Imaging modules for incubation chambers

Abstract

An incubator includes an incubation chamber configured to receive a dish having a well configured for holding a biological specimen. The incubator is configured to provide a temperature-controlled environment in the incubation chamber for culturing the biological specimen when the dish is disposed in the incubation chamber with the biological specimen in the well. The incubator further includes an imaging module configured to be removably disposed in the incubation chamber. The imaging module includes an imaging module housing and a camera arranged in the imaging module housing. The imaging module housing has a support surface configured to support the dish, and the camera is arranged to image the biological specimen when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

Description

[0001] IMAGING MODULES FOR INCUBATION CHAMBERS

[0002] CLAIM OF PRIORITY

[0003] This application claims priority to U.S. Patent Application No. 63 / 553,691 filed on February 15, 2024, the entire contents of which are hereby incorporated by reference.

[0004] TECHNICAL FIELD

[0005] This disclosure relates to imaging modules that can provide time-lapse imaging capabilities to incubation chambers of incubators.

[0006] BACKGROUND

[0007] Assisted reproductive technology (ART) protocols involve maturing a fertilized oocyte into an embryo within a culture dish that resides in an incubator. During the protocol, the incubator maintains ideal temperature and atmospheric conditions for the embryo and media that overlays the embryo within the culture dish. The embryo may be imaged during the protocol and assessed for its viability at key maturation states based on acquired images. In this regard, time-lapse incubators include digital cameras that capture images of an embryo at regular intervals (e.g., every 10 minutes).

[0008] SUMMARY

[0009] In general, this disclosure relates to imaging modules that can provide timelapse imaging capabilities to non-imaging incubation chambers.

[0010] In one aspect, an incubator includes an incubation chamber configured to receive a dish having a well configured for holding a biological specimen. The incubator is configured to provide a temperature-controlled environment in the incubation chamber for culturing the biological specimen when the dish is disposed in the incubation chamber with the biological specimen in the well. The incubator further includes an imaging module configured to be removably disposed in the incubation chamber. The imaging module includes an imaging module housing and a camera arranged in the imaging module housing. The imaging module housing has a support surface configured to support the dish, and the camera is arranged to image i the biological specimen when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

[0011] Embodiments may include one or more of the following features.

[0012] In some embodiments, the camera is aligned with a transparent portion of the imaging module housing.

[0013] In some embodiments, the transparent portion of the imaging module housing is aligned with the well of the dish when the dish is disposed on the support surface of the imaging module housing.

[0014] In some embodiments, the camera is directed toward a side wall of the imaging module housing such that the camera is configured to image the biological specimen through the side wall of the imaging module housing when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

[0015] In some embodiments, the support surface of the imaging module housing includes a recess configured to receive a peripheral portion of the dish that defines the well.

[0016] In some embodiments, the well is configured to hold the biological specimen adjacent a peripheral side wall of the dish, and the peripheral side wall of the dish is configured to be positioned adjacent the sidewall of the imaging module housing when the dish is disposed on the support surface of the imaging module housing.

[0017] In some embodiments, the well is a conical well.

[0018] In some embodiments, the camera is directed toward the support surface of the imaging module housing such that the camera is arranged to image the biological specimen through the support surface when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

[0019] In some embodiments, the support surface is a top surface of the imaging module housing.

[0020] In some embodiments, the camera is positioned beneath the support surface of the imaging module housing.

[0021] In some embodiments, the camera is arranged to align with the well when the dish is disposed on the support surface of the imaging module housing.

[0022] In some embodiments, the support surface includes a top surface of the imaging module housing and an inner facing side surface of the imaging module housing, the top surface and the inner facing side surface at least partially defining a recess for holding the dish.

[0023] In some embodiments, the camera is a first camera aligned with a first portion of the imaging module housing, and the imaging module further includes a second camera aligned with a second portion of the imaging module housing.

[0024] In some embodiments, the biological specimen in the well is a first biological specimen in a first well, and when the dish is disposed on the support surface of the imaging module housing, the first portion of the imaging module housing is adjacent the first well, and the second portion of the imaging module housing is adjacent a second well of the dish that is configured for holding a second biological specimen.

[0025] In some embodiments, the imaging module further includes a third camera aligned with a third portion of the imaging module housing and a fourth camera aligned with a fourth portion of the imaging module housing.

[0026] In some embodiments, the biological specimen in the well is a first biological specimen in a first well, and when the dish is disposed on the support surface of the imaging module housing, the first portion of the imaging module housing is adjacent the first well, the second portion of the imaging module housing is adjacent a second well of the dish that is configured for holding a second biological specimen, the third portion of the imaging module housing is adjacent a third well of the dish that is configured for holding a third biological specimen, and the fourth portion of the imaging module housing is adjacent a fourth well of the dish that is configured for holding a fourth biological specimen.

[0027] In some embodiments, the camera is arranged to align with the well of the dish when the dish is disposed on the support surface of the imaging module housing.

[0028] In some embodiments, the camera is a first camera, the well is a first well, and the imaging module further includes a second camera arranged to align with a second well of the dish when the dish is disposed on the support surface of the imaging module housing.

[0029] In some embodiments, the imaging module further includes a third camera arranged to align with a third well of the dish and a fourth camera arranged to align with a fourth well of the dish when the dish is disposed on the support surface of the imaging module housing.

[0030] In some embodiments, the imaging module further includes a light source configured to illuminate the biological specimen when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

[0031] In some embodiments, the light source is arranged below the support surface of the imaging module housing.

[0032] In some embodiments, the imaging module further includes a reflector for reflecting light, from the light source, towards the well of the dish.

[0033] In some embodiments, the reflector is a mirror.

[0034] In some embodiments, the camera is positioned peripherally outward of the support surface of the imaging module housing.

[0035] In some embodiments, the imaging module includes at least one mirror positioned beneath the support surface.

[0036] In some embodiments, the at least one mirror is configured to reflect an image of the biological sample when the dish holding the biological specimen is disposed on the support surface of the imaging module housing with the biological specimen in the well.

[0037] In some embodiments, the camera is directed toward the at least one mirror.

[0038] In some embodiments, the camera is directed toward a peripheral side wall of the dish when the dish is disposed on the support surface of the imaging module housing.

[0039] In some embodiments, the camera is positioned beneath the support surface of the imaging module housing.

[0040] In some embodiments, an imaging sensor is positioned beneath the support surface of the imaging module housing.

[0041] In some embodiments, the camera is configured to transmit images of the biological specimen to a processor located outside of the incubator.

[0042] In some embodiments, the imaging module is connected to the processor via a flat cable.

[0043] In some embodiments, the flat cable is configured to exit the incubation chamber between a lid of the incubation chamber and an incubator housing that supports incubation chamber.

[0044] In some embodiments, the imaging module is wirelessly connected to the processor. In some embodiments, the imaging module further includes a temperature sensor configured to detect a temperature within the incubation chamber when the imaging module is disposed in the incubation chamber.

[0045] In some embodiments, the temperature sensor is located adjacent the well of the dish when the dish is disposed on the support surface of the imaging module housing.

[0046] In some embodiments, the imaging module is configured to transmit the detected temperature to a processor located outside the incubator.

[0047] In some embodiments, the imaging module further includes an identification tag reader configured to read an identification tag on the dish when the dish is disposed on the support surface of the imaging module housing.

[0048] In some embodiments, the identification tag reader is an RFID reader.

[0049] In some embodiments, identification tag reader is a barcode reader.

[0050] In some embodiments, the support surface is configured to mate with the dish in a manner to minimize air gaps between the support surface and the dish.

[0051] In some embodiments, the dish includes one or more projections that matingly engage one or more recesses defined by the support surface when the dish is disposed on the support surface.

[0052] In some embodiments, the support surface includes one or more projections that matingly engage one or more recesses defined by the dish when the dish is disposed on the support surface.

[0053] In some embodiments, the incubator further includes a heating element configured to heat the support surface of the imaging module housing.

[0054] In some embodiments, the imaging module has a height, measured vertically when the imaging module is resting on a horizontal surface, of 100 mm or less.

[0055] In some embodiments, the height of the imaging module is about 30 mm.

[0056] In some embodiments, the imaging module housing includes a transparent material.

[0057] In some embodiments, the imaging module housing includes a plastic material.

[0058] In some embodiments, the imaging module housing includes a glass material.

[0059] In some embodiments, the imaging module housing includes aluminum. In some embodiments, the biological specimen in the well is a first biological specimen in a first well, and the incubator is configured to move the dish from a first position in which the first well is aligned with the camera to a second position in which a second well of the dish that is configured for holding a second biological specimen is aligned with the camera.

[0060] In some embodiments, the dish has a polygonal shape.

[0061] In some embodiments, the dish has a hexagonal shape.

[0062] In some embodiments, the dish has a circular shape.

[0063] In some embodiments, the well is configured to hold the biological specimen adjacent a peripheral side wall of the dish.

[0064] In some embodiments, at least a portion of the peripheral side wall adjacent the well is transparent to allow the biological specimen in the well to be viewed through the transparent portion of the peripheral side wall.

[0065] In some embodiments, the well is conical.

[0066] In some embodiments, the biological specimen is an embryo.

[0067] In some embodiments, the biological specimen is a blastocyst.

[0068] In some embodiments, the incubator is a flatbed incubator.

[0069] In some embodiments, the incubator has a height, measured vertically when the incubator is resting on a horizontal surface, of about 21.9 cm or less.

[0070] In some embodiments, the height of the incubator is about 18 cm.

[0071] In some embodiments, the incubation chamber is configured to receive the dish and at least one other dish when the imaging module is not disposed in the incubation chamber.

[0072] In some embodiments, the incubation chamber is configured to receive only one of the dishes when the imaging module is disposed in the incubation chamber.

[0073] In some embodiments, the incubation chamber has a depth, measured vertically when the incubator is resting on a horizontal surface, of about 100 mm or less.

[0074] In some embodiments, the incubation chamber has a depth of about 60 to about 100 mm.

[0075] In some embodiments, the incubation chamber has a depth of about 15 mm to about 20 mm.

[0076] In some embodiments, the incubation chamber has a depth of about 19 mm. In some embodiments, the incubation chamber has a length of about 5 cm to about 20 cm.

[0077] In some embodiments, the incubation chamber has a width of about 5 cm to about 15 cm.

[0078] In some embodiments, the incubator further includes a heating element configured to heat the incubation chamber.

[0079] In some embodiments, the heating element is disposed in or on the support surface of the imaging module housing.

[0080] In some embodiments, the incubation chamber is insulated.

[0081] In some embodiments, the incubation chamber includes a lid having an open position to provide access to the incubation chamber and a closed position to close the incubation chamber.

[0082] In some embodiments, the lid includes an insulating material.

[0083] In some embodiments, the lid includes a heating element.

[0084] In some embodiments, the incubator further includes a sensor to detect when the lid is in the closed position or the open position.

[0085] In some embodiments, the incubator further includes a user interface for inputting operational parameters for controlling the incubator.

[0086] In another aspect, an imaging module is configured to be removably disposed in a chamber of an incubator. The imaging module includes an imaging module housing and a camera arranged in the imaging module housing, the imaging module housing having a support surface configured to support a dish having a well for holding a biological specimen, and the camera being configured to image the biological specimen when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

[0087] In another aspect, a modular incubator system includes an incubator that has multiple incubation chambers, where each of the incubation chambers is configured to receive a dish having a well for holding a biological specimen. The incubator is configured to provide a temperature-controlled environment in each of the incubation chambers for culturing the biological specimen when the dish is disposed in one of the incubation chambers with the biological specimen in the well. The incubator also includes an imaging module configured to be removably disposed in any one of the incubation chambers. The imaging module includes an imaging module housing and a camera arranged in the imaging module housing, the imaging module housing having a support surface configured to support the dish, and the camera being configured to image the biological specimen when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

[0088] In some embodiments, the imaging module is disposed in one of the incubation chambers and at least one other incubation chamber is free of any imaging module.

[0089] In some embodiments, the at least one other incubation chamber that is free of any imaging module lacks imaging capability.

[0090] In some embodiments, the incubation chambers that are free of the imaging module lack imaging capability.

[0091] In some embodiments, the incubator is a non-imaging incubator.

[0092] In some embodiments, the imaging module, when disposed in the one of the incubation chambers, provides imaging capability for the one of the incubation chambers.

[0093] In some embodiments, the modular incubator system further includes additional imaging modules configured to be removably disposed in any one of the incubation chambers.

[0094] In some embodiments, an incubation dish includes a dish body having a peripheral side wall and defining a well configured to hold a biological specimen adjacent the peripheral side wall, at least a portion of the peripheral side wall adjacent the well being transparent to allow the well to be viewed through the peripheral side wall.

[0095] In some embodiments, the dish has a polygonal shape.

[0096] In some embodiments, the dish has a hexagonal shape.

[0097] In some embodiments, the dish has a circular shape.

[0098] In some embodiments, the well is configured to hold the biological specimen in contact with the peripheral side wall.

[0099] In some embodiments, the well is configured to allow a camera directed toward an outer surface of the peripheral side wall to image the biological specimen in the well.

[0100] In some embodiments, the well is a conical well. In some embodiments, the well is a first well, the biological specimen is a first biological specimen, and the dish body defines a second well configured to hold a second biological specimen adjacent the peripheral side wall of the dish body.

[0101] In some embodiments, at least a portion of the peripheral side wall adjacent the second well is transparent to allow the second well to be viewed through the peripheral side wall.

[0102] In some embodiments, the second well is configured to allow a camera directed toward an outer surface of the peripheral side wall adjacent the second well to image the second biological specimen in the second well.

[0103] In some embodiments, a center of the well is no more than about 2 mm from an outer surface of the peripheral side wall.

[0104] Embodiments may provide one or more of the following advantages.

[0105] In some cases, the imaging modules described herein can be placed in incubation chambers of non-imaging incubators to convert those incubators into imaging incubators. In this regard, the imaging modules and other components of an imaging system may be retrofitted to such incubators. This retrofit installation can be a more cost-efficient way of obtaining imaging capabilities in an incubator than purchasing a new incubator that is already equipped with imaging equipment.

[0106] Furthermore, one or more of the imagining modules described herein can be used to convert a non-imaging incubator to an imaging incubator on a chamber-bychamber basis. For example, an imaging module can be disposed in fewer than all of the incubation chambers of the non-imaging incubator. This selective installation can be a cost-efficient way of upgrading a non-imaging incubator to include imaging capabilities. The owner of the non-imaging incubator may, for example, only purchase imaging modules for those incubation chambers for which an imaging capability is desired. Moreover, the owner may purchase one or two imaging modules at a time, making the upgrade of the non-imaging incubator to one having imaging capabilities much more affordable than purchasing a new incubator that is already equipped with imaging equipment.

[0107] In some cases, imaging capabilities of incubators described herein (e.g., equipped with an imaging system described herein), allow for an improved incubation process as compared to processes carried out by incubators that have no such imaging capability. For example, biological specimens (e.g., embryos and other specimens) can be inspected without removing them from their ideal culture conditions. Additionally, the incubator enables inspection of the biological specimens from any site having an internet connection, rather than requiring inspection of the specimens under a microscope. Inspection of the specimens may be faster since the images can be viewed without manual processing of the specimens. Also, a greater portion of the specimen’s development process (e.g., almost the entire development process in the case of an ART procedure) can be seen by reviewing a series of images taken by the imaging module.

[0108] In certain cases, the imaging modules described herein can be used in incubation chambers of incubators that are not significantly larger (e.g., not significantly deeper) than non-imaging incubators (e.g., non-imaging flatbed incubators). An imaging module may, for example, be used in incubators that are approximately the same size (e.g., height) as known non-imaging incubators or may be used in the non-imaging incubators themselves to provide them with imaging capabilities. This can advantageously preserve highly valued space at a workstation or on another type of worksurface within a laboratory on which the incubator resides.

[0109] In some cases, dishes described herein include wells designed to hold biological specimens adjacent a peripheral side wall of the dish. This can allow the specimen to be imaged using a horizontally oriented camera of the imaging module, which can help to limit the height of the imaging module and thus the height of the incubator, thereby preserving valuable space at the workstation.

[0110] Other aspects, features, and advantages will be apparent from the description, the drawings, and the claims.

[0111] DESCRIPTION OF DRAWINGS

[0112] FIG. l is a perspective view of a portion of an incubator, including a housing, an imaging module, and a culture dish.

[0113] FIG. 2 is a perspective view of the incubator of FIG. 1, including certain additional components of an imaging system of the incubator.

[0114] FIG. 3 is an enlarged perspective view of an open incubation chamber of the incubator of FIG. 1.

[0115] FIG. 4 is side cross-sectional view of the incubation chamber of FIG. 3.

[0116] FIG. 5 is a block diagram of a gas delivery system of the incubator of FIG. 1.

[0117] FIG. 6 is a perspective view of a preparation compartment of the incubator of FIG. 1. FIG. 7 is a block diagram illustrating communications among various portions of the incubator of FIG. 1 and a separate monitoring system.

[0118] FIG. 8 is a top view of the imaging module of FIG. 1, residing within the incubation chamber of FIG. 3 and supporting the culture dish of FIG. 1.

[0119] FIG. 9 is a side cross-sectional view of the imaging module and culture dish of FIG. 8.

[0120] FIG. 10 is a top view of the culture dish of FIG. 8.

[0121] FIG. 11 is a perspective view of a peripheral well of the culture dish of FIG. 10.

[0122] FIG. 12 is a side cross-sectional view of the peripheral well of FIG. 11.

[0123] FIG. 13 is a top view of an imaging module supporting a rectangular culture dish.

[0124] FIG. 14 is a side cross-sectional view of an imaging module including cameras and light sources disposed directly beneath a support surface of the imaging module.

[0125] FIG. 15 is a side cross-sectional view of an imaging module including cameras disposed directly beneath a support surface of the imaging module and light sources disposed laterally of the support surface.

[0126] FIG. 16 is a side cross-sectional view of an imaging module including cameras, mirrors, and lenses disposed below a support surface of the imaging module.

[0127] FIG. 17 is an exploded view of the culture dish, a lens, a mirror, and a camera of FIG. 16.

[0128] FIG. 18 is a side view of a well of a culture dish, equipped with an attached lens.

[0129] FIG. 19 is a side cross-sectional view of an imaging module including image sensors and lenses disposed directly beneath a support surface of the imaging module.

[0130] FIG. 20 is a top view of an imaging module including a fixed camera and supporting a rotatable, circular culture dish.

[0131] FIG. 21 is a top view of an imaging module including fixed cameras and supporting a translatable, rectangular culture dish.

[0132] FIG. 22 is a top view of a culture dish including a peripheral well along each hexagonal wall portion of the dish. DETAILED DESCRIPTION

[0133] FIGS. 1 and 2 illustrate an incubator 100 that is designed to house biological specimens 320 as part of a developmental protocol. Example biological specimens 320 that may be housed within the incubator 100 include reproductive specimens (e.g., human and non-human embryos) and other biological specimens, such as various types of mammalian cell cultures. For example, a human embryo may be cultured within the incubator 100 as part of an ART protocol. In other examples, biological specimens 320, more generally, may be cultured within the incubator 100 as part of any number of cell culture protocols.

[0134] The incubator 100 is operable by a user (e.g., a scientist or laboratory technician) to provide optimal growth conditions for biological specimens 320 and has a time-lapse imaging capability to provide visualization of the biological specimens during their growth cycles. Accordingly, the incubator 100 includes a housing 102, an imaging system 104 that is assembled with (e.g., retrofitted or otherwise installed within) the housing 102, a user interface module 106 that is supported on the housing 102, and a control system 101 (shown in FIG. 7) that is located within the housing 102. In some embodiments, an optional, separate monitoring system 198 (shown in FIG. 7) is located exteriorly of the incubator 100 and may receive data from and / or send data to the incubator 100.

[0135] The housing 102 includes an incubation compartment 108 that forms a flatbed-style configuration, a base compartment 110 that supports the incubation compartment 108, and an optional preparation compartment 112 that extends upward from the base compartment 110. The incubation compartment 108 includes an outer peripheral wall 114 and a top wall 116 with multiple (e.g., ten) substantially rectangular (e.g., rectangular-round) openings 118 arranged in two (e.g., front and rear) rows.

[0136] Referring to FIGS. 1-3, the incubation compartment 108 is sized to accommodate multiple receptacles 120 that are respectively installed to the housing 102 at the openings 118. Accordingly, the receptacles 120 include a bottom wall portion 122 and four side wall portions 124 (shown in FIG. 3) and have the same cross-sectional shape (e.g., substantially rectangular) as the shape of the openings 118. Each receptacle 120 is sized to receive one or more culture dishes directly. The size of the receptaclel20 also allows the receptaclel20 to alternatively receive an imaging module 200 of the imaging system 104. The imaging module 200 can, itself, support a culture dish 300, as will be discussed in more detail below with respect to FIGS. 8 and 9.

[0137] Referring to FIG. 3, in some embodiments, each receptacle 120 is attached (e.g., bolted or otherwise fastened or adhered) to the top wall 116 of the incubator 100 along an edge of the respective opening 118. The receptacle 120 can, for example, be screwed or otherwise fastened to the top wall 116 and / or to other structures within the housing 102 of the incubator 100. The receptacle 120 is attached in a manner such that a top surface of the receptacle 120 is substantially flush with the top wall 116 of the incubation compartment 108.

[0138] The receptacle 120, as noted above, includes the bottom wall portion 122 and the side wall portion 124, which cooperate with a lid 126 of the incubator 100 to define an incubator chamber 128. In some embodiments, the receptacle 120 has a length (e.g., extending along an x axis between opposite inner surfaces) of about 5 cm to about 20 cm (e.g., about 15 cm) and a width (e.g., extending along ay axis between opposite inner surfaces) of about 5 cm to about 15 cm (e.g., about 10 cm). In some embodiments, the receptacle 120 has a depth (e.g., extending along a z axis from the top wall 116 to an upper surface of the bottom wall portion 122) of about 100 mm or less. For example, in some embodiments, the receptacle 120 has a depth of about 60 mm to about 100 mm. In some embodiments, the receptacle 120 has a depth of about 15 mm to about 20 mm (e.g., about 19 mm).

[0139] Referring to FIGS. 1-3, the housing 102 is equipped with multiple lids 126 that respectively cover the multiple receptacles 120. Each receptacle 120 and respective lid 126 together form the incubation chamber 128 that is sized to contain the imaging module 200 while the imaging module 200 supports the culture dish 300. The lid 126 is coupled to a connector block 132 with an internal pin that extends through the connector block 132 and the lid 126. The lid 126 is pivotable with respect to the connector block 132 between an open position that provides access to the incubation chamber 128 and a closed position that substantially isolates the incubation chamber 128 from an ambient environment. A gas nozzle 103 is connected to the sidewall portion 124 of the receptacle 120 for delivering a gas mixture to the incubation chamber 128. A similar gas nozzle may be found in the opposite sidewall of the receptacle 120 for removing gas from the incubation chamber 128. After the lid 126 has been closed, the incubator 102 is operable to achieve and substantially maintain programmed (e.g., user-set or pre-set) temperature and gas conditions within the incubation chamber 128.

[0140] Referring to FIGS. 3 and 4, the lid 126 includes a base plate 134 that encloses a broad heating element 136 (e.g., a heater foil or another type of heating element) and one or more gaskets 138 that are secured to an inner surface of the base plate 134 (e.g., at one or more respective recesses). The receptacle 120 is also equipped with one or more heating elements 130 (e.g., heater foils) that are exteriorly attached to one or both of the bottom wall portion 122 and the side wall portion 124 within the incubation compartment 108. When the lid 126 is closed against the housing 102, the one or more gaskets 138 seal against the receptacle 120 and the top wall 116 to isolate the incubation chamber 128.

[0141] The receptacle 120 is further equipped with a control temperature sensor 170 (e.g., a thermostat) and a monitoring temperature sensor 172 that are secured exteriorly to the bottom wall portion 122. The control sensor 170 is coupled to the control system 101 (shown in FIG. 7), and the monitoring sensor 172 is coupled to a monitoring system 198 (shown in FIG. 7) that is located within the housing 102 of the incubator. The control temperature sensor 170 is also coupled to and controls (e.g., via the control system 101) operation of the heating elements 130, 136 to achieve a set (e.g., target) temperature within the incubation chamber 128. The monitoring sensor 172 monitors a temperature of the receptacle 120 as an indication of the temperature within the incubation chamber 128. The monitoring system 198 is separate (e.g., electrically isolated) from the control system 101.

[0142] The receptacle 120 is made of one or more materials that are suitable for adequately conducting heat generated by the heating elements 136 to an interior region of the incubation chamber 128 and to a culture dish or an imaging module 300 positioned directly on the receptacle 120. Example materials from which the receptacle 120 may be made include aluminum and other suitable materials. Example materials from which the lid 126 may be made include materials that provide strong insulation properties. In some embodiments, the lid 126 may also be equipped with an internal heating element and conducting material.

[0143] As shown in FIGS. 1 and 2, the base compartment 110 includes two lateral walls 105, a bottom wall 107, a rear wall 109, and a top wall 111. The top wall 111 opens to the incubation compartment 108 and the preparation compartment 112. The base compartment 110 supports a power connection port on the rear wall 109 for connecting the incubator 100 to a wall outlet via cable connection. The base compartment 110 contains components of a gas delivery system 180, the preparation compartment 112, the control system 101, the monitoring system 198, and other supporting electronic components.

[0144] FIG. 5 illustrates a block diagram of the gas delivery system 180 of the incubator 100. The gas delivery system 180 includes a manifold 173 that is installed to the rear wall 109. Remaining components of the gas delivery system 180 are contained within the base compartment 110. The manifold 173 receives and routes carbon dioxide (CO2) 174 and nitrogen (N2) 176 to a gas mixing chamber 178 through a gas line 182. The gas delivery system 180 includes a filtration module 183 along the gas line 182 that includes a HEPA filter and a volatile organic compound (VOC) filter. The gas mixing chamber 178 is equipped with a CO2 sensor 184 and an oxygen (02) sensor 186 to monitor CO2 and 02 concentrations of a mixture containing the incoming CO2 and N2 gases. Based on concentration measurements acquired at the sensors 184, 186, valves on the manifold 173 are operated (e.g., opened and closed) to adjust the flow rates of CO2 174 and N2 176 to achieve pre-set (e.g., target) CO2 and 02 concentrations of the gas mixture.

[0145] From the gas mixing chamber 178, the mixed gas flows through a gas line 188 to a gas monitoring chamber 190. The monitoring chamber 190 is located just upstream of the incubation chambers 128 to allow for an additional measurement of the concentration profile of the gas mixture before the mixture is delivered to the chambers 128. In this regard, the monitoring chamber 190 is equipped with a sampling port 192 through which a small sample flow of the gas mixture can flow to an external gas sensor that measures both CO2 and 02 concentrations. The monitoring chamber 190 and the external gas sensor are operationally separate (e.g., electrically isolated) from the control system 101 to allow for independent verification of the gas concentration profile of the mixture. From the monitoring chamber 190, the gas mixture flows into a gas line 194 that delivers the gas mixture to the incubation chambers 128 via multiple, respective distribution lines 196 and respective gas nozzles 103 that are attached to the receptacles 120.

[0146] Referring to FIG. 6, the preparation compartment 112 provides a space that may be optionally used for a brief period to warm a bottle of culture media. The preparation compartment 112 includes a cylindrical wall 113, a pivotable lid 117, and a top support wall 119. The top support wall 119 supports an internal receptacle 121 that is sized to accommodate the bottle of culture media, and the internal receptacle 121 is equipped with one or more exterior heating elements (not visible) for warming the bottle. The internal receptacle 121 is also equipped with an exterior temperature sensor (not visible) that monitors a temperature within the compartment 112 and that is coupled to the control system 101. The lid 117 carries an open / close sensor that causes the gas delivery to stop while the lid 117 is open and to flow while the lid is closed.

[0147] In some embodiments, the housing 102 of the incubator 100 has a height, measured vertically when the incubator 100 is resting on a horizontal surface, of about 21.9 cm or less. For example, in some embodiments, a height of the incubator 100 is about 18 cm.

[0148] Referring to FIGS. 1, 2, and 7, the user interface module 106 is a touchscreen display that presents system information to a user. Such information includes settings, monitored properties (e.g., temperatures and gas concentrations), specimen information (e.g., identification information and other information), and visual warnings and alerts, among other information. The module 106 also presents user interfaces that provide input fields for receiving various operational inputs from the user. The user interface module 106 is coupled to the control system 101, as indicated in FIG. 7. In some embodiments, the user interface module 106 may additionally, optionally, be in wireless communication with a separate computer.

[0149] Still referring to FIG. 7, the control system 101 is programmed to control operations of the incubator 100 based on stored data and based on input parameters received at the user interface module 106. Accordingly, the control system 101 is electronically coupled to the incubation chambers 128 and preparation compartment 112 (e.g., to the above-discussed heating elements and sensors). The control system 101 is also electronically coupled to the user interface module 106 and to the components of the gas delivery system 180. The control system 101 includes one or more processors 125 and supporting electronic components 127 for carrying out its functionalities. In some embodiments, the control system 101, additionally, optionally, include a wireless transmitter for sending data to a separate computer.

[0150] As indicated in FIG. 7, the separate monitoring system 198 can communicate with the gas delivery system 180 (e.g., via the external gas sensor at the gas monitoring chamber 190) and with the incubation chambers 128 (e.g., via the monitoring sensors 172). The monitoring system 198 includes one or more processors 129 and supporting electronic components 131 for carrying out its functionalities. The monitoring system 198 is electronically isolated from the control system 101 to provide backup (e.g., duplicate or redundant) system checks that cannot be compromised by a state of the control system 101. In some embodiments, the monitoring system 198 further communicates with the user interface module 106. In some embodiments, the monitoring system 198 includes a wireless transmitter for sending data to a separate computer.

[0151] Referring again to FIG. 2, the imaging system 104 includes one or more imaging modules 200 and a control and data processing unit 202. The unit 202 controls various functionalities of the imaging modules 200 and processes output data sent from the imaging modules 200. In some embodiments, the unit 202 receives data wirelessly from the user interface module 106. In some embodiments, the unit 202 receives data from the control system 101. In some embodiments, the unit 202 includes a transmitter 253 that sends data (e.g., images, associated metadata, and other data) wirelessly over a network 258 to one or more computing devices 260 and to a server system 262 to be stored in a database 264. The unit 202 includes a housing 248 that contains internal electronics 250 and one or more processors 252 for carrying out its functionalities. In some embodiments, the unit 202 may be plugged into a wall outlet for power. In some embodiments, the unit 202 includes an on-board power supply (a battery) as a primary or backup power supply.

[0152] Still referring to FIG. 2, the imaging system 104 also includes a power distribution component 204 (e.g., a bus bar) that transmits power between the imaging modules 200 and the unit 202. The power distribution component 204 includes two branches 254 that respectively extend along the two rows of incubation chambers 128. The power distribution component 204 is coupled to the imaging modules 200 via cables 246, which will be discussed in more detail below with respect to FIG. 8.

[0153] Referring to FIGS. 8 and 9, the imaging module 200 is sized and shaped to fit within the incubation chamber 128 (e.g., with the lid 126 closed against the top wall 116 of the housing 102) to confer an imaging capability to the incubation chamber 128. The imaging module 200 therefore includes a housing 206 that has a substantially rectangular outer shape (e.g., outer envelope). In some embodiments, the imaging module 200 may be unattached to any portion of the incubation chamber 128 and maintained in position by a loose friction fit between the housing 206 and the side wall portion 124 of the incubation chamber 128. The housing 206 includes a top wall 208, a bottom wall 210, and an outer side wall 212 that extends vertically between the top and bottom walls 208, 210. The housing 206 also includes a base wall 214 and an inner side wall 216 that extends vertically between the top wall 208 and the base wall 214.

[0154] The base wall 214 and the inner side wall 216 together define a dish receptacle (e.g., recess) 218 (refer to FIG. 1) that is sized and shaped to locate a culture dish 300 at an observation position on the housing 206 of the imaging module 200. For example, the inner side wall 216 is formed complementarily to a side wall 306 of the culture dish 300, and the base wall 214 defines a support surface 220 that is formed complementarily to a bottom wall 308 of the culture dish 300. Accordingly, the base wall 214 includes a horizontal portion 232 and multiple (e.g., four) downwardly- projecting portions 256 that extend towards the inner side wall 216. The portions 256 and the inner side wall 216 together form recesses 234 in the dish receptacle 218.

[0155] Both the inner side wall 216 of the housing 206 and the side wall 306 of the culture dish 300 have a polygonal (e.g., hexagonal) cross-sectional shape. The inner side wall 216 includes two transparent or translucent wall portions arranged on each of a front and rear side of the dish receptacle 218 that serve as viewing windows 222 into the culture dish 300. The inner side wall 216 also includes two wall portions 224 (e.g., blanks) arranged on opposite lateral sides of the culture dish 300, as shown in FIG. 8. The wall portions 224 do not provide a viewing functionality and therefore may be any of opaque, transparent, or translucent. In some cases, the entire inner side wall 216 is transparent or translucent.

[0156] Within an interior region 226 of the housing 206, the imaging module 200 includes four miniature cameras 228 and two miniature light sources 230 (e.g., LEDs) located on opposite sides of each camera 228. Each camera 228 and its accompanying light sources 230 are positioned adjacent a respective viewing window 222 of the inner side wall 216. The cameras 228 and the light sources 230 face the viewing window 222 such that the light sources 230 directly illuminate the culture dish 300 through the viewing windows 222 and such that the cameras 228 and the light sources 230 are oriented perpendicularly to the viewing window 222. As shown in FIG. 9, the cameras 228 are horizontally oriented and vertically aligned with specimens 320 residing within wells 310 of the dish 300 to image the specimens 320. Each camera 228 includes a camera housing 238 containing an imaging sensor 240 and electronics 242 that control the imaging sensor 240. The electronics 242 also process, store, and transmit images acquired by the camera 228.

[0157] Additionally, in some embodiments, the housing 206 of the imaging module 200 optionally includes a heating element 133 for direct heating of the imaging module 200. In some embodiments, the heating element 133 may be positioned at (e.g., within or underneath) the support surface 220. In other embodiments, the heating element 133 may be positioned on a different portion of the housing 206, such as on the outer side wall 212 or on the bottom wall 210. In some embodiments, the imaging module 200 includes one or more temperature sensors 236 (e.g., resistance temperature detectors (RTDs) or thermocouples). In some embodiments, a temperature sensor 236 may be positioned adjacent a recess 234 for detecting a temperature within close proximity to the biological specimen 320. In other embodiments, the temperature sensor 236 may be positioned on the horizontal portion 232 of the dish receptacle 218.

[0158] In some embodiments, the housing 206 is also equipped with an identification tag reader 244 that is positioned within or underneath the support surface 220 for reading an identification tag 326 on the culture dish 300 when the culture dish 300 is seated on the support surface 220. In some embodiments, the tag reader 244 is a radio frequency identification (RFID) tag reader. In other embodiments, the tag reader 244 is a barcode reader or a 2D barcode reader (e.g., a QR code reader).

[0159] In some embodiments, the inner side wall 216 of the housing 206 has a height that extends along the z axis). In some embodiments, the base wall 214 of the housing 206 has a total length that extends along the x axis between opposite vertices of the hexagonal inner side wall 216 In some embodiments, the base wall 214 has a total width that extends along they axis between opposite wall portions 224. In some embodiments, each recess 234 of the dish receptacle 218 has a certain length and projects radially inward from the inner side wall 216 at an angle fl of about 45 degrees to about 89 degrees. The horizontal portion 232 is spaced apart from the top wall 208.

[0160] In some embodiments, the viewing windows 222 of the inner side wall 216 are made of transparent or translucent plastic or glass and have a wall thickness of about 0.5 mm to about 1.5 mm. In some embodiments, the remaining portions of the housing 206 (including the wall portions 224) are made of aluminum or another metal. The construction provided by such materials and wall thickness facilitates the transfer of heat through the housing 206 for warming the culture dish 300 seated within the dish receptacle 218.

[0161] As discussed above, the imaging module 200 is sized and shaped to fit within the incubation chamber 128. Therefore, in some embodiments, the housing 206 has a total length (e.g., extending along the x axis shown in FIG. 3 when the imaging module 200 is in the incubation chamber 128) of about 5 cm to about 20 cm and a total a width (e.g., extending along the y axis shown in FIG. 3 when the imaging module 200 is in the incubation chamber 128) of about 5 cm to about 15 cm. In some embodiments, the housing 206 has a total height (e.g., extending along the z axis shown in FIG. 3 when the imaging module 200 is in the incubation chamber 128) of about 100 mm or less. For example, in some embodiments, the housing 206 has a height of about 30 mm.

[0162] Referring to FIGS. 7 and 8, the imaging module 200 also includes a multistrand cable 246 that is connected to the housing 206 to power internal components of the imaging module 200, including the camera 228, light sources 230, optional heating element 133, temperature sensors 236, and any other electronic components of the imaging module 200. The cable 246 also delivers control signals from the unit 202 to these components and delivers output data from these components to the unit 202. In some embodiments, the cable 246 connects to the housing 206 at a connection port along the outer side wall 212 of the housing.

[0163] The cable has a flat, thin construction such that the cable 246 can extend out of the incubation chamber 128 between the lid 126 and the top wall 116 of the incubation compartment 108 without creating a significant gap between the lid 126 and the top wall 116. For example, when the lid 126 is closed against the top wall 116, the one or more gaskets 138 on the lid 126 seal around the cable 246 to limit air leaks from the incubation chamber 128 to the ambient environment, thereby maintaining isolation of the incubation chamber 128.

[0164] While the cable 246 has been described as forming a hardwire connection between the imaging module 200 and the unit 202, in some embodiments, the cable 246 may include a wireless transmitter that is located outside of the incubation chamber 128 and can transmit and receive signals and data from the unit 202 instead of using a bus bar to transmit such information to the unit 202. In some embodiments, the lid 126 defines a shallow, flat recess along an inner surface to accommodate the cable 246. In some embodiments, the cable 246 has a width of about 0.5 cm to about 3 cm and a thickness of about 0.5 mm to about 2 mm. The cable 246 typically has a length (e.g., extending between the housing 206 and the respective branch 254 of the power distribution component 204) of about 5 cm to about 15 cm.

[0165] In some cases, the imaging module 200 can be placed in chambers, such as the incubation chambers 128, of non-imaging incubators to convert those incubators into imaging incubators. In this regard, the imaging module 200 and other components of the imaging system 104 may be retrofitted to such incubators. This retrofit installation can be a more cost-efficient way of obtaining imaging capabilities in an incubator than purchasing a new incubator that is already equipped with imaging equipment.

[0166] Furthermore, one or more of the imagining modules 200 can be used to convert a non-imaging incubator to an imaging incubator on a chamber-by-chamber basis. For example, an imaging module 200 can be disposed in fewer than all of the incubation chambers of the non-imaging incubator. This selective installation can be a cost-efficient way of upgrading a non-imaging incubator to include imaging capabilities. The owner of the non-imaging incubator may, for example, only purchase imaging modules 200 for those incubation chambers for which an imaging capability is desired. Moreover, the owner may purchase one or two imaging modules 200 at a time, making the upgrade of the non-imaging incubator to one having imaging capabilities much more affordable than purchasing a new incubator that is already equipped with imaging equipment.

[0167] In some cases, the imaging capabilities of the incubator 100, equipped with the imaging system 104, allow for an improved incubation process as compared to processes carried out by incubators that have no such imaging capability. For example, biological specimens (e.g., embryos and other specimens) can be inspected without removing them from their ideal culture conditions. Additionally, the incubator 100 enables inspection of the biological specimens from any site having an internet connection, rather than requiring inspection of the specimens under a microscope. Inspection of the specimens may be faster since the images can be viewed without manual processing of the specimens. Also, a greater portion of the specimen’s development process (e.g., almost the entire development process in the case of an ART procedure) can be seen by reviewing a series of images taken by the imaging module 200. In certain cases, the imaging module 200 can be used in incubation chambers of incubators that are not significantly larger (e.g., not significantly deeper) than nonimaging incubators (e.g., non-imaging flatbed incubators). The imaging module 200 may, for example, be used in incubators that are approximately the same size (e.g., height) as known non-imaging incubators or may be used in the non-imaging incubators themselves to provide them with imaging capabilities. This can advantageously preserve highly valued space at a workstation or on another type of worksurface within a laboratory on which the incubator resides.

[0168] Referring to FIGS. 8-10, the culture dish 300 is constructed in a manner such that the dish 300 can securely mate with the dish receptacle 218 of the imaging module 200. The culture dish 300 includes a multi-well plate 302 and a removable lid 304 that covers the plate 302. The plate 302 includes the sidewall 306 and the bottom wall 308, which are respectively formed complementarily to the inner side wall 116 and the base wall 214 of the imaging module 200. The sidewall 306 therefore includes four specimen wall portions 312 and two additional wall portions 314 that together provide a hexagonal cross-sectional shape. The plate 302 includes four peripheral specimen wells 310 respectively arranged along the four specimen wall portions 312. As shown in FIG. 8, when the culture dish 300 is disposed within the dish receptacle 218 of the imaging module 200, the wells 310 are aligned with the viewing windows 222.

[0169] Referring to FIGS. 9-12, each well 310 has a conical (e.g., half-cone) three- dimensional shape such that the well 310 extends downward from a flat portion 316 of the bottom wall 308 to the specimen wall portion 312. Such downward projection causes a specimen 320 within the well 310 to move downward under the force of gravity to a specimen seat 318 of the well 310. The specimen 320 can grow and develop atop the specimen seat 318 within one or more drops of culture media 324 during a developmental protocol. In some embodiments, the specimen 320 resides within a total of about 20 pL to about 50 pL of culture media 324. Additionally, an interior region 322 of the plate 302 (e.g., including a volume above the wells 310 and extending along the flat portion 316) can typically accommodate about 3 mL to about 12 mL of oil 325 that overlays the culture media 324 and flat portion 316 of the culture dish 300.

[0170] In some embodiments, the half-cone shape of the well 310 may be provided by one rounded structure or by multiple flat portions that together approximate the shape of a half-cone. The shape of the downwardly-projecting portions 256 of the housing 206 are formed complementarily, accordingly. Owing to its half-cone shape, the well 310 has a semicircular cross-sectional shape in an x'y' plane and a triangular cross- sectional shape in an y'z plane. Furthermore, an included angle of the well 310 is equal to the angle fl defined above with respect to the housing 206 of the imaging module 200. In some embodiments, the well 310 has a radius of about 0.2 cm to about 1 cm.

[0171] An overall profile of the culture dish 300 is sized just slightly smaller than that of the dish receptacle 218 of the housing 206 to achieve a custom, loose friction fit between the culture dish 300 and the imaging module 200. Accordingly, the culture dish 300 has a maximum width (e.g., extending between any two opposite vertices of the hexagonal side wall 306) of about 5 cm to about 18 cm and a minimum width (e.g., extending between any two opposite wall portions 314, 316) of about 4 cm to about 16 cm. The plate 310 extends above the housing 206 of the imaging module 200 when the culture dish 300 is positioned within the dish receptacle 218.

[0172] Both the plate 302 and the lid 304 are made of one or more transparent or translucent materials, such as polystyrene. Additionally, the culture dish 300 is equipped with an identification tag 326 that is adhered to a lower surface of the bottom wall 308. The tag 326 is readable by the tag reader 244 on the imaging module 200. In some embodiments, the tag 326 is an RFID tag. In other embodiments, the tag 326 is a barcode or a 2D barcode (e.g., a QR code).

[0173] In an example operation, a biological specimen 320 (e.g., a human embryo) may be cultured and observed in the incubator 100 during an ART protocol. Appropriate gas and temperature conditions for a selected incubation chamber 128, equipped with an imaging module 200, are verified at the user interface module 106 of the incubator 100. Once the conditions are verified, the culture dish 300, carrying the specimen 320 within a peripheral well 310 and culture media 324 within the interior region 322, is placed on the support surface 220 (e.g., within the dish receptacle 218) of the imaging module 200. The dish 300 is positioned such that the wells 310 are aligned with the viewing windows 222, as shown in FIGS. 8 and 9. The lid 126 is closed to isolate the imaging module 320 within the incubation chamber 128.

[0174] The specimen 320 (e.g., initially, a successfully fertilized oocyte or blastocyst) is left to grow undisturbed during a developmental period (e.g., about 5-6 days) without any manual inspection or manipulation of the imaging module 200 or the incubation chamber 128. During the developmental period, the respective camera 228 acquires an image of the specimen 320 through the viewing window 222, with the specimen illuminated by the respective light sources 230. The image acquisition frequency reflects one or more user inputs provided at the user interface module 106 either prior to or just after placement of the culture dish 300 within the dish receptacle 218. In some examples, the camera 228 acquires images at a regular frequency of about 10 minutes throughout the developmental period.

[0175] Via the cable 246, the camera 228 sequentially sends each image to the control and data processing unit 202 soon after capture and initial processing at the camera 228. The unit 202 then further processes the image and sequentially transmits the image over a wireless network 258, as indicated in FIG. 7. For example, the images are transmitted to a computing device 260 and to the server system 262 to be stored in the database 264. At the computing device 260, the images are analyzed to determine the developmental status of the specimen 320.

[0176] The status may be determined by the user after having viewed and analyzed the images or determined algorithmically by the computing device 260. The specimen 320 may then be removed from the culture dish 300 or permitted to remain in the dish 300 for an additional culture and imaging period (e.g., about one day) if the specimen 320 is assessed as immature. A removed specimen 320 that was assessed as mature and viable may be treated for transfer to a patient, biopsy, or cryopreservation. A removed specimen 320 that was assessed as unviable may be discarded.

[0177] Other embodiments of incubators, imaging modules, and culture dishes are possible. For example, while the imaging module 200 has been described and illustrated as being placed in an incubation chamber 128 (e.g., without any physical connection to the incubation chamber 128 and with the flat cable 246 extending out of the incubation chamber 128), in some embodiments, an imaging module that is otherwise substantially similar in construction and function to the imaging module 200 may be provided as a plug-in imaging module that can be plugged into any specially designed incubation chambers of an incubator. Such incubation chamber is sized and shaped to receive the plug-in imaging module and includes a custom connection port that is designed to mate with the plug-in imaging module. In some embodiments, this type of imaging module receives power from the power source of the incubator 100. This design avoids gas leakage that might otherwise result from a flat cable, such as the cable 246, extending out of the incubation chamber.

[0178] In some embodiments, an incubator that is substantially similar in construction and function to the incubator 100 may include interchangeable non-imaging receptacles 120 and imaging receptacles to which an imaging module 200 is permanently attached. Accordingly, both the non-imaging receptacles 120 and the imaging receptacles are removable and can be reinstalled to a housing of the incubator. Such embodiments enable the imaging receptacles to be integrated into the incubator in much the same way that the receptacles 120 have been described above as being integrated into the incubator 100.

[0179] While the imaging module 200 and the culture dish 300 have been described and illustrated as having hexagonal profiles, in some embodiments, an imaging module and a culture dish that are similar in construction and function to the imaging module 200 and the culture dish 300, respectively, have different polygonal profiles. For example, FIG. 13 illustrates a configuration of an imaging module 201 and a culture dish 301 that have certain rectangular profiles. The culture dish 301 includes a lid and a multi-well plate 303 with three peripheral wells 311 located along opposite specimen wall portions 313 of a side wall 307. Each peripheral well 311 is substantially shaped as a half-cone, as described above with respect to the peripheral wells 310.

[0180] The imaging module 201 includes a housing 207 with a substantially rectangular dish receptacle and support surface that locate the dish 301 at an observation position. The imaging module 201 includes three cameras 229 and a light source 231 positioned between adjacent cameras 229. The cameras 229 and the light sources 231 are located within an interior region 227 of the housing 207. The cameras 229 are positioned along opposite sides of the dish receptacle in alignment with the wells 311. The housing 207 is sized to fit within an incubation chamber 128. The cameras 229 and the light sources 231 are substantially similar in construction and function to the cameras 228 and light sources 230, except that their dimensions may be different to accommodate the rectangular profile of the housing 207.

[0181] The imaging module 201 may further include a temperature sensor, a cable, and a tag reader (not shown). Other features, aspects, and components of the imaging module 201 and the culture dish 301 are similar in construction and function to like features, aspects, and components described above with respect to the imaging module 200 and the culture dish 300.

[0182] While the imaging modules 200, 201 have been described and illustrated as including horizontally-oriented cameras 228, 229 that face a flat side wall 306, 307 of the culture dish 300, 301, in some embodiments, an imaging module that is similar in construction and function to the imaging modules 200, 201 instead includes cameras with a different orientation and position. For example, FIG. 14 illustrates an imaging module 400 that includes vertically-arranged cameras 428 located underneath and facing a bottom wall 508 of a culture dish 500.

[0183] The imaging module 400 includes a housing 406 with a flat base wall 418 that defines a support surface 420 for the culture dish 500. The base wall 418 forms part of a relatively shallow dish receptacle 418 and is made of a transparent material in at least those portions spanning and located directly beneath wells 510 of the culture dish 500. Accordingly, the dish receptacle 418 locates the culture dish 500 at an observation position. The imaging module 400 includes a housing 406 and one or more pairs of cameras 428 located on opposite sides of the housing 406 within an interior region 426. The imaging module 400 also includes a light source 430 positioned between each pair of cameras 428 for illuminating the culture dish 500. Each camera 428 is aligned with a well 510 of the culture dish 500. The cameras 428 and the light sources 430 are substantially similar in construction and function to the cameras 228 and light sources 230, except that their dimensions may be different in association with the profile of the housing 406. The imaging module 400 further includes a temperature sensor, a cable, and a tag reader (not shown).

[0184] The culture dish 500 includes a lid 504 and a multi-well plate 502 that defines the wells 510. A lower surface of the bottom wall 508 of the plate 502 is substantially flat across the entire wall 508. The plate 502 and the lid 504 may have a circular or polygonal cross-sectional shape. The wells 510 have a conical or otherwise tapered shape. The lid 504 of the culture dish 500 optionally includes two reflectors 528 located on opposite sides of the lid 504 (e.g., radially inward of the two wells 510). The reflectors 528 reflect incident light from the light sources 430 towards the specimens 320 to enhance illumination of the specimens 320.

[0185] Owing to the vertical orientation of the cameras 428, the housing 406 of the imaging module 400 is taller than the housing 206 of the imaging module 200. For this reason, an assembly of the imaging module 400 and the culture dish 500 accordingly may only fit within incubation chambers that can accommodate such depth.

[0186] Other features, aspects, and components of the imaging module 400 and the culture dish 500 are similar in construction and function to like features, aspects, and components described above with respect to the imaging module 200 and the culture dish 300. In some embodiments, a culture dish that is otherwise substantially similar in construction and function to the culture dish 500 does not include the reflectors 528.

[0187] FIG. 15 illustrates an imaging module 401 that is similar in construction and function to the imaging module 400, except that light sources 431 are located along sides of wells 511 of a culture dish 501 instead of underneath the wells 511. As a result, the biological specimens 320 within the wells 511 can be exposed to direct light from the light sources 431. A lid 505 of the culture dish 501 does not include reflectors in the illustrated embodiment. However, reflectors may be used to further increase the light level to which biological specimens in the wells 511 are exposed. A housing 407 of the imaging module 401 is dimensioned to accommodate the lateral arrangements of the light sources 431. The imaging module 401 and the culture dish 501 are otherwise substantially similar in construction and function to the imaging module 400 and the culture dish 500.

[0188] In some embodiments, an imaging module that is similar in construction and function to the imaging module 400 (e.g., with cameras located below a culture dish) has horizontally-oriented cameras to reduce vertical space required within a housing of the imaging module underneath a culture dish. For example, FIG. 16 illustrates such an imaging module 600, which is designed to support the culture dish 501. The imaging module 600 includes a housing 606 and one or more pairs of cameras 628 located on opposite sides of the housing 606 within an interior region 626. The imaging module 600 also includes a light source 630 positioned between each pair of cameras 628 for illuminating a culture dish 600. The cameras 628 and the light sources 630 are substantially similar in construction and function to the cameras 228 and light sources 230, except that their dimensions may be different in association with the profile of the housing 606. The imaging module 600 may further include a temperature sensor, a cable, and a tag reader (not shown).

[0189] The cameras 628 are oriented horizontally and positioned underneath a base wall 614 (e.g., defining a support surface 620) of the housing 606. However, instead of the camera 628 being aligned with the wells 511, the cameras 628 are positioned radially (e.g., peripherally) outward of the wells 511. The imaging module 600 therefore includes a mirror 666 positioned underneath each well 511 and vertically aligned with the respective camera 628. The mirror 666 is oriented at an angle of about 30 degrees to about 60 degrees with respect to a bottom wall 610 of the housing 606. The mirror 666 receives light rays emanating from a region of the culture dish 501 within proximity to the well 511. The mirror 666 reflects the light rays into the camera 628, and the camera 628 forms an image from the reflected light rays.

[0190] The imaging module 600 also includes a lens 668 located directly below each well 511, resulting in a magnification of the images produced from the light rays passing through the lens 668 to the mirror 666. Such magnification, owing to a presence of the lens 668, is able to be achieved without increasing a size of an interior region of the imaging module 600. In some embodiments, the lens 668 is built into the base wall 614 of the housing 606, either as a molded-in feature or as an assembled component. In other embodiments, a lens may alternatively be built into the bottom wall 508 of the plate 502 of the culture dish. For example, the lens 668 may be attached to the plate 502 in a snap-on or screw arrangement. FIG. 17 illustrates an exploded view a configuration for which a lens 668 is attached to a well 511, and FIG. 18 illustrates an enlarged view of the lens 668 attached to the well 511. In some cases, the lens 668 is reusable, which is advantageous if the optics in the lens 668 are expensive.

[0191] Due to the horizontal orientation of the cameras 628, the housing 606 is shallower than the housing 406. Other features, aspects, and components of the imaging module 600 are similar in construction and function to like features, aspects, and components described above with respect to the imaging module 400.

[0192] FIG. 19 illustrates an imaging module 601 that is substantially similar in construction and function to the imaging module 600, except that an imaging sensor 641 of a camera 629 is positioned underneath the well 511 and a lens 669 instead of a mirror. The remaining components of the camera 629 are spaced apart from the sensor 641 and located radially (e.g., peripherally) outward of the wells 511. Elimination of mirrors reduces the vertical space required by a housing 607 underneath the culture dish 501. Therefore, the housing 607 may be shallower than the housing 606. The imaging module 601 can be contained in incubation chambers of relatively less depth as compared to the incubation chambers that are sized to accommodate the imaging module 400.

[0193] The imaging module 601 may further include a temperature sensor, a cable, and a tag reader (not shown). Other features, aspects, and components of the imaging module 601 are similar in construction and function to like features, aspects, and components described above with respect to the imaging module 400.

[0194] While the imaging modules 600, 601 have been described and illustrated with light sources positioned underneath a base wall of the housing 606, 607, in some embodiments, an imaging module that is substantially similar in construction and function to either of the imaging modules 600, 601 may include light sources that are instead located along sides of the wells of the culture dish instead of underneath the wells, such as the light sources 431 of the imaging module 401.

[0195] While the above-discussed imaging modules and culture dishes have been described and illustrated such that the culture dishes remain in a fixed position with respect to the imaging modules, in some embodiments, an imaging module includes a mechanism for moving a culture dish to align a selected well of the culture dish with a camera of the imaging module. For example, FIG. 20 illustrates an imaging module 700 with the capability to rotate (e.g., spin) a culture dish 701 to align a selected well 711 of the culture dish with a camera 728. The culture dish 701 includes a lid and a cylindrical multi -well plate 703 with multiple wells 711 (e.g., conical wells) arranged in a circular pattern (e.g., along the circumference of a circle that is centered on a central axis 729 of the plate 703).

[0196] The imaging module 700 includes a housing 706 containing a single, horizontally-oriented camera 728 and a light source 730 within an interior region of the housing 706. The camera 728 and the light source 730 are positioned on opposite sides of the housing 706. The camera 728 faces a side wall 707 of the plate 703 and is vertically aligned with the wells 711 to image a specimen disposed within the selected well 711 at an observation position 731. Accordingly, the camera 728 faces a transparent or translucent viewing window of the housing 706.

[0197] In some embodiments, the housing 706 is equipped with a rotatable support platform (e.g., a carousel platform or another type of rotatable mechanism) within a dish receptacle of the culture dish 701. The plate 703 includes a cooperating connector along a bottom wall that can be securely and removably coupled to the rotatable platform. The housing 706 is also equipped with a motorized mechanism underneath the dish receptacle to rotate the platform until a selected well 711 is located at the observation position 731. In other embodiments, the housing 106 may alternatively be equipped with wheels positioned adjacent sides of the dish 701 for rotating the dish 701. The wells 711 are positioned close enough to the side wall 707 of the plate 703 to be imaged by the camera 728. For example, in some embodiments, a center of each well 707 is positioned at a distance (e.g., measured along a straight line) of no more than about 2 mm from the side wall 707.

[0198] The imaging module 701 may further include a temperature sensor, a cable, and a tag reader, and the plate may be equipped with an identification tag (not shown). Other features, aspects, and components of the imaging module 700 are similar in construction and function to like features, aspects, and components described above with respect to the imaging module 200.

[0199] In another example, FIG. 21 illustrates an imaging module 800 with the capability to translate a rectangular culture dish 801 to align selected wells 811 of the dish 801 with oppositely arranged cameras 828. The culture dish 801 is substantially similar in construction and function to the culture dish 301, except that the dish 801 includes exterior features by which the dish 801 can be coupled to a translational mechanism of the imaging module 800. Accordingly, the dish 801 includes a lid and a multi-well plate 803 with multiple (e.g., three) peripheral wells 811 located on each of two opposite sides of the plate 803. The wells 811 have a half-cone shape and are substantially similar in construction and function to the wells 311.

[0200] The imaging module 800 includes a housing 806 containing two horizontally- oriented cameras 828 and four light sources 830 within an interior region 826. The cameras 828 are positioned adjacent the culture dish 801 on opposite sides of the housing 706. A light source 830 is positioned at each side of each camera 828. The camera 828 faces a side wall 807 of the plate 803 and is vertically aligned with the wells 811 to image a specimen disposed within the selected well 811 at an observation position. Accordingly, the camera 828 faces a transparent or translucent viewing window of the housing 806.

[0201] In some embodiments, the housing 806 is equipped with a translatable support platform (e.g., a carriage) that is movable along a linear track 833. The plate 803 includes a cooperating connector along a bottom wall that can be securely and removably coupled to the translatable platform. The housing 806 is also equipped with a motorized mechanism underneath the platform to translate the platform until selected wells 811 are located at the observation position 831.

[0202] The imaging module 800 may further includes a temperature sensor, a cable, and a tag reader, and the culture dish 801 may include an identification tag. Other features, aspects, and components of the imaging module 800 are similar in construction and function to like features, aspects, and components described above with respect to the imaging module 201.

[0203] While the culture dish 300 has been described and illustrated as including four peripheral wells 310 positioned on four of the six hexagonal sidewall portions, in some embodiments, a culture dish 851 that is otherwise substantially similar in construction and function to the dish 300 may include a peripheral well 853 positioned along all six hexagonal sidewall portions, as illustrated in FIG. 22.

[0204] While the above discussed incubators, imaging modules, and culture dishes have been described and illustrated with respect to certain dimensions, sizes, shapes, arrangements, materials, and methods, in some embodiments, an incubator, imaging module, or culture dish that is otherwise substantially similar in construction and function to any of the above-discussed incubators, imaging modules, and culture dishes may include one or more different dimensions, sizes, shapes, arrangements, configurations, and materials or may be utilized according to different methods. Therefore, other embodiments are also within the scope of the following claims.

Claims

WHAT IS CLAIMED IS:

1. An incubator comprising: an incubation chamber configured to receive a dish having a well configured for holding a biological specimen, the incubator being configured to provide a temperature-controlled environment in the incubation chamber for culturing the biological specimen when the dish is disposed in the incubation chamber with the biological specimen in the well; and an imaging module configured to be removably disposed in the incubation chamber, the imaging module comprising an imaging module housing and a camera arranged in the imaging module housing, the imaging module housing having a support surface configured to support the dish, and the camera being arranged to image the biological specimen when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

2. The incubator of claim 1, wherein the camera is aligned with a transparent portion of the imaging module housing.

3. The incubator of claim 2, wherein the transparent portion of the imaging module housing is aligned with the well of the dish when the dish is disposed on the support surface of the imaging module housing.

4. The incubator of any of the preceding claims, wherein the camera is directed toward a side wall of the imaging module housing such that the camera is configured to image the biological specimen through the side wall of the imaging module housing when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

5. The incubator of claim 4, wherein the support surface of the imaging module housing comprises a recess configured to receive a peripheral portion of the dish that defines the well.

6. The incubator of claim 5, wherein the well is configured to hold the biological specimen adjacent a peripheral side wall of the dish, and the peripheral side wall ofthe dish is configured to be positioned adjacent the side wall of the imaging module housing when the dish is disposed on the support surface of the imaging module housing.

7. The incubator of any of the preceding claims, wherein the well is a conical well.

8. The incubator of any of the preceding claims, wherein the camera is directed toward the support surface of the imaging module housing such that the camera is arranged to image the biological specimen through the support surface when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

9. The incubator of any of the preceding claims, wherein the support surface is a top surface of the imaging module housing.

10. The incubator of claim 9, wherein the camera is positioned beneath the support surface of the imaging module housing.

11. The incubator of claim 10, wherein the camera is arranged to align with the well when the dish is disposed on the support surface of the imaging module housing.

12. The incubator of any of claims 1-8, wherein the support surface comprises a top surface of the imaging module housing and an inner facing side surface of the imaging module housing, the top surface and the inner facing side surface at least partially defining a recess for holding the dish.

13. The incubator of any of the preceding claims, wherein the camera is a first camera aligned with a first portion of the imaging module housing, and the imaging module further comprises a second camera aligned with a second portion of the imaging module housing.

14. The incubator of claim 13, wherein the biological specimen in the well is a first biological specimen in a first well, and when the dish is disposed on the supportsurface of the imaging module housing, the first portion of the imaging module housing is adjacent the first well, and the second portion of the imaging module housing is adjacent a second well of the dish that is configured for holding a second biological specimen.

15. The incubator of claim 13, wherein the imaging module further comprises a third camera aligned with a third portion of the imaging module housing and a fourth camera aligned with a fourth portion of the imaging module housing.

16. The incubator of claim 15, wherein the biological specimen in the well is a first biological specimen in a first well, and when the dish is disposed on the support surface of the imaging module housing, the first portion of the imaging module housing is adjacent the first well, the second portion of the imaging module housing is adjacent a second well of the dish that is configured for holding a second biological specimen, the third portion of the imaging module housing is adjacent a third well of the dish that is configured for holding a third biological specimen, and the fourth portion of the imaging module housing is adjacent a fourth well of the dish that is configured for holding a fourth biological specimen.

17. The incubator of any of the preceding claims, wherein the camera is arranged to align with the well of the dish when the dish is disposed on the support surface of the imaging module housing.

18. The incubator of claim 17, wherein the camera is a first camera, wherein the well is a first well, and wherein the imaging module further comprises a second camera arranged to align with a second well of the dish when the dish is disposed on the support surface of the imaging module housing.

19. The incubator of claim 18, wherein the imaging module further comprises a third camera arranged to align with a third well of the dish and a fourth camera arranged to align with a fourth well of the dish when the dish is disposed on the support surface of the imaging module housing.

20. The incubator of any of the preceding claims, wherein the imaging module further comprises a light source configured to illuminate the biological specimen when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

21. The incubator of claim 20, wherein the light source is arranged below the support surface of the imaging module housing.

22. The incubator of claim 20, wherein the imaging module further comprises a reflector for reflecting light, from the light source, towards the well of the dish.

23. The incubator of claim 22, wherein the reflector is a mirror.

24. The incubator of any of the preceding claims, wherein the camera is positioned peripherally outward of the support surface of the imaging module housing.

25. The incubator of claim 24, wherein the imaging module comprises at least one mirror positioned beneath the support surface.

26. The incubator of claim 25, wherein the at least one mirror is configured to reflect an image of the biological sample when the dish holding the biological specimen is disposed on the support surface of the imaging module housing with the biological specimen in the well.

27. The incubator of claim 26, wherein the camera is directed toward the at least one mirror.

28. The incubator of claim 25, wherein the camera is directed toward a peripheral side wall of the dish when the dish is disposed on the support surface of the imaging module housing.

29. The incubator of any of the preceding claims , wherein the camera is positioned beneath the support surface of the imaging module housing.

30. The incubator of any of the preceding claims, wherein an imaging sensor is positioned beneath the support surface of the imaging module housing.

31. The incubator of any of the preceding claims, wherein the camera is configured to transmit images of the biological specimen to a processor located outside of the incubator.

32. The incubator of claim 31, wherein the imaging module is connected to the processor via a flat cable.33 The incubator of claim 32, wherein the flat cable is configured to exit the incubation chamber between a lid of the incubation chamber and an incubator housing that supports incubation chamber.

34. The incubator of claim 32, wherein the imaging module is wirelessly connected to the processor.

35. The incubator of any of the preceding claims, wherein the imaging module further comprises a temperature sensor configured to detect a temperature within the incubation chamber when the imaging module is disposed in the incubation chamber.

36. The incubator of claim 35, wherein the temperature sensor is located adjacent the well of the dish when the dish is disposed on the support surface of the imaging module housing.

37. The incubator of claim 36, wherein the imaging module is configured to transmit the detected temperature to a processor located outside the incubator.

38. The incubator of any of the preceding claims, wherein the imaging module further comprises an identification tag reader configured to read an identification tag on the dish when the dish is disposed on the support surface of the imaging module housing.

39. The incubator of claim 38, wherein the identification tag reader is an RFID reader.

40. The incubator of claim 38, wherein identification tag reader is a barcode reader.

41. The incubator of any of the preceding claims, wherein the support surface is configured to mate with the dish in a manner to minimize air gaps between the support surface and the dish.

42. The incubator of any of the preceding claims, wherein the dish comprises one or more projections that matingly engage one or more recesses defined by the support surface when the dish is disposed on the support surface.

43. The incubator of any of the preceding claims, wherein the support surface comprises one or more projections that matingly engage one or more recesses defined by the dish when the dish is disposed on the support surface.

44. The incubator of any of the preceding claims, further comprising a heating element configured to heat the support surface of the imaging module housing.

45. The incubator of any of the preceding claims, wherein the imaging module has a height, measured vertically when the imaging module is resting on a horizontal surface, of 100 mm or less.

46. The incubator of claim 45, wherein the height of the imaging module is about 30 mm.

47. The incubator of any of the preceding claims, wherein the imaging module housing comprises a transparent material.

48. The incubator of any of the preceding claims, wherein the imaging module housing comprises a plastic material.

49. The incubator of any of the preceding claims, wherein the imaging module housing comprises a glass material.

50. The incubator of any of the preceding claims, wherein the imaging module housing comprises aluminum.

51. The incubator of any of the preceding claims, wherein the biological specimen in the well is a first biological specimen in a first well, and the incubator is configured to move the dish from a first position in which the first well is aligned with the camera to a second position in which a second well of the dish that is configured for holding a second biological specimen is aligned with the camera.

52. The incubator of any of the preceding claims, wherein the dish has a polygonal shape.

53. The incubator of claim 52, wherein the dish has a hexagonal shape.

54. The incubator of any of the preceding claims, wherein the dish has a circular shape.

55. The incubator of any of claims 52-53, wherein the well is configured to hold the biological specimen adjacent a peripheral side wall of the dish.

56. The incubator of claim 55, wherein at least a portion of the peripheral side wall adjacent the well is transparent to allow the biological specimen in the well to be viewed through the transparent portion of the peripheral side wall.

57. The incubator of claim 55, wherein the well is conical.

58. The incubator of any of the preceding claims, wherein the biological specimen is an embryo.

59. The incubator of any of the preceding claims, wherein the biological specimen is a blastocyst.

60. The incubator of any of the preceding claims, wherein the incubator is a flatbed incubator.

61. The incubator of any of the preceding claims, wherein the incubator has a height, measured vertically when the incubator is resting on a horizontal surface, of about 21.9 cm or less.

62. The incubator of claim 61, wherein the height of the incubator is about 18 cm.

63. The incubator of any of the preceding claims, wherein the incubation chamber is configured to receive the dish and at least one other dish when the imaging module is not disposed in the incubation chamber.

64. The incubator of claim 63, wherein the incubation chamber is configured to receive only one of the dishes when the imaging module is disposed in the incubation chamber.

65. The incubator of any of the preceding claims, wherein the incubation chamber has a depth, measured vertically when the incubator is resting on a horizontal surface, of about 100 mm or less.

66. The incubator of claim 65, wherein the incubation chamber has a depth of about 60 to about 100 mm.

67. The incubator of claim 66, wherein the incubation chamber has a depth of about 15 mm to about 20 mm.

68. The incubator of claim 67, wherein the incubation chamber has a depth of about 19 mm.

69. The incubator of any of the preceding claims, wherein the incubation chamber has a length of about 5 cm to about 20 cm.

70. The incubator of any of the preceding claims, wherein the incubation chamber has a width of about 5 cm to about 15 cm.

71. The incubator of any of the preceding claims, further comprising a heating element configured to heat the incubation chamber.

72. The incubator of claim 71, wherein the heating element is disposed in or on the support surface of the imaging module housing.

73. The incubator of any of the preceding claims, wherein the incubation chamber is insulated.

74. The incubator of any of the preceding claims, wherein the incubation chamber comprises a lid having an open position to provide access to the incubation chamber and a closed position to close the incubation chamber.

75. The incubator of claim 74, wherein the lid comprises an insulating material.

76. The incubator of claim 74, wherein the lid comprises a heating element.

77. The incubator of claim 74, further comprising a sensor to detect when the lid is in the closed position or the open position.

78. The incubator of any of the preceding claims, further comprising a user interface for inputting operational parameters for controlling the incubator.

79. An imaging module configured to be removably disposed in a chamber of an incubator, the imaging module comprising an imaging module housing and a camera arranged in the imaging module housing, the imaging module housing having a support surface configured to support a dish having a well for holding a biological specimen, and the camera being configured to image the biological specimen when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

80. A modular incubator system comprising: an incubator comprising a plurality of incubation chambers, each of the incubation chambers being configured to receive a dish having a well for holding a biological specimen, the incubator being configured to provide a temperature- controlled environment in each of the incubation chambers for culturing the biological specimen when the dish is disposed in one of the incubation chambers with the biological specimen in the well; and an imaging module configured to be removably disposed in any one of the incubation chambers, the imaging module comprising an imaging module housing and a camera arranged in the imaging module housing, the imaging module housing having a support surface configured to support the dish, and the camera being configured to image the biological specimen when the dish is disposed on the support surface of the imaging module housing with the biological specimen in the well.

81. The modular incubator system of claim 80, wherein the imaging module is disposed in one of the incubation chambers and at least one other incubation chamber is free of any imaging module.

82. The modular incubator system of claim 81, wherein the at least one other incubation chamber that is free of any imaging module lacks imaging capability.

83. The modular incubator system of claim 81, wherein the incubation chambers that are free of the imaging module lack imaging capability.

84. The modular incubator system of any of claims 80-83, wherein the incubator is a non-imaging incubator.

85. The modular incubator system of any of claims 80-84, wherein the imaging module, when disposed in the one of the incubation chambers, provides imaging capability for the one of the incubation chambers.

86. The modular incubator system of any of claims 80-85, further comprising additional imaging modules configured to be removably disposed in any one of the incubation chambers.

87. An incubation dish comprising: a dish body having a peripheral side wall and defining a well configured to hold a biological specimen adjacent the peripheral side wall, at least a portion of the peripheral side wall adjacent the well being transparent to allow the well to be viewed through the peripheral side wall.

88. The incubation dish of claim 87, wherein the dish has a polygonal shape.

89. The incubation dish of claim 88, wherein the dish has a hexagonal shape.

90. The incubation dish of claim 87, wherein the dish has a circular shape.

91. The incubation dish of any of claims 87-89, wherein the well is configured to hold the biological specimen in contact with the peripheral side wall.

92. The incubation dish of claim 91, wherein the well is configured to allow a camera directed toward an outer surface of the peripheral side wall to image the biological specimen in the well.

93. The incubation dish of any of claims 87-92, wherein the well is a conical well.

94. The incubation dish of any of claims 87-93, wherein the well is a first well, the biological specimen is a first biological specimen, and the dish body defines a second well configured to hold a second biological specimen adjacent the peripheral side wall of the dish body.

95. The incubation dish of claim 94, wherein at least a portion of the peripheral side wall adjacent the second well is transparent to allow the second well to be viewed through the peripheral side wall.

96. The incubation dish of claim 95, wherein the second well is configured to allow a camera directed toward an outer surface of the peripheral side wall adjacent the second well to image the second biological specimen in the second well.

97. The incubation dish of any of claims 87-96, wherein a center of the well is no more than about 2 mm from an outer surface of the peripheral side wall.

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