Method and system for automated culture medium supply and control

Abstract

The cell culture medium container comprises a body including a base and a plurality of walls extending from the base, the plurality of walls together defining a container opening, and a sealing lid removablely attached to the body, the sealing lid comprising a removable access lid defined within an access opening of the sealing lid, the removable access lid comprising a removable access lid configured to be removed from the sealing lid, and a seal positioned around the periphery of the sealing lid, the seal configured to removely secure the sealing lid to the container opening, the internal floor of the base having two inclined floor portions, the inclined floor portions intersecting in a direction perpendicular to the surface of the sealing lid along a line located below the access opening.

Description

Background Art

[0001] (Cross - reference to related applications) This application claims the benefit of U.S. Provisional Application No. 63 / 496,560, filed Apr. 17, 2023, the disclosure of which is hereby incorporated by reference in its entirety.

[0002] (Background) Manual cell culture typically requires controlling the temperature of the medium and reagents, mixing the medium and reagents as needed, and performing operations for handling the reagents and medium. These are conventionally manual processes carried out by technicians using a series of discrete benchtop instruments as needed during the cell culture process.

Summary of the Invention

Means for Solving the Problems

[0003] (Abstract) Broadly speaking, the present disclosure is directed to methods and systems for automated media supply and control. In one aspect, the technology relates to a cell culture media container, the cell culture media container being a body including a base and a plurality of walls extending from the base, the plurality of walls together defining a container opening, and including a seal lid removably coupled to the body, the seal lid including a removable access lid defined within an access opening of the seal lid, the removable access lid being configured to be removed from the seal lid, and a seal disposed about a periphery of the seal lid, the seal being configured to removably secure the seal lid to the container opening, and an inner floor of the base having two inclined floor portions, the inclined floor portions intersecting in a direction perpendicular to the surface of the seal lid along a line located under the access opening.

[0004] In some embodiments described above, the body further includes an insulating material. In another embodiment, the insulating material is arranged around a plurality of walls, defining the outermost lateral region of the body and covering the outer surfaces of the plurality of walls. In yet another embodiment, the base of the body is exposed. In yet another embodiment, the insulating material includes one of polystyrene and polyurethane. In various embodiments, the sealing lid is configured to be removed from the container opening in a direction perpendicular to its surface, and the removable access lid is configured to be removed from the access opening in a direction perpendicular to the surface of the sealing lid. For example, a first removal force for removing the sealing lid from the body exceeds a second removal force for removing the removable access lid from the sealing lid. In some embodiments, the seal includes an O-ring gasket. In yet another embodiment, the base includes a first inclined portion that is sloped at a first angle with respect to a plane defined by the first walls of the plurality of walls. In yet another embodiment, the base includes a second inclined portion that is sloped at a second angle with respect to a plane defined by the first walls of the plurality of walls. In further embodiments, the first angle differs from the second angle. For example, the line defines the lowest depth of the culture medium container.

[0005] In other embodiments, the access opening is defined by an elongated access opening axis. In further embodiments, the line is substantially parallel to the elongated access opening axis. In yet another embodiment, the body includes an RFID sensor to which it is attached. In other embodiments, the sealing lid includes a stopper configured to receive a removable access lid. In further embodiments, the body has a flange that defines an opening, the opening includes a periphery, and the sealing lid is configured to tightly fit with the periphery. For example, the body includes one of metal, plastic, or a combination thereof. In additional embodiments, the multiple walls are opaque to external light. In further embodiments, the seal includes a punctureable material. In additional embodiments, the punctureable material includes foil. In additional embodiments, the body includes one of a culture vessel, an adapter block for a centrifuge tube, and a container configured to hold a volume of culture medium corresponding to the volume of one or more pipettes.

[0006] In another aspect, the technology relates to an automated culture medium handling system, which includes a tray configured to arrange one or more cell culture medium containers thereon; one or more stations located directly below the tray, each of which includes a heating element located below the tray and thermally coupled to one or more cell culture medium containers arranged thereon, a cooling element located below the tray and thermally coupled to one or more cell culture medium containers arranged thereon, and a magnetic motor configured to rotatably operate a stirring element held in one or more of the cell culture medium containers arranged thereon; a robot array configured to manipulate the cell culture medium containers; and a controller configured to control the operation of the cell culture medium containers and the one or more stations.

[0007] In one embodiment described above, the surface of the tray is at an angle to the horizontal plane. In another embodiment, one or more stations include a plurality of container stations, and the tray further includes channels positioned between adjacent container stations. In yet another embodiment, the channels are positioned adjacent to the uppermost edge of each container station. In yet another embodiment, the system further includes a trench positioned adjacent to the lowermost edge of each of the container stations. In yet another embodiment, the system further includes a drain section fluidly coupled to the trench. For example, the heating element includes an electric heating element. In another embodiment, the cooling element includes a refrigerant cooling loop. In yet another embodiment, at least one of the heating element and the cooling element includes a hot water circulating channel. In yet another embodiment, the heating element includes a cooling element. In yet another embodiment, the tray defines a circumferential wall that surrounds at least partially one or more stations. For example, the circumferential wall defines openings associated with each of the plurality of stations. In yet another embodiment, the heating and cooling elements of one or more stations are individually controllable. In an additional embodiment, the heating element is positioned between the tray and a magnetic motor. In further embodiments, one or more stations include up to eight container stations. In another embodiment, adjacent culture medium containers have inclined floor surfaces that slope away from each other. In one embodiment, every other culture medium container arranged on a tray has floor surfaces that slope in the same direction. [Brief explanation of the drawing]

[0008] [Figure 1A] Figures 1A-1B illustrate partial external views of cell culture systems according to various embodiments of this disclosure. [Figure 1B] Figures 1A-1B illustrate partial external views of cell culture systems according to various embodiments of this disclosure.

[0009] [Figure 2A] Figures 2A-2H illustrate the automated media handling subsystems of automated cell culture systems according to various embodiments of this disclosure. [Figure 2B] Figures 2A-2H illustrate the automated media handling subsystems of automated cell culture systems according to various embodiments of this disclosure. [Figure 2C] Figures 2A-2H illustrate the automated media handling subsystems of automated cell culture systems according to various embodiments of this disclosure. [Figure 2D] Figures 2A-2H illustrate the automated media handling subsystems of automated cell culture systems according to various embodiments of this disclosure. [Figure 2E] Figures 2A-2H illustrate the automated media handling subsystems of automated cell culture systems according to various embodiments of this disclosure. [Figure 2F] Figures 2A-2H illustrate the automated media handling subsystems of automated cell culture systems according to various embodiments of this disclosure. [Figure 2G] Figures 2A-2H illustrate the automated media handling subsystems of automated cell culture systems according to various embodiments of this disclosure. [Figure 2H] Figures 2A-2H illustrate the automated media handling subsystems of automated cell culture systems according to various embodiments of this disclosure.

[0010] [Figure 3A] Figures 3A and 3B are side views of culture vessels according to various embodiments of the present disclosure. [Figure 3B] Figures 3A and 3B are side views of culture vessels according to various embodiments of the present disclosure.

[0011] [Figure 4A] Figures 4A-4D illustrate perspective and exploded views of a culture vessel according to an embodiment of the present disclosure. [Figure 4B] Figures 4A-4D illustrate perspective and exploded views of a culture vessel according to an embodiment of the present disclosure. [Figure 4C] Figures 4A-4D illustrate perspective and exploded views of a culture vessel according to an embodiment of the present disclosure. [Figure 4D]Figures 4A-4D illustrate a perspective view and an exploded view of a culture medium tank according to an embodiment of the present disclosure.

[0012] [Figure 5A] Figures 5A and 5B are cross-sections of a culture medium tank system according to various embodiments of the present disclosure. [Figure 5B] Figures 5A and 5B are cross-sections of a culture medium tank system according to various embodiments of the present disclosure.

[0013] [Figure 6] Figure 6 illustrates a supply device to an automated cell culture system according to various embodiments of the present disclosure.

[0014] [Figure 7] Figure 7 depicts a block diagram of a computing device configured to control an automated culture medium tank device according to various embodiments of the present disclosure.

MODE FOR CARRYING OUT THE INVENTION

[0015] (Detailed Description) Various embodiments are described in detail herein with reference to the drawings, in which like reference numerals represent like parts and assemblies throughout several views. The reference to various embodiments does not limit the scope of the claims appended hereto. In addition, any example described herein is not intended to be limiting and merely describes some of the many possible embodiments of the appended claims.

[0016] Examples of the present disclosure include containers for storing culture media within an automated cell culture system. These containers are referred to herein as “media troughs” and are typically capable of holding any type of culture medium or reagent used in cell culture. Such media include, for example, induced pluripotent stem cell medium, induction medium, aggregation medium, mesoderm-specific medium, cardiomyocyte differentiation medium, maintenance medium, midbrain organoids, dyes, antibodies, and equivalents, etc., including media and dyes used in cell culture, assays, organoid and spheroid formation and culture, and stem cell culture. The troughs may also contain reagents such as, for example, phosphate-buffered saline, trypsin, or equivalents. The automated cell culture system may have access to these media or reagents as needed for specific cell culture processes, and in the automated cell culture system, the media troughs have certain structural features that allow them to be incorporated into the automated system. Thus, it may be advantageous to have automated and efficient processing of media troughs for mixing media and reagents in and out of various troughs configured to hold the media and reagents therein.

[0017] The embodiments of this disclosure relate to the automated supply of culture media and reagents. In particular, the embodiments of this disclosure relate to methods and systems for automated supply of culture media and reagents. The embodiments of this disclosure include an integrated and automated reagent and culture media supply system, comprising a system including various containers of the system, i.e., storage and pre-preparation arrays for reagents and culture media present in the tanks. The integrated functionality of the system includes various operations, such as cooling, heating, mixing, and pre-preparation of reagents and culture media. In various embodiments, the reagent and culture media supply system may include thermal and protective structures that minimize the effects of harmful factors, such as condensation on the walls of the tanks, and enable precise temperature control of the culture media or liquids held in the culture vessels. The thermal insulation material may be, for example, a removable thermal insulation material. In embodiments, the culture vessels are configured for automated liquid handling, for example, by being coupled to a controller to minimize any residual volume, and include lids to avoid, prevent, or reduce vaporization. To improve process reliability, radio frequency identification (RFID) tags may be integrated into the containers or tanks and may also be connected to the controller. Therefore, the systems according to various embodiments include highly integrated and dedicated functionalities such as cooling, heating, mixing, prevention of condensation, prevention of contamination, minimization of residual volume, and minimization of vaporization, as well as automated container and reagent identification via a controller, for example, via RFID.

[0018] In various embodiments, the system also includes higher process stability and reproducibility, less contamination, and improved reagent stability. The exemplary system also enables the handling of several different media and the automated addition of reagents to the media. Furthermore, the exemplary system provides better process stability and reproducibility, offering greater convenience to the user compared to conventional systems.

[0019] Another technical problem is the need to store different types of culture media and / or reagents at various required temperatures for various lengths of time. Embodiments of this disclosure provide a technical solution to the above technical problem by enabling the need to store different types of culture media on the system for several days, for example, by enabling the correct culture medium temperature to be available when required. Thus, the user can automatically perform tasks such as stem cell passage over long time periods, for example, several days. Thus, the system reduces the user's hands-on time, and RFID tags or chips, also referred to herein as RFID sensors, which are coupled to the controller and can be read by an RFID antenna, can reduce the possibility of errors, for example, the use of inappropriate culture media and / or reagents.

[0020] Various embodiments of the present disclosure include exemplary trays supporting a culture vessel, which is configured to hold culture media and / or reagents, within an automated cell culture system. The culture vessel itself may have structural features that typically allow it to hold various types of culture media and / or reagents used in cell culture and to be incorporated into the automated system. For example, the tray supporting the culture vessel may include heating or cooling components for heating or cooling the vessel, activate a mixer within the vessel, and drain condensates away from the vessel. These exemplary trays enable the automation of the cell culture process.

[0021] Figures 1A-1B illustrate partial external views of cell culture systems according to various embodiments of the present disclosure. In Figure 1A, the automated system 100A includes a plurality of culture vessels 110, which are closed by lids 115 or 118, a centrifuge tube adapter 114, and a small container 125. As will be discussed further below, some of the lids 115 and 118 are sealing lids, and some of the lids 115 and 118 are removable access lids. The access lid 115 may allow, for example, a pipette to be inserted into or out of the culture vessel 110 to add or remove culture medium as needed. In other embodiments, the automated cell culture system 100A includes a robotic array 130 configured to perform several actions, such as opening and closing a removable access lid 115 or 118, grasping and transporting a pipette 120 from an additional culture vessel or container 125, and bringing the pipette 120 into one or more of the culture vessels 110 or containers 125, removing the culture medium and / or reagents from there, and transporting the removed culture medium and / or reagents to a desired location. For example, the robotic array 130 may be a discrete mechanism within the automated cell culture system 100A, or it may be a separate robotic array 130. In the embodiment, the robot array 130 may be configured to, in sequence, open the removable access lid 115, transport the pipette 120 to the culture vessel 110 or small container 125, draw in the amount of culture medium and / or reagent in the pipette 120 from the culture vessel 110 or small container 125, transfer the pipette 120, hold the drawn-in culture medium and / or reagent therein to the desired destination, and close the removable access lid 115 on the culture vessel 110 or small container 125. The robot array 130 may then bring the pipette 120 back into the culture vessel 110 or small container 125. The robot array 130 may be a controller via a computing device, such as the computing device 700 described below with respect to Figure 7.

[0022] The small container 125 may, for example, be smaller in size than the culture vessel 110 and may be provided on the same support tray 140 as the culture vessel 110 in the automated cell culture system 100A. The elongated small container 125 may be coupled to the reservoir 122, for example, via a pump and a through-flow heater or cooler, as will be further discussed below with respect to Figure 2C. The small container 125 may be arranged on the platform or support tray 140, similar to the culture vessel 110, but unlike the culture vessel 110, it may not be insulated. The reservoir 122, which may have the shape of a bottle, may be configured to supply to the small container 125 an amount of liquid or culture medium that is precisely controlled and equal to the volume of the small container 125. For example, the reservoir 122 may be configured to automatically supply liquid or culture medium to the small container 125 via a robotic array 130. The volume of liquid transferred from reservoir 122 to container 125 may be controlled to correspond to the volume of container 125 so that any amount of liquid transferred from container 125 is precisely controlled. Therefore, even if the liquid pump (discussed below with respect to Figure 2C) is not precise enough to control the amount of liquid transferred from reservoir 122 to container 125, the fact that the volume of container 125 is small and controllable allows for precise control of the amount of liquid transferred. Pipette 120 may be configured, under the control of robot array 130, to remove the same amount of liquid or culture medium from container 125 and transfer it to its destination. The liquid or culture medium transferred from reservoir 122 may be temperature-controlled via a through-flow heater or cooling array (not shown), further discussed in Figure 2C. Figure 1B illustrates an automated system 100B, similar to Figure 1A, and also including a culture medium tank 110 and container 125, but in a different configuration. For example, the number and location of the culture vessels 110 and small containers 125 in system 100B shown in Figure 1B may differ from those in system 100A shown in Figure 1A. For example, on a given platform or tray 140, the number and combination of culture vessels 110 and small containers 125 may be configured as needed or required for a given application.A common feature among the various culture medium receivers is that they are all arranged on a platform or tray 140 and can be automatically controlled and used to transfer culture medium or liquid via a robot array 130. Other features, such as heating and cooling, agitation of the culture medium, or automation, may be similar between systems 100A and 100B.

[0023] The automated cell culture system 100A / 100B includes one or more adapters 114, each containing a plurality of crowned centrifuge tubes 118, as will be described in more detail below with reference to Figure 2D. The adapter 114, also referred to as the centrifuge tube adapter 114, may be positioned on the same platform or tray 140 as the culture vessels 110, and therefore may be subject to temperature control in the same manner as the culture vessels 110, for example, and may be stirred via a magnetic stirrer controlled by a robotic array. The adapter 114 may also be removed and replaced by one or more culture vessels 110 or small containers 125. Thus, the number of culture vessels 110 that can be positioned on the platform or tray 140 may be increased to a maximum of eight culture vessels 110 when the adapter 114 is removed from it. On a given platform or tray 140, the number and combination of culture vessels 110, small containers 125, and centrifuge tube adapters 114 may be configured as needed or required for a given application. A common feature among the various culture medium receivers is that they are all arranged on a platform or tray 140 and can be automatically controlled and used to transfer culture medium or liquid via a robot array 130. The centrifuge tube 118 may be automatically controlled via the robot array 130 to be inserted into or removed from the adapter 114, for example, to transfer liquid in and out of the adapter 114. In one embodiment, some of the culture medium tanks 110 may be removed to allow for the installation of the centrifuge tube adapter 114. The support platform or tray 140 includes several stations (described below with reference to Figures 5A and 5B, not shown) directly beneath each culture medium tank 110 and each centrifuge tube adapter 114, each station configured to provide, for example, temperature control or agitation of the liquid in the tank 110 or adapter 114. Alternatively, the support 140 may not include any stations directly beneath the small container 125. Temperature control of the liquid transferred to the small container can be achieved via a once-flow heater and pump (described with reference to Figure 2C, not shown).

[0024] Figures 2A–2H illustrate automated media handling subsystems 200A / 200B of an automated cell culture system according to various embodiments of the present disclosure. In Figure 2A, system 200A includes one or more centrifuge tube adapters 214 and one or more small containers 225 on a platform or tray 240, including up to eight medium tanks 210, also referred to herein as container stations, and one or more small containers 225, including a cooling, heating, and mixing array directly below station 221. The adapters 214 may be configured to hold a plurality of crowned centrifuge tubes 218, and the small containers 225 may be configured to receive pipettes 220. In embodiments, the cooling, heating, and mixing array may be located below the tray 240 at station 221. Since the temperature control functionality is performed on the culture vessel 210 and the adapter 214 itself via a station directly below the support tray 240, the tray 240 may also include structures and materials configured to capture condensates that may unfold on the vessel 210 but could damage other components of the automated system.

[0025] Each culture vessel 210 or centrifuge tube adapter 214 may include one or more external RFID tags or chips, barcodes, cameras, or other devices 235 to identify the culture medium in the culture vessel 210 or adapter 214. The identification device or tag 235 may transmit information via one or more antennas 237 to receptors (not shown) on or near the tray 240. In the embodiment, each culture vessel 210 and small container 225 includes a removable lid 230 on its upper portion, the removable lid 230 configured to be removed manually or automatically under the control of a controller (not shown) to allow storage or mixing of culture medium or reagents therein. Some of the lids 230 are configured to allow access by multiple pipettes 220 simultaneously with those operated by a robotic array, for example, a robotic array 130 illustrated in Figure 1. For example, the pipettes 220 may be movable in and out of the vessel 210 to allow access and removal of any culture medium or reagent present therein, as will be further discussed below with reference to Figures 5A and 5B. The pipette 220 may also be used to transfer liquids in and out of the centrifuge tube 218 located within the centrifuge tube adapter 214.

[0026] Alternatively, the centrifuge tube 218 may be transported in and out of the adapter 214 as needed to transfer the culture medium or liquid within it. Although the centrifuge tube 218 is located within the adapter 214, the culture medium or liquid held within it may be subjected to, for example, temperature control and / or agitation via a magnetic stirrer, since the adapter 214 is arranged across stations 221. Directly below each culture vessel 210 and the centrifuge tube adapter 214 are stations 221, each station 221 configured to provide, for example, temperature control or agitation of the liquid inside each culture vessel 210 and the centrifuge tube adapter 214. A removable lid 230 may be made from, or include, a perforated foil to allow for the dispensing of the culture vessel 210 once it is filled with culture medium or liquid. The support platform or tray 240 may therefore include a plurality of stations 221 directly beneath each culture vessel 210 and each centrifuge tube adapter 214, each station 221 configured to provide, for example, temperature control or agitation of the liquid in the vessel 210 or adapter 214. The support or tray 240 may not include any stations directly beneath the small container 225. Alternatively, a given station 221 may control two of the culture vessels 210 or adapters 214, such that the given station 221 controls heating and agitation of a pair of culture vessels 210 or adapters 214, which saves space beneath the tray 240 and saves power during temperature control and agitation operations.

[0027] Figure 2B illustrates an automated media handling subsystem 200B of an automated cell culture system according to various embodiments of the present disclosure. Figures 2A-2H are described in parallel, and not all components described are depicted in all figures. In Figure 2B, system 200B includes a culture vessel 210, a centrifuge adapter 214 configured to hold a crowned centrifuge tube 218, and a small container 225, the small container 225 may have a pipette 220 inserted therein, the pipette 220 may also be inserted into the culture vessel 210 for manipulating or transferring the medium or liquid held therein. Figure 2B also illustrates a station 221 arranged directly below a tray 240 and coupled thereto. For example, any given station 221 may be configured to control two of the culture vessel 210, adapter 214, and small container 225 in terms of temperature control and agitation control; alternatively, each station 221 may be configured to control one of the culture vessel 210, adapter 214, and small container 225. Heating control may be performed electrically by a station that delivers a certain amount of current to heating coils arranged around the culture vessel 210 or adapter 214. Cooling control may be performed by delivering a certain amount of cooling liquid through fluid coils around the culture vessel 210 and adapter 214. Agitation of the culture medium or liquid held in the culture vessel 210 and adapter 214 may be performed by generating a rotating magnetic field within station 221 and activating magnetic agitation (not shown, but described below with respect to Figures 5A and 5B).

[0028] Figure 2C illustrates a liquid supply dispenser 222, which is fluidly connected to, for example, the reservoir 122 illustrated in Figure 1. In Figure 2A, each of the liquid supply dispensers 222 may be coupled to a pump 224, which is configured to transfer the liquid culture medium contained in the dispenser 222 to one or more of the small containers 225. Since the small containers, unlike the culture tanks 210 and the centrifuge tube adapters 214, are not arranged on the temperature control station 221, temperature control inside the small containers 225 may be performed via one or more through-flow heaters 226 configured to heat the culture medium or liquid being transferred from the dispenser 222 to the small containers 225. Figure 2D illustrates a centrifuge tube adapter 214 arranged on a tray 240, which shares the tray 240 with one or more culture tanks 210. The centrifuge tube adapters 214 are arranged on the station 221, configured, for example, to provide temperature control of the culture medium or liquid inside each centrifuge tube 218.

[0029] Figures 2E and 2F illustrate a perspective view and a side view of a small container 225 according to an embodiment of the present invention, respectively. The small container 225 includes a body 234 and a removable lid 230 attached to the body 234 and removable to allow a pipette 220 to be inserted into the body 234. In the embodiment, the small container 225 may also include an inlet port 232 configured to introduce or remove, for example, culture medium or liquid into or out of the small container 225. Figures 2G and 2H illustrate a side view and a top view of a small container 225 according to an embodiment of the present invention, respectively. In Figures 2G and 2H, the small container 225 has a removable lid 230 attached to the body 234, and the base 236 of the body 234 includes a non-flat portion configured to store liquid or culture medium present inside the body 234 at its bottom portion to facilitate the extraction of liquid or culture medium from the body 234. For example, the non-flat bed 236 may include two sloped sections, the slope direction of each section facing the other so as to form a bottom section in which the culture medium or liquid held in the small container 225 can be stored. In Figure 2H, the small container 225 also includes an inlet port 232 configured, for example, to introduce the culture medium or liquid into the small container 225. The removable lid 230 may be made from, or include, a perforated foil so as to allow the dispensing of the culture medium or liquid once the small container 225 is filled.

[0030] Figures 3A and 3B are side views of a culture vessel 300 according to various embodiments of the present disclosure. In Figures 3A and 3B, the culture vessel 300 includes a wall 315 which may be insulated and / or autoclavable to adequately maintain any culture medium and / or reagent present inside the vessel 300 at a controlled temperature. The wall 315 may also be uninsulated and not autoclavable, or insulated and not autoclavable. The wall 315 may be insulated by having a removable insulating sleeve attached thereto. The insulated and / or autoclavable wall 315 may include an RFID chip or tag, such as the tag 235 illustrated in Figure 2A. The culture vessel 300 may also include a sealing lid 380 on it and a removable lid 370 which is configured to automatically open and close under the control of an automated system, such as the robot array 130 discussed above with respect to Figure 1, for example, to allow the addition or removal of reagents or culture medium to and from the culture vessel 300. In various embodiments, the bottom surface of the seal lid 380 includes a seal 385 configured to seal against the opening of the culture vessel 300. For example, the seal 385 may be or include an O-ring gasket. The removable lid 370 may be arranged along the sides of the culture vessel 300 and may be configured to receive a pipette, such as the pipette 220 discussed above with respect to Figure 2A, to prevent overflow during the transfer of culture medium or reagents into and out of the culture vessel 300.

[0031] The floor of the inner portion of the culture vessel 300 may be inclined with respect to the plane of the wall 315, and may include, for example, two inclined floors 375 and 372. In the embodiment, the inclined floors 375 and 372 may be sloped toward each other, or they may have inclined portions facing each other, as shown in Figure 3A. For example, both the inclined floors 375 and 372 may be sloped toward the area of ​​the floor of the inner portion of the culture vessel 300, allowing for a reduction or elimination of residual volume of culture medium or reagents that accumulates at the bottom of the inner portion of the culture vessel 300, which can occur if the bottom of the inner portion of the culture vessel 300 is flat. The inclined floors 375 and 372 may intersect in a line extending across the depth of the culture vessel 300, the line defining the lowest depth of the culture vessel 300. In addition, the area of ​​the floor where the inclined floors 372 and 375 intersect is directly below the removable lid 370 so that when a pipette is inserted into the removable lid 370, the pipette can access the entire amount of culture medium or liquid present in the culture vessel 300. The vessel 300 may include legs 390 configured to adjust the horizontal level of the vessel 300 so that the inclined floors 372 and 375 inside the inner portion of the vessel 300 remain tilted to reduce or remove any residual culture medium or reagent held therein. In other embodiments, the legs 390 may be fixed at a set height and may be insulated by being covered with an insulating material, such as a removable insulating material, as shown in Figure 3B. In various embodiments, the base 374 of the vessel 300 may also have an inclined portion that is sloped at an angle to a plane defined by the wall 315.

[0032] Figures 4A–4D illustrate perspective and exploded views of a culture vessel 400 according to embodiments of the present disclosure. Figures 4A–4D are described in parallel herein, and not all elements discussed in relation to Figures 4A–4D are described in each of Figures 4A–4D. In an embodiment, Figure 4A–4D illustrates a culture vessel 400 including a seal lid 410 configured to cover the opening 427 of the culture vessel 400 in a sealed manner by a seal connection to a seal periphery 430 positioned around the periphery of the opening 427. The culture vessel 400 may also include a body 440, which may be made of or include metal, rigid plastic, a combination thereof, or other similar rigid and / or insulating material. In a further embodiment, the culture vessel 400 includes a removable access lid 420 configured to be removed from the seal lid 410 to allow access to any culture medium and / or reagent held inside the culture vessel 400 by a pipette, such as the pipette 220 discussed above with respect to Figure 2A. In other embodiments, the removable access cover 420 may be formed as a removable portion of the seal cover 410.

[0033] In one embodiment, the periphery 430 of the access opening 427 defines a settling portion, i.e., a stopper, and the seal lid 410 has an interlocking structure such as a flange or seal 415, as shown in Figure 4C, configured to fit tightly with the periphery 430 to ensure a substantially airtight closure between the seal lid 410 and the body 440 of the culture vessel 400. For example, the removable access lid 420 may have an elongated access opening axis, as shown in Figures 4A and 4B. In one embodiment, the body 440 includes an insulating material that defines its outermost lateral region and covers the outer surfaces of a plurality of walls 418. For example, the insulating material of the walls 418 may include polystyrene, fiberglass, polyurethane, cellulose, and equivalents.

[0034] Figure 4B is a top view of the seal lid 410 and the removable access lid 420. In various embodiments, the removable access lid 420 is removable, for example, automatically, via a robotic array such as the robotic array 130 discussed above with respect to Figure 1, to allow access to the culture medium, liquid, or reagent held in the culture vessel 400. In other embodiments, the seal lid 410 includes a lid rest 425 on its surface, which is adjacent to the removable access lid 420 and is configured to receive the access lid 420 when the access lid 420 is removed from the seal lid 410, for example, during the handling of the culture medium and / or reagent held in the culture vessel 400. In various embodiments, the removable access lid 420 is configured to be removed substantially perpendicularly from the access opening, i.e., along the "Z" axis illustrated in Figure 4A. In other embodiments, the seal lid 410 may also be removed perpendicularly in the "Z" direction from the body 440 of the culture vessel 400. For example, the first removal force for removing the seal lid 410 from the main body 440 substantially exceeds the second removal force for removing the removable access lid 420 from the seal lid 410. Therefore, the removable access lid 420 may be removed without removing the seal lid 410. Figure 4C illustrates an exploded view of the culture medium tank 400, showing the seal lid 410 and the main body 440 of the culture medium tank 400. In this embodiment, the seal lid 410 includes a removable access lid 420 and a lid resting portion 425, and is configured to be fitted in a sealed state with the main body 440 by a tight fit between the seal lid 410 and the sealing periphery 430 of the tank body 440.

[0035] Figure 4D illustrates the bottom bed 412 of the culture vessel 400 according to various embodiments. The bottom bed 412 includes a flange or seal 415, which is configured to fit tightly with the bottom portion of the body 440. The flange or seal 415 also defines the periphery of the inner portion of the body 440. The bed 412 of the culture vessel 400 is double-slope, with one portion 412A sloped in one direction and the other portion 412B sloped in the opposite direction, and both portions 412A and 412B abut along a line 414 marking the lowest point of the bed 412. Referring to Figures 4C and 4D, the vertical "Z" position of the line 414 is directly below the removable access lid 420 to facilitate the efficient and complete removal of any liquid or culture medium present in the culture vessel 400.

[0036] Figures 5A and 5B are cross-sections of culture vessel systems according to various embodiments of the present disclosure. Figures 5A and 5B are described in parallel, and not all components described are depicted in all figures. In Figure 5A, the culture vessel system 500A includes a culture vessel 510, supported by a tray 520 and coupled to a cooling / heating channel or cooling / heating element 530 formed within the body of the tray 520, which may be, for example, a laminated structure. In embodiments, the cooling / heating element 530 may include openings at its ends as a cooling channel to provide rapid liquid cooling to the culture medium and reagents present in the vessel 510, or it may provide electric heating for heating the culture medium and reagents present in the vessel 510, or it may reduce or eliminate the flow of the cooling liquid to control the cooling of the culture medium and reagents present in the vessel 510. For example, the cooling / heating element 530 includes a hot water circulating channel. In other embodiments, the cooling / heating element 530 may be located within the body of the tray 520. In yet another embodiment, a hot water circulation system, a refrigerant-based system, an electric system, or an induced heating and / or cooling element may be used. The cooling / heating element 530 may be controlled by a robot array, such as the robot array 130 described above with respect to Figures 1A and 1B, or by a computing device, such as the computing device 700 discussed below with respect to Figure 7.

[0037] A rotating magnet 525 may selectively drive an iron stirring rod 528, located inside the body 518 of the culture vessel 510, to agitate the culture medium or reagent held inside the vessel 510. The stirring rod 528 is activated via a motor 532 that controls the rotating magnet 525. The culture vessel system 500A may also include a peripheral condensate channel 540 surrounding the culture vessel 510 so that any condensates that may form on the outside of the vessel 510 can be collected in a channel 540, which can be directed towards a common drain 545. The channel 540 may be located adjacent to the uppermost edge of the supporting surface of the floor 550 of the culture vessel 510. The culture vessel system 500A may also include a second condensate collection element 547, which may be in the form of a removable tray, for example, located below the entire tray 520. The culture medium system 500A may also include a trench 542 adjacent to the lowest edge of the supporting surface of the floor 550 of the culture medium tank 510, which is connected to a drain, such as a drain section 545. The tray 520 may define a perimeter that surrounds at least partially the multiple culture medium tanks 510.

[0038] Figure 5A also illustrates RFID sensors 535 embedded within each tank 510. Each tank 510 may have a plurality of insulated walls 515 on all of its sides, the insulation being suitable, for example, for insertion into an autoclave for sterilization purposes. The walls 515 may also be uninsulated and not autoclavable, or insulated and not autoclavable. The walls 515 may be insulated by having a removable insulating sleeve attached thereto. In some embodiments, the tank 510 may also have a sloped or inclined floor 550. For example, two adjacent tanks 510 may have an inclined floor 550 that slopes away from each other. In some embodiments, two adjacent tanks 510 may have a floor 550 that is co-plane with each other. In other embodiments, the floor 550 within each tank 510 may be a double-graded floor, with two parts of the floor 550 intersecting within the area of ​​the floor 550, sloped in opposite directions relative to each other, as will be further discussed below, and directly beneath the pipette 560. The floor 550 may be a durable surface capable of withstanding damage during stirring of the culture medium and / or reagents held in the tank 510 by the stirring rod 528, or may include such a surface. In other embodiments, the walls 515 of the tank 510 may be insulated and / or autoclavable walls 515 to maintain any culture medium and / or reagents held inside the tank 510 at a controlled temperature. In various embodiments, the tank 510 has an internal volume 518 of, for example, 400 ml, or in the range of, for example, 100 ml to 600 ml. In other embodiments, the tank 510 may be disposable.

[0039] The floor 550 of the tank 510 may include a first inclined portion 558 and a second inclined portion 555, the first and second inclined portions 558 and 555 configured to avoid having culture media or reagents captured at the bottom of the tank 510. For example, both inclined portions 558 and 555 may incline toward a common area or intersecting line 556 extending from the front to the back of the floor 550, and thus push any culture media or reagents into the common area 556 away from the corners of the tank 510. In other embodiments, a plurality of pipettes 560, such as eight pipettes 560, may be insertable into the internal volume 518 of the culture vessel 510 in a location corresponding to the common area 556, the pipettes 560 configured to remove, inject, or otherwise manipulate the culture media or reagents held inside the culture vessel 510. The group of pipettes 560 may be simultaneously inserted into the culture medium tank 510 through the opening 570, for example, under the control of a user or a robot 130. For example, the opening 570 may be aligned above the lowest area 556 in the culture medium tank 510.

[0040] In other embodiments, the elongated opening 570 may be formed inside the sealing lid 580 by removing the removable access lid 575, and the pipette 560 may be inserted into the elongated opening 570. In embodiments, the elongated opening 570 may be fitted tightly to the contour of the pipette 560 to avoid overflow during the transfer of culture medium or reagents into and out of the tank 510. In some embodiments, depending on whether it is removed, the access lid 575 may be positioned on a lid rest or stopper 577 adjacent to the elongated opening 570 to prevent its unintentional removal while the culture medium or reagent is being manipulated in the tank 510. In various embodiments, the two lids 575 and 580 are each fixed to the corresponding tank 510 to prevent overflow of culture medium or reagents from the tank 510.

[0041] In the embodiment, both lids 575 and 580 may be, for example, robot-compatible and may be coupled to an automated system controller such as the robot controller 130 discussed above with respect to Figure 1, which is configured to automatically open and close the lids 575 and 580 under the control of a controller such as the computing device 700 discussed below with respect to Figure 7. One or more temperature sensors 572 may be added to the culture medium tank 510, which are coupled to a controller such as the computing device 700 or the robot array 130. Thus, temperature control may be performed, for example, via the computing device 700, and the temperature of the culture medium or liquid present inside the tank 510 is sensed via the temperature sensors 572, and in response to the sensed temperature and the desired temperature, the controller (computing device 700) may control the heating or cooling operation of the culture medium tank 510 and any culture medium or liquid held therein.

[0042] The lids 575 and 580 may have a color with variable opacity, depending on the need to shield the culture medium held in the tank 510 from external light. The lids 575 and 580 may be permeable, for example, black, or opaque, or they may have milky white or other colors with different levels of opacity. For example, the lids 575 and 580 and the insulated wall 515 of the culture medium tank 510 may be opaque to light so as to shield the culture medium or liquid held therein from light. In other embodiments, the lids 575 and 580 and the insulated wall 515 of the culture medium tank 510 may be permeable to light so as to expose the culture medium or liquid held therein to light.

[0043] In various embodiments, a pair of tanks 510 may be arranged back-to-back on a single base or tray 520. The base or tray 520 may include an inclined upper surface that matches the slope of the bottom surface 550 of the tanks 510, as discussed above with respect to Figure 3A. In some embodiments, the base 520 may include a plurality of feet, such as the feet 390 shown in Figure 3A, so that the sides of the tanks can be substantially vertical when the tanks 510 are placed on the base 520. In some embodiments, the base 520 may not be insulated so that the culture medium in the tanks 510 can be heated and cooled more easily. In other embodiments, the base 520 may be exposed, as shown in Figure 5A.

[0044] In Figure 5B, the culture medium system 500B includes features similar to those of the culture medium system 500A discussed above. Figure 5B further illustrates a station 521 including one or more motors 532 configured to control, for example, agitation magnets 528 inside the culture medium tank 510. For example, a single motor 532 may control two of the magnets in the culture medium tank 510. It is conceivable that the space directly beneath the culture medium system 500B could be saved by having one station 521 control the agitation of two culture medium tanks. The station 521 may also control the temperature of the liquid or culture medium held in the corresponding culture medium tank 510, for example, by controlling the electrical heating of the liquid or culture medium, or by controlling the amount of cooling liquid that will be supplied to the culture medium tank 510 from a liquid supply dispenser such as the reservoir 122 illustrated in Figure 1B or from a liquid supply device 600 illustrated in Figure 6 and discussed further below. In the embodiment illustrated in Figure 5B, a single station 521 may control the cooling, heating, and stirring of two culture vessels 510. In other embodiments, a single station 521 may control the cooling, heating, and stirring of more than two culture vessels 510, or alternatively, a single station 521 may control the cooling, heating, and stirring of one culture vessel 521. By having multiple stations 521 under the culture vessels 510, redundancy can be achieved, and different media can be controlled differently.

[0045] Figure 6 illustrates a supply device for an automated cell culture system according to various embodiments of the present disclosure. In the embodiments, the liquid supply device 600 is configured to supply culture medium or liquid at a controlled temperature to one or more small containers, such as the small containers 125 or 225 discussed above. The liquid supply device 600 includes one or more reservoirs 610, each configured to hold an amount of liquid, such as up to 2 liters. In the embodiments, the liquid supply device 600 may include a surrounding coil 630, which is a tube wound in a coil around the reservoirs 610 and can circulate a cooling or refrigerant liquid or gas to cool the liquid held inside the reservoirs 610. Alternatively, the surrounding coil 630 may circulate a warm or hot liquid or gas to heat the liquid held in the liquid supply device 600, or another electric coil may be formed in a loop around the reservoirs 610 and electrically heat the liquid or culture medium held therein. The liquid supply device 600 further includes a sieve 615 for positioning the reservoir 610 above it. The liquid supply device 600 may be enclosed within an uncooled portion, such as a rigid uncooled portion 605, which may include, for example, an insulating material. The insulating material of portion 605 can preserve the thermal integrity of the liquid held inside the reservoir 610. In an additional embodiment, the liquid supply device 600 may include a liquid level sensor 612 for monitoring the level of the liquid held inside the reservoir 610.

[0046] Figure 7 depicts a block diagram of a computing device that may be used, for example, as a controller for a culture vessel illustrated in the above figure. In the illustrated embodiment, the computing device 700 may include a bus 702 or other communication mechanism with similar functions for communicating information and at least one processing element 704 (collectively referred to as processing element 704) coupled to the bus 702 for processing information. As will be understood by those skilled in the art, the processing element 704 may include multiple processing elements or cores, which may be packaged as a single processor or in a distributed array. Furthermore, multiple virtual processing elements 704 may be included within the computing device 700 and provide control or management operations for a cell culture system, for example, via a robot array such as the robot array 130 discussed above with respect to Figure 1, as described and illustrated above.

[0047] The computing device 700 may also include one or more volatile memories 706, which may include, for example, random access memory (RAM) or other dynamic memory components, coupled to one or more buses 702 for use by at least one processing element 704. The computing device 700 may further include static non-volatile memory 708, such as read-only memory (ROM) or other static memory components, coupled to the bus 702 for storing information and instructions for use by at least one processing element 704. A storage component 710, such as a storage disk or storage memory, may be provided for storing information and instructions for use by at least one processing element 704. As will be understood, the computing device 700 may also include a distributed storage component 712, such as a networked disk or other storage resource available to the computing device 700. In embodiments, any of the volatile memories 706, non-volatile memories 708, storage components 710, and distributed storage components may be referred to as data repositories.

[0048] The computing device 700 may be coupled to one or more displays 714 for displaying information to the user. An optional user input device 716, such as a keyboard and / or touch screen, may be coupled to a bus 702 to communicate information and command selections to at least one processing element 704. An optional cursor control device or graphical input device 718, such as a mouse, trackball, or cursor directional keys, communicates graphical user interface information and command selections to at least one processing element. The computing device 700 may further include input / output (I / O) components such as serial, digital, or network connections, or other computing components, and other input / output components to enable communication with, for example, various components of the cell culture system and robot array 130 discussed above with respect to Figure 1.

[0049] In various embodiments, the computing device 700 can be connected to one or more other computer systems via a network to form a networked system. Such a network may include, for example, one or more private networks or a public network such as the Internet. In a networked system, one or more computer systems can store and provide data to other computer systems. One or more computer systems that store and provide data may be referred to as a server or cloud in a cloud computing scenario. One or more computer systems may include, for example, one or more web servers. Other computer systems that send data to and receive data from the server or cloud may be referred to as, for example, a client or cloud device. For example, various operations of the cell culture system and robot array 130 discussed above with respect to Figure 1 may be supported by the operation of a distributed computing system.

[0050] The computing device 700 may be capable of controlling the operation of the culture medium tank components through a communication device, such as a communication device 720, and handling data generated by the culture medium tank components. In some embodiments, culture medium or reagent handling data is provided by the computing device 700 in response to at least one processing element 704 executing instructions contained in memory 706 or 708 and performing actions with respect to the data received from the culture medium tank. The execution of instructions contained in memory 706 and / or 708 by at least one processing element 704 can control the operation of the cell culture system and robot array 130 discussed above with respect to Figure 1, for example.

[0051] As used herein, the term “computer-readable medium” refers to any medium involved in providing instructions to the processing element 704 for execution. Such a medium can take many forms, but is not limited to non-volatile media, volatile media, and transmission media. Non-volatile media include, for example, optical or magnetic disks such as disk storage device 710. Volatile media include dynamic memory such as memory 706. Transmission media include coaxial cables, copper wires, and optical fibers, including wires including bus 702.

[0052] Common forms of computer-readable media or computer program products include, for example, floppy disks, flexible disks, hard disks, magnetic tapes, or any other magnetic media, CD-ROMs, digital video discs (DVDs), Blu-ray® discs, any other optical media, thumb drives, memory cards, RAM, PROM, and EPROM, FLASH®-EPROM, any other memory chips or cartridges, or any other tangible media that a computer can read.

[0053] Various forms of computer-readable media may be involved in transporting one or more sequences of one or more instructions to the processing element 704 for execution. For example, the instructions may first be transported on a magnetic disk of a remote computer. The remote computer may load the instructions into its dynamic memory and transmit the instructions over a telephone line using a modem. A modem local to computing device 700 may receive the data over the telephone line and convert the data into an infrared signal using an infrared transmitter. An infrared detector coupled to bus 702 may receive the data transported in the infrared signal and place the data on bus 702. Bus 702 transports the data from there to memory 706, from which the processing element 704 reads and executes the instructions. Instructions received by memory 706 and / or memory 708 may optionally be stored on storage device 710 either before or after execution by processing element 704.

[0054] (Selected Embodiment) Illustrative examples of the systems and methods described herein are provided below. A particular embodiment of a system or method described herein may include one or more of the appendices described below, and any combination thereof.

[0055] Note 1: A cell culture medium container comprising a body comprising a base and a plurality of walls extending from the base, wherein the plurality of walls together define a container opening, and a sealing lid removablely attached to the body, wherein the sealing lid comprises a removable access lid defined within an access opening of the sealing lid, the removable access lid comprising a removable access lid removablely attached to the sealing lid, and a seal positioned around the periphery of the sealing lid, the seal configured to removely secure the sealing lid to the container opening, and the internal floor of the base having two inclined floor portions, the inclined floor portions intersecting in a direction perpendicular to the surface of the sealing lid along a line located below the access opening.

[0056] Note 2: The main body is the container described in Note 1, which also includes insulating material.

[0057] Note 3: The insulating material is arranged around multiple walls, defining the outermost lateral region of the main body and covering the outer surfaces of the multiple walls, as described in Note 2 of the container.

[0058] Note 4: The base of the main body is exposed to the container described in Note 3.

[0059] Note 5: The insulating material is one of polystyrene, fiberglass, polyurethane, and cellulose, as specified in Note 3 or Note 4.

[0060] Note 6: The container according to any one of the notes 1-5, wherein the sealing lid is configured to be removed from the container opening in a direction perpendicular to its surface, and the removable access lid is configured to be removed from the sealing lid at the access opening in a direction perpendicular to the surface of the sealing lid.

[0061] Note 7: The container as described in Note 6, wherein the first removal force for removing the seal lid from the main body exceeds the second removal force for removing the removable access lid from the seal lid.

[0062] Note 8: The seal is an O-ring gasket, as specified in any one of the items in Notes 1-7 of the container.

[0063] Note 9: The container according to any one of Notes 1-8, wherein the base includes a first inclined portion that is sloped at a first angle with respect to a plane defined by the first wall of a plurality of walls.

[0064] Note 10: The container according to Note 9, wherein the base further includes a second inclined portion that is sloped at a second angle with respect to a plane defined by the first wall of the multiple walls.

[0065] Note 11: The first angle is different from the second angle, as described in Note 10 for the container.

[0066] Note 12: The line defines the lowest depth inside the culture medium container, as described in any one of the items in Notes 1-11.

[0067] Note 13: The container as described in any one of Notes 1-12, wherein the access opening is defined by an extensional access opening axis.

[0068] Note 14: The line is approximately parallel to the axis of the extensional access opening, as described in Note 13 for the container.

[0069] Note 15: The main body is the container described in any one of the items in Notes 1-14, including the RFID sensor to which it is attached.

[0070] Note 16: The container according to any one of the notes 1-15, including a stopper, wherein the sealing lid is configured to receive a removable access lid thereon.

[0071] Note 17: The container according to any one of the notes 1-16, wherein the body has a flange that defines an opening, the opening including a periphery, and the sealing lid is configured to fit snugly with the periphery.

[0072] Note 18: The container is one of the containers described in any one of the notes 1-17, and the body is made of metal, plastic, or a combination thereof.

[0073] Note 19: A container as described in any one of the notes 1-18, wherein multiple walls are opaque to external light.

[0074] Note 20: The seal is for a container described in any one of the items in Notes 1-19, containing perforable material.

[0075] Note 21: Penetrable materials include the containers described in Note 20, including foil.

[0076] Note 22: The container according to any one of the items in Note 1-21, the main body comprising one of a culture medium tank, an adapter block for a centrifuge tube, and a container configured to hold a volume of culture medium corresponding to the volume of one or more pipettes.

[0077] Note 23: An automated culture medium handling system comprising: a tray configured to arrange one or more cell culture medium containers thereon; one or more stations located directly below the tray, each of which includes a heating element located below the tray and thermally coupled to one or more cell culture medium containers arranged thereon, a cooling element located below the tray and thermally coupled to one or more cell culture medium containers arranged thereon, and a magnetic motor configured to rotatably operate a stirring element in one or more of the cell culture medium containers arranged thereon; a robot array configured to operate the cell culture medium containers; and a controller configured to control the operation of the cell culture medium containers and one or more stations.

[0078] Note 24: The tray surface is at a certain angle to the horizontal plane, as described in Note 23.

[0079] Note 25: One or more stations include multiple stations, and the system as described in Note 23 or Note 24 includes channels, where trays are located between adjacent stations.

[0080] Note 26: The channel is the system described in Note 25, located adjacent to the uppermost edge of each station.

[0081] Note 27: The system described in any one of the notes 23-26, further including a moat located adjacent to the lowest edge of each station.

[0082] Note 28: The system described in Note 27, further including a drainage section that is fluidly coupled to the moat.

[0083] Note 29: The heating element is a system as described in any one of the items in Note 23-28, including an electric heating element.

[0084] Note 30: The cooling element is a system as described in any one of the items in Notes 23-29, including a refrigerant cooling loop.

[0085] Note 31: A tray according to any one of the items in Note 23-30, wherein at least one of the heating element and the cooling element includes a hot water circulation channel.

[0086] Note 32: The heating element is a system as described in any one of the items in Notes 29-31, including a cooling element.

[0087] Note 33: The tray defines a peripheral wall that surrounds at least one or more stations, as described in any one of the systems described in Note 23-32.

[0088] Note 34: The surrounding wall is the system described in Note 33, which defines an opening associated with each of the multiple stations.

[0089] Note 35: The system described in any one of the notes 23-34, wherein the heating and cooling elements of one or more stations are individually controllable.

[0090] Note 36: The heating element is located between the tray and the magnetic motor in the system described in any one of the items in Notes 23-35.

[0091] Note 37: One or more stations is a system described in any one of the items in Notes 23-36, including a maximum of eight stations.

[0092] Note 38: The system according to Note 37, wherein adjacent culture medium containers have a sloped floor surface that is angled away from each other.

[0093] Note 39: The system according to Note 37 or claim 38, wherein every other culture medium container arranged on the tray has a floor surface that is sloped in the same direction.

[0094] According to various embodiments, instructions operable to be executed by a processing element to carry out the method are stored on a computer-readable medium. The computer-readable medium can be a device that stores digital information. For example, the computer-readable medium includes a compact disc read-only memory (CD-ROM), as is known in the art, for storing software or firmware. The computer-readable medium is accessed by a processor which is suitable for executing instructions configured to be executed.

[0095] This disclosure describes several embodiments of the Art with reference to the accompanying drawings, which show only a few of the possible embodiments. However, other aspects can also be embodied in many different forms and should not be construed as being limited to the embodiments described herein. Rather, these embodiments are provided so as to fully convey to those skilled in the art that this disclosure is thorough and complete and that the scope of the possible embodiments can be fully communicated.

[0096] Specific examples have been described herein, but the scope of the Art is not limited to those specific examples. Those skilled in the art will recognize other examples or improvements that fall within the scope of the Art. Accordingly, specific structures, functions, or media are disclosed only as illustrative examples. Examples of the Art are also disclosed in general, unless otherwise described herein, but may be combined with elements or components not expressly illustrated in combination. The scope of the Art is defined by the following claims and any equivalents therein.

[0097] The various embodiments described above are provided for illustrative purposes only and should not be construed as limiting the claims appended herein. Those skilled in the art will readily recognize various modifications and changes that can be made without following the exemplary embodiments and uses illustrated and described herein and without departing from the entire scope of the following claims.

Claims

1. A cell culture medium container, A main body comprising a base and a plurality of walls extending from the base, wherein the plurality of walls together define a container opening, A seal lid and Equipped with, The aforementioned sealing lid is A removable access cover defined within the access opening of the seal cover, the removable access cover being removablely coupled to the seal cover, A seal is positioned around the periphery of the seal lid, and the seal is configured to removably secure the seal lid to the container opening. Equipped with, The container has an internal floor at the base having two inclined floor sections, the inclined floor sections intersecting in a direction perpendicular to the surface of the sealing lid along a line located below the access opening.

2. The container according to claim 1, wherein the main body further comprises an insulating material.

3. The container according to claim 1 or 2, wherein the thermal insulation material is arranged around the plurality of walls, defines the outermost lateral region of the main body, and covers the outer surfaces of the plurality of walls.

4. The container according to claim 3, wherein the base of the main body is exposed.

5. The container according to claim 3 or 4, wherein the thermal insulation material comprises one of polystyrene, fiberglass, polyurethane, and cellulose.

6. The sealing lid is configured to be removed from the container opening in a direction perpendicular to its surface, The container according to any one of claims 1 to 5, wherein the removable access cover is configured to be removed from the seal cover at the access opening in a direction perpendicular to the surface of the seal cover.

7. The container according to claim 6, wherein the first removal force for removing the seal lid from the main body exceeds the second removal force for removing the removable access lid from the seal lid.

8. The container according to any one of claims 1 to 7, wherein the seal comprises an O-ring gasket.

9. The container according to any one of claims 1 to 8, wherein the base portion comprises a first inclined portion that is sloped at a first angle with respect to a plane defined by the first wall of the plurality of walls.

10. The container according to claim 9, wherein the base further comprises a second inclined portion that is sloped at a second angle with respect to the plane defined by the first wall of the plurality of walls.

11. The container according to claim 10, wherein the first angle is different from the second angle.

12. The container according to any one of claims 1 to 11, wherein the line defines the lowest depth inside the culture medium container.

13. The container according to any one of claims 1 to 12, wherein the access opening is defined by an elongated access opening axis.

14. The container according to claim 13, wherein the line is substantially parallel to the axis of the extensional access opening.

15. The container according to any one of claims 1 to 14, wherein the main body is equipped with an RFID sensor attached thereto.

16. The container according to any one of claims 1 to 15, wherein the sealing lid is provided with a stopper, and the stopper is configured to receive the removable access lid thereon.

17. The container according to any one of claims 1 to 16, wherein the body defines an opening, the opening has a periphery, and the sealing lid has a flange configured to fit snugly with the periphery.

18. The container according to any one of claims 1 to 17, wherein the main body comprises one of metal, plastic, or a combination thereof.

19. The container according to any one of claims 1 to 18, wherein the plurality of walls are opaque to external light.

20. The container according to any one of claims 1 to 19, wherein the seal comprises a perforable material.

21. The container according to claim 20, wherein the perforable material comprises foil.

22. The container according to any one of claims 1 to 21, wherein the main body comprises one of a culture medium tank, an adapter block for a centrifuge tube, and a container configured to hold a volume of culture medium corresponding to the volume of one or more pipettes.

23. An automated culture medium handling system, A tray, wherein the tray is configured to arrange one or more cell culture medium containers on it, One or more stations located directly below the tray, each of the one or more stations is A heating element is provided, which is positioned below the tray and thermally coupled to one or more cell culture medium containers arranged on top of the tray. A cooling element is provided, which is positioned below the tray and thermally coupled to one or more cell culture medium containers arranged on top of the tray. A magnetic motor and One or more stations equipped with, A robot array configured to manipulate the cell culture medium container, A controller configured to control the operation of the cell culture medium container and one or more stations, A system equipped with these features.

24. The system according to claim 23, wherein the surface of the tray is at a certain angle with respect to the horizontal plane.

25. The system according to claim 23 or 24, wherein the one or more stations comprises a plurality of stations, and the tray further comprises channels arranged between adjacent stations.

26. The system according to claim 25, wherein the channel is located adjacent to the uppermost edge of each station.

27. The system according to any one of claims 23 to 26, further comprising a moat positioned adjacent to the lowest edge of each station.

28. The system according to claim 27, further comprising a drainage section fluidly coupled to the aforementioned trench.

29. The system according to any one of claims 23 to 28, wherein the heating element comprises an electric heating element.

30. The system according to any one of claims 23 to 29, wherein the cooling element comprises a refrigerant cooling loop.

31. The tray according to any one of claims 23 to 30, wherein at least one of the heating element and the cooling element is provided with a hot water circulation channel.

32. The system according to any one of claims 29 to 31, wherein the heating element comprises the cooling element.

33. The system according to any one of claims 23 to 32, wherein the tray defines a peripheral wall that surrounds at least partially the one or more stations.

34. The system according to claim 33, wherein the peripheral wall defines an opening associated with each of the plurality of stations.

35. The system according to any one of claims 23 to 34, wherein the heating element and the cooling element of one or more stations are individually controllable.

36. The system according to any one of claims 23 to 35, wherein the heating element is disposed between the tray and the magnetic motor.

37. The system according to any one of claims 23 to 36, wherein the one or more stations comprises a maximum of eight stations.

38. The system according to claim 37, wherein adjacent culture medium containers have a sloped floor surface that is sloped so as to move away from each other.

39. The system according to claim 37 or 38, wherein every other culture medium container arranged on the tray has a floor surface that is sloped in the same direction.

Images