A method of ranking embryos to indicate their development potential. The method comprises: obtaining values for a plurality of characteristics relating to the morphological development of the embryos during an observation period; determining for respective ones of the embryos whether or not the embryo has undergone a direct cleavage event, and ranking the embryos determined to have undergone a direct cleavage event with a ranking that indicates a lower development potential than for the embryos not determined to have undergone a direct cleavage event; and for the embryos not determined to have undergone a direct cleavage event, determining whether or not a duration of a predefined developmental stage for the embryo exceeds a predefined threshold duration, and ranking embryos for which the duration of the predefined developmental stage is determined to exceed the predefined threshold duration with a ranking that indicates a lower development potential than for the embryos for which the duration of the predefined developmental stage is not determined to exceed the predefined threshold duration; and for the embryos for which the duration of the predefined developmental stage is not determined to exceed the predefined threshold duration, determining whether or not the relative durations of two predefined developmental stages for the embryo is outside a predefined range, and ranking embryos for which the relative durations of two predefined developmental stages for the embryo is outside a predefined range with a ranking that indicates a lower development potential than for the embryos for which the relative durations of two predefined developmental stages for the embryo is not outside the predefined range.
Apparatus and methods for monitoring embryos in an incubator are described. The apparatus comprises an incubation chamber defined by an incubation chamber housing and a slide carrier comprising a plurality of compartment walls that define compartments for holding embryo slides within the incubation chamber for incubation. The slide carrier is moveable, for example by rotation, relative to the incubation chamber housing to allow a selected compartment to be moved to a loading position defined at least in part by a loading port wall associated with the incubation chamber housing. The loading port wall is arranged to cooperate with the wall of a compartment in the loading position to restrict the extent to which the environment of the compartment in the loading position is in fluid communication with the environments of other compartments in the incubation chamber.
Apparatus and methods for helping a user establish values (e.g. timings) for a plurality of parameters of interest (e.g. cell divisions) relating to the development of an embryo from a series of images of the embryo are described. For each parameter of interest an image is selected for display to a user seeking to establish a value for the parameter of interest. For example, the selected image may be an image predicted to be an image reflecting the value for the parameter of interest. For example, the selected image may be based on a calculated timing for a particular developmental event. The timing may be calculated from a numerical analysis of the images or maybe predetermined. If the user is unable to determine a value for the parameter of interest from the selected image, the user may scroll through neighboring images until the user can determine a value for the parameter of interest. A value for the proud of interest may then be established in response to user input, for example a user providing an indication that a timing associated with a currently displayed image from the series of images should be taken to be the value of the parameter of interest. The different parameters of interest may be established in an iterative manner in which an initial image for display to a user is selected for each parameter of interest based on the parameter of interest.
C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
G06F 3/00 - Input arrangements for transferring data to be processed into a form capable of being handled by the computerOutput arrangements for transferring data from processing unit to output unit, e.g. interface arrangements
G06K 9/46 - Extraction of features or characteristics of the image
G06K 9/62 - Methods or arrangements for recognition using electronic means
G06K 9/66 - Methods or arrangements for recognition using electronic means using simultaneous comparisons or correlations of the image signals with a plurality of references, e.g. resistor matrix references adjustable by an adaptive method, e.g. learning
G06T 11/60 - Editing figures and textCombining figures or text
G06T 7/246 - Analysis of motion using feature-based methods, e.g. the tracking of corners or segments
A method of ranking embryos to indicate their development potential. The method comprises: obtaining values for a plurality of characteristics relating to the morphological development of the embryos during an observation period; determining for respective ones of the embryos whether or not the embryo has undergone a direct cleavage event, and ranking the embryos determined to have undergone a direct cleavage event with a ranking that indicates a lower development potential than for the embryos not determined to have undergone a direct cleavage event; and for the embryos not determined to have undergone a direct cleavage event, determining whether or not a duration of a predefined developmental stage for the embryo exceeds a predefined threshold duration, and ranking embryos for which the duration of the predefined developmental stage is determined to exceed the predefined threshold duration with a ranking that indicates a lower development potential than for the embryos for which the duration of the predefined developmental stage is not determined to exceed the predefined threshold duration; and for the embryos for which the duration of the predefined developmental stage is not determined to exceed the predefined threshold duration, determining whether or not the relative durations of two predefined developmental stages for the embryo is outside a predefined range, and ranking embryos for which the relative durations of two predefined developmental stages for the embryo is outside a predefined range with a ranking that indicates a lower development potential than for the embryos for which the relative durations of two predefined developmental stages for the embryo is not outside the predefined range.
A tray (100; 400; 500; 600) for accommodating a cell culture (101), such as an embryo, for use during culturing thereof and for optical monitoring of the cell culture, e.g. during in vitro fertilization comprises a carrier structure (104;404;504;604) defining at least one accommodating zone (102; 402; 502; 602) for accommodating the cell culture. At least one focal lens (110; 410; 510; 610), notably a numerical aperture increasing lens is integrally formed with the carrier structure to facilitate monitoring of the cell culture through the carrier structure. A diameter of the focal lens may exceed a diameter of the at least one accommodating zone. The focal lens may be integrally molded with the carrier structure from a thermoplastic material.
A culture dish for holding one or more object to be cultured is described. The culture dish has a main body comprising at least one well for receiving an object to be cultured and a quantity of culturing media for the object, such as a water-based growth media, and a reservoir for receiving a quantity of cover media, such as mineral oil. The at least one well is provided in a floor of the reservoir so that when in normal use cover media in the reservoir overlays culturing media in the at least one well. The reservoir is defined by the reservoir floor and a reservoir wall extending away from the reservoir floor. At least a section of the reservoir wall is angled away from the vertical so as to be inclined with respect to a horizontal plane defined by a surface of cover media in the reservoir when the culture dish is in normal use. The angled section of the reservoir wall can help reduce the appearance of a meniscus in the cover media overlaying the wells, and can furthermore be positioned so as to provide a ready indication of when the reservoir contains an appropriate level of cover media for culturing.
Apparatus and methods for helping a user establish values (e.g. timings) for a plurality of parameters of interest (e.g. cell divisions) relating to the development of an embryo from a series of images of the embryo are described. For each parameter of interest an image is selected for display to a user seeking to establish a value for the parameter of interest. For example, the selected image may be an image predicted to be an image reflecting the value for the parameter of interest. For example, the selected image may be based on a calculated timing for a particular developmental event. The timing may be calculated from a numerical analysis of the images or maybe predetermined. If the user is unable to determine a value for the parameter of interest from the selected image, the user may scroll through neighbouring images until the user can determine a value for the parameter of interest. A value for the proud of interest may then be established in response to user input, for example a user providing an indication that a timing associated with a currently displayed image from the series of images should be taken to be the value of the parameter of interest. The different parameters of interest may be established in an iterative manner in which an initial image for display to a user is selected for each parameter of interest based on the parameter of interest.
G06K 9/00 - Methods or arrangements for reading or recognising printed or written characters or for recognising patterns, e.g. fingerprints
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
G06F 3/00 - Input arrangements for transferring data to be processed into a form capable of being handled by the computerOutput arrangements for transferring data from processing unit to output unit, e.g. interface arrangements
Apparatus and methods for monitoring embryos in an incubator are described. The apparatus comprises an incubation chamber defined by an incubation chamber housing and a sample platform comprising a plurality of receptacles for holding embryos within the incubation chamber for incubation. The sample platform may comprise a slide carrier on which embryo slides containing the receptacles may be placed incubation. The sample platform is rotatable about a rotation axis relative to the incubation chamber housing so as to allow receptacles to be selectively rotated to a monitoring position that is aligned with a viewing port provided in the incubation chamber housing, for example an opening or window. An imaging device is located outside the incubation chamber and arranged to image embryos within the incubation chamber at the monitoring position through the viewing port.
Apparatus and methods for monitoring embryos in an incubator are described. The apparatus comprises an incubation chamber defined by an incubation chamber housing and a slide carrier comprising a plurality of compartment walls that define compartments for holding embryo slides within the incubation chamber for incubation. The slide carrier is moveable, for example by rotation, relative to the incubation chamber housing to allow a selected compartment to be moved to a loading position defined at least in part by a loading port wall associated with the incubation chamber housing. The loading port wall is arranged to cooperate with the wall of a compartment in the loading position to restrict the extent to which the environment of the compartment in the loading position is in fluid communication with the environments of other compartments in the incubation chamber.
A tray (100; 400; 500; 600) for accommodating a cell culture (101), such as an embryo, for use during culturing thereof and for optical monitoring of the cell culture, e.g. during in vitro fertilization comprises a carrier structure (104;404;504;604) defining at least one accommodating zone (102; 402; 502; 602) for accommodating the cell culture. At least one focal lens (110; 410; 510; 610), notably a numerical aperture increasing lens is integrally formed with the carrier structure to facilitate monitoring of the cell culture through the carrier structure. A diameter of the focal lens may exceed a diameter of the at least one accommodating zone. The focal lens may be integrally moulded with the carrier structure from a thermoplastic material.
The present invention relates to a device, a system and a method for performing monitoring and/or cultivation of microscopic objects. Microscopic objects are in particular microscopic organisms like bacteria and cell cultures, such as cultivation objects like tissue samples and embryos, providing optimal and safe cultivation conditions for incubation during embryo development and for facilitating the selection of optimal embryos to be used in vitro fertilization (IVF) by facilitating embryo handling for automated digital imaging and time-lapse microscopy.
The invention relates to an incubator having a chamber for cultivating embryos and a gas control system for maintaining a constant atmosphere in the incubating chamber. In a first aspect the invention relates to an incubator for incubating embryos, comprising an incubating chamber adapted to contain the embryos, and a gas unitary module in fluid communication with the incubating chamber comprising at least two proportional valves, a CO2 gas sensor and an O2 gas sensor, wherein the gas unitary module is adapted to receive a gas supply of N2 at one of said proportional valves and CO2 at another of said proportional valves, and control the proportional valves based on feedback from the gas sensors such that supply of N2 and CO2 to the incubation chamber is regulated to sustain a predefined level of O2 and/or CO2 in said incubating chamber.
A computer implemented method for automatically detecting variations and/or abnormalities in the developmental conditions of in vitro incubating embryos, the method comprising the steps of: a) obtaining a first dataset comprising morphokinetic parameters relating to the development of a first group of embryos, b) obtaining a second dataset comprising morphokinetic parameters relating to the development of a second group of embryos, c) modifying the first and second datasets by extracting morphokinetic parameter outliers from the first dataset and or the second datasets, d) calculating the difference between specific morphokinetic parameters from the modified first dataset and the corresponding morphokinetic parameters from the modified second dataset, and monitoring said morphokinetic difference thereby detecting variations in the developmental conditions of the first and second group of embryos.
Methods for determining a development potential for an embryo, for example an in vitro incubating human embryo, and apparatus for implementing such methods are described. In some examples a method comprises obtaining values for a plurality of morphokinetic characteristics relating to the development of an embryo during an observation period, for example characteristics relating to the temporal or morphological development of the embryo. A value for a continuous variable is determined by combining differences between the obtained values for these characteristics and corresponding reference values in a pre-defined manner. The reference values may, for example, be determined from values for the plurality of characteristics obtained for at least one reference embryo of known development potential. A development potential for the embryo is then established based on the determined value for the continuous variable.
The present invention relates to a method and to a system for selecting embryos for in vitro fertilization based on observed cell kinetics and cell morphology. One embodiment of the invention relates to a method for determining embryo quality comprising monitoring the embryo for a time period, said time period comprising the transformation of the embryo from initial compaction or morula to blastocyst and determining one or more blastocyst quality criteria for said embryo, and based on said one or more blastocyst quality criteria determining the embryo quality.
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
Goods & Services
(1) Laboratory incubators, laboratory incubators with built-in microscopes; laboratory equipment, namely, apparatus and instruments for medical analysis of in-vitro embryos.
18.
Adaptive embryo selection criteria optimized through iterative customization and collaboration
The present invention relates to a system and a method for determining quality criteria in order to select the most viable embryos after in vitro fertilization. The present invention may further be applied for iteratively adapting embryo quality criteria based on new knowledge, historical selection & fertilization data and cooperation between fertility clinics.
The present invention relates to a method and to a system for selecting embryos for in vitro fertilization based on the timing, and duration of observed cell cleavages and associated cell morphology. One embodiment of the invention relates to a method for determining embryo quality comprising monitoring the embryo for a time period, and determining one or more quality criteria for said embryo, wherein said one or more quality criteria is based on the extent of irregularity of the timing of cell divisions when the embryo develops from four to eight blastomeres, and/or wherein said one or more quality criteria is based on determining the time of cleavage to a five blastomere embryo (t5) and wherein t5 is between 48.7 hours and 55.6 hours, and/or wherein said one or more quality criteria is based on the ratio of two time intervals, each of said two time intervals determined as the duration of a time period between two morphological events in the embryo development from fertilization to eight blastomeres, and based on said one or more quality criteria determining the embryo quality.
The present invention relates to a device, a system and a method for performing monitoring and/or cultivation of microscopic objects. Microscopic objects are in particular microscopic organisms like bacteria and cell cultures, such as cultivation objects like tissue samples and embryos, providing optimal and safe cultivation conditions for incubation during embryo development and for facilitating the selection of optimal embryos to be used in in vitro fertilization (IVF) by facilitating embryo handling for automated digital imaging and time-lapse microscopy.
The present invention relates to a system arranged for assisting secure handling of cells in order to minimize the risk of handling mistakes resulting in mix-up of cell samples. The system allows for one to one identification of cells during a whole culturing period. This is obtained by providing a culturing system with loading/exit control means which ensures that only one device is capable of being loaded/removed at a time.
The present invention relates to a device, a system and a method for performing monitoring and/or cultivation of microscopic objects. Microscopic objects are in particular microscopic organisms like bacteria and cell cultures, such as cultivation objects like tissue samples and embryos, providing optimal and safe cultivation conditions for incubation during embryo development and for facilitating the selection of optimal embryos to be used in in vitro fertilization (IVF) by facilitating embryo handling for automated digital imaging and time-lapse microscopy.
The invention concerns a system and method for determining embryo quality comprising monitoring the embryo for a time period, said time period having a length sufficient to comprise at least one cell division period and at least a part of an inter-division period, and determining the length of the at least one cell division period; and/or ii) determining the extent and/or spatial distribution of cellular or organelle movement during the cell division period; and/or iii) determining duration of an inter-division period; and/or iv) determining the extent and/or spatial distribution of cellular or organelle movement during the inter-division period thereby obtaining an embryo quality measure. Thus, the selection of optimal embryos to be implanted after in vitro fertilization (IVF) is facilitated based on the timing, duration, spatial distribution, and extent of observed cell divisions and associated cellular and organelle movement.
The present invention relates to a method and a system for determination of a change in a cell population, as well as a method for using said method and system for estimating a quality measure of embryos and for selecting embryos for in vitro fertilisation, said method comprising the steps of sequentially acquiring at least two images of the cell population, comparing at least a part of the at least two images obtaining at least one difference image, computing a parameter from the at least one difference image, based on said computed parameter determining whether a change has occurred.
