WO2020084324A1 - Environment sensor for mammalian ivf incubator - Google Patents

Environment sensor for mammalian ivf incubator Download PDF

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Publication number
WO2020084324A1
WO2020084324A1 PCT/IB2018/001461 IB2018001461W WO2020084324A1 WO 2020084324 A1 WO2020084324 A1 WO 2020084324A1 IB 2018001461 W IB2018001461 W IB 2018001461W WO 2020084324 A1 WO2020084324 A1 WO 2020084324A1
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WO
WIPO (PCT)
Prior art keywords
sensor
mammalian
incubator
ivf
sensor body
Prior art date
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PCT/IB2018/001461
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French (fr)
Original Assignee
Montanari, Bernard
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Publication date
Application filed by Montanari, Bernard filed Critical Montanari, Bernard
Priority to PCT/IB2018/001461 priority Critical patent/WO2020084324A1/en
Publication of WO2020084324A1 publication Critical patent/WO2020084324A1/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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • 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
    • C12M41/48Automatic or computerized control

Definitions

  • the present invention relates to the general field of environment sensors, when used in, and applied to mammalian in vitro fertilization (TVF) incubators.
  • Mammalian IVF incubators generally provide a controlled and monitored development environment in which mammalian embryos, for example, human embryos, are developed to a developmental stage where they can be implanted in the uterus of a corresponding female host mammal.
  • One of the main functions of an IVF incubator of this kind is to maintain an appropriate temperature for gamete function and embryo development. Any variations in temperature in such incubators can impact a number of aspects of gamete and embiyo function, including meiotic spindle stability and embryo metabolism. Maintaining an accurate temperature, whilst being able to also accurately measure said temperature inside the incubator is a desirable objective in order to reduce environmental stress on the cells being incubated.
  • IVF incubators Temperature is generally maintained and controlled within IVF incubators using a heating system.
  • Most box-type IVF incubators generally use either a water jacket system or an air jacket system, in which air is warmed in die incubator chamber, with an optional ventilation system, such as a fan, to circulate air within the chamber.
  • the chamber In benchtop, desktop, or top-loading IVF incubators, the chamber is warmed, for example, with heating elements either directly in contact with, or integrated into, the walls of the chamber.
  • at least some of the chamber walls, e.g. top, bottom, and sides might be In direct heat transfer contact with a culture dish and the enclosed medium contained therein.
  • Each type of incubator warming system identified above has advantages and disadvantages, for example, water-jacketed incubators retain heat for a longer period of time when the incubator door is opened, or a power failure occurs.
  • the downside of these units is that they tend to be heavy and consume greater amounts of energy to power die incubator. Furthermore, there is always the concern that the incubator, and/or incubator chamber, might become contaminated due to the presence of the water jacket.
  • aii>jacketed incubators warm up quickly, but unfortunately do not retain heat for long periods.
  • Another advantage of air-jacketed units is that they also enable heat-sterilization decontamination cycles to be carried out, which are unavailable for water-jacketed systems.
  • such TVF incubators also often Include at least one environment sensor, such as a temperature sensor, or a gas sensor, as these can be used to determine whether any fluctuations in environment conditions within the chamber are occurring and alert the user to the risk or presence thereof.
  • environment sensors In desktop, benchtop and top-loading GUT incubators, the environment sensors are generally integrated into the walls, bottom or lid of the culture chamber, however these sensors suffer from a lack of precision, as they can not be placed at a location sufficiently close to the culture dish, and therefore are also affected by any temperature gradients within the culture chamber.
  • some environment sensors are rod-shaped, and electrically connected via wiring to a data recorder located outside the incubator.
  • rod-shaped environment sensors similarly to the chamber wall integrated sensors, they can not be positioned at a location sufficiently close to the culture dish, due to the spatial limitations and constraints of die culture chambers, and additionally, when intmdum] into the culture chambers, occupy a significant volume within the culture chamber that necessarily reduces the available working volume into which culture dishes can be introduced, thereby reducing the operational output of the incubator unit as a whole.
  • one object of the present invention is a sensor far a mammalian in-vitro fertilisation (IVF) incubator system comprising at least one or more incubator chambers, die sensor comprising : a sensor body, configured and dimensioned to be housed within an incubator chamber of the mammalian in-vitro fertilisation incubator system ; at least one or more sensor systems, configured and adapted to sense at least one or more changes in an internal environment space within the incubator chamber of the mammalian in ⁇ vitro fertilisation incubator system ; wherein the at least one or more sensor systems are located on, or within, said sensor body ; wherein said sensor body is removably located within said incubator chamber ⁇ ; and wherein said removable sensor body is configured and dimensioned to cover substantially all of a bottom surface area of said incubator chamber when placed inside, and at a bottom, of said chamber.
  • IVF mammalian in-vitro fertilisation
  • a mammalian in-vitro fertilisation (TVF) incubator system is an incubator device for the culture and development of mammalian embryos to a developmental stage suitable for implantation into a corresponding mammalian uterus - commonly, such embryos are developed to either what is known in the art as die cleavage stage, or alternatively, the blastocyst stage before embryo transfer.
  • the term "mammalian” covers a whole spectrum of potential animals, die invention is particularly suited, and adapted, to human embryo culture, which is the preferred mammalian cell choice, although to die extent that other mammalian embryo cells could be, or are cultured, under similar circumstances, these are also included in the present definition.
  • the IVF incubator system comprises one or more incubator chambers, also known as culture chambers, in which culture recipients, which are generally dish-like or dish-shaped recipients, for example Petri dishes, or plate-shaped or plate-like recipients, such as a slide plate, or culture plates equipped with one or more culture wells, for example, 4 or 8 wells or multiples thereof, are introduced and which contain die embiyos to be cultured in a culture medium, as is known in the art.
  • the culture chambers generally tend to have a generally box-shaped configuration, with a bottom, side-walls and a top defining a volume to contain the controlled development and culture environment.
  • Traditional box-type or chest incubators tend to resemble refrigerators or autoclaves, with shelves and trays for holding and separating die dish recipients.
  • the incubator chambers are not generally subdivided into individual smaller inoAator volumes.
  • Typical box-type or chest-type incubators are well known per se, for example, the FormaTM range as sold by the company Fisher Scientific, USA, and in particular die“3110 Single 184L incubator” model.
  • Desktop, benchtop or top-loading incubators on the other hand are designed to allow grouping of sets of dish recipients containing the cells to be cultured, with each group of dishes generally being contained within a relatively small volume individual culture or incubator chamber, die incubator generally comprising more than one such chamber.
  • Each individual chamber is often comprised of a bottom wall and a series of connected lateral walls, with an individually hinged c!osable lid, which sits on an upper lip or projecting flange of each chamber.
  • Such systems are well known per se, for example, die K- SystemsTM range as sold by the company Origio, France, under the models“G185 Long Term Flat Bed Incubator” and the "G210 InviCell Long Term Incubator”.
  • the sensor as used with reference to the present specification description, claims and drawings, is capable of detecting changes or fluctuations in the environment conditions within the culture diamber or incubator chamber of the IVF incubator, and thus is also correspondingly configured and dimensioned for this role and functionality. Accordingly, and as used herein in the present specification, description, claims and with regard to the drawings, the expression“sensor” and “environment sensor” are interchangeable.
  • the sensor comprises a sensor body, configured and dimensioned to be housed within the incubator chamber of the mammalian TVF incubator System.
  • the sensor body is preferably and advantageously removably located within the incubator chamber or culture chamber, meaning that it can be introduced, or placed, into the incubator chamber as required, and subsequently removed therefrom when no longer required, such as for example, for maintenance, sterilisation or cleaning operations of the incubator
  • the term“removable” as used herein means that the sensor body is a freestanding object.
  • the incubator chamber generally comprises a bottom or lower wall, forming a closed, bottom surface of the chamber, with side walls extending upwards from the bottom forming an upper opening, and a top wall that cavers the upper opening, whereby the top wall is advantageously a hinged lid that facilitates easy opening and closing of the lid.
  • the removable sensor body is configured and dimensioned to cover substantially all of the bottom surface area of the incubator chamber when placed inside, and at the bottom, of said chamber:
  • the sensor further comprises at least one or more sensor systems.
  • the term “sensor system” refers to an assembly of electrical and/or microelectronic components, combined together to function as a sensor, whereby the sensor system is configured and adapted to sense at least one or more changes in the internal environment space within the incubator chamber of the mammalian in- vitro fertilisation incubator system.
  • the internal environment space is the useful working inner volume of die incubator changer when the lid of the incubator chamber is closed.
  • the at least one or more sensor system is selected from a temperature sensor, a carbon dioxide sensor, an oxygen sensor, a humidity sensor, a volatile organic compounds (VOC) sensor, and combinations thereof.
  • the at least one or more sensor system Is a temperature sensor.
  • the at least one or more sensor system is a temperature sensor selected from a thermocouple temperature sensor, a thermoconducting temperature sensor, and a thermistor.
  • the at least one or more temperature sensor comprises at least two distinct, spaced apart, temperature detection sites.
  • the at least one or more temperature sensor comprises at least four distinct, spaced apart, temperature detection sites.
  • the at least one or more sensor systems are located on, or within, said sensor body, for example, housed within said sensor body, or odierwise attached or affixed to an outer surface of the sensor body.
  • the sensor body comprises a first wall, a second wall located in parallel and spaced apart relationship to said first wall, and at least one side wall extending between said first wall and said second wall, and connecting said first wall to said second wall.
  • the first and second wall generally form a top and bottom of the sensor body, whilst die side wall or walls form the sides of the sensor body.
  • the sensor body optionally and advantageously further comprises one or more openings or orifices, whereby die openings can be located in any of the side wall or side walls, and/or on die top or bottom walls.
  • the openings or orifices in the sensor body preferably traverse an outside surface of said sensor body, and are orifice is configured to allow fluid exchange between an environment space of die incubation chamber and an interior space of said sensor body.
  • fluid exchange in this context, it is to be generally understood that die inventors are referring to gaseous exchange, rather than liquid exchange, for example, where the gaseous fluids can be water vapour, carbon dioxide, or other gases dial are commonly used in incubator chambers such as oxygen and nitrogen.
  • the sensor body advantageously comprises corresponding orifices or openings In both top and bottom wall surfaces, be they in different locations on each surface or In superposed locations, it is possible for the sensor body to allow for fluid flow, from for example, the top of the sensor body to the bottom of the sensor body and vice-versa, thereby allowing for complete circulation of toe environment fluids between the bottom surface of toe Incubator chamber and toe volume or incubator region above toe sensor body within the incubator chamber.
  • Such improved circulation enables a more accurate reading in any changes to the environment to be determined by toe at least one or more sensor systems.
  • the sensor body has a width and a length which are both substantially greater than a height of said sensor body.
  • these terms have their usual meaning, in other words, the sensor body is thinner than it is either long or wide.
  • toe sensor body has a height which is between about 1/45 and 1/84 of the width of said sensor body.
  • the sensor body has a height which is between about 1/60 aid about 1/92 of toe length of said sensor body.
  • toe sensor body is comprised of thermally conducting material.
  • the sensor body is comprised of a metal selected from stainless steel, aluminium, copper, a galvanized or plated metal, and combinations thereof.
  • toe sensor body is a substantially hollow body.
  • substantially hollow body it is to be understood that die sensor body top, bottom and side walls together form a hollowed out sensor body, and defining an inner volume. Where openings or orifices are also present in the top, bottom or side wails, the inner volume of the sensor body communicates with the environment of the incubator chamber.
  • the sensor body is substantially plate-like. A plate-like sensor body allows for easy introduction and removal of the sensor into the incubator chamber, and furthermore occupies a relatively small volume within die chamber.
  • the sensor body is substantially disc-like.
  • a disc-like sensor body is advantageously chosen when die incubation chamber as defined by the bottom and side walls Is not rectangular or square, but for example, polygonal such as octagonal, or substantially circular, or the like.
  • the at least one or more sensor system is attached to an outside surface of the sensor body. This is an advantageous configuration because the sensor system thus lies in close proximity to, and more advantageously under, any recipient dish that is positioned or located over the top of the sensor body.
  • the at least one or more sensor system Is attached to a groove located in the outside surface of said sensor body. Additionally, and advantageously, the at least one or more sensor system lies flush with the outside surface of said sensor body when attached to the groove provided in the outside surface of said sensor body.
  • the recipient dishes are also provided with a raised edge that projects from the bottom of the dish, which not only lifts the bottom of the dish off and away from the surface on which the dish rests, thereby increasing air circulation between die dish and its surroundings, but also die projecting edge mates with, and self-locates in, a corresponding groove having substantially the same circumference and width as those of the projecting edge of the dish, to help retain the dish on a support plate in which the grooves have been provided.
  • die support plate with locating grooves Is generally positioned over the sensor body.
  • the support plate Is generally only a few millimetres in height, for example from between 1 mm to 2 mm thick, so as not to compromise the space required for die recipient dishes.
  • die support plate and sensor body are one and the same, i.e. the sensor body also integrates the functionality of the support plate, providing direct support for the recipient dishes.
  • This has the added advantage of making yet more usable Inner volume available within the culture chamber.
  • the at least one or more sensor system comprises a sensor system body, having a first sensTM ⁇ system extremity located at a first side wall of the sensor body, and a second sensor system extremity located distant from said first side wall, wherein the sensor system body is connected to both the first sensor system extremity and the second sensor system extremity.
  • the at least one or more sensor system extends from a first side wall in the direction of an opposing side wall.
  • the second sensor system extremity is located at a terminal position on the sensor body, said terminal position being configured to correspond to the superposed position of an Incubator recipient dish located above said terminal position when said sensor body is located within the incubator chamber.
  • the at least one or more sensor system comprises a first and second sensor system, die first and second sensor systems being identical or different.
  • the at least one or more sensor system comprises a first and second sensor system, the first and second sensor system being located substantially in parallel to each other on an outside surface of the sensor body.
  • the at least one or more sensor system comprises a first and second temperature sensor, and each temperature sensor comprises two distinct, spaced apart, temperature detection sites.
  • die at least one sensor system is electrically connected to an electrical connection port housed within the sensor body and configured to receive a flat wire or ribbon electrical connector.
  • the flat wire or ribbon electrical connector is connected to a data recorder.
  • the data recorder is wirelessly connected to a wireless network router.
  • the data recorder and the wireless network router communicate with each other via a wireless radiofrequency preferably of 433 MHz.
  • the wireless network router further comprises a Bluetooth wireless communications circuit.
  • the wireless network router further communicates with a sensor controller system via the Bluetooth wireless communications circuit
  • the sensor controller system is a Bluetooth enabled smartphone or handheld tablet device, and further comprises a software program loaded into a memory of said smartphone or handheld tablet device, and configured to provide control commands to the sensor.
  • the sensor controller system is further configured to display information to a user of the sensor controller system via an interactive graphical user interface of said sensor controller system, said information being transmitted by the data recorder via the network router to said sensor controller system.
  • Figure 1 A is a schematic perspective view of a desktop or benchtop IVF incubator, with a sensor according to the invention located therein;
  • Figure IB is magnified or close-up view of the culture chamber and sensor of Figure 1A;
  • Figure 2 A is a schematic perspective view of a variant of a desktop or benchtop IVF incubator, with a different example of the sensor according to the invention located therein;
  • Figure 2B is magnified or close-up view of die culture chamber and sensor of Figure 2A;
  • Figure 3 is a schematic cross-sectional view of the desktop incubator of Figure LA showing an incubator chamber with a sensor according to the invention located therein, along with recipient culture dishes placed above the sensor on a support plate;
  • Figures 4A and 4B are schematic two dimensional representations of a top and longitudinal cross-section of a first embodiment of the sensor according to die present invention
  • Figures 5A and 5B are schematic two dimensional representations of a top and longitudinal cross-section of a second embodiment of the sensor according to die present invention.
  • Figure 6 is a schematic block diagram of a surveillance and control system for an IVF incubator including one or more sensors according to die invention.
  • FIG. 1 A is a schematic perspective illustration of a typical benchtop or desktop human embiyo IVF incubator indicated generally by reference numeral (1), with Figure IB representing a magnified, or zoomed-in view of the culture chamber area containing a sensor according to the invention.
  • the IVF incubator (1) is provided with eight culture chambers (2).
  • Each culture chamber (2) has a generally box-shaped configuration, with a bottom (3), side-walls (4, 5, 6, 7) and a top (8) defining a volume to contain the controlled development and culture environment.
  • die top (8) is a hinged lid (8), with the hinge (9, Fig.
  • the culture chamber (2) is typically comprised of a heat conductive material, for example, stainless steel.
  • a sensor according to die invention is placed inside and at the bottom (3) of the culture chamber (2).
  • the sensor (11) is adapted in size and configured to occupy substantially all of the available surface area of the bottom of the culture chamber (2).
  • the sensor (11) is removably located within the chamber, given that it can be removed as easily as h can be Introduced, for example, for purposes of maintenance, or for example, when die sensor is no longer required.
  • the sensor (11) comprises a sensor body (12), which comprises a first wall (13), a second wall
  • the first and second walls (13, 14) form a top and bottom of the senses ⁇ body (12), whilst the side wall (15) or walls form the sides of the sensor body (12).
  • the sensor body (12) further comprises one or more openings or orifices (16), whereby the openings can be located in any of the side wall
  • the openings or orifices (16) in die sensor body (12) preferably traverse an outside surface of said sensor body (12), and are configured to allow fluid exchange between an environment space (17, Fig; 3) of the incubation chamber (2) and an interior space (18, Fig.4B, 5B) of said sensor body (12), but also optionally to enable operation of any other sensors that are built into the incubator (1) to operate.
  • fluid exchange refers to gaseous exchange, rather than liquid exchange, for example, where the gaseous fluids can be water vapour, carbon dioxide, or other gases that are commonly used In incubator chambers such as oxygen and nitrogen.
  • the sensor body (12) can allow fra: fluid to flow, from for example, the top of the sensor body to the bottom of the sensor body and vice-versa, thereby allowing for complete circulation of the environment fluids between the bottom surface (3) of the incubator chamber (2) and the environment space (17, Fig. 3) above die sensor body (12) within the incubator chamber (2).
  • Such improved circulation enables a more accurate reading in any changes to the environment to be determined by the at least one or more sensor systems provided In the sensor (11), as will be described herein.
  • the sensor body (12) has a width and a length which are both substantially greater than a corresponding height of said sensor body (12). In other words, the sensor body (12) Is significantly thinner than it is either long or wide.
  • the advantage of such a sensor body configuration is that it becomes possible to place the sensor (11) at the bottom of the incubator chamber (2) without sacrificing the number of recipient dishes (25) that can be incubated at the same time in the incubation chamber (2). Indeed, this sensor body configuration completely obviates the problem encountered with traditionally used cylindrical-shaped or pen-shaped sensors, which occupy a far greater volume in the Incubation chamber and reduce the number of possible culture recipients (25) that can be introduced into die incubator. Indeed, the problem with current sensors is such dial it is common to see a complete culture chamber dedicated to receiving a sensor, precluding any use of that culture chamber for anything related to actually culturing embiyos.
  • said sensor body (12) preferably has a height which is between about 1/45 and 1/84 of the width of said sensor body. In another preferred embodiment, the sensor body has a height which is between about 1/60 and about 1/92 of the length of said sensor body. Exemplary dimensions of suitable sensor bodies for sensors according to the present invention are provided in the following table:
  • the sensor body (12) is generally comprised of a thermally conducting material.
  • the sensor body is made of a metal selected from stainless steel, aluminium, copper, a galvanized or plated metal, and combinations thereof, wherein aluminium and/or stainless steel sensor bodies have been found to be particularly advantageous, due for example, to the ease with which they can be maintained, cleaned, sterilized, and the like, and due to their resistance to the environment in which they are placed.
  • the sensor body (12) has substantially plate-like shape.
  • a plate-like shaped sensor body (12) allows for easy introduction and removal of the sensor (11) into the incubator chamber (2), and furthermore occupies a relatively small volume within the chamber, thereby not impeding placement of culture recipients and enabling the maximum volume of the culture chamber to be used to the greatest of effect
  • the sensor body (12) can also be substantially disc-like.
  • a disc-like sensor body (12) is advantageous when the incubation chamber (2) as defined by the bottom (3) and side walls (4, 5, 6, 7) Is not rectangular or square, but for example, polygonal such as octagonal, or substantially circular, elliptical or die like.
  • Hie sensor (11) further comprises at least one or more sensor systems (19, Fig. 3) In and/or on the sensor body (12), configured and adapted to sense at least one or more changes in the internal environment space (17) within the incubator chamber (2) of the IVF incubator.
  • the at least me or more sensor systems are located on, or within, die sensor body (12) as will be described herein.
  • the sensor system as indicated generally by the reference numeral (19) is for example, a temperature sensor, and is located on an outside surface of the wall (13) of the sensor body (12).
  • the sensor system (19) is located in a groove provided in the outside surface of wall (13) whereby the groove is configured with at least one opening to permit fluid communication with an inner volume (18, Figs.4B, 5B) of the sensor body (12).
  • the sensor system (19) lies flush with die outside surface of the wall (13) of the sensor body (12) when attached to the groove, presenting an overall smooth surface contiguous with the surface of the wall (13).
  • the sensor system is affixed in the groove, for example, by the use of a suitable glue or adhesive, welding or a snap-fit or press-fit configuration that is adapted to the environment into which the sensor body is to be placed, and chosen to avoid or minimize die risk of separation or detachment of the sensor system (19) from the sensor body (12) under conditions of use.
  • the sensor system (19) comprises a generally strip shaped or filamentous body (20) of electrically conducting material, for example an electrically conducting strip, or ribbon, which extends from a first extremity (23) of a first side wall (15) of the sensor body (12) towards an opposing side wall (15) of said sensor body (12) and a corresponding second extremity (24) of said filamentous body (20).
  • the electrically conducting strip body (20) does not extend from the first extremity (23) the whole length of the sensor body (12) to terminate at a second extremity (24) located opposite-facing side wall (15).
  • the electrically conducting strip body (20) terminates at the second extremity (24) only part way along the length of the sensor body (12), generally more than half the length, and preferably, more than 2/3 of the length of the sensor body.
  • the electrically conducting strip body (20) terminates at a point along the length of the sensor body which substantially corresponds to a superimposed position of a corresponding culture recipient placed over the top thereof in the culture chamber.
  • the sensor system (19) comprises at least one or more sensor circuits, preferably at least two sensor circuits (21, 22), located at spaced apart positions along the strip-shaped or filamentous body (20).
  • the sensor circuits (21, 22) project and extend away from the strip-shaped or filamentous member inwards into the inner volume (18) of the sensor body (12). In this configuration, the sensor circuits (21, 22) are protected from potentially damaging outside contact, friction, interference and the like, and yet still in direct contact with the inner volume (18) of the sensor body (12), which is in fluid communication with the environment volume (17) of tire culture chamber (2).
  • the first and second sensor circuits are positioned along the stripshaped or filamentous body (20) so that their positions correspond, as closely as possible, to the location of a superimposed culture chamber placed above the sensor body (12).
  • Figure 2A is a schematic perspective illustration of another typical benchtop or desktop human embryo IVF incubator indicated generally by reference numeral (1), with Figure 2B representing a magnified, or zoomed-in view of the culture chamber area containing another example of a sensor (11) according to die invention.
  • the IVF incubator (1) is provided with four culture chambers (2) instead of eight culture chambers as in Figure 1A.
  • the sensor (11) in Figures 2A and 2B is substantially square in shape, in comparison to die sensor illustrated in Figures 1A and IB, in which the sensor (11) is substantially rectangular in shape.
  • Figure 4A is a schematic two-dimensional representation of the top wall (13) of a sensor body (12) of a sensor (11) according to the invention, showing a single sensor system (19) comprising an electrically conducting strip body (20) and two sensor circuits (21 , 22), which are preferably temperature sensor circuits.
  • An opening or orifice (16) is provided in the top wall (13) of the sensor body (12) to permit fluid communication with the environment of the culture chamber (2) and the inner volume (18) of the sensor body.
  • Figure 4B represents a schematic cross-section of die sensor of Figure 4A along the lineA-A.
  • Figure 5A is a schematic two-dimensional representation of die top wall (13) of a sensor body (12) of a sensor (11) according to the invention, showing a dual sensor system (19, 19A) comprising two electrically conducting strip bodies (20, 20A) and two sensor circuits (21, 21A, 22, 22A), which are preferably all temperature sensor circuits.
  • Figure 5B represents a schematic cross-section of the sensor (11) of Figure 5A along die line B-B.
  • Figure 5 illustrates an example of a sensor according to the Invention, in which there are two sensor systems (19, 19A) located on the outer surface of the wall (13), and a noticeable difference in width of the plate-like sensor body (12).
  • the sensor (11) of Figure 5 is thus adapted to a culture chamber (2) with a wider base than that in which the sensor (11) of Figure 4 can fit.
  • Each sensor system (19, 19A) of the sensor in Figure 5 comprises a respective electrically conducting strip (20, 20A) located in a respective groove of the outer surface of wall (13), and each strip having two sensor circuits (21, 21 A, 22, 22A) located at spaced apart positions along their respective strip (20, 20A).
  • each sensor system extends from a first extremity, wherein the first extremities are located at respective opposite-facing side walls (15).
  • each sensor system can have the same sensor circuits (21, 21A, 22, 22A), or a range of different sensor circuits, as desired.
  • all of the sensor circuits are temperature sensors. In such a case, the temperature sensors can be
  • Figures 1, 2 and 3 also illustrate schematically how the sensor (11) is located within the culture with respect to other elements usually present in a culture chamber of the IVF Incubator, hi particular, culture recipients (25A, 25B, 25C, 25D), which are generally dish-like or dish-shaped recipients, for example Petri dishes, or plate-shaped or plate-like recipients, such as a slide plate, or culture plates equipped with one or more culture wells, for example, 4 or 8 wells or multiples thereof, are introduced and generally contain the embryos to be cultured in a culture medium, as is known in the art.
  • the culture recipients (25A, 25B, 25C, 25D) have been placed on top of a support plate (26) having a support surface (27).
  • the culture recipients (25) are often also provided with a raised edge that projects from the bottom of the dish, which not only lifts the bottom of die dish off and away from die support surface (27) on which the dish (25) rests, thereby increasing air circulation between the dish and its surroundings, but also the projecting edge mates with, and self-locates in, a corresponding groove or series of grooves (28) having substantially the same circumference and width as those of the projecting edge of the dish (25), to help retain the dish (25) on the support plate (26) In which the grooves (28) have been provided.
  • the support plate (26) with locating grooves (28) is generally positioned over the sensor body (12).
  • the support plate (26) is generally only a few millimetres in height, for example from between 1 mm to 2 mm thick, so as not to compromise the space required for the recipient dishes (25).
  • the culture recipients can be placed directly on top of the sensor body (12), with die functions of support plate being integrated into the sensor body (12), rendering a separate support plate (26) unnecessary.
  • the at least one sensor system (19, 19A) Is electrically connected to an electrical connection port (29) housed within the sensor body (12) and configured to receive a flat wire or ribbon electrical connector (30).
  • the flat wire electrical connector (30) connects to a data recorder (31), which collects and stores the data collected by the sensor at a predetermined interval
  • a data recorder (31) which collects and stores the data collected by the sensor at a predetermined interval
  • a chamber sensor (11) is connected via an electrical connection port (29, 29A) and flat wire or ribbon electrical connector (30) to a data recorder (31).
  • each incubator has an associated data recorder (31).
  • the data recorder (30) is preferably then wirelessly connected m a wireless network router (32). The arrows at both ends of the connector in the block diagram indicate that communication between the data recorder and die router operates in both directions.
  • the data recorder (31) and the wireless network router (32) communicate data and signals with each other via a wireless radiofrequency of 433 MHz.
  • This frequency is considered to be the most appropriate and least likely to cause deleterious effects with regard to the neighbouring culture chamber of the TVF incubator.
  • the network router is connected to die internet via a suitable telecommunications network, for example via a suitable radiofrequency network, as are cunendy known or under development, or via an alternative rnmnumiratinns system such as a satellite link or copper-wire or optical fibre based physical infrastructure, or combinations thereof.
  • the network router also preferably comprises a
  • Bluetooth communications circuit configured to enable data and signal transfer between the router and a suitably enabled sensor controller system
  • the sensor controller system is a Bluetooth enabled smartphone (33) or handheld tablet device, and further comprises a software program loaded into a memory of the smartphone or handheld tablet device, and configured to provide control commands to the sensor.
  • the sensor controller system is further configured to display information m a user of the sensor controller system via an interactive graphical user interface of said sensor controller system, said information being transmitted by the data recorder (31) via the network router (32) to said sensor controller system on the smartphone or tablet device (33).
  • the smartphone or tablet device is configured to communicate via said suitable telecommunications network with a distributed, or“cloud-based” service application on a cloud network (34), and provide information thereto and receive data, instructions and signals therefrom, in association with the control and surveillance of the sensors.
  • the distributed, or“cloud-based 1 * service application is preferably also accessed, operated and interacted with via an internet browser based application (35), otherwise known as a web application, enabling remote control and surveillance of the sensors to be carried ouL

Abstract

Sensor for a mammalian in-vitro fertilisation (IVF) incubator system comprising at least one or more incubator chambers, the sensor comprising a sensor body, configured and dimensioned to be housed within an incubator chamber of the mammalian in-vitro fertilisation incubator system and at least one or more sensor systems, configured and adapted to sense at least one or more changes in an internal environment space within the incubator chamber of the mammalian in-vitro fertilisation incubator system. The at least one or more sensor systems is located on, or within, the sensor body and the sensor body is removably located within the incubator chamber. Additionally, the removable sensor body is configured and dimensioned to cover substantially all of a bottom surface area of said incubator chamber when placed inside, and at a bottom, of said chamber.

Description

ENVIRONMENT SENSOR FOR MAMMALIAN TVF INCUBATOR
The present invention relates to the general field of environment sensors, when used in, and applied to mammalian in vitro fertilization (TVF) incubators. Mammalian IVF incubators generally provide a controlled and monitored development environment in which mammalian embryos, for example, human embryos, are developed to a developmental stage where they can be implanted in the uterus of a corresponding female host mammal. One of the main functions of an IVF incubator of this kind is to maintain an appropriate temperature for gamete function and embryo development. Any variations in temperature in such incubators can impact a number of aspects of gamete and embiyo function, including meiotic spindle stability and embryo metabolism. Maintaining an accurate temperature, whilst being able to also accurately measure said temperature inside the incubator is a desirable objective in order to reduce environmental stress on the cells being incubated.
Temperature is generally maintained and controlled within IVF incubators using a heating system. Most box-type IVF incubators generally use either a water jacket system or an air jacket system, in which air is warmed in die incubator chamber, with an optional ventilation system, such as a fan, to circulate air within the chamber. In benchtop, desktop, or top-loading IVF incubators, the chamber is warmed, for example, with heating elements either directly in contact with, or integrated into, the walls of the chamber. In such systems, at least some of the chamber walls, e.g. top, bottom, and sides might be In direct heat transfer contact with a culture dish and the enclosed medium contained therein. Each type of incubator warming system identified above has advantages and disadvantages, for example, water-jacketed incubators retain heat for a longer period of time when the incubator door is opened, or a power failure occurs. The downside of these units is that they tend to be heavy and consume greater amounts of energy to power die incubator. Furthermore, there is always the concern that the incubator, and/or incubator chamber, might become contaminated due to the presence of the water jacket. On the other hand, aii>jacketed incubators warm up quickly, but unfortunately do not retain heat for long periods. Another advantage of air-jacketed units is that they also enable heat-sterilization decontamination cycles to be carried out, which are unavailable for water-jacketed systems. In direct heating systems such as those found in the desktop, benchtop, and top-loading TVF incubators, the direct heat contact provides for rapid heal recovery even after the unit is opened or culture dish is removed, but even then, maintaining die correct temperature profile can still be problematic. Even within any given Incubator chamber, temperature can vaiy in significant proportions due to unequal heat distribution, leading to the creation of temperature gradients. Whilst such temperature gradients are more common in box-type IVF incubators, they also occur in box-type units, between individual culture chambers, and even across die wanned surfaces of various desktop, benchtop and top loading IVF incubators.
As a corollary to the problem Identified above, such TVF incubators also often Include at least one environment sensor, such as a temperature sensor, or a gas sensor, as these can be used to determine whether any fluctuations in environment conditions within the chamber are occurring and alert the user to the risk or presence thereof. In desktop, benchtop and top-loading GUT incubators, the environment sensors are generally integrated into the walls, bottom or lid of the culture chamber, however these sensors suffer from a lack of precision, as they can not be placed at a location sufficiently close to the culture dish, and therefore are also affected by any temperature gradients within the culture chamber. Alternatively, some environment sensors are rod-shaped, and electrically connected via wiring to a data recorder located outside the incubator. The problem with these rod-shaped environment sensors is that, similarly to the chamber wall integrated sensors, they can not be positioned at a location sufficiently close to the culture dish, due to the spatial limitations and constraints of die culture chambers, and additionally, when intmdum] into the culture chambers, occupy a significant volume within the culture chamber that necessarily reduces the available working volume into which culture dishes can be introduced, thereby reducing the operational output of the incubator unit as a whole.
Consequently, there is a need to be able to provide accurate environment sensor readings, for example, temperature sensor readings, that can be communicated to a control system for such IVF incubators, the sensor being both positionable at a location sufficiently close to the culture recipient to provide accurate readings of die environment at the culture recipient, whilst at the same time not reducing die working volume of the incubator culture chamber in which the culture recipients are the introduced. This need is met by the objects of the present invention as explicitly or implicitly expressed hereinafter and throughout die specification, claims and drawings.
Accordingly, one object of the present invention is a sensor far a mammalian in-vitro fertilisation (IVF) incubator system comprising at least one or more incubator chambers, die sensor comprising : a sensor body, configured and dimensioned to be housed within an incubator chamber of the mammalian in-vitro fertilisation incubator system ; at least one or more sensor systems, configured and adapted to sense at least one or more changes in an internal environment space within the incubator chamber of the mammalian in· vitro fertilisation incubator system ; wherein the at least one or more sensor systems are located on, or within, said sensor body ; wherein said sensor body is removably located within said incubator chamber·; and wherein said removable sensor body is configured and dimensioned to cover substantially all of a bottom surface area of said incubator chamber when placed inside, and at a bottom, of said chamber.
As indicated in the general introduction to the background of the present invention, a mammalian in-vitro fertilisation (TVF) incubator system, is an incubator device for the culture and development of mammalian embryos to a developmental stage suitable for implantation into a corresponding mammalian uterus - commonly, such embryos are developed to either what is known in the art as die cleavage stage, or alternatively, the blastocyst stage before embryo transfer. Whilst the term "mammalian" covers a whole spectrum of potential animals, die invention is particularly suited, and adapted, to human embryo culture, which is the preferred mammalian cell choice, although to die extent that other mammalian embryo cells could be, or are cultured, under similar circumstances, these are also included in the present definition. The IVF incubator system comprises one or more incubator chambers, also known as culture chambers, in which culture recipients, which are generally dish-like or dish-shaped recipients, for example Petri dishes, or plate-shaped or plate-like recipients, such as a slide plate, or culture plates equipped with one or more culture wells, for example, 4 or 8 wells or multiples thereof, are introduced and which contain die embiyos to be cultured in a culture medium, as is known in the art. The culture chambers generally tend to have a generally box-shaped configuration, with a bottom, side-walls and a top defining a volume to contain the controlled development and culture environment. Traditional box-type or chest incubators tend to resemble refrigerators or autoclaves, with shelves and trays for holding and separating die dish recipients. As such, the incubator chambers are not generally subdivided into individual smaller inoAator volumes. Typical box-type or chest-type incubators are well known per se, for example, the Forma™ range as sold by the company Fisher Scientific, USA, and in particular die“3110 Single 184L incubator” model. Desktop, benchtop or top-loading incubators on the other hand are designed to allow grouping of sets of dish recipients containing the cells to be cultured, with each group of dishes generally being contained within a relatively small volume individual culture or incubator chamber, die incubator generally comprising more than one such chamber. It is to be understood that with regard to the terms "incubator chamber” and“culture chamber”, as used herein in the present specification, description, claims and with regard to the drawings, these terms are interchangeable. Each individual chamber is often comprised of a bottom wall and a series of connected lateral walls, with an individually hinged c!osable lid, which sits on an upper lip or projecting flange of each chamber. Such systems are well known per se, for example, die K- Systems™ range as sold by the company Origio, France, under the models“G185 Long Term Flat Bed Incubator” and the "G210 InviCell Long Term Incubator”.
The sensor, as used with reference to the present specification description, claims and drawings, is capable of detecting changes or fluctuations in the environment conditions within the culture diamber or incubator chamber of the IVF incubator, and thus is also correspondingly configured and dimensioned for this role and functionality. Accordingly, and as used herein in the present specification, description, claims and with regard to the drawings, the expression“sensor” and “environment sensor” are interchangeable. The sensor comprises a sensor body, configured and dimensioned to be housed within the incubator chamber of the mammalian TVF incubator System. The sensor body is preferably and advantageously removably located within the incubator chamber or culture chamber, meaning that it can be introduced, or placed, into the incubator chamber as required, and subsequently removed therefrom when no longer required, such as for example, for maintenance, sterilisation or cleaning operations of the incubator It will thus be understood that the term“removable” as used herein means that the sensor body is a freestanding object. As mentioned above, the incubator chamber generally comprises a bottom or lower wall, forming a closed, bottom surface of the chamber, with side walls extending upwards from the bottom forming an upper opening, and a top wall that cavers the upper opening, whereby the top wall is advantageously a hinged lid that facilitates easy opening and closing of the lid. Preferably, the removable sensor body is configured and dimensioned to cover substantially all of the bottom surface area of the incubator chamber when placed inside, and at the bottom, of said chamber:
The sensor further comprises at least one or more sensor systems. In the present specification, description, claims and with regard to the drawings, the term "sensor system” refers to an assembly of electrical and/or microelectronic components, combined together to function as a sensor, whereby the sensor system is configured and adapted to sense at least one or more changes in the internal environment space within the incubator chamber of the mammalian in- vitro fertilisation incubator system. In this regard, and to all intents and purposes, the internal environment space is the useful working inner volume of die incubator changer when the lid of the incubator chamber is closed.
According to yet another object of the invention, the at least one or more sensor system is selected from a temperature sensor, a carbon dioxide sensor, an oxygen sensor, a humidity sensor, a volatile organic compounds (VOC) sensor, and combinations thereof. Preferably, the at least one or more sensor system Is a temperature sensor. Even more preferably, the at least one or more sensor system is a temperature sensor selected from a thermocouple temperature sensor, a thermoconducting temperature sensor, and a thermistor.
According to a still further object of the invention, the at least one or more temperature sensor comprises at least two distinct, spaced apart, temperature detection sites.
According to yet another object of the invention, the at least one or more temperature sensor comprises at least four distinct, spaced apart, temperature detection sites.
Furthermore, and according to another object of the invention, the at least one or more sensor systems are located on, or within, said sensor body, for example, housed within said sensor body, or odierwise attached or affixed to an outer surface of the sensor body.
According to one object of the invention, the sensor body comprises a first wall, a second wall located in parallel and spaced apart relationship to said first wall, and at least one side wall extending between said first wall and said second wall, and connecting said first wall to said second wall. The first and second wall generally form a top and bottom of the sensor body, whilst die side wall or walls form the sides of the sensor body. The sensor body optionally and advantageously further comprises one or more openings or orifices, whereby die openings can be located in any of the side wall or side walls, and/or on die top or bottom walls. The openings or orifices in the sensor body preferably traverse an outside surface of said sensor body, and are orifice is configured to allow fluid exchange between an environment space of die incubation chamber and an interior space of said sensor body. By fluid exchange in this context, it is to be generally understood that die inventors are referring to gaseous exchange, rather than liquid exchange, for example, where the gaseous fluids can be water vapour, carbon dioxide, or other gases dial are commonly used in incubator chambers such as oxygen and nitrogen. When the sensor body advantageously comprises corresponding orifices or openings In both top and bottom wall surfaces, be they in different locations on each surface or In superposed locations, it is possible for the sensor body to allow for fluid flow, from for example, the top of the sensor body to the bottom of the sensor body and vice-versa, thereby allowing for complete circulation of toe environment fluids between the bottom surface of toe Incubator chamber and toe volume or incubator region above toe sensor body within the incubator chamber. Such improved circulation enables a more accurate reading in any changes to the environment to be determined by toe at least one or more sensor systems.
According to another object of the invention, the sensor body has a width and a length which are both substantially greater than a height of said sensor body. For the purposes of the present invention, when reference is made to length, width and height, these terms have their usual meaning, in other words, the sensor body is thinner than it is either long or wide. The advantage of such a sensor body configuration is that it becomes possible to place the sensor at the bottom of the incubator chamber without sacrificing the number of recipient dishes that can be incubated at the same time in toe incubation chamber. Indeed, this sensor body configuration completely obviates the problem encountered with traditionally used cylindrical-shaped or pen-shaped sensors, which occupy a far greater volume in toe incubation chamber.
In one prefeired embodiment, toe sensor body has a height which is between about 1/45 and 1/84 of the width of said sensor body.
In another preferred embodiment, the sensor body has a height which is between about 1/60 aid about 1/92 of toe length of said sensor body.
Advantageously, both of the above embodiments can be combined in even more preferred embodiments of toe invention.
According to yet another object of die invention, toe sensor body is comprised of thermally conducting material. Preferably, and advantageously, the sensor body is comprised of a metal selected from stainless steel, aluminium, copper, a galvanized or plated metal, and combinations thereof.
According to a still further object of toe invention, toe sensor body is a substantially hollow body. By“substantially hollow body”, it is to be understood that die sensor body top, bottom and side walls together form a hollowed out sensor body, and defining an inner volume. Where openings or orifices are also present in the top, bottom or side wails, the inner volume of the sensor body communicates with the environment of the incubator chamber. According to yet another object of the invention, the sensor body is substantially plate-like. A plate-like sensor body allows for easy introduction and removal of the sensor into the incubator chamber, and furthermore occupies a relatively small volume within die chamber.
Similarly, and according to still a further object of the invention, the sensor body is substantially disc-like. A disc-like sensor body is advantageously chosen when die incubation chamber as defined by the bottom and side walls Is not rectangular or square, but for example, polygonal such as octagonal, or substantially circular, or the like.
According to yet another object of the invention, the at least one or more sensor system is attached to an outside surface of the sensor body. This is an advantageous configuration because the sensor system thus lies in close proximity to, and more advantageously under, any recipient dish that is positioned or located over the top of the sensor body.
According to yet another object of the Invention, the at least one or more sensor system Is attached to a groove located in the outside surface of said sensor body. Additionally, and advantageously, the at least one or more sensor system lies flush with the outside surface of said sensor body when attached to the groove provided in the outside surface of said sensor body.
Usually, the recipient dishes are also provided with a raised edge that projects from the bottom of the dish, which not only lifts the bottom of the dish off and away from the surface on which the dish rests, thereby increasing air circulation between die dish and its surroundings, but also die projecting edge mates with, and self-locates in, a corresponding groove having substantially the same circumference and width as those of the projecting edge of the dish, to help retain the dish on a support plate in which the grooves have been provided. In this configuration, die support plate with locating grooves Is generally positioned over the sensor body. The support plate Is generally only a few millimetres in height, for example from between 1 mm to 2 mm thick, so as not to compromise the space required for die recipient dishes. According to another object of the invention, die support plate and sensor body are one and the same, i.e. the sensor body also integrates the functionality of the support plate, providing direct support for the recipient dishes. This has the added advantage of making yet more usable Inner volume available within the culture chamber.
In still yet another object of the invention, the at least one or more sensor system comprises a sensor system body, having a first sens™· system extremity located at a first side wall of the sensor body, and a second sensor system extremity located distant from said first side wall, wherein the sensor system body is connected to both the first sensor system extremity and the second sensor system extremity.
According to yet another object of the invention, the at least one or more sensor system extends from a first side wall in the direction of an opposing side wall. According to yet another object of the invention, the second sensor system extremity is located at a terminal position on the sensor body, said terminal position being configured to correspond to the superposed position of an Incubator recipient dish located above said terminal position when said sensor body is located within the incubator chamber.
According to a still further object of the invention, the at least one or more sensor system comprises a first and second sensor system, die first and second sensor systems being identical or different.
According to yet another object of the invention, the at least one or more sensor system comprises a first and second sensor system, the first and second sensor system being located substantially in parallel to each other on an outside surface of the sensor body. According to a still further object of the invention, the at least one or more sensor system comprises a first and second temperature sensor, and each temperature sensor comprises two distinct, spaced apart, temperature detection sites.
According to yet another object of the invention, die at least one sensor system is electrically connected to an electrical connection port housed within the sensor body and configured to receive a flat wire or ribbon electrical connector. Preferably, the flat wire or ribbon electrical connector is connected to a data recorder.
According to a still further object of the invention, the data recorder is wirelessly connected to a wireless network router. Preferably, the data recorder and the wireless network router communicate with each other via a wireless radiofrequency preferably of 433 MHz. According to another object of the invention, the wireless network router further comprises a Bluetooth wireless communications circuit. Preferably, the wireless network router further communicates with a sensor controller system via the Bluetooth wireless communications circuit
According to a still further object of the invention, the sensor controller system is a Bluetooth enabled smartphone or handheld tablet device, and further comprises a software program loaded into a memory of said smartphone or handheld tablet device, and configured to provide control commands to the sensor.
According to yet another object of the invention, the sensor controller system is further configured to display information to a user of the sensor controller system via an interactive graphical user interface of said sensor controller system, said information being transmitted by the data recorder via the network router to said sensor controller system.
BRIEF DESCRIPTION OF THE FIGURES
Figure 1 A is a schematic perspective view of a desktop or benchtop IVF incubator, with a sensor according to the invention located therein;
Figure IB is magnified or close-up view of the culture chamber and sensor of Figure 1A;
Figure 2 A is a schematic perspective view of a variant of a desktop or benchtop IVF incubator, with a different example of the sensor according to the invention located therein;
Figure 2B is magnified or close-up view of die culture chamber and sensor of Figure 2A;
Figure 3 is a schematic cross-sectional view of the desktop incubator of Figure LA showing an incubator chamber with a sensor according to the invention located therein, along with recipient culture dishes placed above the sensor on a support plate;
Figures 4A and 4B are schematic two dimensional representations of a top and longitudinal cross-section of a first embodiment of the sensor according to die present invention;
Figures 5A and 5B are schematic two dimensional representations of a top and longitudinal cross-section of a second embodiment of the sensor according to die present invention;
Figure 6 is a schematic block diagram of a surveillance and control system for an IVF incubator including one or more sensors according to die invention.
DETAILED DESCRIPTION OF THE INVENTION
The invention will now be described hi greater detail, with reference to the accompanying figures, which serve to illustrate example embodiments of the invention. Figure 1 A is a schematic perspective illustration of a typical benchtop or desktop human embiyo IVF incubator indicated generally by reference numeral (1), with Figure IB representing a magnified, or zoomed-in view of the culture chamber area containing a sensor according to the invention. In this example, the IVF incubator (1) is provided with eight culture chambers (2). Each culture chamber (2) has a generally box-shaped configuration, with a bottom (3), side-walls (4, 5, 6, 7) and a top (8) defining a volume to contain the controlled development and culture environment. In Figures 1A and IB, die top (8) is a hinged lid (8), with the hinge (9, Fig. 3) located at one side of the culture chamber (2) above one of the side walls of the culture chamber, the lid (8), when closed, resting on a continuous flange (10) or lip which is integral to, and projects outwardly from, the chamber (2) at the top of the respective side walls (4, 5, 6, 7) and serves to seal the chamber (2) from the outside environment when the incubator is in operation. The culture chamber (2) is typically comprised of a heat conductive material, for example, stainless steel.
A sensor according to die invention, indicated generally by die reference numeral (11), is placed inside and at the bottom (3) of the culture chamber (2). The sensor (11) is adapted in size and configured to occupy substantially all of the available surface area of the bottom of the culture chamber (2). As will be apparent from Figures 1 and 2, the sensor (11) is removably located within the chamber, given that it can be removed as easily as h can be Introduced, for example, for purposes of maintenance, or for example, when die sensor is no longer required. The sensor (11) comprises a sensor body (12), which comprises a first wall (13), a second wall
(14) located in parallel and spaced apart relationship to said first wall (13), and at least one side wall (15) extending between said first wall (13) and said second wall (14), and connecting said first wall (13) to said second wall (14), thereby defining a generally hollow body (12). The first and second walls (13, 14) form a top and bottom of the senses· body (12), whilst the side wall (15) or walls form the sides of the sensor body (12). The sensor body (12) further comprises one or more openings or orifices (16), whereby the openings can be located in any of the side wall
(15) or side walls, and/or on the top or bottom walls (13, 14). The openings or orifices (16) in die sensor body (12) preferably traverse an outside surface of said sensor body (12), and are configured to allow fluid exchange between an environment space (17, Fig; 3) of the incubation chamber (2) and an interior space (18, Fig.4B, 5B) of said sensor body (12), but also optionally to enable operation of any other sensors that are built into the incubator (1) to operate. In this context, it is to be generally understood that fluid exchange refers to gaseous exchange, rather than liquid exchange, for example, where the gaseous fluids can be water vapour, carbon dioxide, or other gases that are commonly used In incubator chambers such as oxygen and nitrogen. If the sensor body (12) advantageously comprises corresponding orifices or openings in both top and bottom wall surfaces (13, 14), be they in different locations on each surface or in superimposed locations, the sensor body (12) can allow fra: fluid to flow, from for example, the top of the sensor body to the bottom of the sensor body and vice-versa, thereby allowing for complete circulation of the environment fluids between the bottom surface (3) of the incubator chamber (2) and the environment space (17, Fig. 3) above die sensor body (12) within the incubator chamber (2). Such improved circulation enables a more accurate reading in any changes to the environment to be determined by the at least one or more sensor systems provided In the sensor (11), as will be described herein.
The sensor body (12) has a width and a length which are both substantially greater than a corresponding height of said sensor body (12). In other words, the sensor body (12) Is significantly thinner than it is either long or wide. The advantage of such a sensor body configuration is that it becomes possible to place the sensor (11) at the bottom of the incubator chamber (2) without sacrificing the number of recipient dishes (25) that can be incubated at the same time in the incubation chamber (2). Indeed, this sensor body configuration completely obviates the problem encountered with traditionally used cylindrical-shaped or pen-shaped sensors, which occupy a far greater volume in the Incubation chamber and reduce the number of possible culture recipients (25) that can be introduced into die incubator. Indeed, the problem with current sensors is such dial it is common to see a complete culture chamber dedicated to receiving a sensor, precluding any use of that culture chamber for anything related to actually culturing embiyos.
Following on from the general shape and dimension considerations of the sensor body (12) according to the invention, said sensor body (12) preferably has a height which is between about 1/45 and 1/84 of the width of said sensor body. In another preferred embodiment, the sensor body has a height which is between about 1/60 and about 1/92 of the length of said sensor body. Exemplary dimensions of suitable sensor bodies for sensors according to the present invention are provided in the following table:
Figure imgf000012_0001
The sensor body (12) is generally comprised of a thermally conducting material. Preferably, and advantageously, the sensor body is made of a metal selected from stainless steel, aluminium, copper, a galvanized or plated metal, and combinations thereof, wherein aluminium and/or stainless steel sensor bodies have been found to be particularly advantageous, due for example, to the ease with which they can be maintained, cleaned, sterilized, and the like, and due to their resistance to the environment in which they are placed.
As will be understood from the above, the sensor body (12) has substantially plate-like shape. A plate-like shaped sensor body (12) allows for easy introduction and removal of the sensor (11) into the incubator chamber (2), and furthermore occupies a relatively small volume within the chamber, thereby not impeding placement of culture recipients and enabling the maximum volume of the culture chamber to be used to the greatest of effect
Similarly, the sensor body (12) can also be substantially disc-like. A disc-like sensor body (12) is advantageous when the incubation chamber (2) as defined by the bottom (3) and side walls (4, 5, 6, 7) Is not rectangular or square, but for example, polygonal such as octagonal, or substantially circular, elliptical or die like. Hie sensor (11) further comprises at least one or more sensor systems (19, Fig. 3) In and/or on the sensor body (12), configured and adapted to sense at least one or more changes in the internal environment space (17) within the incubator chamber (2) of the IVF incubator. The at least me or more sensor systems are located on, or within, die sensor body (12) as will be described herein.
As can be seen in particular from Figure 3, the sensor system as indicated generally by the reference numeral (19), is for example, a temperature sensor, and is located on an outside surface of the wall (13) of the sensor body (12). In the particular examples illustrated by the Figures, the sensor system (19) is located in a groove provided in the outside surface of wall (13) whereby the groove is configured with at least one opening to permit fluid communication with an inner volume (18, Figs.4B, 5B) of the sensor body (12). The sensor system (19) lies flush with die outside surface of the wall (13) of the sensor body (12) when attached to the groove, presenting an overall smooth surface contiguous with the surface of the wall (13). The sensor system is affixed in the groove, for example, by the use of a suitable glue or adhesive, welding or a snap-fit or press-fit configuration that is adapted to the environment into which the sensor body is to be placed, and chosen to avoid or minimize die risk of separation or detachment of the sensor system (19) from the sensor body (12) under conditions of use. As illustrated in the Figures, the sensor system (19) comprises a generally strip shaped or filamentous body (20) of electrically conducting material, for example an electrically conducting strip, or ribbon, which extends from a first extremity (23) of a first side wall (15) of the sensor body (12) towards an opposing side wall (15) of said sensor body (12) and a corresponding second extremity (24) of said filamentous body (20). In these examples, the electrically conducting strip body (20) does not extend from the first extremity (23) the whole length of the sensor body (12) to terminate at a second extremity (24) located opposite-facing side wall (15). As can be seen from the Figures, in particular Figures 2, 3, and 4, the electrically conducting strip body (20) terminates at the second extremity (24) only part way along the length of the sensor body (12), generally more than half the length, and preferably, more than 2/3 of the length of the sensor body. Ideally, the electrically conducting strip body (20) terminates at a point along the length of the sensor body which substantially corresponds to a superimposed position of a corresponding culture recipient placed over the top thereof in the culture chamber.
The sensor system (19) comprises at least one or more sensor circuits, preferably at least two sensor circuits (21, 22), located at spaced apart positions along the strip-shaped or filamentous body (20). The sensor circuits (21, 22) project and extend away from the strip-shaped or filamentous member inwards into the inner volume (18) of the sensor body (12). In this configuration, the sensor circuits (21, 22) are protected from potentially damaging outside contact, friction, interference and the like, and yet still in direct contact with the inner volume (18) of the sensor body (12), which is in fluid communication with the environment volume (17) of tire culture chamber (2). The first and second sensor circuits are positioned along the stripshaped or filamentous body (20) so that their positions correspond, as closely as possible, to the location of a superimposed culture chamber placed above the sensor body (12).
Figure 2A is a schematic perspective illustration of another typical benchtop or desktop human embryo IVF incubator indicated generally by reference numeral (1), with Figure 2B representing a magnified, or zoomed-in view of the culture chamber area containing another example of a sensor (11) according to die invention. In tins example, the IVF incubator (1) is provided with four culture chambers (2) instead of eight culture chambers as in Figure 1A. Additionally, the sensor (11) in Figures 2A and 2B is substantially square in shape, in comparison to die sensor illustrated in Figures 1A and IB, in which the sensor (11) is substantially rectangular in shape. Similarly, in the example of Figures 2A and 2B, there are four culture recipients (25A, 25B, 25C, 25D), rather than two culture recipients as illustrated in Figures 1A and IB. Furtheiraore, the sensor is equipped with two sensor systems (19 A, 19BX whereby each sensor system can be the same, or one can be different to the other. Apart from these differences, like references denote the same components as described for Figures 1A and IB.
Turning now to the details of Figures 4 and 5, Figure 4A is a schematic two-dimensional representation of the top wall (13) of a sensor body (12) of a sensor (11) according to the invention, showing a single sensor system (19) comprising an electrically conducting strip body (20) and two sensor circuits (21 , 22), which are preferably temperature sensor circuits. An opening or orifice (16) is provided in the top wall (13) of the sensor body (12) to permit fluid communication with the environment of the culture chamber (2) and the inner volume (18) of the sensor body. Figure 4B represents a schematic cross-section of die sensor of Figure 4A along the lineA-A.
Similarly, Figure 5A is a schematic two-dimensional representation of die top wall (13) of a sensor body (12) of a sensor (11) according to the invention, showing a dual sensor system (19, 19A) comprising two electrically conducting strip bodies (20, 20A) and two sensor circuits (21, 21A, 22, 22A), which are preferably all temperature sensor circuits. Figure 5B represents a schematic cross-section of the sensor (11) of Figure 5A along die line B-B.
The main differences therefore between Figure 4 and Figure 5 are that Figure 5 illustrates an example of a sensor according to the Invention, in which there are two sensor systems (19, 19A) located on the outer surface of the wall (13), and a noticeable difference in width of the plate-like sensor body (12). The sensor (11) of Figure 5 is thus adapted to a culture chamber (2) with a wider base than that in which the sensor (11) of Figure 4 can fit. Each sensor system (19, 19A) of the sensor in Figure 5 comprises a respective electrically conducting strip (20, 20A) located in a respective groove of the outer surface of wall (13), and each strip having two sensor circuits (21, 21 A, 22, 22A) located at spaced apart positions along their respective strip (20, 20A). In Figure 5, the electrically conducting strips (20, 20A) both extend from the same side wall (15) towards an opposite facing side wall (15), die first and second sensor systems (19, 19A) being located in parallel to each other, however it will be understood that a configuration can also be envisaged in which each sensor system extends from a first extremity, wherein the first extremities are located at respective opposite-facing side walls (15).
It will be understood that each sensor system can have the same sensor circuits (21, 21A, 22, 22A), or a range of different sensor circuits, as desired. In the illustrated examples, all of the sensor circuits are temperature sensors. In such a case, the temperature sensors can
advantageously and preferably have the following operational characteristics:
Figure imgf000016_0001
Figures 1, 2 and 3 also illustrate schematically how the sensor (11) is located within the culture with respect to other elements usually present in a culture chamber of the IVF Incubator, hi particular, culture recipients (25A, 25B, 25C, 25D), which are generally dish-like or dish-shaped recipients, for example Petri dishes, or plate-shaped or plate-like recipients, such as a slide plate, or culture plates equipped with one or more culture wells, for example, 4 or 8 wells or multiples thereof, are introduced and generally contain the embryos to be cultured in a culture medium, as is known in the art. The culture recipients (25A, 25B, 25C, 25D) have been placed on top of a support plate (26) having a support surface (27). The culture recipients (25) are often also provided with a raised edge that projects from the bottom of the dish, which not only lifts the bottom of die dish off and away from die support surface (27) on which the dish (25) rests, thereby increasing air circulation between the dish and its surroundings, but also the projecting edge mates with, and self-locates in, a corresponding groove or series of grooves (28) having substantially the same circumference and width as those of the projecting edge of the dish (25), to help retain the dish (25) on the support plate (26) In which the grooves (28) have been provided. In this configuration, the support plate (26) with locating grooves (28) is generally positioned over the sensor body (12). The support plate (26) is generally only a few millimetres in height, for example from between 1 mm to 2 mm thick, so as not to compromise the space required for the recipient dishes (25). In an alternative embodiment, the culture recipients can be placed directly on top of the sensor body (12), with die functions of support plate being integrated into the sensor body (12), rendering a separate support plate (26) unnecessary.
As can be seen further from Figure 3, the at least one sensor system (19, 19A) Is electrically connected to an electrical connection port (29) housed within the sensor body (12) and configured to receive a flat wire or ribbon electrical connector (30). The flat wire electrical connector (30) connects to a data recorder (31), which collects and stores the data collected by the sensor at a predetermined interval Turning now to Figure 6, a block representation of a surveillance and control system, which can be used m conjunction with the sensors of the present invention, is given along with an indication of data, signal and or communications flow. As indicated above, a chamber sensor (11) is connected via an electrical connection port (29, 29A) and flat wire or ribbon electrical connector (30) to a data recorder (31). Where a desktop or benchtop IVF incubator is being used, there will be multiple culture chambers, and correspondingly, multiple sensors, each sensor having a flat wire connector to the data recorder (31). Where multiple incubators are being deployed, each incubator has an associated data recorder (31). A flat wire connector (30), and preferably a shielded flat wire connector, is preferred to allow electrical signals to flow between the sensor (11) and the data recorder (31), in order to avoid any electromagnetic interference or side-effects being produced which might have a deleterious effect on the cells being culture in the culture chamber ( 2). Furthermore, the data recorder (30) is preferably then wirelessly connected m a wireless network router (32). The arrows at both ends of the connector in the block diagram indicate that communication between the data recorder and die router operates in both directions. Preferably, the data recorder (31) and the wireless network router (32) communicate data and signals with each other via a wireless radiofrequency of 433 MHz. This frequency is considered to be the most appropriate and least likely to cause deleterious effects with regard to the neighbouring culture chamber of the TVF incubator. The network router is connected to die internet via a suitable telecommunications network, for example via a suitable radiofrequency network, as are cunendy known or under development, or via an alternative rnmnumiratinns system such as a satellite link or copper-wire or optical fibre based physical infrastructure, or combinations thereof. The network router also preferably comprises a
Bluetooth communications circuit configured to enable data and signal transfer between the router and a suitably enabled sensor controller system, wherein the sensor controller system is a Bluetooth enabled smartphone (33) or handheld tablet device, and further comprises a software program loaded into a memory of the smartphone or handheld tablet device, and configured to provide control commands to the sensor. Furthermore, the sensor controller system is further configured to display information m a user of the sensor controller system via an interactive graphical user interface of said sensor controller system, said information being transmitted by the data recorder (31) via the network router (32) to said sensor controller system on the smartphone or tablet device (33). Additionally, the smartphone or tablet device is configured to communicate via said suitable telecommunications network with a distributed, or“cloud-based” service application on a cloud network (34), and provide information thereto and receive data, instructions and signals therefrom, in association with the control and surveillance of the sensors. The distributed, or“cloud-based1* service application is preferably also accessed, operated and interacted with via an internet browser based application (35), otherwise known as a web application, enabling remote control and surveillance of the sensors to be carried ouL

Claims

1) Sensor for a mammalian in-vitro fertilisation (1VF) incubator system comprising at least one or more incubator chambers, the sensor comprising : a sensor body, configured and dimensioned to be housed within an incubator chamber of the mammalian in-vitro fertilisation incubator system ; at least one or more sensor systems, configured and adapted to sense at least one or more changes in an internal environment space within die incubator chamber of the mammalian in- vitro fertilisation incubator system ; wherein the at least one or more sensor systems are located on, or within, said sensor body ; wherein said sensor body is removably located within said incubator chamber; and wherein said removable sensor body is configured and dimensioned to cover substantially all of a bottom surface area of said incubator chamber when placed inside, and at a bottom, of said chamber.
2) Sensor for a mammalian IVF incubator system according to claim 1, wherein said sensor body comprises a first wall, a second wall located in parallel and spaced apart relationship to said first wall, and at least one side wall extending between said first wall and said second wall, and connecting said first wall to said second wall. 3) Sensor for a mammalian IVF incubator system according to claim 1 or claim 2, wherein said sensor body has a width and a length which are both substantially greater than a height of said sensor body.
4) Sensor for a mammalian IVF incubator system according to any one of preceding claims
1 to 3, wherein said sensor body has a height which is between about 1/45 and 1/84 of the width of said sensor body.
5) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 4, wherein said sensor body has a height which is between about 1/60 and about 1/92 of the length of said sensor body. 6) Sensor for a mammalian IVF Incubator system according to any one of preceding claims 1 to 5, wherein said sensor body is comprised of thermally conducting material.
7) Sensor far a mammalian IVF incubator system according to any one of preceding claims 1 to 6, wherein said sensor body is comprised of a metal selected from stainless steel, aluminium, copper, a galvanized or plated metal, and combinations thereof.
8) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 7, wherein said sensor body is a substantially hollow body.
9) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 8, wherein said sensor body is substantially plate-like. 10) Sensor for a mammalian TVF incubator system according to any one of preceding claims
1 to 9, wherein said sensor body is substantially disc-like.
11) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 10, wherein said at least one or more sensor system is attached to an outside surface of said sensor body. 12) Sensor for a mammalian IVF incubator system according to any one of preceding claims
1 to 11, wherein said at least one or more sensor system is attached to a groove located in an outside surface of said sensor body.
13) Sensor for a mammalian TVF Incubator system according to any one of preceding claims
1 to 11, wherein said at least one or more sensor system is attached to a groove located in an outside surface of said sensor body and said at least one or sensor system lies flush with the outside surface of said sensor body when attached to said groove.
14) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 13, wherein said at least one or more sensor system comprises a sensor system body, a first sensor system extremity located at a first side wall of the sensor body, and a second sensor system extremity located distant from said first side wall, wherein the sensor system body is connected to both die first sense»: system extremity and the second sensor system extremity.
15) Sensor for a mammalian IVF incubator system according to any one of preceding claims
1 to 14, wherein said at least one or more sensor system extends from a first side wall in the direction of an opposing side wall. 16) Sensor for a mammalian IVF Incubator system according to any one of preceding claims 1 to 15, wherein said at least one or more sensor system comprises a sensor system body, a first sensor system extremity located at a first side wall of die sensor body, and a second sensor system extremity located distant from said first side wall, wherein the second sensor system extremity is located at a terminal position on the sensor body, said terminal position being configured to correspond to the superposed position of an incubator well located above said terminal position when said sensor body is located within die incubator chamber.
17) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 16, wherein the sensor body further comprises an orifice traversing an outside surface of said sensor body, and said orifice is configured to allow fluid exdiange between an internal environment space of the incubation chamber and an interior space of said sensor body.
18) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 17, wherein said at least one or more sensor system is selected from a temperature sensor, a carbon dioxide sensor, an oxygen sensor, a humidity sensor, a volatile organic compounds (VOC) sensor, and combinations thereof.
19) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 18, wherein said at least one or more sensor system is a temperature sensor.
20) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 19, wherein said at least one or more sensor system is a temperature sensor selected from a thermocouple temperature sensor, a theimoconducting temperature sensor, and a thermistor.
21) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 20, wherein said at least one or more temperature sensor comprises at least two distinct, spaced apart, temperature detection sites.
22) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 21 , wherein said at least one or more temperature sensor comprises at least four distinct, spaced apart, temperature detection sites.
23) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 21, wherein said at least one or more sensor system comprises a first and second sensor system, die first and second sensor systems being identical or different 24) Sensor for a mammalian IVF incubator system according to any one of preceding claims
1 to 23, wherein said at least one or more sensor system comprises a first and second sensor system, the first and second sensor system being located substantially in parallel to each other on an outside surface of the sensor body.
25) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 23, wherein said at least one or more sensor system comprises a first and second temperature sensor, and each temperature sensor comprises two distinct, spaced apart, temperature detection sites.
26) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 25, wherein said at least one sensor system is electrically connected to an electrical connection port housed within the sensor body and configured to receive a flat wire or ribbon electrical connector.
27) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 26, wherein the flat wire or ribbon electrical connector Is connected to a data recorder.
28) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 27, wherein the data recorder is wirelessly connected to a wireless network router. 29) Sensor for a mammalian TVF incubator system according to any one of preceding claims 1 to 28 wherein the data recorder and the wireless network router communicate with each other via a wireless radiofrequency of 433 MHz.
30) Sensor for a mammalian IVF incubator system according to any one of preceding claims
1 to 29, wherein the wireless network router further comprises a Bluetooth wireless
communications circuit.
31) Sensor for a mammalian IVF incubator system according to any one of preceding claims
1 to 30, wherein the wireless network router further communicates with a sensor controller system via the Bluetooth wireless communications circuit
32) Sensor for a mammalian IVF incubator system according to any one of preceding claims 1 to 31, wherein the sensor controller system is a Bluetooth enabled smartphone or handheld tablet device, and further comprises a software program loaded into a memory of said smartphone or handheld tablet device, and configured to provide control commands to die sensor.
33) Sensor for a mammalian TVF incubator system according to any one of preceding claims 1 to 32, wherein die sensor controller system is further configured to display information to a user of the sensor controller system via an interactive graphical user interface of said sensor controller system, said information being transmitted by the data recorder via the network router to said sensor controller system.
PCT/IB2018/001461 2018-10-25 2018-10-25 Environment sensor for mammalian ivf incubator WO2020084324A1 (en)

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