • said flow loop (244) comprises a UV sanitizer (266) for sanitizing gas flowing in said flow loop (244) via electromagnetic radiation in the UV range, wherein said UV sanitizer optionally being arranged immediately downstream in relation to said main gas return line (212).
  • a modular incubator system (500) according to any of the clauses 50 - 61, wherein said gas source (202) comprises one or more filters (268), such as HEPA and/or VOCs filters, wherein such a filter is being arranged immediately upstream in relation to said main gas supply line (210), and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for N2gas (250) into said gas mixing box (242); and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for CO2 gas (251) into said gas mixing box (242).
  • filters (268) such as HEPA and/or VOCs filters
  • a modular incubator system (500) according to any of the clauses 50 - 62, wherein said gas source (202) comprises a gas mixing control system (270), wherein said gas mixing control system is electrically connected to one or more of the following sensors for receiving sensing signals therefrom: said N2 mass flow sensor (253) for sensing the amount of N2 flowing into said gas mixing box; said CO2 mass flow sensor (255) for sensing the amount of CO2 flowing into said gas mixing box; said mass flow sensor (256) for sensing the amount of return gas entering said gas mixing box; said O2 sensor (258) for sensing the concentration of O2 exiting said main gas return line (212) of said gas distribution system (204); said CO2 sensor (260) for sensing the concentration of CO2 exiting said main gas return line (212) of said gas distribution system (204); said temperature sensor (262) for sensing the temperature circulating in said flow loop (244); said pressure sensor (264) for sensing an absolute pressure in said flow loop (244), said pressure sensor (248) for sensing the pressure of
  • a modular incubator system (500) according to clause 63, wherein said gas mixing control system (270) is electrically connected to one or more of the following elements for control thereof: said N2 valve (252) for regulating the inflow of N2 into said gas mixing box (242); said CO2 valve (254) for regulating the inflow of CO2 to said gas mixing box (242); said pump (246) for circulating gas in said flow loop (244); said release valve (249).
  • said gas mixing control system (270) is electrically connected to one or more of the following elements for control thereof: said N2 valve (252) for regulating the inflow of N2 into said gas mixing box (242); said CO2 valve (254) for regulating the inflow of CO2 to said gas mixing box (242); said pump (246) for circulating gas in said flow loop (244); said release valve (249).
  • a modular incubator system (500) according to clause 63 or 64, wherein said gas mixing control system (270) is being configured to receive input from said pressure sensor (248) and on the basis thereof control said pump (246), optionally also to activate said release valve (249) in order to maintain a desired and predetermined pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204).
  • Clause 66 A modular incubator system (500) according to any of the clauses 63 - 65, wherein said gas mixing control system (270) is being configured to receive input from said mass flow sensor (256), and on the basis on said input to determine the total amount of CO2 gas and N2 gas needed to be supplied via said inlet for CO2 gas (251) and via said inlet for N2 gas (250) according to desired and predetermined criteria.
  • said gas mixing control system (270) is being configured to receive input from said mass flow sensor (256), and on the basis on said input to determine the total amount of CO2 gas and N2 gas needed to be supplied via said inlet for CO2 gas (251) and via said inlet for N2 gas (250) according to desired and predetermined criteria.
  • a modular incubator system (500) according to any of the clauses 63 - 66, wherein said gas mixing control system (270) is being configured to receive input from said CO2 sensor (260) and said O2 sensor (258), and on the basis of the CO2 concentration sensed, is configured to control said CO2 valve (254), by transmitting a control signal thereto, and thereby regulating the inflow of CO2 gas in order to reach a desired and predetermined CO2 concentration, and wherein subsequently, said gas mixing control system (270) on the basis of the O2 concentration sensed, is configured to control said N2 valve (252), by transmitting a control signal thereto, and thereby regulating the inflow of N2 gas in order to reach a desired and predetermined O2 concentration.
  • Clause 68 A modular incubator system (500) according to any of the clauses 63 - 67, wherein said gas mixing control system (270) is configured to use the input from said temperature sensor (262) for compensating the temperature sensitivity of said O2 sensor (258).
  • a modular incubator system (500) according to any of the clauses 63 - 68, wherein said gas mixing control system (270) is configured to use the input from said pressure sensor (264) for compensating the pressure sensitivity of said CO2 sensor (260).
  • Clause 70 A modular incubator system (500) according to any of the clauses 63 - 69, wherein said gas mixing control system (270) is being configured to maintain a pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204), relative to the ambient atmospheric pressure, of 3 - 20 mbar, such as 5 - 18 mbar, such as 10 - 15 mbar above that ambient atmospheric pressure.
  • a modular incubator system (500) according to any of the clauses 63 - 70, wherein said gas mixing control system (270) is being configured to maintain a CO2 concentration of gas entering said main gas supply line (210) of said gas distribution system (204) in the range of 5 - 10 %, such as 6 - 9 % or 7 - 8 %; and/or an O2 concentration of gas entering said main gas supply line 210 of said gas distribution system 204 in the range of 5 - 10%, such as 6 - 9 % or 7 - 8 %.
  • a modular incubator system (500) according to any of the preceding clauses, wherein the number of modular incubator chambers (300) of said modular incubator system (500) is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
  • a modular incubator system (500) according to any of the preceding clauses, wherein the number of docking ports (402) in said docking station (400) of said modular incubator system 500 is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
  • a modular incubator system (500) according to any of the preceding clauses, wherein said docking station (400) comprises said docking ports (402) in an arrangement of one or more shelves of adjacently positioned docking ports (402), wherein in case said docking station comprises two or more shelves, said shelves are being arranged above each other.
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber comprises an incubation chamber engagement means (326) and wherein in respect of one or more docking ports (402) of said docking station (400), said docking port comprises a docking port engagement means (414), wherein said incubation chamber engagement means (326) is being configured to enter into engagement with said docking port engagement means (414) so as to provide easy and proper positioning and optionally also fixing said modular incubator chamber( 300) in said docking port (402), as well as detaching said modular incubator chamber (300) from said docking port (402) of said docking station (400).
  • a modular incubator system (500) according to any of the preceding clauses, wherein said modular incubator system (500) comprises an image processing unit (660) for image processing of images captured by said image capturing device (408), wherein said modular incubator system (400) furthermore comprises a data storage (658) for storing images captured by said image capturing units (408) and/or for storing images processed by said image processing unit.
  • said modular incubator system (500) comprises an image processing unit (660) for image processing of images captured by said image capturing device (408), wherein said modular incubator system (400) furthermore comprises a data storage (658) for storing images captured by said image capturing units (408) and/or for storing images processed by said image processing unit.
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more specific docking ports (402) of said docking station (400), said specific docking port comprises its own dedicated image capturing device (408) which is configured to only capture images relating to a modular incubator chamber (300) which is being docked in said specific docking port (402).
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of a number N of adjacently arranged docking ports (402) of said docking station (400), said adjacently arranged docking ports (402) share a common image capturing device (408) in the sense that one and only one image capturing device is responsible for capturing images relating to a modular incubator chamber (300) which is being docked in one of said N adjacently arranged docking ports (402) s wherein said docking station comprises a displacement device (482) for enabling displacement of said common image capturing device (408) in relation to said N adjacently arranged docking ports (402) of said docking station (400), such as being provided with an electric signal thereto.
  • a modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said modular incubator chambers (300), said modular incubator chamber comprises in its interior (306) an electric heating element (318) for heating the interior of said modular incubator chamber, and wherein said modular incubator chamber comprises a power source (320) for providing power to said heating element (318), wherein said electric heating element (318) is being electrically connected to said power source (320).
  • a modular incubator system (500) according to any of the clauses 81 or 82, wherein said heating element (318) is being thermally connected to a heat distribution element for distributing heat dissipated in said heating element; wherein said heat distribution element is being arranged, at least partly, in the interior (306) of said modular incubator chamber (300).
  • a modular incubator system (500) according to any of the clauses 81 - 83, wherein said chamber comprises a thermostat (374) and an electric thermostatic circuit (376), wherein said electric heating element (318), said power source (320) and said thermostat (374) are being electrically connected in said electric thermostatic circuit (376) so as to enable thermostatic control of the temperature inside said modular incubator chamber (300).
  • a modular incubator system (500) according to any of the preceding clauses, wherein said modular incubator system (500) comprises a control unit (650) for controlling the operation of said modular incubator system (500).
  • an input device such as an alphanumerical input device for allowing a user to provide settings input relating to a desired operational protocol of said modular incubator system.
  • a modular incubator system (500) according to any of the clauses 85 - 87, wherein in respect of one or more docking ports (402) of said docking station (400) said control unit (650) is being configured for independently controlling one or more of the following: temperature in the interior (306) of said modular incubator chamber (300) by controlling said electric heating element (318), said thermostat (374) or said thermostatic circuit (376), providing power to said electric power source (320); providing signals to said display (324) a modular incubator chamber (300), said inclination angle adjustment element (332), said rotational adjustment element (334) of said inclination angle adjustment element (332), said displacement adjustment element (336) of said inclination angle adjustment element (332), switching on and off of said active light source (352), or adjusting light intensity emitted therefrom, said image capturing device (408) of a docking station (408), said displacement device (482) for displacing said image capturing device (408), said actuator of said X-stage or XY-stage (466), said actuator of said iris dia
  • a modular incubator system (500) according to any of the clauses 85 - 88, wherein said control unit (650) is being coupled to a data processing unit (656) and optionally also to a data storage (658) for aiding in handling information during controlling of said modular incubator system.
  • a modular incubator system (500) according to any of the clauses 85 - 89, wherein said control unit (650) is being configured for conducting automatic operation of said modular incubator system (500) by configuring said control unit (650) to independently control one or more of the following: temperature in the interior (306) of said modular incubator chamber (300) by controlling said electric heating element (318), said thermostat (374) or said thermostatic circuit (376), providing power to said electric power source (320); providing signals to said display (324) a modular incubator chamber (300), said inclination angle adjustment element (332), said rotational adjustment element (334) of said inclination angle adjustment element (332), said displacement adjustment element (336) of said inclination angle adjustment element (332), switching on and off of said active light source (352), or adjusting light intensity emitted therefrom, said image capturing device (408) of a docking station (408), said displacement device (482) for displacing said image capturing device (408), said actuator of said X-stage or XY-stage (466), said actuator of said
  • a modular incubator system (500) according to any of the clauses 85 - 90, wherein said control unit (650) is being configured for enabling time lapse capturing of images by said image capturing devices (408).
  • Clause 97 Use according to any of the clauses 94, 95 or 96, wherein said biological material M is being an oocyte or an embryo, such as a human oocyte or a human embryo.
  • a method of incubating a viable biological material M comprises: i) providing a modular incubator system (500) according to any of the clauses 1 - 91; ii) providing a viable biological material M; iii) arranging said viable biological material M in a culture dish (310) and subsequently arranging said culture dish on the culture dish support (308) in the interior (306) of said modular incubator chamber (300) of said modular incubator system (400); iv) docking said modular incubator chamber (300) in a docking port (402) of said docking station (400) of said incubator system (500); v) allowing said viable biological material M to be incubated in said modular incubator chamber (300); vi) while performing step v) enabling said light directing element (350) of said modular incubator chamber (300) to direct light to an area of said culture dish support (308) in said light aiming direction (A); vii) while performing step v) and vi) making said image capturing device (408) capture image(s) of said viable biological material
  • a method according to clause 98 further comprising the step of: viii) removing said incubator chamber (300) from said docking port (402) of said docking station (400), when desired, in order to manually inspect the viable biological material M, and optionally also to remove, add or exchange growth medium/media in said culture dish (310).

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Abstract

A modular incubator system (500) for incubating a viable biological material M is disclosed. The modular incubator system comprises one or more modular incubator chambers (300) in combination with a docking station (400) comprising a plurality of docking ports (402) for receiving an incubator chamber (300). The modular incubator chambers (300), comprises a housing (302) with a lid (304) for sealing off access to the interior of the modular incubator chamber. The modular incubator chamber, at said interior (306) thereof, comprises a culture dish support (308) for positioning a culture dish (310) with the view to accommodate one or more biological materials M within the housing (302) of said modular incubator chamber (300). The housing (302) of the modular incubator chamber (300) also comprises a transparent window (316) for enabling capturing of images of a biological material M being accommodated in the interior thereof, through that transparent window. Moreover, the housing comprises a light directing element (350) for directing light to an area of said culture dish support (308) in a light aiming direction (A). The docking ports (402) of the docking station (400) comprises an image capturing device (408) for capturing an image of the interior (306) of a modular incubator chamber (300), once being docked in said docking port (402), by focusing said image capturing device (408) in a focus direction (B). Once being docked in the docking port (402), the light aiming direction (A) of light propagating from the light directing element (350) of said modular incubator chamber (300) is being inclined relative to said focus direction (B) of said image capturing device (408) of said docking port (402) at an inclination angle a, wherein said inclination angle a + 0°. Hereby easier and more reliable determination of the cell division stage of a viable biological material being incubated is provided.

Description

A modular incubator system providing improved illumination for image capture of an incubated biological material
Field of the invention
The present invention relates in general to the field of incubators for incubating a viable biological material.
More specifically the present invention relates in a first aspect to a modular incubator system comprising one or more modular incubator chambers in combination with a docking station for incubating a viable biological material.
In a second aspect the present invention relates to a modular incubator chamber for incubating a viable biological material.
In a third aspect the present invention relates to a docking station for incubating a viable biological material.
In a fourth aspect the present invention relates to a use of the modular incubator system according to the first aspect for incubating a viable biological material.
In a fifth aspect the present invention relates to a use of the modular incubator chamber according to the second aspect for incubating a viable biological material.
In a sixth aspect the present invention relates to a use of the docking station according to the third aspect for incubating a viable biological material.
In a seventh aspect the present invention relates to a method for incubating a viable biological material.
Background of the invention
The development of in vitro fertilization (IVF) has for the latest few decades resulted in considerably improved methods and techniques which have increased success rates of IVF mediated pregnancies and births.
In vitro fertilization involves capturing a ripened egg from a female ovary, fertilizing the ovary with a spermatozoon, incubating the fertilized egg under a controlled environment and subsequently inserting the fertilized and incubated egg in a female’s uterus.
As in vitro fertilization is most commonly used by females or couples which notoriously are having problems in getting pregnant the natural way, thus implying some degree of reduced fertility by the male or female counterpart of the couple, or both, and as in vitro fertilization techniques involves quite expensive procedures, these in vitro fertilization techniques are usually performed in a way that seek to optimize efficiency, especially in view of the fact that frequently more than one insertion of a fertilized egg into the female’ uterus will be necessary in order to encounter a successful pregnancy.
Additionally, compared to the natural way of getting pregnant, in respect of a couple wherein an individual is having a generic disease or in case of suspicion of such, an IVF mediated pregnancy may be advantageous.
Accordingly, in order to make the in vitro fertilization techniques efficient, the female is typically provided with a hormone treatment prior to harvesting eggs from her ovary. Such hormone treatment will make the female ovary ovulate not only one egg, but a multitude of eggs at the same time.
In order to increase the chance of a viable and successful pregnancy more than one egg from the same female will accordingly be fertilized and incubated concurrently in an incubator.
Prior art incubators include a compartment which allows for accommodating more than one culture dish comprising the fertilized eggs.
Some prior art incubators comprise a housing having one or more doors for providing access to the interior of the incubator. The interior of the incubator holds one or more culture dishes accommodating the embryos to be cultured. Such incubators may be provided with various regulation means for controlling humidity, temperature and gas composition of the interior of the incubator.
Recently, smaller modular incubators have been put on the marked. These modular incubators are configured to be stored in a docking station which may provide the controlling of physical and chemical parameters to be imposed to the embryos being accommodated therein. Once any manual manipulation steps in respect of the embryo is needed, the modular incubator may be removed from the docking station and arranged on a laboratory bench for easy access to the embryo.
Performing a successful in vitro fertilization and incubation of a fertilized egg is not an easy task. One of the major reasons for the rather low success rate of in vitro fertilizations is the absence of reliable methods for selecting the highest quality embryo(s) for transfer.
The lack of methods for assessing embryo quality has led to substantial efforts to develop improved assays of embryo viability. One current reliable method for predicting embryo quality is to examine embryo morphology prior to transfer into the female’s uterus using standard light microscopy systems.
In methods for examination of embryo morphology quality, image capturing means are provided in the prior art incubator and these image capturing means may be equipped with microscopic optics which allow for capturing close-up images of each fertilized egg with the view to only select those embryos that exhibit a normal or healthy development and to only insert those embryos into the female’s uterus. Time lapse imaging provides for visual study of the visible physical development, such as time of division of cells at different stages, overall speed of division of cells etc.
The prior art use of microscopic optics in studying morphological quality of an embryo with the view to select the healthiest oocyte(s) typically involves direction of light to the oocyte from one side thereof (such as from above or from below) and studying the morphological quality of the oocyte by use of microscopic optics arranged at an opposite thereof (such as from below or from above the oocyte).
Although such method allows for providing close-up images of the oocyte, this prior art morphological assessment nevertheless presents some drawback.
One of these drawbacks is that when providing light from the opposite side of the oocyte to be studied, relative to the microscopic optics, it often happens that the cell walls of individual cells of the oocyte may be blurred out thereby making it difficult to assess the actual stage of cell division. Especially, it may be difficult to assess the stage of development of the embryo in respect of the stage of cell divisions in this type of optical set-up, such as the two pronuclei (2 PN stage), the four cell stage, the eight cell stage etc.
Prior art attempts to solve this contrasting problem involves applying phase contrast techniques, Hofman contrast techniques, DIC (differential interference contrast) etc. However, these techniques improve visual contrast at very specific cell division stage at the cost of decreasing visual contrast at other cell division stages
Accordingly, a need persists for improved technology for studying morphological development of an embryo during incubation thereof.
It is an objective of the present invention to fulfil such need.
Brief description of the invention
This objective is fulfilled according to the present invention in its various aspects.
Accordingly, the present invention relates in a first aspect to a modular incubator system for incubating a viable biological material, said modular incubator system comprising:
-one or more modular incubator chambers in combination with
-a docking station; wherein in respect of one or more of said one or more modular incubator chambers, said modular incubator chamber comprises a housing; wherein said housing comprises a lid, wherein said lid is being configured to be able to shift between an open configuration allowing access to the interior of said modular incubator chamber and a closed configuration, sealing off access to the interior of said modular incubator chamber; wherein said modular incubator chamber, at said interior thereof, comprises a culture dish support for positioning a culture dish with the view to accommodate one or more biological materials within the housing of said modular incubator chamber; wherein said housing of said modular incubator chamber comprises a transparent window for enabling capturing of images of a biological material being accommodated in the interior thereof, through said transparent window; wherein said housing comprises a light directing element for directing light to an area of said culture dish support in a light aiming direction A; wherein said docking station comprises one or more docking ports for receiving a housing of an incubator chamber; wherein in respect of one or more docking ports of said docking station, said docking port comprises an image capturing device for capturing an image of the interior of a modular incubator chamber, once being docked in said docking port, by focusing said image capturing device in a focus direction B; wherein in respect of one or more of said one or more modular incubator chambers and in respect of one or more of said one or more docking ports of said docking station, the position of said transparent window of said modular incubator chamber is adapted to the position of said image capturing device in said docking port in a way that enables capturing of images by said image capturing device through said transparent window of said modular incubator chamber; wherein in respect of one or more of said one or more modular incubator chambers and in respect of one or more of said one or more docking ports of said docking station, once being docked in said docking port, said light aiming direction A of said light propagating from said light directing element of said modular incubator chamber is being inclined relative to said focus direction B of said image capturing device of said docking port at an inclination angle a, wherein said inclination angle a 0°.
The present invention relates in a second aspect to a modular incubator chamber, wherein said modular incubator chamber is comprising features as defined in respect of the modular incubator chamber of the modular incubator system of the first aspect of the present invention.
The present invention relates in a third aspect to a docking station, wherein said docking station is comprising features as defined in respect of the docking station of the modular incubator system of the first aspect of the present invention.
In a fourth aspect the present invention provides a use of a modular incubator system according to the first aspect of the present invention for incubating a viable biological material. In a fifth aspect the present invention provides a use of a modular incubator chamber according to the second aspect of the present invention for incubating a viable biological material.
In a sixth aspect the present invention provides a use of a docking station according to the third aspect of the present invention for incubating a viable biological material.
In a seventh aspect the present invention provides a method of incubating a viable biological material M, wherein said method comprises: i) providing a modular incubator system according to the first aspect of the present invention; ii) providing a viable biological material; iii) arranging said viable biological material in a culture dish and subsequently arranging said culture dish on the culture dish support in the interior of said modular incubator chamber of said modular incubator system; iv) docking said modular incubator chamber in a docking port of said docking station of said incubator system; v) allowing said viable biological material to be incubated in said modular incubator chamber; vi) while performing step v) enabling said light directing element of said modular incubator chamber to direct light to an area of said culture dish support in said light aiming direction A; vii) while performing step v) and vi) making said image capturing device capture image(s) of said viable biological material M in the interior of said modular incubator chamber, at a focus direction B; wherein said focus direction A of light propagating from said light directing element of said modular incubator chamber is being inclined relative to said focus direction B of said image capturing device of said docking port at an inclination angle a which is 0°.
The present invention in its various aspects provides improved contrasting effects in capturing images of a viable biological material being incubated in an incubator.
Hereby, easier and more reliable determination of the development of an actual cell division, such as in respect of an embryo or an oocyte is attained.
Brief description of the figures
Fig. 1 is a perspective view illustrating the general concept of providing an incubator as a modular incubator system comprising a plurality of modular incubator chambers in combination with a docking station.
Fig. 2a is a perspective view of the modular incubator chamber of the modular incubator system illustrated in Fig. 1 as seen from above. Fig. 2b is a plan view of a modular incubator chamber of the modular docking system of fig. 1.
Fig. 2c is a plan view of the modular incubator chamber illustrated in Fig. 2 as seen from a rear end.
Fig. 3 is a cross-sectional view of the modular incubator chamber of the modular incubator system illustrated in Fig. 1.
Fig. 4 is a diagram illustrating the principle of the concept of the present invention.
Fig. 5 is a diagram illustrating the concept of a light aiming direction as employed in the present application.
Fig. 6 is diagrammatic representation of an embodiment illustrating in more details the principle of the present invention.
Fig. 7 is a diagrammatic representation of another embodiment illustrating in more details the principle of the present invention.
Fig. 8 is diagrammatic representation of yet another embodiment illustrating in more details the principle of the present invention.
Fig. 9 is a diagrammatic representation of a still other embodiment illustrating in more details the principle of the present invention.
Fig. 10 is diagrammatic representation of a yet still other embodiment illustrating in more details the principle of the present invention.
Fig. 11 is diagrammatic representation of an embodiment alternative to the one illustrated in Fig. 10, illustrating in more details the principle of the present invention.
Fig. 12 is a diagram illustrating the principle of including an inclination angle adjustment element for adjusting the inclination angle a
Fig. 13a, 13b and 12c are diagrams illustrating the principle of including a shadowing element in the docking ports 402 of the docking station.
Fig. 14a and 14b are drawings illustrating the working modes of valves of a valve system to be used with the modular incubator chamber and the associated docking port of the docking station of the docking system of the present invention.
Fig. 15 is a diagram illustrating one embodiment of a design of a gas supply system comprising a gas source and a gas distribution system to be used with the docking station of the modular incubator system of the present invention.
Fig. 16 is a diagram illustrating the concept of gas source which may be incorporated in the docking station of the modular incubator system of the present invention.
Fig. 17 is a diagram illustrating the working mode of the controlling of the modular incubator system according to the invention. Fig. 18a - 18c are microscopic photographs illustrating the effect of providing an inclined light, relative to a focus direction, when capturing images of a viable biological material.
Detailed description of the invention
The first aspect of the present invention
In a first aspect the present invention relates to a modular incubator system 500 for incubating a viable biological material M, said modular incubator system comprising:
-one or more modular incubator chambers 300 in combination with
-a docking station 400; wherein in respect of one or more of said one or more modular incubator chambers 300, said modular incubator chamber 300 comprises a housing 302; wherein said housing 302 comprises a lid 304, wherein said lid is being configured to be able to shift between an open configuration allowing access to the interior 306 of said modular incubator chamber and a closed configuration, sealing off access to the interior of said modular incubator chamber; wherein said modular incubator chamber, at said interior 306 thereof, comprises a culture dish support 308 for positioning a culture dish 310 with the view to accommodate one or more biological materials M within the housing 302 of said modular incubator chamber 300; wherein said housing 302 of said modular incubator chamber 300 comprises a transparent window 316 for enabling capturing of images of a biological material M being accommodated in the interior thereof, through said transparent window; wherein said housing comprises a light directing element 350 for directing light to an area of said culture dish support 308 in a light aiming direction A; wherein said docking station 400 comprises one or more docking ports 402 for receiving a housing 302 of an incubator chamber 300; wherein in respect of one or more docking ports 402 of said docking station 400, said docking port 402 comprises an image capturing device 408 for capturing an image of the interior 306 of a modular incubator chamber 300, once being docked in said docking port 402, by focusing said image capturing device 408 in a focus direction B; wherein in respect of one or more of said one or more modular incubator chambers 300 and in respect of one or more of said one or more docking ports 402 of said docking station 400, the position of said transparent window 316 of said modular incubator chamber 300 is adapted to the position of said image capturing device 408 in said docking port 402 in a way that enables capturing of images by said image capturing device 408 through said transparent window 316 of said modular incubator chamber 300; wherein in respect of one or more of said one or more modular incubator chambers 300 and in respect of one or more of said one or more docking ports 402 of said docking station 400, once being docked in said docking port 402, said light aiming direction A of said light propagating from said light directing element 350 of said modular incubator chamber 300 is being inclined relative to said focus direction B of said image capturing device 408 of said docking port 402 at an inclination angle a, wherein said inclination angle a 0°.
Accordingly, the modular incubator system of the first aspect of the present invention is for monitoring the development of a viable biological material during incubation thereof. The monitoring is performed by the image capturing device 408 which is arranged at or in a docking port 402 of the docking station 400 of the modular incubator system 500. According to the invention it is assured that the light aiming direction A of the light provided in the interior 306 of the modular incubator chamber by the light directing element 350 is being inclined relative to said focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is 0°.
Hereby easier and more reliable determination of the degree of cell divisions taking place in the viable biological material is attained.
In the present invention the term “modular incubator system” shall be construed to mean a system comprising a docking station in combination with one or more incubator chambers, wherein the one or more incubator chambers is/are configured to be docked in respective docking ports of that docking station. The modular incubator system is intended for incubation or cultivation of a viable biological material.
The incubator system comprising the docking station and one or more incubator chamber(s) in general is configured for providing some kind of interaction between the docking station and the incubator chambers being docked therein.
Such interactions may be one or more of the following: providing a gas having a desired composition to the incubator chamber(s); providing electricity to the incubator chamber(s) for powering hearing elements thereof and/or for powering a light source in the incubator chamber(s); allowing monitoring of the viable biological material being present in the incubator chamber(s), such as by means of an image capturing device which is located in the docking station.
In should be understood that within the meaning of the present application, the term “modular incubator system” shall be construed in such a way that the incubator chambers are configured to be used for incubation of a viable biological material, irrespective of whether the individual incubator chamber is being docked in a docking port of the docking station, or whether that incubator chamber is removed from the docking port of the docking station.
In this way, it is to be understood that cultivation or incubation of a viable biological material of the individual incubator chambers may take place and/or be continued even after that incubator chamber has been removed from its docking station and placed e.g. on a laboratory bench. Hereby manual manipulation operations, such as shift or control of culture or growth media, manual inspection by use of a laboratory microscope or the like can take place. Such operation are preferably carried out under a hood providing a desired gas atmosphere.
In preferred embodiment, and in order to make such manual manipulation operations practical conceivable, when the individual incubation chamber has been removed from a docking port, the incubation chamber is configured in a way that enables support on a planar, horizontal support surface. This may be attained by providing the bottom part of the incubator chamber with one or more supports or simply by making the bottom part of the incubator chamber comprise a flat surface.
In preferred embodiments the incubation chamber, in the orientation intended during use for incubation, is having its maximum dimension in a horizontal direction.
In this way the dimension of the incubation chamber in a horizontal direction is greater than the dimension in a vertical direction. Hereby, adequate stability is attended when the incubator chamber is used for incubation at a location outside a docking port of the docking station.
The individual incubator chambers may in embodiments comprise a display, such as an electronic display, for providing information relating to the identity of the viable biological material being accommodated in the incubator chamber.
It should be understood that in some embodiments the present invention does not relate to methods or uses which involve treatment of the human or animal body by surgery or diagnostic methods practiced on the human or animal body.
It should also be understood that that in other embodiments the present invention may relate to methods or uses which involve treatment of the human or animal body by surgery or diagnostic methods practiced on the human or animal body.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300 and in respect of one or more of said one or more docking ports 402 of said docking station 400, the inclination angle a is selected from the ranges of 0.5 - 25°, such as 1 - 24°, for example 2 - 23°, e.g. 3 - 22°, such as 4 - 21°, for example 5 - 20°, such as 6 - 19°, for example 7 - 18°, such as 8 - 17°, for example 9 - 16°, such as 10 - 15°, e.g. 11 - 14° or 12 - 13°.
These inclination angles will provide the desired effect of making the cell division stages of the viable biological material being incubated easier and more reliable detectable.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300 and in respect of one or more of said one or more docking ports 402 of said docking station 400, once being docked in said docking port 402 of said docking station, said light directing element 350 is being positioned in the interior 306 of said modular incubator chamber 300 at a position which is displaced relative to the focus direction B of said image capturing device 408 of said docking port 402, in a direction perpendicular to said focus direction B, thereby providing said inclination angle a between said light aiming direction A and said focus direction B.
Arranging the light directing element 350 in a position in the interior 306 of the modular incubator chamber 300 which is displaced relative to the focus direction B of the image capturing device 408 is a simple way of providing the desired inclination angle between the light aiming direction A and said focus direction B.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said culture dish support 308 is defining a planar support surface P for supporting said culture dish 310.
In an embodiment and in respect of one or more of said one or more docking ports 402 of said docking station 400, once being docked in said docking port 402 of said docking station 400, said focus direction B of said image capturing device 408 of said docking port 402 is being essentially perpendicular to said planar support surface P of said culture dish support 308 of said modular incubator chamber 300, and said light aiming direction A of said light directing element 350 of said modular incubator chamber 300 is not being perpendicular to said planar support surface P of said culture dish support 308.
It is preferred to arrange the culture dish 310 on a support 308 in the modular incubator chamber 300 in such a way that focus direction B of the image capturing device 408 of the docking port 402 is being essentially perpendicular to a planar support surface P of the culture dish support 308.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said light directing element 350 is being attached to said lid 304 of the housing 306 of said modular incubator chamber 300, at an inner side thereof.
Hereby a desired direction from above and downward will be defined for the light aiming direction A of the light directing element 350.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said light directing element 350, comprises a diffuser, such as a diffuser lens.
Hereby the light of the light directing element can be softened.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said transparent window 316 of said modular incubator chamber 300 is located at a bottom part 330 of said housing 302 of said chamber. As it is preferred to arrange the image capturing device 408 at a position in the docking port 402 of the docking station where it will focus in an upward direction, the transparent window 316 of the modular incubator chamber 300 is conveniently arranged at a bottom part 330 of the housing 302 of said modular incubator chamber 300.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, the light directing element 350 is geometrically configured to make said light propagate at a maximum spreading angle of propagation of 1 - 65°, such as 5 - 60°, e.g. 10 - 55°, such as 15 - 50°, for example 20 - 45°, e.g. 25 - 40° or 30 - 35°.
Having a not too large spreading angle of light form the light directing element 350 ensures minimizing any undesired reflections of light within the interior 306 of the modular incubator chamber 300.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300 said light aiming direction A is directed towards said transparent window 316 in said housing 302 of said modular incubator 300.
As the viable biological material M to be monitored is being arranged above the transparent window 316, light aimed at the that transparent window 316 will also be aimed at or near to that viable biological material.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said modular incubator chamber 300 comprises inclination angle adjustment element 332 for adjusting the inclination angle a between said light aiming direction A and said focus direction B, wherein said inclination angle adjustment element 332 is configured to enable adjustment of said inclination angle a so that this inclination angle a may attain an angle selected from the ranges 0.5 - 25°, such as 1 - 24°, for example 2 - 23°, e.g. 3 - 22°, such as 4 - 21°, for example 5 - 20°, such as 6 - 19°, for example 7 - 18°, such as 8 - 17°, for example 9 - 16°, such as 10 - 15°, e.g. 11 - 14° or 12 - 13°.
Hereby the degree or magnitude of the inclination angle may be adjusted during incubation and monitoring of the viable biological material.
In one embodiment that inclination angle adjustment element 332 comprises a rotational adjustment element 334 which is being configured, upon being adjusted, to enable changing the light aiming direction A of light direction propagation from said light directing element 350 by changing the spatial orientation of said light directing element 350; and/or wherein said inclination angle adjustment element 332 comprises a displacement adjustment element 336 which is being configured, upon being adjusted, to enable changing a position of said light directing element 350. In these embodiments either solely the light aiming direction A is being adjusted or the position of said light directing element 350 is being adjusted; or a combination thereof is being performed.
In one embodiment the rotational adjustment element 334 and/or said displacement adjustment element 336 is/are electrically controlled by electric actuators which provides for changing the light aiming direction A of light direction propagation from said light directing element 350 and/or for changing the position of said light directing element 350 upon being supplied by an electric signal thereto.
Hereby remote control of varying of the inclination angle a can be performed while monitoring and incubating the viable biological material.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more docking ports 402 of said docking station 400, said docking port 402 comprises a shadowing element 450 which is configured to enable blocking part of the light being propagated towards the optics of said image capturing device 408.
A shadowing element will enable further control of the contrasting effects necessary for proper monitoring of the degree of cell divisions which have taken place in the viable biological material.
In an embodiment the shadowing element 450 comprises a shadowing plate 452 comprising a through-going hole 454 having a fixed geometry and/or size, such as a round hole, such as a circular hole; or a rectangular hole, wherein said shadowing plate 452 is being arranged relative to said image capturing device 408 so that the focus direction B of said image capturing device 408 passes through that hole 452.
This embodiment is a very simple way of providing such additional contrasting effects.
In another embodiment the shadowing element 450 comprises an iris diaphragm 458 having a plurality of iris lamellas 460 which are movable in relation to each other and thereby are configured, upon being subjected to an external force, to vary the size of a through-going hole 462 formed in the centre of said iris diaphragm; wherein said iris diaphragm 458 is being arranged relative to said image capturing device 408 so that the focus direction B of said image capturing device 408 passes through that hole 462.
In an embodiment the iris diaphragm 458 comprises an actuator 464, such as a remote- controlled electric actuator which is mechanically connected to said iris lamellas 460 and which is configured to enable movement of said iris lamellas in concert so as to vary the size of said through-going hole 462.
Hereby the degree of the shadowing or contrasting effect can be remotely controlled while monitoring and incubating the viable biological material.
In an embodiment the shadowing element 450 is coupled to an X- stage or XY-stage 456 in a way enabling said shadowing element 450 to be independently displaced in one or two displacement directions D1,D2 which each optionally is/are being essentially perpendicular to the focus direction B of said image capturing device 408.
Hereby the position, relative to the biological material being incubated, of the shadowing effect can be controlled.
In an embodiment the X-stage or XY-stage comprises an electric actuator 466, wherein said electric actuator 466 configured to electrically control the displacement of said shadowing element 450 in one or two of said displacement directions D1,D2 upon being supplied by an electric signal thereto.
Hereby remote control of the position, relative to the biological material being incubated, of the shadowing effect can be controlled.
In an embodiment the shadowing element 450 is being arranged outside the optics of said image capturing device 408.
In another embodiment the said shadowing element 450 is being arranged inside the optics of said image capturing device 408.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said light directing element 350 is an active light source 352 being arranged in the interior 306 of the modular incubating chamber 300, wherein said active light source 352 is configured for propagating light in said light aiming direction A, by being supplied with electric power.
As being further explained below the light directing element 350 may either be an active light source 352 which is configured to emit light upon being provided with electric power, or the light directing element 350 may be a passive light direction element which directs incoming light, such as by reflection, into the light aiming direction A.
The above embodiment is very simple in that an active light source 352 being arranged in the interior 306 of the modular incubating chamber 300 for providing light in the light aiming direction A.
In another embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said light directing element 350 is a passive light directing element in the form of a light conveyor 354 being arranged in the interior 306 of the modular incubating chamber 300, wherein said light conveyor 354 is configured for directing incoming light, in said light aiming direction A, such as by reflecting said incoming light.
In an embodiment and in respect of one or more of said one or more modular incubator chambers 300, said housing 302 of said modular incubator chamber 300 comprises a light transmission element 356 for providing light to said light conveyor 354,350 from a position outside said chamber 300; and wherein in respect of one or more of said one or more docking ports 402 of said docking station 400, said docking port 402 comprises an active light source 352; wherein the position of said light transmission element 356 of said housing 302 of said modular incubator chamber 300 and the position of said active light source 352 of said docking port 402 are adapted to each other in such a way that once being docked in said docking port 402 of said docking station 400, light emitted from said active light source 352 of said docking port 402 will be able to transmit said light transmission element 356 of said housing 302 of said modular incubator chamber 300 and propagate to said light conveyor 354,350 in the interior of said housing 302.
In an embodiment and in respect of one or more of said one or more modular incubator chambers 300, said light transmission element 356 of said housing 302 of said modular incubator chamber 300 is being arranged at a top of said housing 302, such as at the lid 304 of said housing 302 and is being the same entity as said light conveyor 350,354.
In an embodiment and in respect of one or more of said one or more modular incubator chambers 300, said light transmission element 356 of said housing 302 of said modular incubator chamber 300 is being arranged at a side of said housing 302.
In an embodiment of these embodiments the light conveyor 354 is being a light deflector, such as an optical prism or lens.
Accordingly, in the above embodiments an active light source 352 arranged outside the interior 306 of the modular incubator chamber 300, that is at or in the docking port 402, provides light to a light conveyor 354 arranged in the interior 306 of the modular incubator chamber 300.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said light transmission element 356 of said housing 302 of said modular incubator chamber 300 is being arranged at a bottom 330 of said housing 302, wherein said housing 302 in the interior thereof comprises a light reflector 358, wherein said light reflector 358 is being configured to reflect upwardly propagating light into an essentially horizontally propagating light, propagating towards said light conveyor 350,354; and wherein said light conveyor 350,354 is configured to reflect said essentially horizontally propagating light into said light aiming direction A.
In this embodiment light emitted from an active light source 352 arranged in or at the docking port 402 is directed into the interior 306 of the modular incubator chamber 300, where it is deflected by the reflector 358, whereafter the light hits the light conveyor 354.
In an embodiment the light conveyor 350,354 is being a light reflector, such as a mirror.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more docking ports 402 of said docking station 400, said active light source 352 is arranged in said docking port 402 at a position so as to be configured to direct emitted light in a direction essentially parallel to said focus direction B of said image capturing device 408, and wherein in respect of one or more of said one or more modular incubator chambers 300, said light conveyor 350,354 is configured to direct said emitted light in said light aiming direction A.
In an embodiment the light conveyor 350,354 is being a light reflector, such as a mirror.
In one embodiment of the above two embodiments the active light source 352 is being arranged adjacent to said image capturing device 408.
In another embodiment the active light source 352 is being arranged within the optics of said capturing device 408.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention said active light source 352 is being selected from the group of one or more LEDs, one or more laser diodes, one or more incandescent light bulbs.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention said transparent window 316 and/or said light transmission element 356 is made of glass or plastic.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention said image capturing device(s) 408 comprise(s) microscopic optics so as to enable capturing of microscope images.
Hereby magnified images may be captured which improves study of the morphological nature of the biological materials being incubated.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said housing 302 of said modular incubator chamber 300, such as at an outer portion thereof, is being provided with electric connectors 322 for providing electric power and/or electric signals to said modular incubator chamber; and wherein in respect of one or more docking ports 402 of said docking station 400, said docking port is being provided with electric connectors 410, thereby allowing providing electric power and/or electric signals between said docking port 402 of said docking station 400 and a modular incubator chamber 300 being docked therein.
Via such connectors 322, 410 control instructions can be send to a modular incubator chamber 300 via its corresponding docking port 402 and its electric connectors 410 of the docking station 400.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said lid 304 is being a hinged lid which is being connected to said housing of said modular incubator chamber 302 via a hinge.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said housing 302 of said modular incubator chamber 300 comprises a display 324 which is being configured to display information relating to an operational status of the incubation taking place in said modular incubator chamber.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said modular incubator chamber 300 comprises a chamber inlet opening for gas 312, wherein said chamber inlet opening for gas 312 is being in fluid connection with the interior 306 of said modular incubator chamber; and wherein said modular incubator chamber 300 furthermore comprises a chamber outlet opening for gas 314, wherein said chamber outlet opening for gas 314 is being in fluid connection with the interior 306 of said modular incubator chamber; and wherein in respect of one or more docking ports 402 of said docking station 400, said docking port 402 comprises a docking port outlet opening for gas 404 and a docking port inlet opening for gas 406; thereby enabling transfer of gas from said docking port 402 of said docking station 400 to the interior 306 of said modular incubator chamber 300 via said docking port outlet opening for gas 404 and said chamber inlet opening for gas 312; and thereby enabling transfer of gas from the interior 306 of said modular incubator chamber 300 to said docking port 402 of said docking station 400 via said chamber outlet opening for gas 314 and said docking port intlet opening for gas 406.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, and in respect of one or more of said one or more docking ports 402 of said docking station 400, the position of said chamber inlet opening for gas 312 of said housing 302 of said modular incubator chamber 300 and the position of said docking port outlet opening for gas 404 of said docking port 402 are adapted to each other in such a way that once docking said modular incubator chamber 300 in said docking port 402, said chamber inlet opening for gas 312 of said housing 302 of said modular incubator chamber 300 and said docking port outlet opening for gas 404 of said docking port 402 will be in fluid connection, thereby enabling transfer of gas from said docking port 402 to said modular incubator chamber 300; and wherein the position of said chamber outlet opening for gas 314 of said housing 302 of said modular incubator chamber 300 and the position of said docking port inlet opening for gas 406 of said docking port 402 are adapted to each other in such a way that once docking said modular incubator chamber 300 in said docking port 402, said chamber outlet opening for gas 314 of said housing 302 of said modular incubator chamber 300 and said docking port inlet opening for gas 406 of said docking port 402 will be in fluid connection, thereby enabling transfer of gas from said modular incubator chamber 300 to said docking port 402.
These embodiment ensure that gas having a desired composition can be delivered from a gas source 202 via a gas distribution system 204 to the interior 306 of the modular incubator chamber 300 via the docking port outlet opening for gas 404 and the chamber inlet opening for gas 312, and gas from the interior 306 of the modular incubator chamber 300 can be returned to the gas source 202 via the chamber outlet opening for gas 314 and the docking port inlet opening for gas 406. In an embodiment of the modular incubator system 500 according to the first aspect of the present invention the docking port outlet opening for gas 404 of said docking port 402 comprises a valve 4 and said chamber inlet opening for gas 312 of said housing 302 comprises a valve 2; and said chamber outlet opening for gas 314 comprises a valve 2 and said docking port inlet opening for gas 406 of said docking port 402 comprises a valve 4.
Hereby can be assured that gas will only flow into the docking port 402 once a modular incubator chamber 300 is being arranged in that docking port 402. In other words, no gas will flow through the docking port 402 unless a modular incubator chamber 300 is being docked therein. Moreover, this embodiment assures that once a modular incubator chamber 300 is being removed form a docking port, no atmospheric air will enter through the chamber inlet opening for gas 312 and the chamber outlet opening for gas 314 of that chamber 300.
Accordingly, there will be no contamination of the gas atmosphere being present in the interior 306 of the modular incubator chamber 300, once that chamber 300 is being removed from its docking port 402.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said valve 2 of said chamber inlet opening for gas 312 and said valve 2 of said chamber outlet opening for gas 314 each comprises a valve body 6 having a front end 10, a rear end 12 and a through-going channel 14 therein, and a spring-loaded displaceable valve element 8, wherein said displaceable valve element 8 is being arranged in said through-going channel 14; wherein said displaceable valve element 8 is being configured to be displaceable in said through-going channel 14 of said valve body 6 in such a way, that when not acted upon by an external force, said spring-loaded displaceable valve element 8 is not being displaced in said through-going channel 14 of said valve body 6, thereby making said valve attain a closed configuration blocking passage of gas through said through-going channel 14, and in such a way, that when acted upon by an external force, said spring-loaded displaceable valve element 8 is being displaced in said through-going channel 14 of said valve body 6, thereby making said valve 2 attain an open configuration, allowing passage of gas through said through-going channel 14; and whereinin in respect of one or more of said one or more docking ports 402 of said docking station 400, said valve 4 of said docking port outlet opening for gas 404 and said valve 4 of said docking port inlet opening for gas 406 each comprises a valve body 16 having a front end 20, a rear end 22 and a through-going channel 24 therein, and a spring-loaded displaceable valve element 18, wherein said displaceable valve element 18 is being arranged in said through-going channel 24; wherein said displaceable valve element 18 is being configured to be displaceable in said through-going channel 24 of said valve body 16 in such a way, that when not acted upon by an external force, said spring-loaded displaceable valve element 18 is not being displaced in said through-going channel 24 of said valve body 16, thereby making said valve attain a closed configuration blocking passage of gas through said through-going channel 24, and in such a way, that when acted upon by an external force, said spring-loaded displaceable valve element 18 is being displaced in said through-going channel 24 of said valve body 16, thereby making said valve 4 attain an open configuration, allowing passage of gas through said through-going channel 24.
Hereby, each of the two valves 2,4 will be able to change configuration between an open and a closed configuration by displacement of the respective valve element 8,18 in the associated valve body 6,16.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more docking ports 402 of said docking station 400, and in respect of one or more of said one or more modular incubator chambers 300 said valves 2,4 are having dimensions and geometries in such a way that once docking said modular incubator chamber 300 in said docking port 402 of said docking station 400, said displaceable valve element 8 of said valve 2 and said displaceable valve element 18 of said valve 4 will displace each other into their respective valve bodies 6,16, thereby opening said valves 2,4 of said docking port outlet opening for gas 404 and said chamber inlet opening for gas 312; and thereby opening said valves 2,4 of said chamber outlet opening for gas 314 and said docking port inlet opening for gas 406.
Hereby, each of the two valves 2,4 will open the other valve 4,2 once being brought into contact with each other by making their respective front ends 10,20 meet.
In an embodiment of the modular incubator system according to the first aspect of the present invention and in respect of one or more of said docking ports 402 of said docking station 400 of said modular incubator system 500, preferably in respect of all said docking ports 402, said docking port outlet opening for gas 404 comprises a flow restrictor for restricting the magnitude of flow of gas flowing into said docking port 402.
In one embodiment the flow restrictor may comprises a tube through which the gas is conveyed to said docking port 402, wherein said tube optionally is having a cross-sectional area selected from the ranges of 0.2 - 8 mm2, such as 0.5 - 7 mm2, for example 1 - 6 mm2, such as 2 - 5 mm2 or 3 - 4 mm2; and/or the length of said tube is optionally selected from the ranges of 5 - 30 mm, such as 8 -25 mm, for example 10 - 22 mm, e.g. 15 - 20 mm.
Such a flow restrictor aids in balancing the flow of gas through the docking ports 402 comprising a modular incubator chamber 300 with the capacity of the gas supply system 200 and thereby also aids in making the flow of gas through the different docking ports 402 equal to each other.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention the docking station 400 comprises a gas distribution system 204 for supplying gas to and from one or more of said one or more docking ports 402, wherein said gas distribution system 204 comprises a main gas supply line 210 and a main gas return line 212, wherein in respect of one or more of said docking ports 402, said docking port inlet opening for gas 404 is being fluidly connected to said main gas supply line 210, and said docking port outlet opening for gas 406 is being fluidly connected to said main gas return line 212. In one embodiment said gas distribution system 204 comprises a number of manifold pairs 214, wherein each manifold pair comprises an inlet manifold 216 and an outlet manifold 218, wherein said inlet manifold 216 is being fluidly connected to said main gas supply line 210 and wherein said outlet manifold 218 is being fluidly connected to said main gas return line 212; wherein each manifold pair 214 is connected to one or more docking ports 402 of said docking station 400 in such a way that in respect of a specific manifold pair 214, and in respect of said one or more docking ports 402 being connected thereto, said docking port outlet opening for gas 404 of said docking port 402 is being fluidly connected to said inlet manifold 216, and said docking port inlet opening for gas 406 of said docking port 402 is being fluidly connected to said outlet manifold 218.
In one embodiment said docking station 400 comprises a gas supply system 200, wherein said gas supply system 200 comprises a gas source 202 and said gas distribution system 204, wherein said gas source comprises a supply gas outlet 206 and a return gas inlet 208, wherein said supply gas outlet 206 of said gas source 202 is being fluidly connected to said main gas supply line 210 of said gas distribution system 204, and wherein said return gas inlet 208 of said gas source 202 is being fluidly connected to said main gas return line 212 of said gas distribution system 204.
In these embodiments comprising a gas distribution system 204 it is possible to supply gas from a gas source 202 to the docking ports 402 via the main gas supply line 210 and to return gas from the docking ports to the gas source 202 via the main gas return line 212.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas source 202 of said gas supply system 200 comprises a gas mixing box 242 fluidly connected to said supply gas outlet 206 and said return gas inlet 208 of said gas source, wherein said main gas supply line 210 of said gas distribution system 204 is being fluidly connected to said supply gas outlet 206, and wherein said main gas return line 212 of said gas distribution system 204 is being fluidly connected to said return gas inlet 208 of said gas source 202, thereby forming a flow loop 244 comprising said gas distribution system 204 and said gas mixing box 242; wherein said flow loop comprises a pump 246.
Hereby circulating gas in said loop, and also through the gas distribution system 204 of the docking station 400 is possible.
The purpose of the gas source is to provide and deliver a desired gas composition to the gas distribution system 204 including the various docking ports 402 of the docking station 400.
In one embodiment of this embodiment the pump 246 is being arranged downstream in relation to said main gas return line 212.
In one embodiment the flow loop 244 comprises a pump oscillation damper 247, wherein said pump oscillation damper optionally is being arranged immediately downstream in relation to said pump 246.
The pump oscillation damper will equalize small and rapid pressure variations caused by each pump stroke of the pump. In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the flow loop 244 comprises a pressure sensor, such as a differential pressure sensor 248 for sensing the pressure of gas supplied to said main gas supply line 210 of said gas distribution system 204, wherein said pressure senor 248 optionally is being arranged immediately upstream in relation to said main gas supply line 210 of said gas distribution system 204.
The pressure sensor 248 allows for regulating the pump 246 in order to maintain a desired pressure in the flow loop 244 by feedback.
In one embodiment the pressure sensor 248 is being a differential pressure sensor, sensing a pressure relative to the pressure of the return gas inlet 208.
In one embodiment the flow loop 244 comprises a release valve 249 for enabling pressure relief in said flow loop, wherein said release valve optionally is being arranged immediately downstream in relation to said main gas return line 212 of said gas distribution system 402.
The pressure release valve 249 enables improved control of the pressure in the flow loop 344.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas mixing box 242 comprises an inlet for N2 gas 250; and an inlet for CO2 gas 251, wherein said inlet for N2 gas 250 is fluidly connected to an N2 valve 252 for regulating the inflow of N2, and an N2 mass flow sensor 253 arranged downstream of said N2 valve 252 for sensing the amount of N2 flowing into said gas mixing box 242; and wherein said inlet for CO2 gas 251 is fluidly connected to a CO2 valve 254 for regulating the inflow of CO2, and an CO2 mass flow sensor 255 arranged downstream of said CO2 valve 254 for sensing the amount of CO2 flowing into said gas mixing box 242.
Herby it is possible to control the inlet of N2 gas and the inlet of CO2 gas into the gas mixing box 242 with the view to obtain a desired, predetermined and optimum gas composition in the gas mixing box 242.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the flow loop 244 comprises a mass flow sensor 256 arranged at an upstream position in relation to said gas mixing box 242 for sensing the amount of return gas entering said gas mixing box.
Information relating to the amount of return gas entering said gas mixing box is used for determining the total amount of N2 gas and CO2 gas which needs to be introduced into the gas mixing box 242.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas source 202 comprises an O2 sensor 258 for sensing the concentration of O2 exiting said gas distribution system 204; and wherein said gas source 202 comprises a CO2 sensor 260 for sensing the concentration of CO2 exiting said gas distribution system 204, wherein said O2 sensor and/or said CO2 sensor optionally is/are being arranged downstream in relation to said pump 246.
Information relating to the concentration of O2 and the concentration of CO2 exiting said gas distribution system 204 is used for determining the specific amount of N2 gas and the specific amount of CO2 gas which needs to be introduced into the gas mixing box 242. In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas source 202 comprises a temperature sensor 262 for sensing the temperature of gas circulating in said flow loop 244, wherein said temperature sensor optionally is being arranged downstream in relation to said pump 246, preferably at a position corresponding to the position of said O2 sensor 258.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas source 202 comprises a pressure sensor 264 for sensing the absolute pressure in said flow loop 244 wherein said pressure sensor optionally is being arranged downstream in relation to said pump 246, preferably at a position corresponding to the position of said CO2 sensor 260.
The temperature sensor 262 and pressure sensor 264 are useful for performing compensation of the readings of the O2 sensor 258 due to temperature sensitivity thereof and the readings of the CO2 sensor 260 due to sensitivity thereof towards pressure.
In an embodiment of the modular incubator system according to the first aspect of the present invention, the flow loop 244 comprises a UV sanitizer 266 for sanitizing gas flowing in said flow loop 244 via electromagnetic radiation in the UV range, wherein said UV sanitizer optionally being arranged immediately downstream in relation to said main gas return line 212.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas source 202 comprises one or more filters 268, such as HEPA and/or VOCs filters, wherein such a filter is being arranged immediately upstream in relation to said main gas supply line 210, and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for N2gas 250 into said gas mixing box 242; and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for CO2 gas 251 into said gas mixing box 242.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas source 202 comprises a gas mixing control system 270, wherein said gas mixing control system is electrically connected to one or more of the following sensors for receiving sensing signals therefrom: said N2 mass flow sensor 253 for sensing the amount of N2 flowing into said gas mixing box; said CO2 mass flow sensor 255 for sensing the amount of CO2 flowing into said gas mixing box; said mass flow sensor 256 for sensing the amount of return gas entering said gas mixing box; said O2 sensor 258 for sensing the concentration of O2 exiting said main gas return line 212 of said gas distribution system 204; said CO2 sensor 260 for sensing the concentration of CO2 exiting said main gas return line 212 of said gas distribution system 204; said temperature sensor 262 for sensing the temperature circulating in said flow loop 244; said pressure sensor 264 for sensing an absolute pressure in said flow loop 244, said pressure sensor 248 for sensing the pressure of gas supplied to said gas main gas supply line 210 of said distribution system 204.
This embodiment enables gaining information of various parameters which are to be used in providing a feed back when controlling the operation of the gas source 202.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas mixing control system 270 is electrically connected to one or more of the following elements for control thereof: said N2 valve 252 for regulating the inflow of N2 into said gas mixing box 242; said CO2 valve 254 for regulating the inflow of CO2 to said gas mixing box 242; said pump 246 for circulating gas in said flow loop 244; said release valve 249.
This embodiment enables providing a feed back when controlling the operation of the gas source 202.
In one embodiment the gas mixing control system 270 is being configured to receive input from said pressure sensor 248 and on the basis thereof control said pump 246, optionally also to activate said release valve 249 in order to maintain a desired and predetermined pressure of gas supplied to said main gas supply line 210 of said gas distribution system 204.
Hereby the pressure in the flow loop 244 can be controlled.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas mixing control system 270 is being configured to receive input from said mass flow sensor 256, and on the basis on said input to determine the total amount of CO2 gas and N2 gas needed to be supplied via said inlet for CO2 gas 251 and via said inlet for N2 gas 250 according to desired and predetermined criteria.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas mixing control system 270 is being configured to receive input from said CO2 sensor 260 and said O2 sensor 258, and on the basis of the CO2 concentration sensed, is configured to control said CO2 valve 254, by transmitting a control signal thereto, and thereby regulating the inflow of CO2 gas in order to reach a desired and predetermined CO2 concentration, and wherein subsequently, said gas mixing control system 270 on the basis of the O2 concentration sensed, is configured to control said N2 valve 252, by transmitting a control signal thereto, and thereby regulating the inflow of N2 gas in order to reach a desired and predetermined O2 concentration.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas mixing control system 270 is configured to use the input from said temperature sensor 262 for compensating the temperature sensitivity of said O2 sensor 258.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas mixing control system 270 is configured the maintain a CO2 concentration of gas entering said main gas supply line 210 of said gas distribution system 204 in the range of 5 - 10%, such as 6 - 9 % or 7 - 8 %; and/or an O2 concentration of gas entering said main gas supply line 210 of said gas distribution system 204 in the range of 5 - 10%, such as 6 - 9 % or 7 - 8 %.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas mixing control system 270 is configured to use the input from said pressure sensor 264 for compensating the pressure sensitivity of said CO2 sensor 260.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention, the gas mixing control system 270 is being configured to maintain a pressure of gas supplied to said main gas supply line 210 of said gas distribution system 204, relative to the ambient atmospheric pressure, of 3 - 20 mbar, such as 5 - 18 mbar, such as 10 - 15 mbar above that ambient atmospheric pressure.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention the number of modular incubator chambers 300 of said modular incubator system 500 is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention the number of docking ports 402 in said docking station 400 of said modular incubator system 500 is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention said docking station 400 comprises said docking ports 402 in an arrangement of one or more shelves of adjacently positioned docking ports 402, wherein in case said docking station comprises two or more shelves, said shelves are being arranged above each other.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said one or more modular incubator chambers 300, said modular incubator chamber comprises an incubation chamber engagement means 326 and wherein in respect of one or more docking ports 402 of said docking station 400, said docking port comprises a docking port engagement means 414, wherein said incubation chamber engagement means 326 is being configured to enter into engagement with said docking port engagement means 414.
Hereby easy and proper positioning and optionally also fixing said modular incubator chamber 300 in said docking port 402, as well as detaching said modular incubator chamber 300 from said docking port 402 of said docking station 400 is enabled.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention the modular incubator system 500 comprises an image processing unit 660 for image processing of images captured by said image capturing device 408, wherein said modular incubator system 400 furthermore comprises a data storage 658 for storing images captured by said image capturing units 408 and/or for storing images processed by said image processing unit.
An image processing unit is beneficial for manipulating the images captured, such as for adjusting contrast, for filtering and for generating time-lapse series of images.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention one or more of said image capturing devices 408 of said docking ports 402 of said docking station is/are being coupled to said image processing unit 660. In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more specific docking ports 402 of said docking station 400, said specific docking port comprises its own dedicated image capturing device 408 which is configured to only capture images relating to a modular incubator chamber 300 which is being docked in said specific docking port 402.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and respect of a number N of adjacently arranged docking ports 402 of said docking station 400, said adjacently arranged docking ports 402 share a common image capturing device 408 in the sense that one and only one image capturing device is responsible for capturing images relating to a modular incubator chamber 300 which is being docked in one of said N adjacently arranged docking ports 402 s wherein said docking station comprises a displacement device 482 for enabling displacement of said common image capturing device 408 in relation to said N adjacently arranged docking ports 402 of said docking station 400, such as being provided with an electric signal thereto.
Hereby one image capturing device is responsible for the capturing of images of biological materials being accommodated in different modular incubator chambers which are being docked in different docking port 402 of the docking station 400 on/at the same shelf.
In an embodiment the number N is being an integer selected in the ranges of 2 - 25 or more, such as 4 - 22, for example 6 - 20, such as 8 - 18, such as 10 - 16 or 12 - 14.
Independently, one or more image capturing devices 408, preferably all image capturing devices 408 of the docking station 400 may comprise or be coupled to a displacement device 482, such as an electrically driven and remotely controlled displacement device 482 for enabling displacement of said common image capturing device 408 in a direction transversal to the longitudinal direction X of a modular incubator chamber 300 being docked in a docking port 402 with the view to enable such capturing device 408 to focus on more than one culture well in a culture dish 310 being accommodated in the interior of the modular incubator chamber 300, wherein such culture wells are arranged in such direction transversal to the longitudinal direction X.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more of said modular incubator chambers 300, said modular incubator chamber comprises in its interior 306 an electric heating element 318 for heating the interior of said modular incubator chamber, and wherein said modular incubator chamber comprises a power source 320 for providing power to said heating element 318, wherein said electric heating element 318 is being electrically connected to said power source 320.
In an embodiment said power source 320 is being an electric power source, such as a battery, for example a rechargeable battery.
In an embodiment said heating element 318 is being thermally connected to a heat distribution element for distributing heat dissipated in said heating element; wherein said heat distribution element is being arranged, at least partly, in the interior 306 of said modular incubator chamber 300.
In an embodiment said chamber comprises a thermostat 374 and an electric thermostatic circuit 376, wherein said electric heating element 318, said power source 320 and said thermostat 374 are being electrically connected in said electric thermostatic circuit 376 so as to enable thermostatic control of the temperature inside said modular incubator chamber 300.
The above embodiments provide for upholding a desirable and predetermined and optionally also optimum temperature in the interior 306 of the modular incubator chamber 300 in a situation where the modular incubator chamber is removed from its associated docking port 402 with the view to perform visual inspection and manual replenishing, removal, or exchange of growth medium to the biological materials being incubated.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention said modular incubator system 500 comprises a control unit 650 for controlling the operation of said modular incubator system 500.
In an embodiment said control unit 650 is being coupled to an input device 652, such as an alphanumerical input device for allowing a user to provide settings input relating to a desired operational protocol of said modular incubator system.
In an embodiment said control unit 650 is being coupled to a display unit 654 for displaying, to a user, information relating to settings and/or operational status of said modular incubator system 300.
In an embodiment of the modular incubator system 500 according to the first aspect of the present invention and in respect of one or more docking ports 402 of said docking station 400 said control unit 650 is being configured for independently controlling one or more of the following: temperature in the interior 306 of said modular incubator chamber 300 by controlling said electric heating element 318, said thermostat 374 or said thermostatic circuit 376, providing power to said electric power source 320; providing signals to said display 324 of said modular incubator chamber 300, said inclination angle adjustment element 332, said rotational adjustment element 334 of said inclination angle adjustment element 332, said displacement adjustment element 336 of said inclination angle adjustment element 332, switching on and off of said active light source 352, or adjusting light intensity emitted therefrom, said image capturing device 408 of a docking station 408, said displacement device 482 for displacing said image capturing device 408, said actuator of said X-stage or XY-stage 466, said actuator of said iris diaphragm 464 ,said gas mixing control system 270; said gas mixing control system 660.
In an embodiment said control unit 650 is being coupled to a data processing unit 656 and optionally also to a data storage 658 for aiding in handling information during controlling of said modular incubator system.
In an embodiment said control unit 650 is being configured for conducting automatic operation of said modular incubator system 500 by configuring said control unit 650 to independently control one or more of the following: temperature in the interior 306 of said modular incubator chamber 300 by controlling said electric heating element 318, said thermostat 374 or said thermostatic circuit 376, providing power to said electric power source 320; providing signals to said display 324 a modular incubator chamber 300, said inclination angle adjustment element 332, said rotational adjustment element 334 of said inclination angle adjustment element 332, said displacement adjustment element 336 of said inclination angle adjustment element 332, switching on and off of said active light source 352, or adjusting light intensity emitted therefrom, said image capturing device 408 of said docking station 408, said displacement device 482 for displacing said image capturing device 408, said actuator of said X-stage or XY-stage 466, said actuator of said iris diaphragm 464, said gas mixing control system 270.
In an embodiment control unit 650 is being configured for enabling time lapse capturing of images by said image capturing devices 408.
In the above embodiments the operation of the modular docking system 500 can easily be controlled centrally.
The second aspect of the present invention
The present invention relates in a second aspect to a modular incubator chamber 300, wherein said modular incubator chamber 300 is comprising features as defined in respect of the modular incubator chamber 300 of the modular incubator system 500 of the first aspect of the present invention.
The third aspect of the present invention
The present invention relates in a third aspect to a docking station 400, wherein said docking station is comprising features as defined in respect of the docking station 400 of the modular incubator system 500 of the first aspect of the present invention.
The fourth aspect of the present invention
In a fourth aspect the present invention provides a use of a modular incubator system 500 according to the first aspect of the present invention for incubating a viable biological material M.
In an embodiment said biological material is being an oocyte or an embryo, such as a human oocyte or a human embryo.
The fifth of the
Figure imgf000028_0001
invention T1
In a fifth aspect the present invention provides a use of a modular incubator chamber 300 according to the second aspect of the present invention for incubating a viable biological material M.
In an embodiment said biological material is being an oocyte or an embryo, such as a human oocyte or a human embryo.
The sixth aspect of the present invention
In a sixth aspect the present invention provides a use of a docking station 400 according to the third aspect of the present invention for incubating a viable biological material M.
In an embodiment said biological material is being an oocyte or an embryo, such as a human oocyte or a human embryo.
The seventh aspect of the present invention
In a seventh aspect the present invention provides a method of incubating a viable biological material M, wherein said method comprises: i) providing a modular incubator system 500 according to the first aspect of the present invention; ii) providing a viable biological material M; iii) arranging said viable biological material M in a culture dish 310 and subsequently arranging said culture dish on the culture dish support 308 in the interior 306 of said modular incubator chamber 300 of said modular incubator system 400; iv) docking said modular incubator chamber 300 in a docking port 402 of said docking station 400 of said incubator system 500; v) allowing said viable biological material M to be incubated in said modular incubator chamber 300; vi) while performing step v) enabling said light directing element 350 of said modular incubator chamber 300 to direct light to an area of said culture dish support 308 in said light aiming direction A; vii) while performing step v) and vi) making said image capturing device 408 capture image(s) of said viable biological material M in the interior 306 of said modular incubator chamber 300, at a focus direction B; wherein said focus direction A of light propagating from said light directing element 350 of said modular incubator chamber 300 is being inclined relative to said focus direction B of said image capturing device 408 of said docking port 302 at an inclination angle a which is 0°.
In an embodiment of the method of the seventh aspect of the present invention the method further comprising the step of: viii) removing said incubator chamber 300 from said docking port 402 of said docking station 400, when desired, in order to manually inspect the viable biological material M, and optionally also to remove, add or exchange growth medium/media in said culture dish 310.
It is noted that in the claims relating to the second aspect of the present invention, viz. the modular incubator chamber, reference is made to that features of this modular incubator chamber may be as defined in respect of the claims relating to the first aspect of the present invention, viz. the modular incubator system.
This shall be construed to mean that embodiment of the modular incubator chamber per se may be as defined in the claims relating to embodiments of the modular incubator system.
This shall also be construed to mean that to the extent that an interrelationship between the modular incubator chamber and the docking station or a docking port thereof is defined in such embodiments relating to the modular incubator system, the corresponding embodiment of the modular incubator chamber, claimed by reference to the modular incubator system, shall be considered suitable to enter into such interrelationship.
Likewise, it is noted that in the claims relating to the third aspect of the present invention, viz. the docking station, reference is made to that features of this docking station may be as defined in respect of the claims relating to the first aspect of the present invention, viz. the modular incubator system.
This shall be construed to mean that embodiment of the docking station per se may be as defined in the claims relating to embodiments of the modular incubator system.
This shall also be construed to mean that to the extent that an interrelationship between the modular incubator chamber and the docking station or a docking port thereof is defined in such embodiments relating to the modular incubator system, the corresponding embodiment of the docking station, claimed by reference to the modular incubator system, shall be considered suitable to enter into such interrelationship.
Referring now to the figures for better illustrating the present invention, Fig. 1 is a perspective view illustrating the general concept of providing an incubator as a modular incubator system comprising a plurality of modular incubator chambers in combination with a docking station comprising a plurality of docking ports.
Accordingly, Fig. 1 shows the modular incubator system 500 for incubating a viable biological material. The modular incubator system 500 comprises a docking station 400 in combination with a number of modular incubator chambers 300. The docking station 400 comprises a plurality of docking ports 402. Each docking port 402 is configured for receiving and holding a modular incubator chamber 300. Each docking port 402 comprises docking port engagement means 414 which is configured to enter into engagement with a corresponding incubation chamber engagement means 326 arranged underneath each modular incubation chamber 300.
In Fig. 1 it is seen that the docking station 400 of the incubator system 500 comprises three shelves arranged above each other and each comprising six docking ports 402. Three of these docking ports 402 have been occupied by a modular incubator chamber 300 and a fourth modular incubation chamber is on its way to be docked in a docking port 402.
The arrangement of an incubator for IVF procedures as an incubator system 500 comprising a plurality of modular incubator chambers 300 in combination with a docking station 400 allows for having, in a single apparatus, a relative huge number of incubations taking place under individual incubations environments, such as under an individual chemical environment in relation to e.g. gaseous atmosphere and composition of growth medium, and under an individual physical environment in relation to e.g. temperature.
Hereby it is possible to conduct a relatively large number of parallelly conducted incubations under similar conditions in the individual modular incubator chambers, while altering only one parameter from one modular incubator chamber to another. The difference in development of the viable biological material being incubated in the various modular incubator chambers can then be assigned to the one incubation parameter that is altered from one modular chamber to the other.
This allows for determining optimum incubation conditions of an embryo or an oocyte being incubated.
Whenever it is needed to change or add growth medium to the biological material being incubated or whenever other manual procedures are needed in respect of a specific modular incubator chamber, that modular incubator chamber 300 is simple removed from its respective docking port 402 of the docking station 400 and transferred to a laboratory bench where such manual procedures can be conducted.
However, during most of the time, the modular incubator chamber will be docked in a docking port 402 of the docking station 400.
Image capturing device(s) 408 is/are provided in respect of one or more of the docking ports 402 of the docking station 400. The image capturing device(s) 408 of the docking station 400 provide(s) for monitoring the morphological changes taking place during incubation.
The image capturing device comprises microscope optics for capturing close-up images.
The image capturing device(s) 408 may be configured for automatically capturing of images of the biological material being incubated in a modular incubator chamber 300.
Also seen in Fig. 1 is that the docking ports 402 comprises an electric connector 410 for supplying electric power from the docking port to a modular incubator chamber 300 being docked into that docking port, or for transferring electric signals between a modular incubator chamber 300 and a docking port 402.
In order to enable image capturing of a biological material being accommodated in the interior of a modular incubator chamber by an image capturing device 408 being arranged in the docking system 400 it is clear that the modular incubator chamber must allow transmittal of light through the housing of the modular incubator chamber.
Such transmittal of light through the housing of the modular incubator chamber is attained by providing the housing of the modular incubator chamber 300 with a transparent window which allows for an image capturing device, located outside the interior of the chamber 300, to capture images of a viable biological material being accommodated in the interior of that incubator chamber 300 as further described below.
Fig. 2a is a perspective view showing a modular incubator chamber of the docking system of Fig. 1.
Fig. 2a shows the modular incubator chamber 300 for incubating a viable biological material. The modular incubator chamber comprises a housing 302 and the housing comprises a lid 304 which is being configured to be able to shift between an open configuration allowing access to the interior 306 of the modular incubator chamber and a closed configuration, sealing off access to the interior 306 of said modular incubator chamber. The chamber is having a first end 340 and a second end 342.
Fig. 2a also shows that the housing 302 of the modular incubator chamber 300 comprises a display 324 which is being configured to display information relating to details of the incubation taking place in said modular incubator chamber and that the housing 302 at a first end 340 thereof, is being provided with electric connectors 322 for providing electric power to the modular incubator chamber or for conveying electric signals between the modular incubator chamber 300 and the corresponding docking port 402.
Fig. 2b is a plan top view of the modular incubator chamber 300 illustrated in Fig. 2a.
Fig. 2c is a plan rear view of the modular incubator chamber 300 illustrated in Fig. 2a and 2b as seen from its first end.
Fig. 2c shows that the modular incubator chamber 300 comprises a chamber engagement means 326. These first engagement means 326 are configured to enter into engagement with a docking port engagement means 414 in a docking port 402 of the docking station 400.
Fig. 3 is a cross-sectional view of the modular incubator chamber 300 illustrated in Fig. 2.
Fig. 3 shows that the housing 302 of the modular incubator chamber 300 comprises a transparent window 316 for allowing capturing of images of a biological material being accommodated in the interior thereof, through said transparent window. As seen the window is arranged at the bottom 330 of the housing 302 of the modular incubator chamber 300. The modular incubator chamber 300 also comprises, in its interior 306, an electric heating element 318 for heating the interior of said modular incubator chamber. The modular incubator chamber also comprises a power source 320 in the form of a rechargeable battery for providing power to said heating element 318 which is being electrically connected to the power source 320. A light directing element 350 in the form of an active light source 352 is attached to an inner side of the lid 304 of the modular incubator chamber 300.
As seen in Fig. 3 the interior 306 of the modular incubator chamber 300 comprises a culture dish support 308 for positioning a culture dish 310. Hereby, one or more biological materials can be accommodated and incubated within the housing 302 of the modular incubator chamber 300.
Also seen in Fig. 3 is the engagement means 326 which is being adapted to engage with engagement means 414 of the docking port into which the modular incubator chamber 300 is to be docked.
Fig. 4 illustrates the principle of the present invention.
Fig. 4 is a diagram illustrating the relative orientations of a light aiming direction A of light emitted from a light source 352,350 and the focus direction B of an image capturing device.
Fig. 4 shows a viable biological material M being accommodated in a culture dish 310. An image capturing device 408 is arranged below the culture dish 310 and the image capturing device 408 is focusing in a focus direction B.
A light providing element 350 in the form of a light source 352 is providing light for illuminating the biological material M during image capturing. The light emitted from the light source 352 is propagating in a light aiming direction A.
It is seen that the light aiming direction A of the light propagating from the light source 352 is being inclined relative to the focus direction B of the image capturing device 408 at an inclination angle a which is 0°.
Hereby improved visual detection of the individual cells of the viable biological material M is attained.
Fig. 5 illustrates the concept of the term “light aiming direction” as this term may be used in the present application.
Fig. 5 shows the active light source 352 with its centre. The active light source 352 propagates light in a downward direction.
An imaginary plane IP is visualized at a distance D from the light source 352 and the light emitted from the light source 352 will be projected on that imaginary plane IP and will form the projection PR having the projection boundary PRB on the imaginary plane IP.
Now, for a given distance D to the light source, one may rotate the imaginary plane IP in one or two perpendicular rotation planes as illustrated by the arrows Al and A2. When performing this rotation of the imaginary plane IP, the shape and size of the projection boundary PBR will change.
However, for that spatial orientation of the imaginary plane IP, at which, in respect of the given distance D to the light source 352, the area of the projection PR is minimal, one may define the light aiming direction A as the direction from a centre of the light source 352 to the centre CP of the projection PR.
The centre CP of the projection PR may be calculated from the shape of the projection boundary PRB in the same way that one calculates the centre of mass of an object. The object in this case being the two-dimensional geometrical shape PR within the projection boundary PRB.
Fig. 6 is a diagram illustrating in more details the principle of the present invention.
As already mentioned, it has been found that in monitoring the development of a viable biological material by studying the morphological changes taking place, it is desirable to provide some contrast to the object being monitored. Such contrast can be provided by selecting the angle of incoming light onto the biological materiel in relation to the direction of focus of the image capturing device.
Fig. 6 shows part of a modular incubator system 500 comprising a modular incubator chamber 300 which is being docked in a docking port 402 of a docking station 400.
As seen, the modular incubator chamber 300 comprises a housing 302 having a lid 304, a culture dish support 308 for positioning the culture dish 310 containing the viable biological material M.
The housing 302 of the modular incubator chamber comprises a transparent window 316 at the bottom 330 of the housing. The transparent window 316 enables capturing of images of the biological material M through that transparent window 316 by the image capturing device 408 which is arranged at the docking port 402 of the docking station 400 when that image capturing device 408 is focusing in the focus direction B.
The housing 302 of the modular incubator chamber 300 comprises a light directing element 350 in the form of an active light source 352 for directing light to the area of the culture dish support 308 in a light aiming direction A, so as to direct light towards the viable biological material M.
It is seen that the light aiming direction A of light propagating from the light directing element 350,352 of the modular incubator chambers 300 is being inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a. The inclination angle a is seen to be clearly 0°.
Fig 7 is similar to fig. 6 except that the light direction element 350 in the form of an active light source 352 is now arranged outside the interior 306 of the housing 302 of the modular incubator chamber 300. The active light source 352 may be part of the docking port 402 of the docking station 400. In order to direct light from the active light source 352 into the interior 306 of the chamber 306 of the modular incubator chamber 300, the lid 304 has been provided with a light conveyor 354 which allows transmission of light into the interior 306 of the modular incubating chamber. In this way the transmissive light conveyor 354 acts as the light directing element 350.
Again, it is seen that the light aiming direction A of light propagating from the light directing element 350,354 of the modular incubator chambers 300 is inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is clearly 0°.
Fig. 8 illustrates another embodiment of the incubator system 500 according to the first aspect of the present invention, wherein the active light source 352 is being arranged outside of the interior 306 of the housing 302 of the modular incubator chamber.
It is seen in Fig. 8 that a light transmission element 356 is being arranged at a side of the housing 302 of the modular incubating chamber 300 and that an active light source 352 is being arranged so as to direct light through that light transmission element 356 into the interior 306 of the housing 302.
A light directing element 350 in the form of a light conveyor 354 is being arranged in the interior 306 of the modular incubating chamber 300, and the light conveyor 354 is configured for directing incoming light, in said light aiming direction A, such as by reflecting said incoming light.
The light conveyor 354 is a light reflector 358, such as a mirror.
Hereby, light propagating in the light aiming direction A is directed from the light directing element 350,354,358 of the modular incubator chamber 300 and is being inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is clearly 0°.
Fig. 9 illustrates yet another embodiment of the incubator system 500 according to the first aspect of the present invention, wherein the active light source 352 is being arranged outside the interior of the housing of the modular incubator chamber.
Fig. 9 shows an embodiment wherein the optical transmission element 356 of the housing 302 of the modular incubator chamber 300 is being arranged at a bottom 330 of the housing 302.
An active light source 352 is being arranged in the docking port 402 below the modular incubator chamber 300, thereby allowing transmission of light through the optical transmission element 356 into the interior 306 of the housing 302.
The housing 302 of the modular incubator chamber comprises in the interior 306 thereof a light reflector 358. The light reflector 358 is being configured to reflect upwardly propagating light into an essentially horizontally propagating light, propagating towards the light conveyor 350 which is being in the form of a passive light conveyor 354. The light conveyor 354 is configured to reflect the essentially horizontally propagating light into the light aiming direction A.
The light conveyor 354 is a light reflector 358, such as a mirror.
Again, the light aiming direction A of light propagating from the light directing element 350, in the form of the light conveyor 354 of the modular incubator chamber 300, is inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is clearly 0°.
Fig. 10 illustrates yet another embodiment of the incubator system 500 according to the first aspect of the present invention, wherein the active light source 352 is being arranged outside the interior of the housing of the modular incubator chamber.
Fig. 10 shows that the active light source 352 is arranged in the docking port 402 so as to direct emitted light in a direction essentially parallel to the focus direction B of the image capturing device 408 and through the transparent window 316.
A light conveyor 354 is directing the emitted light propagating from the active light source 352 into the light aiming direction A.
Again the light conveyor 354 is a light reflector 358, such as a mirror.
In this embodiment the culture dish 310 is being made from a transparent material.
The light aiming direction A of light propagating from the light directing element 350 in the form of the light conveyor 354 of the modular incubator chambers 300 is inclined relative to the focus direction B of the image capturing device 408 of the docking port 402 at an inclination angle a which is clearly 0°.
Alternative to having the active light source 352 located outside the optics of the image capturing device 408 of the docking port in the embodiment illustrated in Fig. 10, the active light source 352 may also be arranged within the optics of the image capturing device 408.
This embodiment is illustrated in Fig. 11.
Fig. 12 is a diagram illustrating the principle of including an inclination angle adjustment element for adjusting the inclination angle a between the light aiming direction A and the focus direction B of the image capturing device.
Fig. 12 shows an inclination angle adjustment element 332.
A light directing element 350 in the form of an active light source 352 is suspended on a displacement adjustment element 336. The displacement adjustment element 336 is connected to a support 338. The displacement adjustment element 336 is configured to be displaceable, via an electric actuator, included therein, relative to the support 338 upon being supplied with an electric signal thereto as indicated by the linear arrows in Fig. 12. The active light source 352 is attached to a rotational adjustment element 334. The rotational adjustment element 334 is being configured, via an electric actuator, included therein, to change the light aiming direction A of light propagating from the light directing element 350 by rotation of the light direction element 350 as indicated by the curved arrows.
The rotational adjustment element 334 and the displacement adjustment element 336 are electrically controlled by the electric actuators which provide for changing the light aiming direction A of light direction propagation from said light directing element 350 and/or for changing the position of said light directing element 350 upon being supplied by an electric signal thereto.
Accordingly, the displacement adjustment element 336 and the rotational adjustment element 334 will both, upon activation of the corresponding and included actuator, effect a change in the inclination angle between the light aiming direction A of light direction propagation from said light directing element 350 and the focus direction B of the image capturing device 408 in a situation where a modular incubating chamber 300 is comprising the inclination angle adjustment element 332 and is being docked in a docking port 402 of a docking station 400.
Fig. 13a, 13b and 13c are diagrams illustrating the principle of including a shadowing element in the docking ports 402 of the docking station.
Fig. 13a is a partly cross-sectional view showing the image capturing device 408 focusing in the focus direction B. Above the image capturing device 408 is arranged a shadowing element 450. The shadowing element 450 comprises a plate 452 which comprises a hole 454.
The shadowing plate 452 is being arranged relative to the image capturing device 408 so that the focus direction B passes or may pass through that hole 452.
The plate 452 is resting on an XY-stage 456. The XY-stage is configured to enable displacing the plate 456 independently in one or two displacement directions D1,D2 which is/are essentially perpendicular to the focus direction B of said image capturing device 408.
Accordingly, In Fig. 13a, the displacement direction DI defines movement of the plate 452 in a left-right direction, and in Fig. 12a the displacement direction D2 defines movement of the plate 452 in and out of the paper.
The XY-stage is electrically controlled by an electric actuator 466 which provides for displacement of said shadowing plate 452 in the one or two displacement directions D1,D2 upon being supplied by an electric signal thereto.
Fig. 13b is a top view of the shadowing element 450 seen in Fig. 13a. Fig. 13b shows the plate 452 resting on the XY-stage 456. The plate comprises a hole 454. Beneath the plate 452 and through the hole 454 thereof the image capturing device 408 is seen. The image capturing device is focusing in the focus direction B up through the hole 454.
By adjusting the position of the shadowing element 450,452 relative to the image capturing device 408 it is possible to create a partly blocking of the light propagating towards the image capturing device 408. Such blocking of the light will improve contrasting in the images captured.
Instead of an XY-stage, an X-stage may also be used.
Fig. 13 c is a photograph showing a commercially available shadowing element in the form of an iris diaphragm 458.
It is seen that theshadowing element 450 is in the form of an iris diaphragm 458 is comprising a plurality of iris lamellas 460. The iris lamellas are movable in relation to each other and are thereby configured, upon being subjected to an external force, to vary the size of the through- going hole 462 formed in the centre of the iris diaphragm. In use the iris diaphragm 458 is being arranged relative to the image capturing device 408 so that the focus direction B of the image capturing device 408 passes or may pass through that hole 462.
The iris diaphragm 458 comprises an actuator 464 in the form of a remote-controlled electric actuator which is mechanically connected to the iris lamellas 460 and which is configured to enable movement of these iris lamellas in concert so as to vary the size of the through-going hole 462 upon being supplied with an electric signal thereto. The iris diaphragm may be used in conjunction with the XY-atsage or the X-stage.
In Fig. 13a, 13b and 13c the shadowing element is arranged outside the optics of the image capturing device 408. In an alternative embodiment a similar arrangement can be arranged inside the optics of the image capturing device 408 for providing the shadowing effect.
Returning now to Fig. 1, it is seen that the docking ports 402 comprises a docking port outlet opening for gas 404 and a docking port inlet opening for gas 406, and that a valve 4 is arranged in each of these openings.
Fig. 2c shows the modular incubator chamber 300 comprises a chamber inlet opening for gas 312 which is in fluid connection with the interior 306 of the modular incubator chamber
The chamber inlet opening for gas comprises a valve 2.
The housing 302 of said modular incubator chamber 300 furthermore comprises a chamber outlet opening for gas 314, which is being in fluid connection with the interior 306 of the modular incubator chamber 300, thereby allowing conveying gas out of the chamber 300 via the chamber outlet opening for gas 314. The chamber outlet opening for gas comprises a valve 2.
By providing the housing 302 of the modular incubator chamber 300 with a chamber inlet opening for gas 312 and optionally also an associated valve 2 and by providing the modular incubator chamber 300 with a chamber outlet opening for gas 314 and optionally also an associated valve 2 it is possible to convey a gas having a suitable and desired gas composition into the interior of the modular incubator chamber 300 from a docking port 402 of the docking station 400, as will be further explained below, and further it will be possible to make the gas in the interior 306 of the modular incubator chamber 300 exit the interior of the chamber through the chamber outlet opening for gas 314 and associated valve 2 and return to the docking station.
Hereby a constant supply of gas having an optimum chemical composition can be delivered to the interior 300 of the chamber 300. This will ensure optimum incubation conditions in terms of gaseous composition of the environment in the interior 306 of the chamber 300 when incubating a biological material.
Accordingly, when a proper positioning of the of the modular incubator chamber 300 in the docking port 402 has been attained via the engagement means 326 of the chamber 300 and via the engagement means 414 of the docking port 402, the relative position of the two electric connectors 410 and 322 of the docking port and the modular incubator chamber, respectively, will match so as to first to allow electric connection between the connectors 410 and 322.
Likewise, the gas openings 312,404 and 314,406 will match pairwise so that passage of gas from the docking port outlet opening for gas 404 into the interior 306 of the modular incubator chamber 300 via the modular incubator chamber inlet opening for gas 312 and the optional valves 2,4 is enabled, and so that passage of gas from the interior 306 of the modular incubator chamber 300 is possible via the modular incubator chamber outlet opening for gas 314 and into the docking port inlet opening for gas 406 and via the optional valves 2,4 is enabled.
Accordingly, the modular docking system 500 of the present invention allows for continuously providing gas into the interior 306 of the modular incubator chamber 300 from a gas source 412.
This is further illustrated below with reference to Fig. 15 and 16.
However, first we turn to a more detailed description of a valve system to be used with the modular incubator system according to the first aspect of the present invention.
Fig. 14a and 14b illustrate the working modes of valves of a valve system to be used with the modular incubator chamber and the associated docking port of the docking station of the docking system of the present invention.
Fig. 14a is diagrammatic drawing illustrating a valve system 100 to be used with the modular incubator system of the present invention, where the two valves 2,4 of the valve system 100 are not engaged with each other, thereby attaining a closed configuration.
Fig. 14b is diagrammatic drawing illustrating the valve system 100 seen in Fig. 14a in which the two valves 2,4 of the valve system 100 are engaged with each other, thereby attaining an open configuration.
The valve 2 comprises a valve body 6 having a front end 10 and a rear end 12. A through- going channel 14 is arranged in the valve body 6 and a valve element 8 is being arranged in the through-going channel 14. The valve element 6 is spring-loaded by a spring 26. The displaceable valve element 8 is being configured to be displaceable in the through-going channel 14 of the valve body 6 by the spring 26 in such a way, that when not acted upon by an external force, the spring-loaded displaceable valve element 8 is being displaced in the through-going channel 14 of said valve body 6 by the spring 26 towards the front end 10 of the valve body 6. Thereby the valve 2 attains a closed configuration blocking passage of gas through the through-going channel 14.
This situation is illustrated in Fig. 14a.
By analogy, when acted upon by an external force, the spring-loaded displaceable valve element 8 is being displaced in the through-going channel 14 of said valve body 6 towards the rear end 12 of the valve body 6, thereby making the valve 2 attain an open configuration, allowing passage of gas through said through-going channel 14.
This situation is illustrated in Fig. 14b.
As to the valve 4, Fig. 14a shows that the valve 4 comprises a valve body 16 having a front end 20 and a rear end 22. A through-going channel 24 is arranged in the valve body 16 and a valve element 18 is being arranged in the through-going channel 24. The valve element 18 is spring-loaded by a spring 28.
The displaceable valve element 18 is being configured to be displaceable in the through-going channel 24 of the valve body 16 by the spring 28 in such a way, that when not acted upon by an external force, the spring-loaded displaceable valve element 18 is being displaced in the through-going channel 24 of said valve body 16 by the spring 28 towards the first end 20 of the valve body 16. Thereby the valve 4 attains a closed configuration blocking passage of gas through the through-going channel 24. This situation is illustrated in Fig. 14a.
By analogy, when acted upon by an external force, the spring-loaded displaceable valve element 18 is being displaced in the through-going channel 24 of said valve body 16 towards the rear end 22 of the valve body 16, thereby making the valve 4 attain an open configuration, allowing passage of gas through said through-going channel 24.
This situation is illustrated in Fig. 14b.
The valves 2 of the modular incubator chamber 300 and the valves 4 of the docking port 402 of the docking station are having dimensions and geometries in such a way that once docking the modular incubator chamber 300 in the docking port 402 of said docking station 400, the displaceable valve element 8 of the valve 2 and the displaceable valve element 18 of the valve 4 will displace each other into their respective valve bodies 6,16, thereby opening the valves 2,4 of said docking port outlet opening for gas 404 and said chamber inlet opening for gas 312; and also opening the valves 2,4 of the chamber outlet opening for gas 314 and the docking port inlet opening for gas 406.
Accordingly, using such valves 2,4 for the modular incubator chamber 300 and for the docking ports 402 of the docking station will automatically provide for opening the valves 2 of the modular incubator chamber 300 and the valves 4 of docking port 402, once that modular incubator chamber 300 is being docked in that docking port 402, thereby allowing passage of gas through the interior 306 of the modular incubator chamber 300, when being docking in the docking port 402 and also shutting off supply of gas into the docking port 402 and out of the modular incubator chamber 300, when that modular incubator chamber 300 is removed from the docking port.
It should be noted, that whereas the present description and the appended claims describe the modular incubator system 300 and the docking ports 402 in a way where the valves 2 are being arranged in the modular incubator system 300 and in a way where the valves 4 are being arranged in the docking ports 402, the opposite placement of the valves 2,4 is also possible.
In the above sections the general principle of a modular incubator system 500 comprising a docking station 400 with a plurality of docking ports 402 for receiving, by docking, a modular incubator chamber 300 has been described. In the sections below focus will be directed to features of supplying gas to the docking ports 402 of the docking station 400.
Fig. 15 is a diagram illustrating the concept of the gas supply system which may be incorporated in the docking station of the modular incubator system of the present invention.
Fig. 15 shows a gas supply system 200 to be used with a modular incubator system 500 according to the present invention. The gas supply system 200 comprises a gas source 202 and a gas distribution system 204.
The gas distribution system 204 comprises a plurality of docking ports 402 each having a docking port outlet opening for gas 404 and a docking port inlet opening for gas 406.
In respect of all the docking ports, the docking port outlet openings for gas 404 are in fluid connection with an inlet manifold 216 and the docking port inlet openings for gas 406 are in fluid connection with an outlet manifold 218.
A main gas supply line 210 supplies gas from a supply gas outlet 206 of the gas source 202 to the inlet manifolds 216, and a main gas return line 212 returns gas from the outlet manifolds 218 to a return gas inlet 208 of the gas source 202.
Thereby gas can be circulated from the gas source 202 via the gas distribution system 204 to the docking ports 402 and back to the gas source 202.
In order to secure a desired and predetermined and optimum gas composition of the gas supplied to the docking stations, the gas source is provided with specific features as disclosed with reference to figure 16.
Fig. 16 is a diagram illustrating one embodiment of a design of a gas supply system comprising a gas source to be used with the docking station of the modular incubator system of the present invention. In fig. 16 solid lines represent flow lines for gas, whereas dashed lines represent signal lines for conveying electric signals or electric power.
Fig. 16 shows the gas distribution system 204 comprising its main gas supply line 210 and its main gas return line 212 (illustrated with the rectangle in upper left corner).
The main gas supply line 210 and the main gas return line 212 of the gas distribution system 204 is fluidly connected to a gas source 202 as described below.
The gas source 202 of said gas supply system 200 comprises a gas mixing box 242 connected to the supply gas outlet 206 and the return gas inlet 208 of the gas source.
The main gas supply line 210 of the gas distribution system 204 is being fluidly connected to the supply gas outlet 206, and the main gas return line 212 of the gas distribution system 204 is being fluidly connected to the return gas inlet 208 of the gas source 202.
Hereby a flow loop 244 comprising the gas distribution system 204 and the gas mixing box 242 is formed. The flow loop 244 comprises a pump 246 for circulating gas in that loop.
It is seen that the pump 246 is being arranged downstream in relation to the main gas return line 212. Also seen in Fig. 16 is that the flow loop 244 comprises a pump oscillation damper 247, which is being arranged immediately downstream in relation to the pump 246.
Moreover, the flow loop 244 comprises a pressure sensor 248 in the form of a differential pressure sensor for sensing the pressure of gas supplied to the main gas supply line 210 of the gas distribution system 204. The pressure senor 248 is being arranged immediately upstream in relation to the main gas supply line 210 of the gas distribution system 204.
The flow loop 244 further comprises a release valve 248 for enabling pressure relief in the flow loop. The release valve is arranged immediately downstream in relation to the main gas return line 212 of the gas distribution system 402.
Also seen in Fig. 16 is that the gas mixing box 242 comprises an inlet for N2 gas 250; and an inlet for CO2 gas 251.
The inlet for N2 gas 250 is fluidly connected to an N2 valve 252 for regulating the inflow of N2, and an N2 mass flow sensor 253 arranged downstream of the N2 valve 252 for sensing the amount of N2 flowing into said gas mixing box 242.
The inlet for CO2 gas 251 is fluidly connected to a CO2 valve 254 for regulating the inflow of CO2, and an CO2 mass flow sensor 255 arranged downstream of the CO2 valve 254 for sensing the amount of CO2 flowing into the gas mixing box 242.
The flow loop 244 also comprises a mass flow sensor 256 arranged at an upstream position in relation to the gas mixing box 242 for sensing the amount of return gas entering the gas mixing box.
It is seen that the gas source 202 comprises an O2 sensor 258 for sensing the concentration of O2 exiting the gas distribution system 204; and that the gas source 202 comprises a CO2 sensor 260 for sensing the concentration of CO2 exiting the gas distribution system 204. The O2 sensor and the CO2 sensor is arranged downstream in relation to the pump 246.
A temperature sensor 262 for sensing the temperature of gas circulating in said flow loop 244 is included in the gas source 202. The temperature sensor is arranged downstream in relation to the pump 246 at a position corresponding to the position of the O2 sensor 258.
A pressure sensor 264 for sensing the absolute pressure in the flow loop 244 is included in the gas source 202. This pressure sensor is arranged downstream in relation to the pump 246, at a position corresponding to the position of the CO2 sensor 260.
Also seen in Fig. 16 is that the flow loop 244 comprises a UV sanitizer 266 for sanitizing gas flowing in the flow loop 244 via electromagnetic radiation in the UV range. The UV sanitizer is arranged immediately downstream in relation to the main gas return line 212.
It is seen in Fig. 16 that the gas source 202 comprises filters 268 in the form of HEPA/V OCs filters. One such a filter is arranged immediately upstream in relation to the main gas supply line 210. Another such a filter is arranged immediately upstream in relation to the inlet for N2 gas 250 into the gas mixing box 242; and a third such a filter is being arranged immediately upstream in relation to the inlet for CO2 gas 251 into the gas mixing box 242.
Finally, it is seen in Fig. 16 that the gas source 202 comprises a gas mixing control system 270.
It is seen that the gas mixing control system 270 is electrically connected to one or more of the following sensors for receiving sensing signals therefrom: the N2 mass flow sensor 253 for sensing the amount of N2 flowing into the gas mixing box; the CO2 mass flow sensor 255 for sensing the amount of CO2 flowing into the gas mixing box; the mass flow sensor 256 for sensing the amount of return gas entering the gas mixing box; the O2 sensor 258 for sensing the concentration of O2 exiting the main gas return line 212 of the gas distribution system 204; the CO2 sensor 260 for sensing the concentration of CO2 exiting the main gas return line 212 of the gas distribution system 204; the temperature sensor 262 for sensing the temperature circulating in the flow loop 244; the pressure sensor 264 for sensing an absolute pressure in the flow loop 244, the pressure sensor 248 for sensing the pressure of gas supplied to the gas main gas supply line 210 of the distribution system 204.
Also seen in Fig. 16 is that the gas mixing control system 270 is electrically connected to one or more of the following elements for control thereof: the N2 valve 252 for regulating the inflow of N2 into the gas mixing box 242; the CO2 valve 254 for regulating the inflow of CO2 to the gas mixing box 242; the pump 246 for circulating gas in the flow loop 244; the release valve 249.
The control of the gas source by the gas mixing control system 270 is performed in accordance with two control regimes. The first control regime relates to controlling the pressure of gas exiting the supply gas outlet 206, and the second control regime relates to controlling the concentration of CO2 and O2 of gas exiting the supply gas outlet 206. The two control regimes are conducted concurrently. This is further explained below.
The gas mixing control system 270 is being configured to receive input from the pressure sensor 248 and on the basis thereof control the pump 246 and optionally also activate the release valve 249 in order to maintain a desired and predetermined pressure of gas supplied to the main gas supply line 210 of the gas distribution system 204.
The gas mixing control system 270 is further configured to receive input from the mass flow sensor 256, and on the basis on this input to determine the total amount of CO2 gas and N2 gas needed to be supplied via the inlet for CO2 gas 251 and via the inlet for N2 gas 250 according to desired and predetermined criteria.
Based on the information relating to the total amount of CO2 gas and N2 gas needed to be supplied, as described above, the gas mixing control system 270 will be able to determine the mutual proportion of the CO2 gas and N2 gas to be supplied to the gas mixing box 242.
This is performed by receiving input from the CO2 sensor 260 and the O2 sensor 258.
On the basis of the CO2 concentration sensed, the gas mixing control system 270 will control the CO2 valve 254, by transmitting a control signal thereto, and thereby regulate the inflow of CO2 gas in order to reach a desired and predetermined CO2 concentration.
Subsequently, the gas mixing control system 270 will on the basis of the O2 concentration sensed, control the N2 valve 252, by transmitting a control signal thereto, and thereby regulate the inflow of N2 gas in order to reach a desired and predetermined O2 concentration.
By using the gas source as disclosed above, a constant circulation of gas will be supplied to one or more modular incubator chamber 300 being docked in a respective docking port 402 of the docking station 400. By constantly regulating the inflow of CO2 gas and N2 gas based on sensed concentration of CO2 and O2 in the return gas from the gas distribution system 204, an optimum and predetermined gas composition can be maintained.
Due the design of the gas distribution system 204, an constant composition of gas flowing through each modular incubator chamber 300 can be upheld.
It should be noted that when reference is made to an upstream position relative to another position, that upstream position is construed to mean a position still within the gas source 202 and preferably not so much upstream that it passes the gas mixing box 242 or the gas distribution system 204.
Likewise, when reference is made to a downstream position relative to another position, that downstream position is construed to mean a position still within the gas source 202 and preferably not so much downstream that it passes the gas mixing box 242 or the gas distribution system 204.
Fig. 17 is a diagram illustrating the working mode of the controlling of the modular incubator system according to the invention.
Fig. 17 shows the control unit 650 for controlling the operation of the modular incubator system 500. The control unit is coupled to an input device 652 in the form of an alphanumerical input device for allowing a user to provide settings input relating to a desired operational protocol of said modular incubator system. A display unit 654 for displaying, to a user, information relating to settings and/or operational status of one or more of the modular incubator chambers 300 which via a docking port 402 is coupled to the control unit 650.
It is seen that the control unit 650 is coupled to a electric connectors 410 of the docking ports 402 of the docking station 400. Thereby electrical power and electric signals can be provided to one or more modular incubator chambers 300 which is/are being docked into a docking port 402 of the docking station 400 of the modular incubator system 500 via the associated connector 322 of the modular incubator chamber 300.
By being connected to the docking ports 402 of the docking station 400 it will be thereby possible, when one or more modular incubator chambers 300 is/are docked into a docking port 402 of the docking station 400, and by using the control unit 650, to independently control one or more of the following: temperature in the interior 306 of said modular incubator chamber 300 by controlling said electric heating element 318, said thermostat 374 or said thermostatic circuit 376, providing power to said electric power source 320; providing signals to said display 324 of a modular incubator chamber 300, said inclination angle adjustment element 332, said rotational adjustment element 334 of said inclination angle adjustment element 332, said displacement adjustment element 336 of said inclination angle adjustment element 332, switching on and off of said active light source 352, or adjusting light intensity emitted therefrom, said image capturing device 408 of a docking station 400, said displacement device 482 for displacing said image capturing device 408, said actuator of said X-stage or XY-stage 466, said actuator of said iris diaphragm 464, said gas mixing control system 270, said gas mixing control system 660.
The control unit 650 may comprises a CPU or other data processor 656 for processing the information involved in controlling the operation of the modular incubator system 500, e.g. by involving a computer program for handing the information involved in the controlling of the operation and the control unit 650 may also comprise a data storage 658.
Thereby automatic operation of the modular incubator system 500 may be performed in the sense that control unit 650 may inter alia independently control the temperature, the gas composition, the switching on and off of the light source 372, and the image capturing unit 408 of one or more of the modular incubator chambers.
Accordingly, with the modular incubator system 500 of the present invention, viable biological materials can be incubated in one or more modular incubators 300 which are being docked in docking ports 402 of the docking station 400, and at the same time visual monitoring of the biological material can be conducted via the image capturing device 408.
Moreover, at the same time a desired gas composition can be maintained in the interior 306 of each modular incubator chamber 300. As the modular incubator chambers comprises valves 2,4 in the respective inlet opening for gas 312 and outlet opening for gas 314, the gas atmosphere will be maintained and not disturbed by the outside atmosphere (relative to the interior 306 of the modular incubator chamber 300), even when the modular incubator chamber is removed from its respective docking port 402 of the docking station 400 of the modular incubator system 500. Upon such removal of the modular incubator chamber 300 from a docking port 402 of the docking station 400, the power source 320 and the electric heating element 318 will enable upholding the temperature in the interior 306 of the modular incubator chamber 300.
The present invention thereby allows for incubation of a biological material in the modular incubator chamber 300 and at the same time allows for visual monitoring of the morphological development of the biological material, while minimizing the detrimental effects involved in deviating from an optimized and desired gaseous atmosphere in the interior of the modular incubator chamber.
It should be noted that in respect of a number N of adjacently arranged docking ports 402 of the docking station 400, these adjacently arranged docking ports 402 may share a common image capturing device 408 in the sense that one and only one image capturing device is responsible for capturing images relating to a modular incubator chamber 300 which is being docked in one of these N adjacently arranged docking ports 402.
In such a situation, a displacement device 482 in the form of an electrically motorized suspension of the image capturing device 408 is being configured to be displaced, upon receiving a signal thereto, along a displacement track extending below these N number of adjacent docking ports 402 for enabling displacement of that common image capturing device 408 in relation to the N adjacently arranged docking ports 402 of the docking station 400. Thereby the common image capturing device 408 will be able to capture images of a biological material being accommodated in the interior 306 of a modular incubator chamber 300 being docked in any of said N docking ports 402 of the docking station 400.
Although the above embodiments have been disclosed in a way where the first valve 2 of the valve system 100 is arranged in the modular incubator chamber 300 and in such a way that the second valve 4 of the valve system 100 is arranged in the docking port 402, the opposite arrangement may also be possible. Both in respect of valves 2,4 letting gas into the chamber 300 and in respect of valves 2,4 letting gas out the chamber, or both.
Fig. 18a - 18c are microscopic photographs illustrating the effect of providing an inclined light, relative to a focus direction, when capturing images of a viable biological material.
Fig. 18a - 18c show microscope images captured of an incubated mouse embryo under three different inclination angles a between a light aiming direction A of a light directing element (active light source) and a focus direction B of an image capturing device and captured at different times.
The three different inclination angles a between the light aiming direction A of a light directing element and the focus direction B illustrated in Fig. 18a - 18c were 0°, i.e. no inclination (Fig. 18a); 9° (Fig. 18b) and 16.7° (Fig. 18c).
It is seen that at an inclination angle a of 0°, the cell walls are not clearly visible at the intersections between cells. This makes the identification of the number of cells in the biological material difficult and somewhat unreliable. At an inclination angle a of 9°, the cell walls are much more visible at the intersections between cells. Accordingly, identification of the number of cells is much more reliable in this situation.
At an inclination angle a of 16.7°, the cell walls are also clearly visible at the intersections between cells. Moreover, some 3D effect in the images are provided.
Accordingly, the modular incubator system of the present invention improves assessment and reliability in the assessment of the stage (such as the various PN stages) of development of a viable biological material, for example an embryo or an oocyte being incubated in that modular incubator system. It should be understood that all features and achievements discussed above and in the appended claims and clauses in relation to one aspect of the present invention and embodiments thereof apply equally well to the other aspects of the present invention and embodiments thereof.
The present invention may be defined according to one or more of the following clauses:
Clause 1. A modular incubator system (500) for incubating a viable biological material M, said modular incubator system comprising:
-one or more modular incubator chambers (300) in combination with
-a docking station (400); wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber (300) comprises a housing (302); wherein said housing (302) comprises a lid (304), wherein said lid is being configured to be able to shift between an open configuration allowing access to the interior (306) of said modular incubator chamber and a closed configuration, sealing off access to the interior of said modular incubator chamber; wherein said modular incubator chamber, at said interior (306) thereof, comprises a culture dish support (308) for positioning a culture dish (310) with the view to accommodate one or more biological materials M within the housing (302) of said modular incubator chamber (300); wherein said housing (302) of said modular incubator chamber (300) comprises a transparent window (316) for enabling capturing of images of a biological material M being accommodated in the interior thereof, through said transparent window; wherein said housing comprises a light directing element (350) for directing light to an area of said culture dish support (308) in a light aiming direction (A); wherein said docking station (400) comprises one or more docking ports (402) for receiving a housing (302) of an incubator chamber (300); wherein in respect of one or more docking ports (402) of said docking station (400), said docking port (402) comprises an image capturing device (408) for capturing an image of the interior (306) of a modular incubator chamber (300), once being docked in said docking port (402), by focusing said image capturing device (408) in a focus direction (B); wherein in respect of one or more of said one or more modular incubator chambers (300) and in respect of one or more of said one or more docking ports (402) of said docking station (400), the position of said transparent window (316) of said modular incubator chamber (300) is adapted to the position of said image capturing device (408) in said docking port (402) in a way that enables capturing of images by said image capturing device (408) through said transparent window (316) of said modular incubator chamber( 300); wherein in respect of one or more of said one or more modular incubator chambers (300) and in respect of one or more of said one or more docking ports (402) of said docking station (400), once being docked in said docking port (402), said light aiming direction (A) of said light propagating from said light directing element (350) of said modular incubator chamber (300) is being inclined relative to said focus direction (B) of said image capturing device (408) of said docking port (402) at an inclination angle a, wherein said inclination angle a 0°.
Clause 2. A modular incubator system (500) according to clause 1, wherein in respect of one or more of said one or more modular incubator chambers (300) and in respect of one or more of said one or more docking ports (402) of said docking station 400, said inclination angle a is selected from the ranges of 0.5 - 25°, such as 1 - 24°, for example 2 - 23°, e.g. 3 - 22°, such as 4 - 21°, for example 5 - 20°, such as 6 - 19°, for example 7 - 18°, such as 8 - 17°, for example 9 - 16°, such as 10 - 15°, e.g. 11 - 14° or 12 - 13°.
Clause 3. A modular incubator system (500) according to clause 1 or 2, wherein in respect of one or more of said one or more modular incubator chambers (300) and in respect of one or more of said one or more docking ports (402) of said docking station (400), once being docked in said docking port (402) of said docking station, said light directing element (350) is being positioned in the interior (306) of said modular incubator chamber (300) at a position which is displaced relative to the focus direction (B) of said image capturing device (408) of said docking port (402), in a direction perpendicular to said focus direction (B), thereby providing said inclination angle a between said light aiming direction (A) and said focus direction (B).
Clause 4. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said culture dish support (308) is defining a planar support surface P for supporting said culture dish (310).
Clause 5. A modular incubator system (500) according to clause 4, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), once being docked in said docking port (402) of said docking station (400), said focus direction B of said image capturing device (408) of said docking port (402) is being essentially perpendicular to said planar support surface P of said culture dish support (308) of said modular incubator chamber (300), and wherein said light aiming direction A of said light directing element (350) of said modular incubator chamber (300) is not being perpendicular to said planar support surface P of said culture dish support (308).
Clause 6. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is being attached to said lid (304) of the housing (306) of said modular incubator chamber (300), at an inner side thereof.
Clause 7. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350), comprises a diffuser, such as a diffuser lens.
Clause 8. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said transparent window (316) of said modular incubator chamber (300) is located at a bottom part (330) of said housing (302) of said chamber (300).
Clause 9. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is geometrically configured to make said light propagate at a maximum spreading angle of propagation of 1 - 65°, such as 5 - 60°, e.g. 10 - 55°, such as 15 - 50°, for example 20 - 45°, e.g. 25 - 40° or 30 - 35°.
Clause 10. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300) said light aiming direction (A) is directed towards said transparent window (316) in said housing (302) of said modular incubator (300).
Clause 11. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber (300) comprises inclination angle adjustment element (332) for adjusting the inclination angle a between said light aiming direction (A) and said focus direction (B), wherein said inclination angle adjustment element (332) is configured to enable adjustment of said inclination angle a so that this inclination angle a may attain an angle selected from the ranges 0.5 - 25°, such as 1 - 24°, for example 2 - 23°, e.g. 3 - 22°, such as 4 - 21°, for example 5 - 20°, such as 6 - 19°, for example 7 - 18°, such as 8 - 17°, for example 9 - 16°, such as 10 - 15°, e.g. 11 - 14° or 12 - 13°.
Clause 12. A modular incubator system (500) according to clause 11, wherein said inclination angle adjustment element (332) comprises a rotational adjustment element (334) which is being configured, upon being adjusted, to enable changing the light aiming direction A of light direction propagation from said light directing element (350) by changing the spatial orientation of said light directing element (350); and/or wherein said inclination angle adjustment element (332) comprises a displacement adjustment element (336) which is being configured, upon being adjusted, to enable changing a position of said light directing element (350).
Clause 13. A modular incubator system (500) according to clause 12, wherein said rotational adjustment element (334) and/or said displacement adjustment element (336) is/are electrically controlled by electric actuators which provides for changing the light aiming direction (A) of light propagation from said light directing element (350) and/or for changing the position of said light directing element (350) upon being supplied by an electric signal thereto.
Clause 14. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), said docking port (402) comprises a shadowing element (450) which is configured to enable blocking part of the light being propagated towards the optics of said image capturing device (408). Clause 15. A modular incubator system (500) according to clause 14, wherein said shadowing element (450) comprises a shadowing plate (452) comprising a through-going hole (454) having a fixed geometry and/or size, such as a round hole, such as a circular hole; or a rectangular hole, wherein said shadowing plate (452) is being arranged relative to said image capturing device (408) so that the focus direction B of said image capturing device (408) passes through that hole (452).
Clause 16. A modular incubator system (500) according to clause 14 wherein said shadowing element (450) comprises an iris diaphragm (458) having a plurality of iris lamellas (460) which are movable in relation to each other and thereby are configured, upon being subjected to an external force, to vary the size of a through-going hole (462) formed in the centre of said iris diaphragm; wherein said iris diaphragm (458) is being arranged relative to said image capturing device (408) so that the focus direction (B) of said image capturing device (408) passes through that hole (462).
Clause 17. A modular incubator system (500) according to clause 16 wherein said iris diaphragm (458) comprises an actuator (464), such as a remote-controlled electric actuator which is mechanically connected to said iris lamellas (460) and which is configured to enable movement of said iris lamellas in concert so as to vary the size of said through-going hole (462).
Clause 18. A modular incubator system (500) according to any of the clauses 14 - 17, wherein said shadowing element (450) is coupled to an X- stage or XY-stage (456) in a way enabling said shadowing element (450) to be independently displaced in one or two displacement directions (D1,D2) which each optionally is/are being essentially perpendicular to the focus direction (B) of said image capturing device (408).
Clause 19. A modular incubator system (500) according to clause 18, wherein said X-stage or XY-stage comprises an electric actuator (466), wherein said electric actuator (466) configured to electrically control the displacement of said shadowing element (450) in one or two of said displacement directions (D1,D2) upon being supplied by an electric signal thereto.
Clause 20. A modular incubator system (500) according to any of the clauses 14 - 19, wherein said shadowing element (450) is being arranged outside the optics of said image capturing device (408); or wherein said shadowing element (450) is being arranged inside the optics of said image capturing device (408).
Clause 21. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is an active light source (352) being arranged in the interior (306) of the modular incubating chamber (300), wherein said active light source (352) is configured for propagating light in said light aiming direction (A), by being supplied with electric power.
Clause 22. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is a passive light directing element in the form of a light conveyor (354) being arranged in the interior (306) of the modular incubating chamber (300), wherein said light conveyor (354) is configured for directing incoming light, in said light aiming direction (A), such as by reflecting said incoming light.
Clause 23. A modular incubator system (500) according to clause 22, wherein in respect of one or more of said one or more modular incubator chambers (300), said housing (302) of said modular incubator chamber (300) comprises a light transmission element (356) for providing light to said light conveyor (354,350) from a position outside said chamber (300); and wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), said docking port (402) comprises an active light source (352); wherein the position of said light transmission element (356) of said housing 302 of said modular incubator chamber 300 and the position of said active light source (352) of said docking port (402) are adapted to each other in such a way that once being docked in said docking port (402) of said docking station (400), light emitted from said active light source (352) of said docking port (402) will be able to transmit said light transmission element (356) of said housing (302) of said modular incubator chamber (300) and propagate to said light conveyor (354,350) in the interior of said housing (302).
Clause 24. A modular incubator system (500) according to clause 23, wherein in respect of one or more of said one or more modular incubator chambers (300), said light transmission element (356) of said housing (302) of said modular incubator chamber (300) is being arranged at a top of said housing (302), such as at the lid (304) of said housing (302) and is being the same entity as said light conveyor (350,354).
Clause 25. A modular incubator system (500) according to clause 24, wherein said light conveyor (354) is being a light deflector, such as an optical prism or lens.
Clause 26. A modular incubator system (500) according to clause 23, wherein in respect of one or more of said one or more modular incubator chambers (300), said light transmission element (356) of said housing (302) of said modular incubator chamber (300) is being arranged at a side of said housing (302).
Clause 27. A modular incubator system (500) according to clause 26, wherein said light conveyor (350,354) is being a light reflector, such as a mirror.
Clause 28. A modular incubator system (500) according to clause 23, wherein in respect of one or more of said one or more modular incubator chambers (300), said light transmission element (356) of said housing (302) of said modular incubator chamber (300) is being arranged at a bottom (330) of said housing (302), wherein said housing (302) in the interior thereof comprises a light reflector (358), wherein said light reflector (358) is being configured to reflect upwardly propagating light into an essentially horizontally propagating light, propagating towards said light conveyor (350,354); and wherein said light conveyor (350,354) is configured to reflect said essentially horizontally propagating light into said light aiming direction (A)). Clause 29. A modular incubator system (500) according to clause 28, wherein said light conveyor (350,354) is being a light reflector, such as a mirror.
Clause 30. A modular incubator system (500) according to clause 23, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), said active light source (352) is arranged in said docking port (402) at a position so as to be configured to direct emitted light in a direction essentially parallel to said focus direction (B) of said image capturing device (408), and wherein in respect of one or more of said one or more modular incubator chambers (300), said light conveyor (350,354) is configured to direct said emitted light in said light aiming direction (A).
Clause 31. A modular incubator system (500) according to clause 30, wherein said light conveyor (350,354) is being a light reflector, such as a mirror.
Clause 32. A modular incubator system (500) according to clause 30 or 31, wherein said active light source (352) is being arranged adjacent to said image capturing device (408).
Clause 33. A modular incubator system (500) according to clause 30 or 31, wherein said active light source (352) is being arranged within the optics of said capturing device (408).
Clause 34. A modular incubator system (500) according to any of the clauses 21 - 33, wherein said active light source (352) is being selected from the group of one or more LEDs, one or more laser diodes, one or more incandescent light bulbs.
Clause 35. A modular incubator system (500) according to any of the preceding clauses, wherein transparent window (316) and/or said light transmission element (356) is made of glass or plastic.
Clause 36. A modular incubator system (500) according to any of the preceding clauses, wherein said image capturing device (408) comprises microscopic optics so as to enable capturing of microscope images.
Clause 37. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said housing (302) of said modular incubator chamber (300), such as at an outer portion thereof, is being provided with electric connectors (322) for providing electric power and/or electric signals to said modular incubator chamber; and wherein in respect of one or more docking ports (402) of said docking station (400), said docking port is being provided with electric connectors (410), thereby allowing providing electric power and/or electric signals between said docking port (402) of said docking station (400) and a modular incubator chamber (300) being docked therein.
Clause 38. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said lid (304) is being a hinged lid which is being connected to said housing of said modular incubator chamber (302) via a hinge. Clause 39. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said housing (302) of said modular incubator chamber (300) comprises a display (324) which is being configured to display information relating to an operational status of the incubation taking place in said modular incubator chamber.
Clause 40. A modular incubator system (500) according to any of the clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber (300) comprises a chamber inlet opening for gas (312), wherein said chamber inlet opening for gas (312) is being in fluid connection with the interior (306) of said modular incubator chamber; and wherein said modular incubator chamber (300) furthermore comprises a chamber outlet opening for gas (314), wherein said chamber outlet opening for gas (314) is being in fluid connection with the interior (306) of said modular incubator chamber; and wherein in respect of one or more docking ports (402) of said docking station (400), said docking port (402) comprises a docking port outlet opening for gas (404) and a docking port inlet opening for gas (406); thereby enabling transfer of gas from said docking port (402) of said docking station (400) to the interior (306) of said modular incubator chamber (300) via said docking port outlet opening for gas (404) and said chamber inlet opening for gas (312); and thereby enabling transfer of gas from the interior (306) of said modular incubator chamber (300) to said docking port (402) of said docking station (400) via said chamber outlet opening for gas (314) and said docking port inlet opening for gas (406).
Clause 41. A modular incubator system (500) according to clause 40, wherein in respect of one or more of said one or more modular incubator chambers (300), and in respect of one or more of said one or more docking ports (402) of said docking station 400, the position of said chamber inlet opening for gas (312) of said housing (302) of said modular incubator chamber (300) and the position of said docking port outlet opening for gas (404) of said docking port (402) are adapted to each other in such a way that once docking said modular incubator chamber (300) in said docking port (402), said chamber inlet opening for gas (312) of said housing (302) of said modular incubator chamber (300) and said docking port outlet opening for gas (404) of said docking port (402) will be in fluid connection, thereby enabling transfer of gas from said docking port (402) to said modular incubator chamber (300); and wherein the position of said chamber outlet opening for gas (314) of said housing (302) of said modular incubator chamber (300) and the position of said docking port inlet opening for gas (406) of said docking port (402) are adapted to each other in such a way that once docking said modular incubator chamber (300) in said docking port (402), said chamber outlet opening for gas (314) of said housing (302) of said modular incubator chamber (300) and said docking port inlet opening for gas (406) of said docking port (402) will be in fluid connection, thereby enabling transfer of gas from said modular incubator chamber (300) to said docking port (402).
Clause 42. A modular incubator system (500) according to any of the clauses 40 or 41, wherein said docking port outlet opening for gas (404) of said docking port (402) comprises a valve (4) and wherein said chamber inlet opening for gas (312) of said housing (302) comprises a valve (2); and wherein said chamber outlet opening for gas (314) comprises a valve (2) and wherein said docking port inlet opening for gas (406) of said docking port (402) comprises a valve (4).
Clause 43. A modular incubator system (500) according to any of the clauses 40 - 42; wherein in respect of one or more of said one or more modular incubator chambers (300), said valve (2) of said chamber inlet opening for gas (312) and said valve (2) of said chamber outlet opening for gas (314) each comprises a valve body (6) having a front end (10), a rear end (12) and a through-going channel (14) therein, and a spring-loaded displaceable valve element (8), wherein said displaceable valve element (8) is being arranged in said through-going channel (14); wherein said displaceable valve element (8) is being configured to be displaceable in said through-going channel (14) of said valve body (6) in such a way, that when not acted upon by an external force, said spring-loaded displaceable valve element (8) is not being displaced in said through-going channel (14) of said valve body (6), thereby making said valve attain a closed configuration blocking passage of gas through said through-going channel (14), and in such a way, that when acted upon by an external force, said spring-loaded displaceable valve element (8) is being displaced in said through-going channel (14) of said valve body (6), thereby making said valve (2) attain an open configuration, allowing passage of gas through said through-going channel (14); and whereinin respect of one or more of said one or more docking ports (402) of said docking station (400), said valve (4) of said docking port outlet opening for gas (404) and said valve (4) of said docking port inlet opening for gas (406) each comprises a valve body (16) having a front end (20), a rear end (22) and a through-going channel (24) therein, and a spring-loaded displaceable valve element (18), wherein said displaceable valve element (18) is being arranged in said through-going channel (24); wherein said displaceable valve element (18) is being configured to be displaceable in said through-going channel (24) of said valve body (16) in such a way, that when not acted upon by an external force, said spring-loaded displaceable valve element (18) is not being displaced in said through-going channel (24) of said valve body (16), thereby making said valve attain a closed configuration blocking passage of gas through said through-going channel (24), and in such a way, that when acted upon by an external force, said spring-loaded displaceable valve element (18) is being displaced in said through-going channel (24) of said valve body (16), thereby making said valve (4) attain an open configuration, allowing passage of gas through said through-going channel (24).
Clause 44. A modular incubator system (500) according to any of the clauses 40 - 43, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), and in respect of one or more of said one or more modular incubator chambers (300) said valves (2,4) are having dimensions and geometries in such a way that once docking said modular incubator chamber (300) in said docking port (402) of said docking station (400), said displaceable valve element (8) of said valve (2) and said displaceable valve element (18) of said valve (4) will displace each other into their respective valve bodies (6,16), thereby opening said valves (2,4) of said docking port outlet opening for gas (404) and said chamber inlet opening for gas (312); and thereby opening said valves (2,4) of said chamber outlet opening for gas (314) and said docking port inlet opening for gas (406).
Clause 45. A modular incubator system (500) according according to any of the clauses 1 - 44, wherein in respect of one or more of said docking ports (402) of said docking station (400) of said modular incubator system (500), preferably in respect of all said docking ports (402), said docking port outlet opening for gas (404) comprises a flow restrictor for restricting the magnitude of flow of gas flowing into said docking port (402).
Clause 46. A modular incubator system (500) according to clause 45, wherein said flow restrictor comprises a tube through which the gas is conveyed to said docking port (402), wherein said tube optionally is having a cross-sectional area selected from the ranges of 0.2 - 8 mm2, such as 0.5 - 7 mm2, for example 1 - 6 mm2, such as 2 - 5 mm2 or 3 - 4 mm2; and/or wherein the length of said tube optionally is selected from the ranges of 5 - 30 mm, such as 8 -25 mm, for example 10 - 22 mm, e.g. 15 - 20 mm.
Clause 47. A modular incubator system (500) according to any of the clauses 40 - 46, wherein said docking station (400) comprises a gas distribution system (204) for supplying gas to and from one or more of said one or more docking ports (402), wherein said gas distribution system (204) comprises a main gas supply line (210) and a main gas return line (212), wherein in respect of one or more of said docking ports (402), said docking port inlet opening for gas (404) is being fluidly connected to said main gas supply line (210), and said docking port outlet opening for gas (406) is being fluidly connected to said main gas return line (212).
Clause 48. A modular incubator system (500) according to clause 47 wherein said gas distribution system (204) comprises a number of manifold pairs (214), wherein each manifold pair comprises an inlet manifold (216) and an outlet manifold (218), wherein said inlet manifold (216) is being fluidly connected to said main gas supply line (210) and wherein said outlet manifold (218) is being fluidly connected to said main gas return line (212); wherein each manifold pair (214) is connected to one or more docking ports (402) of said docking station (400) in such a way that in respect of a specific manifold pair (214), and in respect of said one or more docking ports (402) being connected thereto, said docking port outlet opening for gas (404) of said docking port (402) is being fluidly connected to said inlet manifold (216), and said docking port inlet opening for gas (406) of said docking port (402) is being fluidly connected to said outlet manifold (218).
Clause 49. A modular incubator system (500) according to clause 47 or 48, wherein said docking station (400) comprises a gas supply system (200), wherein said gas supply system (200) comprises a gas source (202) and said gas distribution system (204), wherein said gas source comprises a supply gas outlet (206) and a return gas inlet (208), wherein said supply gas outlet (206) of said gas source (202) is being fluidly connected to said main gas supply line (210) of said gas distribution system (204), and wherein said return gas inlet (208) of said gas source (202) is being fluidly connected to said main gas return line (212) of said gas distribution system (204). Clause 50. A modular incubator system (500) according to any of the clauses 47 - 49, wherein said gas source (202) of said gas supply system (200) comprises a gas mixing box (242) comprising said supply gas outlet (206) and said return gas inlet (208) of said gas source, wherein said main gas supply line (210) of said gas distribution system (204) is being fluidly connected to said supply gas outlet (206), and wherein said main gas return line (212) of said gas distribution system (204) is being fluidly connected to said return gas inlet (208) of said gas source (202), thereby forming a flow loop (244) comprising said gas distribution system (204) and said gas mixing box (242); wherein said flow loop comprises a pump (246) for circulating gas in said loop.
Clause 51. A modular incubator system (500) according to clause 50, wherein said pump (246) is being arranged downstream in relation to said main gas return line (212).
Clause 52. A modular incubator system (500) according to clause 50 or 51, wherein said flow loop (244) comprises a pump oscillation damper (247), wherein said pump oscillation damper optionally is being arranged immediately downstream in relation to said pump (246).
Clause 53. A modular incubator system (500) according to any of the clauses 50 - 52, wherein said flow loop (244) comprises a pressure sensor, such as a differential pressure sensor (248) for sensing the pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204), wherein said pressure senor (248) optionally is being arranged immediately upstream in relation to said main gas supply line (210) of said gas distribution system (204).
Clause 54. A modular incubator system (500) according to clause 53, wherein said pressure sensor (248) is being a differential pressure sensor, sensing a pressure relative to the pressure of the return gas inlet (208).
Clause 55. A modular incubator system (500) according to any of the clauses 50 -54, wherein said flow loop (244) comprises a release valve (249) for enabling pressure relief in said flow loop, wherein said release valve optionally is being arranged immediately downstream in relation to said main gas return line (212) of said gas distribution system (402).
Clause 56. A modular incubator system (500) according to any of the clauses 50 -55, wherein said gas mixing box (242) comprises an inlet for N2 gas (250); and an inlet for CO2 gas (251), wherein said inlet for N2 gas (250) is fluidly connected to an N2 valve (252) for regulating the inflow of N2, and an N2 mass flow sensor (253) arranged downstream of said N2 valve (252) for sensing the amount of N2 flowing into said gas mixing box (242); and wherein said inlet for CO2 gas (251) is fluidly connected to a CO2 valve (254) for regulating the inflow of CO2, and an CO2 mass flow sensor (255) arranged downstream of said CO2 valve (254) for sensing the amount of CO2 flowing into said gas mixing box (242).
Clause 57. A modular incubator system (500) according to any of the clauses 50 -56, wherein said flow loop (244) comprises a mass flow sensor (256) arranged at an upstream position in relation to said gas mixing box (242) for sensing the amount of return gas entering said gas mixing box.
Clause 58. A modular incubator system (500) according to any of the clauses 50 -57, wherein said gas source (202) comprises an O2 sensor (258) for sensing the concentration of O2 exiting said gas distribution system (204); and wherein said gas source (202) comprises a CO2 sensor (260) for sensing the concentration of CO2 exiting said gas distribution system (204), wherein said O2 sensor and/or said CO2 sensor optionally is/are being arranged downstream in relation to said pump (246).
Clause 59. A modular incubator system (500) according to any of the clauses 50 - 58, wherein said gas source (202) comprises a temperature sensor (262) for sensing the temperature of gas circulating in said flow loop (244), wherein said temperature sensor optionally is being arranged downstream in relation to said pump (246), preferably at a position corresponding to the position of said O2 sensor (258).
Clause 60. A modular incubator system (500) according to any of the clauses 50 - 59, wherein said gas source (202) comprises a pressure sensor (264) for sensing the absolute pressure in said flow loop (244) wherein said pressure sensor optionally is being arranged downstream in relation to said pump (246), preferably at a position corresponding to the position of said CO2 sensor (260).
Clause 61. A modular incubator system (500) according to any of the clauses 50 - 60, wherein said flow loop (244) comprises a UV sanitizer (266) for sanitizing gas flowing in said flow loop (244) via electromagnetic radiation in the UV range, wherein said UV sanitizer optionally being arranged immediately downstream in relation to said main gas return line (212).
Clause 62. A modular incubator system (500) according to any of the clauses 50 - 61, wherein said gas source (202) comprises one or more filters (268), such as HEPA and/or VOCs filters, wherein such a filter is being arranged immediately upstream in relation to said main gas supply line (210), and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for N2gas (250) into said gas mixing box (242); and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for CO2 gas (251) into said gas mixing box (242).
Clause 63. A modular incubator system (500) according to any of the clauses 50 - 62, wherein said gas source (202) comprises a gas mixing control system (270), wherein said gas mixing control system is electrically connected to one or more of the following sensors for receiving sensing signals therefrom: said N2 mass flow sensor (253) for sensing the amount of N2 flowing into said gas mixing box; said CO2 mass flow sensor (255) for sensing the amount of CO2 flowing into said gas mixing box; said mass flow sensor (256) for sensing the amount of return gas entering said gas mixing box; said O2 sensor (258) for sensing the concentration of O2 exiting said main gas return line (212) of said gas distribution system (204); said CO2 sensor (260) for sensing the concentration of CO2 exiting said main gas return line (212) of said gas distribution system (204); said temperature sensor (262) for sensing the temperature circulating in said flow loop (244); said pressure sensor (264) for sensing an absolute pressure in said flow loop (244), said pressure sensor (248) for sensing the pressure of gas supplied to said gas main gas supply line (210) of said distribution system (204).
Clause 64. A modular incubator system (500) according to clause 63, wherein said gas mixing control system (270) is electrically connected to one or more of the following elements for control thereof: said N2 valve (252) for regulating the inflow of N2 into said gas mixing box (242); said CO2 valve (254) for regulating the inflow of CO2 to said gas mixing box (242); said pump (246) for circulating gas in said flow loop (244); said release valve (249).
Clause 65. A modular incubator system (500) according to clause 63 or 64, wherein said gas mixing control system (270) is being configured to receive input from said pressure sensor (248) and on the basis thereof control said pump (246), optionally also to activate said release valve (249) in order to maintain a desired and predetermined pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204).
Clause 66. A modular incubator system (500) according to any of the clauses 63 - 65, wherein said gas mixing control system (270) is being configured to receive input from said mass flow sensor (256), and on the basis on said input to determine the total amount of CO2 gas and N2 gas needed to be supplied via said inlet for CO2 gas (251) and via said inlet for N2 gas (250) according to desired and predetermined criteria.
Clause 67. A modular incubator system (500) according to any of the clauses 63 - 66, wherein said gas mixing control system (270) is being configured to receive input from said CO2 sensor (260) and said O2 sensor (258), and on the basis of the CO2 concentration sensed, is configured to control said CO2 valve (254), by transmitting a control signal thereto, and thereby regulating the inflow of CO2 gas in order to reach a desired and predetermined CO2 concentration, and wherein subsequently, said gas mixing control system (270) on the basis of the O2 concentration sensed, is configured to control said N2 valve (252), by transmitting a control signal thereto, and thereby regulating the inflow of N2 gas in order to reach a desired and predetermined O2 concentration.
Clause 68. A modular incubator system (500) according to any of the clauses 63 - 67, wherein said gas mixing control system (270) is configured to use the input from said temperature sensor (262) for compensating the temperature sensitivity of said O2 sensor (258).
Clause 69. A modular incubator system (500) according to any of the clauses 63 - 68, wherein said gas mixing control system (270) is configured to use the input from said pressure sensor (264) for compensating the pressure sensitivity of said CO2 sensor (260).
Clause 70. A modular incubator system (500) according to any of the clauses 63 - 69, wherein said gas mixing control system (270) is being configured to maintain a pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204), relative to the ambient atmospheric pressure, of 3 - 20 mbar, such as 5 - 18 mbar, such as 10 - 15 mbar above that ambient atmospheric pressure.
Clause 71. A modular incubator system (500) according to any of the clauses 63 - 70, wherein said gas mixing control system (270) is being configured to maintain a CO2 concentration of gas entering said main gas supply line (210) of said gas distribution system (204) in the range of 5 - 10 %, such as 6 - 9 % or 7 - 8 %; and/or an O2 concentration of gas entering said main gas supply line 210 of said gas distribution system 204 in the range of 5 - 10%, such as 6 - 9 % or 7 - 8 %.
Clause 72. A modular incubator system (500) according to any of the preceding clauses, wherein the number of modular incubator chambers (300) of said modular incubator system (500) is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
Clause 73. A modular incubator system (500) according to any of the preceding clauses, wherein the number of docking ports (402) in said docking station (400) of said modular incubator system 500 is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
Clause 74. A modular incubator system (500) according to any of the preceding clauses, wherein said docking station (400) comprises said docking ports (402) in an arrangement of one or more shelves of adjacently positioned docking ports (402), wherein in case said docking station comprises two or more shelves, said shelves are being arranged above each other.
Clause 75. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber comprises an incubation chamber engagement means (326) and wherein in respect of one or more docking ports (402) of said docking station (400), said docking port comprises a docking port engagement means (414), wherein said incubation chamber engagement means (326) is being configured to enter into engagement with said docking port engagement means (414) so as to provide easy and proper positioning and optionally also fixing said modular incubator chamber( 300) in said docking port (402), as well as detaching said modular incubator chamber (300) from said docking port (402) of said docking station (400).
Clause 76. A modular incubator system (500) according to any of the preceding clauses, wherein said modular incubator system (500) comprises an image processing unit (660) for image processing of images captured by said image capturing device (408), wherein said modular incubator system (400) furthermore comprises a data storage (658) for storing images captured by said image capturing units (408) and/or for storing images processed by said image processing unit.
Clause 77. A modular incubator system (500) according to clause (124), wherein one or more of said image capturing devices (408) of said docking ports (402) of said docking station is/are being coupled to said image processing unit (660).
Clause 78. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more specific docking ports (402) of said docking station (400), said specific docking port comprises its own dedicated image capturing device (408) which is configured to only capture images relating to a modular incubator chamber (300) which is being docked in said specific docking port (402).
Clause 79. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of a number N of adjacently arranged docking ports (402) of said docking station (400), said adjacently arranged docking ports (402) share a common image capturing device (408) in the sense that one and only one image capturing device is responsible for capturing images relating to a modular incubator chamber (300) which is being docked in one of said N adjacently arranged docking ports (402) s wherein said docking station comprises a displacement device (482) for enabling displacement of said common image capturing device (408) in relation to said N adjacently arranged docking ports (402) of said docking station (400), such as being provided with an electric signal thereto.
Clause 80. A modular incubator system (500) according to clause 74, wherein said number N is being an integer selected in the ranges of 2 - 25 or more, such as 4 - 22, for example 6 - 20, such as 8 - 18, such as 10 - 16 or 12 - 14.
Clause 81. A modular incubator system (500) according to any of the preceding clauses, wherein in respect of one or more of said modular incubator chambers (300), said modular incubator chamber comprises in its interior (306) an electric heating element (318) for heating the interior of said modular incubator chamber, and wherein said modular incubator chamber comprises a power source (320) for providing power to said heating element (318), wherein said electric heating element (318) is being electrically connected to said power source (320).
Clause 82. A modular incubator system (500) according to clause 81, wherein said power source (320) is being an electric power source, such as a battery, for example a rechargeable battery.
Clause 83. A modular incubator system (500) according to any of the clauses 81 or 82, wherein said heating element (318) is being thermally connected to a heat distribution element for distributing heat dissipated in said heating element; wherein said heat distribution element is being arranged, at least partly, in the interior (306) of said modular incubator chamber (300).
Clause 84. A modular incubator system (500) according to any of the clauses 81 - 83, wherein said chamber comprises a thermostat (374) and an electric thermostatic circuit (376), wherein said electric heating element (318), said power source (320) and said thermostat (374) are being electrically connected in said electric thermostatic circuit (376) so as to enable thermostatic control of the temperature inside said modular incubator chamber (300).
Clause 85. A modular incubator system (500) according to any of the preceding clauses, wherein said modular incubator system (500) comprises a control unit (650) for controlling the operation of said modular incubator system (500).
Clause 86. A modular incubator system (500) according to clause 85, wherein said control unit (650) is being coupled to an input device (652), such as an alphanumerical input device for allowing a user to provide settings input relating to a desired operational protocol of said modular incubator system.
Clause 87. A modular incubator system (500) according to clause 85 or 86, wherein said control unit (650) is being coupled to a display unit (654) for displaying, to a user, information relating to settings and/or operational status of said modular incubator system (300). Clause 88. A modular incubator system (500) according to any of the clauses 85 - 87, wherein in respect of one or more docking ports (402) of said docking station (400) said control unit (650) is being configured for independently controlling one or more of the following: temperature in the interior (306) of said modular incubator chamber (300) by controlling said electric heating element (318), said thermostat (374) or said thermostatic circuit (376), providing power to said electric power source (320); providing signals to said display (324) a modular incubator chamber (300), said inclination angle adjustment element (332), said rotational adjustment element (334) of said inclination angle adjustment element (332), said displacement adjustment element (336) of said inclination angle adjustment element (332), switching on and off of said active light source (352), or adjusting light intensity emitted therefrom, said image capturing device (408) of a docking station (408), said displacement device (482) for displacing said image capturing device (408), said actuator of said X-stage or XY-stage (466), said actuator of said iris diaphragm (464), said gas mixing control system (270); said image processing unit (660).
Clause 89. A modular incubator system (500) according to any of the clauses 85 - 88, wherein said control unit (650) is being coupled to a data processing unit (656) and optionally also to a data storage (658) for aiding in handling information during controlling of said modular incubator system.
Clause 90. A modular incubator system (500) according to any of the clauses 85 - 89, wherein said control unit (650) is being configured for conducting automatic operation of said modular incubator system (500) by configuring said control unit (650) to independently control one or more of the following: temperature in the interior (306) of said modular incubator chamber (300) by controlling said electric heating element (318), said thermostat (374) or said thermostatic circuit (376), providing power to said electric power source (320); providing signals to said display (324) a modular incubator chamber (300), said inclination angle adjustment element (332), said rotational adjustment element (334) of said inclination angle adjustment element (332), said displacement adjustment element (336) of said inclination angle adjustment element (332), switching on and off of said active light source (352), or adjusting light intensity emitted therefrom, said image capturing device (408) of a docking station (408), said displacement device (482) for displacing said image capturing device (408), said actuator of said X-stage or XY-stage (466), said actuator of said iris diaphragm (464), said gas mixing control system (270); said image processing unit (660).
Clause 91. A modular incubator system (500) according to any of the clauses 85 - 90, wherein said control unit (650) is being configured for enabling time lapse capturing of images by said image capturing devices (408).
Clause 92. A modular incubator chamber (300), wherein said modular incubator chamber (300) is comprising features as defined in respect of the modular incubator chamber (300) of the modular incubator system (500) according to any of the clauses 1 - 91.
Clause 93. A docking station (400), wherein said docking station is comprising features as defined in respect of the docking station of the modular incubator system (500) according to any of the clauses 1 - 91. Clause 94. Use of a modular incubator system (500) according to any of the clauses 1 - 91 for incubating a viable biological material M.
Clause 95. Use of a modular incubator chamber (300) according to clause 92 for incubating a viable biological material M.
Clause 96. Use of a docking station (400) according to clause 93 for incubating a viable biological material M.
Clause 97. Use according to any of the clauses 94, 95 or 96, wherein said biological material M is being an oocyte or an embryo, such as a human oocyte or a human embryo.
Clause 98. A method of incubating a viable biological material M, wherein said method comprises: i) providing a modular incubator system (500) according to any of the clauses 1 - 91; ii) providing a viable biological material M; iii) arranging said viable biological material M in a culture dish (310) and subsequently arranging said culture dish on the culture dish support (308) in the interior (306) of said modular incubator chamber (300) of said modular incubator system (400); iv) docking said modular incubator chamber (300) in a docking port (402) of said docking station (400) of said incubator system (500); v) allowing said viable biological material M to be incubated in said modular incubator chamber (300); vi) while performing step v) enabling said light directing element (350) of said modular incubator chamber (300) to direct light to an area of said culture dish support (308) in said light aiming direction (A); vii) while performing step v) and vi) making said image capturing device (408) capture image(s) of said viable biological material M in the interior (306) of said modular incubator chamber (300), at a focus direction (B); wherein said focus direction (A) of light propagating from said light directing element (350) of said modular incubator chamber (300) is being inclined relative to said focus direction (B) of said image capturing device (408) of said docking port (302) at an inclination angle a which is 0°.
Clause 99. A method according to clause 98 further comprising the step of: viii) removing said incubator chamber (300) from said docking port (402) of said docking station (400), when desired, in order to manually inspect the viable biological material M, and optionally also to remove, add or exchange growth medium/media in said culture dish (310). List of reference numerals
2 Valve
4 Valve
6 First valve body of first valve
8 First valve element of first valve
8a First part of first valve element
8b Second part of first valve element
10 Front end of first valve body
12 Rear end of first valve body
14 First throughgoing channel of first valve
16 Second valve body of second valve
18 Second valve element of second valve
20 Front end of second valve
22 Rear end of second valve
24 Second throughgoing channel of second valve
26 First spring of first valve
28 Second spring of second valve
200 Gas supply system
202 Gas source of gas supply system
204 Gas distribution system of gas supply system
206 Supply gas outlet of gas source
208 Return gas inlet of gas source
210 Main gas supply line of gas distribution system
212 Main gas return line of gas distribution system
214 Manifold pair
216 Inlet manifold of manifold pair
218 Outlet manifold of manifold pair
228 Group of docking ports
242 Gas mixing box 244 Flow loop of gas supply system
246 Pump of gas source
247 Pump oscillation damper
248 Pressure sensor for sensing pressure of gas supplied to main gas supply line
249 Pressure release valve
250 Inlet for N2 gas
251 Inlet for CO2 gas
252 N2 valve
253 N2 mass flow sensor
254 CO2 valve
255 CO2 mass flow sensor
256 Mass flow sensor for sensing the amount of return gas flowing into gas mixing box
258 O2 sensor
260 CO2 sensor
262 Temperature sensor
264 Pressure sensor
266 UV sanitizer
268 Filter
270 Gas mixing control system
300 Modular incubator chamber
302 Housing of modular incubator chamber
304 Lid of modular incubator chamber
306 Interior of modular incubator chamber
308 Culture dish support
310 Culture dish
312 Modular incubator chamber inlet opening for gas
314 Modular incubator chamber outlet opening for gas
316 Transparent window of housing of modular incubator chamber
318 Electric heating element 320 Electric power source
322 Electric connectors of modular incubator chamber
324 Display of housing of modular incubator chamber
326 Engagement means of modular incubator chamber
330 Bottom of housing of modular incubator chamber
332 Inclination angle adjustment element
334 Rotational adjustment element of inclination angle adjustment means
336 Displacement adjustment element of inclination angle adjustment means
338 Support for displacement adjustment element
340 First end of modular incubator chamber
342 Second end of modular incubator chamber
350 Light directing element
352 Active light source
354 Light directing element in the form of a passive light conveyor
356 Light transmission element of housing of modular incubator chamber
358 Light reflector of interior of modular incubator chamber
374 Thermostat
376 Thermostatic circuit
400 Docking station
402 Docking port of docking station
404 Docking port outlet opening for gas
406 Docking port inlet opening for gas
408 Image capturing device of docking port of docking station
410 Electric connector of docking port
414 Engagement means of docking port of docking station
450 Shadowing element
452 Shadowing plate of shadowing element
454 Hole in plate of shadowing element
456 X- stage or XY- stage of shadowing element 458 Iris diaphragm of shadowing element
460 Iris lamella of iris diaphragm
462 Through-going hole of iris diaphragm
464 Actuator of iris diaphragm
466 Actuator of X-stage or XY-stage
482 Displacement element for displacing image capturing device
500 Modular incubator system
650 Control unit
652 Input device
654 Display unit
656 Data processing unit
658 Data storage
660 Image processing unit
A Light aiming direction of light directing element
A1,A2 Rotational direction
B Focus direction of image capturing device
D Distance
D1,D2 Displacement directions of XY-stage of shadowing element
IP Imaginary plane
M Viable biological material
P Planer support surface defined by culture dish support
PR Projection on imaginary plane
PRB Boundary of projection on imaginary plane
X Longitudinal direction of modular incubator chamber a Inclination angle

Claims

Claims
1. A modular incubator system (500) for incubating a viable biological material M, said modular incubator system comprising:
-one or more modular incubator chambers (300) in combination with
-a docking station (400); wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber (300) comprises a housing (302); wherein said housing (302) comprises a lid (304), wherein said lid is being configured to be able to shift between an open configuration allowing access to the interior (306) of said modular incubator chamber and a closed configuration, sealing off access to the interior of said modular incubator chamber; wherein said modular incubator chamber, at said interior (306) thereof, comprises a culture dish support (308) for positioning a culture dish (310) with the view to accommodate one or more biological materials M within the housing (302) of said modular incubator chamber (300); wherein said housing (302) of said modular incubator chamber (300) comprises a transparent window (316) for enabling capturing of images of a biological material M being accommodated in the interior thereof, through said transparent window; wherein said housing comprises a light directing element (350) for directing light to an area of said culture dish support (308) in a light aiming direction (A); wherein said docking station (400) comprises one or more docking ports (402) for receiving a housing (302) of an incubator chamber (300); wherein in respect of one or more docking ports (402) of said docking station (400), said docking port (402) comprises an image capturing device (408) for capturing an image of the interior (306) of a modular incubator chamber (300), once being docked in said docking port (402), by focusing said image capturing device (408) in a focus direction (B); wherein in respect of one or more of said one or more modular incubator chambers (300) and in respect of one or more of said one or more docking ports (402) of said docking station (400), the position of said transparent window (316) of said modular incubator chamber (300) is adapted to the position of said image capturing device (408) in said docking port (402) in a way that enables capturing of images by said image capturing device (408) through said transparent window (316) of said modular incubator chamber( 300); wherein in respect of one or more of said one or more modular incubator chambers (300) and in respect of one or more of said one or more docking ports (402) of said docking station (400), once being docked in said docking port (402), said light aiming direction (A) of said light propagating from said light directing element (350) of said modular incubator chamber (300) is being inclined relative to said focus direction (B) of said image capturing device (408) of said docking port (402) at an inclination angle a, wherein said inclination angle a
Figure imgf000069_0001
0°; wherein in respect of one or more of said one or more modular incubator chambers (300) and in respect of one or more of said one or more docking ports (402) of said docking station (400), once being docked in said docking port (402) of said docking station, said light directing element (350) is being positioned in the interior (306) of said modular incubator chamber (300) at a position which is displaced relative to the focus direction (B) of said image capturing device (408) of said docking port (402), in a direction perpendicular to said focus direction (B), thereby providing said inclination angle a between said light aiming direction (A) and said focus direction (B).
2. A modular incubator system (500) according to claim 1, wherein in respect of one or more of said one or more modular incubator chambers (300) and in respect of one or more of said one or more docking ports (402) of said docking station 400, said inclination angle a is selected from the ranges of 0.5 - 25°, such as 1 - 24°, for example 2 - 23°, e.g. 3 - 22°, such as 4 - 21°, for example 5 - 20°, such as 6 - 19°, for example 7 - 18°, such as 8 - 17°, for example 9 - 16°, such as 10 - 15°, e.g. 11 - 14° or 12 - 13°.
3. A modular incubator system (500) according to claim 1 or 2, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubation chamber (300), in the orientation intended during use for incubation, is having its maximum dimension in a horizontal direction.
4. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said culture dish support (308) is defining a planar support surface P for supporting said culture dish (310).
5. A modular incubator system (500) according to claim 4, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), once being docked in said docking port (402) of said docking station (400), said focus direction B of said image capturing device (408) of said docking port (402) is being essentially perpendicular to said planar support surface P of said culture dish support (308) of said modular incubator chamber (300), and wherein said light aiming direction A of said light directing element (350) of said modular incubator chamber (300) is not being perpendicular to said planar support surface P of said culture dish support (308).
6. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is being attached to said lid (304) of the housing (306) of said modular incubator chamber (300), at an inner side thereof.
7. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350), comprises a diffuser, such as a diffuser lens.
8. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said transparent window (316) of said modular incubator chamber (300) is located at a bottom part (330) of said housing (302) of said chamber (300).
9. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is geometrically configured to make said light propagate at a maximum spreading angle of propagation of 1 - 65°, such as 5 - 60°, e.g. 10 - 55°, such as 15 - 50°, for example 20 - 45°, e.g. 25 - 40° or 30 - 35°.
10. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300) said light aiming direction (A) is directed towards said transparent window (316) in said housing (302) of said modular incubator (300).
11. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber (300) comprises inclination angle adjustment element (332) for adjusting the inclination angle a between said light aiming direction (A) and said focus direction (B), wherein said inclination angle adjustment element (332) is configured to enable adjustment of said inclination angle a so that this inclination angle a may attain an angle selected from the ranges 0.5 - 25°, such as 1 - 24°, for example 2 - 23°, e.g. 3 - 22°, such as 4 - 21°, for example 5 - 20°, such as 6 - 19°, for example 7 - 18°, such as 8 - 17°, for example 9 - 16°, such as 10 - 15°, e.g. 11 - 14° or 12 - 13°.
12. A modular incubator system (500) according to claim 11, wherein said inclination angle adjustment element (332) comprises a rotational adjustment element (334) which is being configured, upon being adjusted, to enable changing the light aiming direction A of light direction propagation from said light directing element (350) by changing the spatial orientation of said light directing element (350); and/or wherein said inclination angle adjustment element (332) comprises a displacement adjustment element (336) which is being configured, upon being adjusted, to enable changing a position of said light directing element (350).
13. A modular incubator system (500) according to claim 12, wherein said rotational adjustment element (334) and/or said displacement adjustment element (336) is/are electrically controlled by electric actuators which provides for changing the light aiming direction (A) of light propagation from said light directing element (350) and/or for changing the position of said light directing element (350) upon being supplied by an electric signal thereto.
14. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), said docking port (402) comprises a shadowing element (450) which is configured to enable blocking part of the light being propagated towards the optics of said image capturing device (408).
15. A modular incubator system (500) according to claim 14, wherein said shadowing element (450) comprises a shadowing plate (452) comprising a through-going hole (454) having a fixed geometry and/or size, such as a round hole, such as a circular hole; or a rectangular hole, wherein said shadowing plate (452) is being arranged relative to said image capturing device (408) so that the focus direction B of said image capturing device (408) passes through that hole (452).
16. A modular incubator system (500) according to claim 14 wherein said shadowing element (450) comprises an iris diaphragm (458) having a plurality of iris lamellas (460) which are movable in relation to each other and thereby are configured, upon being subjected to an external force, to vary the size of a through-going hole (462) formed in the centre of said iris diaphragm; wherein said iris diaphragm (458) is being arranged relative to said image capturing device (408) so that the focus direction (B) of said image capturing device (408) passes through that hole (462).
17. A modular incubator system (500) according to claim 16 wherein said iris diaphragm (458) comprises an actuator (464), such as a remote-controlled electric actuator which is mechanically connected to said iris lamellas (460) and which is configured to enable movement of said iris lamellas in concert so as to vary the size of said through-going hole (462).
18. A modular incubator system (500) according to any of the claims 14 - 17, wherein said shadowing element (450) is coupled to an X- stage or XY-stage (456) in a way enabling said shadowing element (450) to be independently displaced in one or two displacement directions (D1,D2) which each optionally is/are being essentially perpendicular to the focus direction (B) of said image capturing device (408).
19. A modular incubator system (500) according to claim 18, wherein said X-stage or XY- stage comprises an electric actuator (466), wherein said electric actuator (466) configured to electrically control the displacement of said shadowing element (450) in one or two of said displacement directions (D1,D2) upon being supplied by an electric signal thereto.
20. A modular incubator system (500) according to any of the claims 14 - 19, wherein said shadowing element (450) is being arranged outside the optics of said image capturing device (408); or wherein said shadowing element (450) is being arranged inside the optics of said image capturing device (408).
21. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is an active light source (352) being arranged in the interior (306) of the modular incubating chamber (300), wherein said active light source (352) is configured for propagating light in said light aiming direction (A), by being supplied with electric power.
22. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said light directing element (350) is a passive light directing element in the form of a light conveyor (354) being arranged in the interior (306) of the modular incubating chamber (300), wherein said light conveyor (354) is configured for directing incoming light, in said light aiming direction (A), such as by reflecting said incoming light.
23. A modular incubator system (500) according to claim 22, wherein in respect of one or more of said one or more modular incubator chambers (300), said housing (302) of said modular incubator chamber (300) comprises a light transmission element (356) for providing light to said light conveyor (354,350) from a position outside said chamber (300); and wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), said docking port (402) comprises an active light source (352); wherein the position of said light transmission element (356) of said housing 302 of said modular incubator chamber 300 and the position of said active light source (352) of said docking port (402) are adapted to each other in such a way that once being docked in said docking port (402) of said docking station (400), light emitted from said active light source (352) of said docking port (402) will be able to transmit said light transmission element (356) of said housing (302) of said modular incubator chamber (300) and propagate to said light conveyor (354,350) in the interior of said housing (302).
24. A modular incubator system (500) according to claim 23, wherein in respect of one or more of said one or more modular incubator chambers (300), said light transmission element (356) of said housing (302) of said modular incubator chamber (300) is being arranged at a top of said housing (302), such as at the lid (304) of said housing (302) and is being the same entity as said light conveyor (350,354).
25. A modular incubator system (500) according to claim 24, wherein said light conveyor (354) is being a light deflector, such as an optical prism or lens.
26. A modular incubator system (500) according to claim 23, wherein in respect of one or more of said one or more modular incubator chambers (300), said light transmission element (356) of said housing (302) of said modular incubator chamber (300) is being arranged at a side of said housing (302).
27. A modular incubator system (500) according to claim 26, wherein said light conveyor (350,354) is being a light reflector, such as a mirror.
28. A modular incubator system (500) according to claim 23, wherein in respect of one or more of said one or more modular incubator chambers (300), said light transmission element (356) of said housing (302) of said modular incubator chamber (300) is being arranged at a bottom (330) of said housing (302), wherein said housing (302) in the interior thereof comprises a light reflector (358), wherein said light reflector (358) is being configured to reflect upwardly propagating light into an essentially horizontally propagating light, propagating towards said light conveyor (350,354); and wherein said light conveyor
(350,354) is configured to reflect said essentially horizontally propagating light into said light aiming direction (A)).
29. A modular incubator system (500) according to claim 28, wherein said light conveyor
(350,354) is being a light reflector, such as a mirror.
30. A modular incubator system (500) according to claim 23, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), said active light source (352) is arranged in said docking port (402) at a position so as to be configured to direct emitted light in a direction essentially parallel to said focus direction (B) of said image capturing device (408), and wherein in respect of one or more of said one or more modular incubator chambers (300), said light conveyor (350,354) is configured to direct said emitted light in said light aiming direction (A).
31. A modular incubator system (500) according to claim 30, wherein said light conveyor
(350,354) is being a light reflector, such as a mirror.
32. A modular incubator system (500) according to claim 30 or 31, wherein said active light source (352) is being arranged adjacent to said image capturing device (408).
33. A modular incubator system (500) according to claim 30 or 31, wherein said active light source (352) is being arranged within the optics of said capturing device (408).
34. A modular incubator system (500) according to any of the claims 21 - 33, wherein said active light source (352) is being selected from the group of one or more LEDs, one or more laser diodes, one or more incandescent light bulbs.
35. A modular incubator system (500) according to any of the preceding claims, wherein transparent window (316) and/or said light transmission element (356) is made of glass or plastic.
36. A modular incubator system (500) according to any of the preceding claims, wherein said image capturing device (408) comprises microscopic optics so as to enable capturing of microscope images.
37. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said housing (302) of said modular incubator chamber (300), such as at an outer portion thereof, is being provided with electric connectors (322) for providing electric power and/or electric signals to said modular incubator chamber; and wherein in respect of one or more docking ports (402) of said docking station (400), said docking port is being provided with electric connectors (410), thereby allowing providing electric power and/or electric signals between said docking port (402) of said docking station (400) and a modular incubator chamber (300) being docked therein.
38. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said lid (304) is being a hinged lid which is being connected to said housing of said modular incubator chamber (302) via a hinge.
39. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said housing (302) of said modular incubator chamber (300) comprises a display (324) which is being configured to display information relating to an operational status of the incubation taking place in said modular incubator chamber.
40. A modular incubator system (500) according to any of the claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber (300) comprises a chamber inlet opening for gas (312), wherein said chamber inlet opening for gas (312) is being in fluid connection with the interior (306) of said modular incubator chamber; and wherein said modular incubator chamber (300) furthermore comprises a chamber outlet opening for gas (314), wherein said chamber outlet opening for gas (314) is being in fluid connection with the interior (306) of said modular incubator chamber; and wherein in respect of one or more docking ports (402) of said docking station (400), said docking port (402) comprises a docking port outlet opening for gas (404) and a docking port inlet opening for gas (406); thereby enabling transfer of gas from said docking port (402) of said docking station (400) to the interior (306) of said modular incubator chamber (300) via said docking port outlet opening for gas (404) and said chamber inlet opening for gas (312); and thereby enabling transfer of gas from the interior (306) of said modular incubator chamber (300) to said docking port (402) of said docking station (400) via said chamber outlet opening for gas (314) and said docking port inlet opening for gas (406).
41. A modular incubator system (500) according to claim 40, wherein in respect of one or more of said one or more modular incubator chambers (300), and in respect of one or more of said one or more docking ports (402) of said docking station 400, the position of said chamber inlet opening for gas (312) of said housing (302) of said modular incubator chamber (300) and the position of said docking port outlet opening for gas (404) of said docking port (402) are adapted to each other in such a way that once docking said modular incubator chamber (300) in said docking port (402), said chamber inlet opening for gas (312) of said housing (302) of said modular incubator chamber (300) and said docking port outlet opening for gas (404) of said docking port (402) will be in fluid connection, thereby enabling transfer of gas from said docking port (402) to said modular incubator chamber (300); and wherein the position of said chamber outlet opening for gas (314) of said housing (302) of said modular incubator chamber (300) and the position of said docking port inlet opening for gas (406) of said docking port (402) are adapted to each other in such a way that once docking said modular incubator chamber (300) in said docking port (402), said chamber outlet opening for gas (314) of said housing (302) of said modular incubator chamber (300) and said docking port inlet opening for gas (406) of said docking port (402) will be in fluid connection, thereby enabling transfer of gas from said modular incubator chamber (300) to said docking port (402).
42. A modular incubator system (500) according to any of the claims 40 or 41, wherein said docking port outlet opening for gas (404) of said docking port (402) comprises a valve (4) and wherein said chamber inlet opening for gas (312) of said housing (302) comprises a valve (2); and wherein said chamber outlet opening for gas (314) comprises a valve (2) and wherein said docking port inlet opening for gas (406) of said docking port (402) comprises a valve (4).
43. A modular incubator system (500) according to any of the claims 40 - 42; wherein in respect of one or more of said one or more modular incubator chambers (300), said valve (2) of said chamber inlet opening for gas (312) and said valve (2) of said chamber outlet opening for gas (314) each comprises a valve body (6) having a front end (10), a rear end (12) and a through-going channel (14) therein, and a spring-loaded displaceable valve element (8), wherein said displaceable valve element (8) is being arranged in said through-going channel (14); wherein said displaceable valve element (8) is being configured to be displaceable in said through-going channel (14) of said valve body (6) in such a way, that when not acted upon by an external force, said spring-loaded displaceable valve element (8) is not being displaced in said through-going channel (14) of said valve body (6), thereby making said valve attain a closed configuration blocking passage of gas through said through-going channel (14), and in such a way, that when acted upon by an external force, said spring-loaded displaceable valve element (8) is being displaced in said through-going channel (14) of said valve body (6), thereby making said valve (2) attain an open configuration, allowing passage of gas through said through-going channel (14); and whereinin respect of one or more of said one or more docking ports (402) of said docking station (400), said valve (4) of said docking port outlet opening for gas (404) and said valve (4) of said docking port inlet opening for gas (406) each comprises a valve body (16) having a front end (20), a rear end (22) and a through-going channel (24) therein, and a spring-loaded displaceable valve element (18), wherein said displaceable valve element (18) is being arranged in said through-going channel (24); wherein said displaceable valve element (18) is being configured to be displaceable in said through-going channel (24) of said valve body (16) in such a way, that when not acted upon by an external force, said spring-loaded displaceable valve element (18) is not being displaced in said through-going channel (24) of said valve body (16), thereby making said valve attain a closed configuration blocking passage of gas through said through-going channel (24), and in such a way, that when acted upon by an external force, said spring-loaded displaceable valve element (18) is being displaced in said through-going channel (24) of said valve body (16), thereby making said valve (4) attain an open configuration, allowing passage of gas through said through-going channel (24).
44. A modular incubator system (500) according to any of the claims 40 - 43, wherein in respect of one or more of said one or more docking ports (402) of said docking station (400), and in respect of one or more of said one or more modular incubator chambers (300) said valves (2,4) are having dimensions and geometries in such a way that once docking said modular incubator chamber (300) in said docking port (402) of said docking station (400), said displaceable valve element (8) of said valve (2) and said displaceable valve element (18) of said valve (4) will displace each other into their respective valve bodies (6,16), thereby opening said valves (2,4) of said docking port outlet opening for gas (404) and said chamber inlet opening for gas (312); and thereby opening said valves (2,4) of said chamber outlet opening for gas (314) and said docking port inlet opening for gas (406).
45. A modular incubator system (500) according according to any of the claims 1 - 44, wherein in respect of one or more of said docking ports (402) of said docking station (400) of said modular incubator system (500), preferably in respect of all said docking ports (402), said docking port outlet opening for gas (404) comprises a flow restrictor for restricting the magnitude of flow of gas flowing into said docking port (402).
46. A modular incubator system (500) according to claim 45, wherein said flow restrictor comprises a tube through which the gas is conveyed to said docking port (402), wherein said tube optionally is having a cross-sectional area selected from the ranges of 0.2 - 8 mm2, such as 0.5 - 7 mm2, for example 1 - 6 mm2, such as 2 - 5 mm2 or 3 - 4 mm2; and/or wherein the length of said tube optionally is selected from the ranges of 5 - 30 mm, such as 8 -25 mm, for example 10 - 22 mm, e.g. 15 - 20 mm.
47. A modular incubator system (500) according to any of the claims 40 - 46, wherein said docking station (400) comprises a gas distribution system (204) for supplying gas to and from one or more of said one or more docking ports (402), wherein said gas distribution system (204) comprises a main gas supply line (210) and a main gas return line (212), wherein in respect of one or more of said docking ports (402), said docking port inlet opening for gas (404) is being fluidly connected to said main gas supply line (210), and said docking port outlet opening for gas (406) is being fluidly connected to said main gas return line (212).
48. A modular incubator system (500) according to claim 47 wherein said gas distribution system (204) comprises a number of manifold pairs (214), wherein each manifold pair comprises an inlet manifold (216) and an outlet manifold (218), wherein said inlet manifold (216) is being fluidly connected to said main gas supply line (210) and wherein said outlet manifold (218) is being fluidly connected to said main gas return line (212); wherein each manifold pair (214) is connected to one or more docking ports (402) of said docking station (400) in such a way that in respect of a specific manifold pair (214), and in respect of said one or more docking ports (402) being connected thereto, said docking port outlet opening for gas (404) of said docking port (402) is being fluidly connected to said inlet manifold (216), and said docking port inlet opening for gas (406) of said docking port (402) is being fluidly connected to said outlet manifold (218).
49. A modular incubator system (500) according to claim 47 or 48, wherein said docking station (400) comprises a gas supply system (200), wherein said gas supply system (200) comprises a gas source (202) and said gas distribution system (204), wherein said gas source comprises a supply gas outlet (206) and a return gas inlet (208), wherein said supply gas outlet (206) of said gas source (202) is being fluidly connected to said main gas supply line (210) of said gas distribution system (204), and wherein said return gas inlet (208) of said gas source (202) is being fluidly connected to said main gas return line (212) of said gas distribution system (204).
50. A modular incubator system (500) according to any of the claims 47 - 49, wherein said gas source (202) of said gas supply system (200) comprises a gas mixing box (242) comprising said supply gas outlet (206) and said return gas inlet (208) of said gas source, wherein said main gas supply line (210) of said gas distribution system (204) is being fluidly connected to said supply gas outlet (206), and wherein said main gas return line (212) of said gas distribution system (204) is being fluidly connected to said return gas inlet (208) of said gas source (202), thereby forming a flow loop (244) comprising said gas distribution system (204) and said gas mixing box (242); wherein said flow loop comprises a pump (246) for circulating gas in said loop.
51. A modular incubator system (500) according to claim 50, wherein said pump (246) is being arranged downstream in relation to said main gas return line (212).
52. A modular incubator system (500) according to claim 50 or 51, wherein said flow loop (244) comprises a pump oscillation damper (247), wherein said pump oscillation damper optionally is being arranged immediately downstream in relation to said pump (246).
53. A modular incubator system (500) according to any of the claims 50 - 52, wherein said flow loop (244) comprises a pressure sensor, such as a differential pressure sensor (248) for sensing the pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204), wherein said pressure senor (248) optionally is being arranged immediately upstream in relation to said main gas supply line (210) of said gas distribution system (204).
54. A modular incubator system (500) according to claim 53, wherein said pressure sensor (248) is being a differential pressure sensor, sensing a pressure relative to the pressure of the return gas inlet (208)..
55. A modular incubator system (500) according to any of the claims 50 -54, wherein said flow loop (244) comprises a release valve (249) for enabling pressure relief in said flow loop, wherein said release valve optionally is being arranged immediately downstream in relation to said main gas return line (212) of said gas distribution system (402).
56. A modular incubator system (500) according to any of the claims 50 -55, wherein said gas mixing box (242) comprises an inlet for N2 gas (250); and an inlet for CO2 gas (251), wherein said inlet for N2 gas (250) is fluidly connected to an N2 valve (252) for regulating the inflow of N2, and an N2 mass flow sensor (253) arranged downstream of said N2 valve (252) for sensing the amount of N2 flowing into said gas mixing box (242); and wherein said inlet for CO2 gas (251) is fluidly connected to a CO2 valve (254) for regulating the inflow of CO2, and an CO2 mass flow sensor (255) arranged downstream of said CO2 valve (254) for sensing the amount of CO2 flowing into said gas mixing box (242).
57. A modular incubator system (500) according to any of the claims 50 -56, wherein said flow loop (244) comprises a mass flow sensor (256) arranged at an upstream position in relation to said gas mixing box (242) for sensing the amount of return gas entering said gas mixing box.
58. A modular incubator system (500) according to any of the claims 50 -57, wherein said gas source (202) comprises an O2 sensor (258) for sensing the concentration of O2 exiting said gas distribution system (204); and wherein said gas source (202) comprises a CO2 sensor (260) for sensing the concentration of CO2 exiting said gas distribution system (204), wherein said O2 sensor and/or said CO2 sensor optionally is/are being arranged downstream in relation to said pump (246).
59. A modular incubator system (500) according to any of the claims 50 - 58, wherein said gas source (202) comprises a temperature sensor (262) for sensing the temperature of gas circulating in said flow loop (244), wherein said temperature sensor optionally is being arranged downstream in relation to said pump (246), preferably at a position corresponding to the position of said O2 sensor (258).
60. A modular incubator system (500) according to any of the claims 50 - 59, wherein said gas source (202) comprises a pressure sensor (264) for sensing the absolute pressure in said flow loop (244) wherein said pressure sensor optionally is being arranged downstream in relation to said pump (246), preferably at a position corresponding to the position of said CO2 sensor (260).
61. A modular incubator system (500) according to any of the claims 50 - 60, wherein said flow loop (244) comprises a UV sanitizer (266) for sanitizing gas flowing in said flow loop (244) via electromagnetic radiation in the UV range, wherein said UV sanitizer optionally being arranged immediately downstream in relation to said main gas return line (212).
62. A modular incubator system (500) according to any of the claims 50 - 61, wherein said gas source (202) comprises one or more filters (268), such as HEPA and/or VOCs filters, wherein such a filter is being arranged immediately upstream in relation to said main gas supply line (210), and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for N2 gas (250) into said gas mixing box (242); and/or wherein such a filter is being arranged immediately upstream in relation to the inlet for CO2 gas (251) into said gas mixing box (242).
63. A modular incubator system (500) according to any of the claims 50 - 62, wherein said gas source (202) comprises a gas mixing control system (270), wherein said gas mixing control system is electrically connected to one or more of the following sensors for receiving sensing signals therefrom: said N2 mass flow sensor (253) for sensing the amount of N2 flowing into said gas mixing box; said CO2 mass flow sensor (255) for sensing the amount of CO2 flowing into said gas mixing box; said mass flow sensor (256) for sensing the amount of return gas entering said gas mixing box; said O2 sensor (258) for sensing the concentration of O2 exiting said main gas return line (212) of said gas distribution system (204); said CO2 sensor (260) for sensing the concentration of CO2 exiting said main gas return line (212) of said gas distribution system (204); said temperature sensor (262) for sensing the temperature circulating in said flow loop (244); said pressure sensor (264) for sensing an absolute pressure in said flow loop (244), said pressure sensor (248) for sensing the pressure of gas supplied to said gas main gas supply line (210) of said distribution system (204).
64. A modular incubator system (500) according to claim 63, wherein said gas mixing control system (270) is electrically connected to one or more of the following elements for control thereof: said N2 valve (252) for regulating the inflow of N2 into said gas mixing box (242); said CO2 valve (254) for regulating the inflow of CO2 to said gas mixing box (242); said pump (246) for circulating gas in said flow loop (244); said release valve (249).
65. A modular incubator system (500) according to claim 63 or 64, wherein said gas mixing control system (270) is being configured to receive input from said pressure sensor (248) and on the basis thereof control said pump (246), optionally also to activate said release valve (249) in order to maintain a desired and predetermined pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204).
66. A modular incubator system (500) according to any of the claims 63 - 65, wherein said gas mixing control system (270) is being configured to receive input from said mass flow sensor (256), and on the basis on said input to determine the total amount of CO2 gas and N2 gas needed to be supplied via said inlet for CO2 gas (251) and via said inlet for N2 gas (250) according to desired and predetermined criteria.
67. A modular incubator system (500) according to any of the claims 63 - 66, wherein said gas mixing control system (270) is being configured to receive input from said CO2 sensor (260) and said O2 sensor (258), and on the basis of the CO2 concentration sensed, is configured to control said CO2 valve (254), by transmitting a control signal thereto, and thereby regulating the inflow of CO2 gas in order to reach a desired and predetermined CO2 concentration, and wherein subsequently, said gas mixing control system (270) on the basis of the O2 concentration sensed, is configured to control said N2 valve (252), by transmitting a control signal thereto, and thereby regulating the inflow of N2 gas in order to reach a desired and predetermined O2 concentration.
68. A modular incubator system (500) according to any of the claims 63 - 67, wherein said gas mixing control system (270) is configured to use the input from said temperature sensor (262) for compensating the temperature sensitivity of said O2 sensor (258).
69. A modular incubator system (500) according to any of the claims 63 - 68, wherein said gas mixing control system (270) is configured to use the input from said pressure sensor (264) for compensating the pressure sensitivity of said CO2 sensor (260).
70. A modular incubator system (500) according to any of the claims 63 - 69, wherein said gas mixing control system (270) is being configured to maintain a pressure of gas supplied to said main gas supply line (210) of said gas distribution system (204), relative to the ambient atmospheric pressure, of 3 - 20 mbar, such as 5 - 18 mbar, such as 10 - 15 mbar above that ambient atmospheric pressure.
71. A modular incubator system (500) according to any of the claims 63 - 70, wherein said gas mixing control system (270) is being configured to maintain a CO2 concentration of gas entering said main gas supply line (210) of said gas distribution system (204) in the range of 5 - 10 %, such as 6 - 9 % or 7 - 8 %; and/or an O2 concentration of gas entering said main gas supply line 210 of said gas distribution system 204 in the range of 5 - 10%, such as 6 - 9 % or 7 - 8 %.
72. A modular incubator system (500) according to any of the preceding claims, wherein the number of modular incubator chambers (300) of said modular incubator system (500) is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
73. A modular incubator system (500) according to any of the preceding claims, wherein the number of docking ports (402) in said docking station (400) of said modular incubator system 500 is selected from the ranges 1 - 100, such as 2 - 95, for example 5 - 90, e.g. 10 - 85, such as 15 - 80, for example 20 - 75, e.g. 25 - 70, 30 - 65, such as 35 - 60, e.g. 40 - 55 or 45 - 50.
74. A modular incubator system (500) according to any of the preceding claims, wherein said docking station (400) comprises said docking ports (402) in an arrangement of one or more shelves of adjacently positioned docking ports (402), wherein in case said docking station comprises two or more shelves, said shelves are being arranged above each other.
75. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said one or more modular incubator chambers (300), said modular incubator chamber comprises an incubation chamber engagement means (326) and wherein in respect of one or more docking ports (402) of said docking station (400), said docking port comprises a docking port engagement means (414), wherein said incubation chamber engagement means (326) is being configured to enter into engagement with said docking port engagement means (414) so as to provide easy and proper positioning and optionally also fixing said modular incubator chamber( 300) in said docking port (402), as well as detaching said modular incubator chamber (300) from said docking port (402) of said docking station (400).
76. A modular incubator system (500) according to any of the preceding claims, wherein said modular incubator system (500) comprises an image processing unit (660) for image processing of images captured by said image capturing device (408), wherein said modular incubator system (400) furthermore comprises a data storage (658) for storing images captured by said image capturing units (408) and/or for storing images processed by said image processing unit.
77. A modular incubator system (500) according to claim (124), wherein one or more of said image capturing devices (408) of said docking ports (402) of said docking station is/are being coupled to said image processing unit (660).
78. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more specific docking ports (402) of said docking station (400), said specific docking port comprises its own dedicated image capturing device (408) which is configured to only capture images relating to a modular incubator chamber (300) which is being docked in said specific docking port (402).
79. A modular incubator system (500) according to any of the preceding claims, wherein in respect of a number N of adjacently arranged docking ports (402) of said docking station (400), said adjacently arranged docking ports (402) share a common image capturing device (408) in the sense that one and only one image capturing device is responsible for capturing images relating to a modular incubator chamber (300) which is being docked in one of said N adjacently arranged docking ports (402) s wherein said docking station comprises a displacement device (482) for enabling displacement of said common image capturing device (408) in relation to said N adjacently arranged docking ports (402) of said docking station (400), such as being provided with an electric signal thereto.
80. A modular incubator system (500) according to claim 74, wherein said number N is being an integer selected in the ranges of 2 - 25 or more, such as 4 - 22, for example 6 - 20, such as 8 - 18, such as 10 - 16 or 12 - 14.
81. A modular incubator system (500) according to any of the preceding claims, wherein in respect of one or more of said modular incubator chambers (300), said modular incubator chamber comprises in its interior (306) an electric heating element (318) for heating the interior of said modular incubator chamber, and wherein said modular incubator chamber comprises a power source (320) for providing power to said heating element (318), wherein said electric heating element (318) is being electrically connected to said power source (320).
82. A modular incubator system (500) according to claim 81, wherein said power source (320) is being an electric power source, such as a battery, for example a rechargeable battery.
83. A modular incubator system (500) according to any of the claims 81 or 82, wherein said heating element (318) is being thermally connected to a heat distribution element for distributing heat dissipated in said heating element; wherein said heat distribution element is being arranged, at least partly, in the interior (306) of said modular incubator chamber (300).
84. A modular incubator system (500) according to any of the claims 81 - 83, wherein said chamber comprises a thermostat (374) and an electric thermostatic circuit (376), wherein said electric heating element (318), said power source (320) and said thermostat (374) are being electrically connected in said electric thermostatic circuit (376) so as to enable thermostatic control of the temperature inside said modular incubator chamber (300).
85. A modular incubator system (500) according to any of the preceding claims, wherein said modular incubator system (500) comprises a control unit (650) for controlling the operation of said modular incubator system (500).
86. A modular incubator system (500) according to claim 85, wherein said control unit (650) is being coupled to an input device (652), such as an alphanumerical input device for allowing a user to provide settings input relating to a desired operational protocol of said modular incubator system.
87. A modular incubator system (500) according to claim 85 or 86, wherein said control unit (650) is being coupled to a display unit (654) for displaying, to a user, information relating to settings and/or operational status of said modular incubator system (300).
88. A modular incubator system (500) according to any of the claims 85 - 87, wherein in respect of one or more docking ports (402) of said docking station (400) said control unit (650) is being configured for independently controlling one or more of the following: temperature in the interior (306) of said modular incubator chamber (300) by controlling said electric heating element (318), said thermostat (374) or said thermostatic circuit (376), providing power to said electric power source (320); providing signals to said display (324) a modular incubator chamber (300), said inclination angle adjustment element (332), said rotational adjustment element (334) of said inclination angle adjustment element (332), said displacement adjustment element (336) of said inclination angle adjustment element (332), switching on and off of said active light source (352), or adjusting light intensity emitted therefrom, said image capturing device (408) of a docking station (408), said displacement device (482) for displacing said image capturing device (408), said actuator of said X-stage or XY-stage (466), said actuator of said iris diaphragm (464), said gas mixing control system (270); said image processing unit (660).
89. A modular incubator system (500) according to any of the claims 85 - 88, wherein said control unit (650) is being coupled to a data processing unit (656) and optionally also to a data storage (658) for aiding in handling information during controlling of said modular incubator system.
90. A modular incubator system (500) according to any of the claims 85 - 89, wherein said control unit (650) is being configured for conducting automatic operation of said modular incubator system (500) by configuring said control unit (650) to independently control one or more of the following: temperature in the interior (306) of said modular incubator chamber (300) by controlling said electric heating element (318), said thermostat (374) or said thermostatic circuit (376), providing power to said electric power source (320); providing signals to said display (324) a modular incubator chamber (300), said inclination angle adjustment element (332), said rotational adjustment element (334) of said inclination angle adjustment element (332), said displacement adjustment element (336) of said inclination angle adjustment element (332), switching on and off of said active light source (352), or adjusting light intensity emitted therefrom, said image capturing device (408) of a docking station (408), said displacement device (482) for displacing said image capturing device (408), said actuator of said X-stage or XY-stage (466), said actuator of said iris diaphragm (464), said gas mixing control system (270); said image processing unit (660).
91. A modular incubator system (500) according to any of the claims 85 - 90, wherein said control unit (650) is being configured for enabling time lapse capturing of images by said image capturing devices (408).
92. A modular incubator chamber (300), wherein said modular incubator chamber (300) is comprising features as defined in respect of the modular incubator chamber (300) of the modular incubator system (500) according to any of the claims 1 - 91.
93. A docking station (400), wherein said docking station is comprising features as defined in respect of the docking station of the modular incubator system (500) according to any of the claims 1 - 91.
94. Use of a modular incubator system (500) according to any of the claims 1 - 91 for incubating a viable biological material M.
95. Use of a modular incubator chamber (300) according to claim 92 for incubating a viable biological material M.
96. Use of a docking station (400) according to claim 93 for incubating a viable biological material M.
97. Use according to any of the claims 94, 95 or 96, wherein said biological material M is being an oocyte or an embryo, such as a human oocyte or a human embryo.
98. A method of incubating a viable biological material M, wherein said method comprises: i) providing a modular incubator system (500) according to any of the claims 1 - 91; ii) providing a viable biological material M; iii) arranging said viable biological material M in a culture dish (310) and subsequently arranging said culture dish on the culture dish support (308) in the interior (306) of said modular incubator chamber (300) of said modular incubator system (400); iv) docking said modular incubator chamber (300) in a docking port (402) of said docking station (400) of said incubator system (500); v) allowing said viable biological material M to be incubated in said modular incubator chamber (300); vi) while performing step v) enabling said light directing element (350) of said modular incubator chamber (300) to direct light to an area of said culture dish support (308) in said light aiming direction (A); vii) while performing step v) and vi) making said image capturing device (408) capture image(s) of said viable biological material M in the interior (306) of said modular incubator chamber (300), at a focus direction (B); wherein said focus direction (A) of light propagating from said light directing element (350) of said modular incubator chamber (300) is being inclined relative to said focus direction (B) of said image capturing device (408) of said docking port (302) at an inclination angle a which is 0°.
99. A method according to claim 98 further comprising the step of: viii) removing said incubator chamber (300) from said docking port (402) of said docking station (400), when desired, in order to manually inspect the viable biological material M, and optionally also to remove, add or exchange growth medium/media in said culture dish (310).
PCT/EP2023/067017 2022-11-07 2023-06-22 A modular incubator system providing improved illumination for image capture of an incubated biological material WO2024099600A1 (en)

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KR100813915B1 (en) * 2006-10-31 2008-03-18 전자부품연구원 Cell culture detection apparatus
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Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE20011308U1 (en) * 2000-06-27 2000-11-23 Hoelzel Christian Plug-in coupling for liquid and gaseous media
US20100316446A1 (en) * 2005-01-04 2010-12-16 Larry Runyon Method and system for bioreaction
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