Tumbling device for a cell culture management device for wetting surfaces in a cell culture container

Abstract

A tumbling device (144) for a cell culture management device (10) comprises: - a receiving device (721, 724, 728) for receiving a cell culture container (12), - an inner frame (704) which supports the receiving device (721, 724, 728), - an outer frame (702) which can be mounted on a stationary base frame by means of at least one bearing element (706), - an outer drive (708) for driving the outer frame (702) so as to move relative to the bearing elements (706) thereof, - an inner drive (718) for driving the inner frame (704) so as to move relative to the bearing elements (706) thereof, and - a control device (44) for controlling the operation of the inner drive (708) and the outer drive (708), the inner frame (704) being mounted on the outer frame (702) so as to be pivotal about a first pivot axis (S1), the outer frame (702) being pivotal, relative to the at least one bearing element (706) thereof, about a second pivot axis (S2) running transversely to the first pivot axis (S1), and the inner drive (718) and the outer drive (708) being drivable independently of each other, by means of the control device (44), so as to move.

Description

[0001] Tumble device for a cell culture management device for wetting surfaces in a cell culture container

[0002] Description

[0003] The present invention relates to the technical field of cell culture management devices for managing cell cultures in at least one cell culture container. The cell culture management device should have the highest possible degree of automation in order to minimize the risk of human error and contamination during the cultivation of living cells and to achieve the highest possible degree of reproducibility of management processes and their results.

[0004] Since such a cell culture management device, which is hereinafter also referred to simply as "management device," typically includes cell culture containers in which the cell cultures are maintained or cultivated, and these containers are usually exchanged between successive cultivation cycles, the management device can comprise a different number and / or type of components depending on its operating state. Therefore, the management device is described and explained below in an operational state as a reference state, unless expressly stated otherwise in a specific case. In its reference state, the cell culture management device preferably comprises: a piping arrangement for conveying fluid media, comprising,

[0005] + a valve block assembly with a valve block housing and with a delivery channel formed in the valve block housing,

[0006] + a supply line arrangement with at least one supply line,

[0007] + a container piping arrangement with at least one container piping and + a disposal piping arrangement with at least one disposal piping, a plurality of media reservoirs which provide different fluid media for their introduction into the piping arrangement, at least one cell culture container, a piping valve arrangement comprising

[0008] + a storage valve arrangement with at least one storage valve,

[0009] + a disposal valve arrangement with at least one disposal valve as well as

[0010] + a container valve arrangement with at least one container valve, and a pump for conveying fluid media in the pipe arrangement.

[0011] In the operational reference state, a plurality of media reservoirs are preferably connected to the valve block assembly via the reservoir line arrangement, with the reservoir valve arrangement interposed. Furthermore, in the operational reference state, at least one cell culture container is preferably connected to the valve block assembly via the container line arrangement, with the container valve arrangement interposed, and a detachable line coupling. Additionally, in the operational reference state, the disposal line arrangement is preferably connected to the valve block assembly via the reservoir line arrangement.The disposal line assembly preferably incorporates the disposal valve assembly, such that the disposal line assembly, or at least one disposal line thereof, can be selectively blocked or opened for media flow by the disposal valve assembly. The disposal line assembly can be fluid-transferred to the valve block assembly via an intermediate disposal valve assembly.

[0012] Most line valves in a line valve arrangement consist of a valve seat and a valve body that can be displaced relative to the valve seat. Some line valves can be designed as pinch valves, which can also block or release the flow of media in their associated line, but in which a distinction between the valve seat and valve body is either not possible or not practical, depending on the design. The operating state of each line valve can be changed between a closed state, in which the line valve blocks flow, and a free state, in which the line valve allows flow.

[0013] The conveying channel of the valve block assembly has outlets. In the reference state, the supply line assembly, the tank line assembly, and the disposal line assembly each preferably open into the conveying channel at at least one outlet.

[0014] In the reference state, at least one valve component of the majority of line valves is included in or on the valve block housing.

[0015] Such a management device is known, for example, from WO 2014 / - 114610 A1, WO 2016 / 008636 A1, and WO 2017 / 216237 A1. The valve block arrangement known from these publications allows for the efficient supply of a liquid medium, such as a nutrient solution, to a cell culture container connected to the valve block arrangement via a fluid transfer mechanism. It also allows for the disposal of used medium from the connected cell culture container via the disposal line arrangement. Finally, the valve block arrangement also enables the cleaning of the conveying channel and the valve components accessible via the conveying channel by means of a cleaning fluid, which can be discharged directly from the valve block arrangement via a disposal line.

[0016] Integrating at least one valve component of the line valves into or onto the valve block housing not only ensures a spatially compact unit and a simple and efficient way to clean the integrated valve components, but also protects the valve components from unwanted external influences and enables switching of the line valves by an advantageously compact and space-saving line valve switching device. A further valve block arrangement and a cell culture container detachably coupled to the valve block arrangement for fluid transfer in a management device are known from WO 2015 / 063136 A1.

[0017] Very similar automated cell culture management devices are known from WO 2020 / 038874 A1 and WO 2021 / 165397 A1. These known management devices each use a rotary valve to select one line from several possible lines in the line arrangement as the line actively connected to the cell culture container. The known rotary valve has a central pin as the valve body, which is surrounded by a sleeve with several ports. A channel formed in the pin is always connected to the cell culture container. The channel formed in and passing through the pin can be connected to any media port on the sleeve by relative rotation of the pin and sleeve, but only to one at a time.

[0018] The cell culture management devices known from WO 2020 / 038874 A1 and WO 2021 / 165397 A1 also feature a shaking device with a receiving plate for a cell culture container, which shakes the cell culture container in a rocking, vibrating or circularly whirling motion during the management of the cell cultures in order to distribute liquid absorbed in the cell culture container within the volume of the cell culture container.

[0019] Other cell culture management devices are known from US 10590374 B2, US 11268058 B2, and US 11447732 B2. These known management devices can also manage more than one cell culture container, specifically exactly two cell culture containers, simultaneously.

[0020] The valve block arrangement of the management device discussed in the present application preferably comprises a multi-part valve block. This multi-part valve block includes a reservoir-side valve block with a reservoir-side valve block housing and a reservoir-side delivery channel section of the delivery channel extending along a virtual reservoir-side flow path, as well as a tank-side valve block formed separately from the reservoir-side valve block housing, with a tank-side valve block housing formed separately from the reservoir-side valve block housing and with a tank-side delivery channel section of the delivery channel extending along a virtual tank-side flow path. The reservoir line arrangement opens into the reservoir-side delivery channel section. This allows fluid media from the media reservoirs to be introduced directly into the reservoir-side delivery channel section from the media reservoirs.

[0021] In contrast to the supply line arrangement, the disposal line arrangement and the container line arrangement preferably terminate in the container-side conveying channel section. This allows the at least one cell culture container connected to the valve block arrangement to discharge used media directly into the container-side conveying channel section, from where the used media can be directly discharged from the line arrangement via the disposal line arrangement.

[0022] The present invention relates in particular to a receiving device for receiving a cell culture container in a cell culture management device.

[0023] The object of the present invention is to provide a technical teaching which makes it possible to use liquid media in a cell culture management device, such as the one described above, as efficiently as possible, in order to manage a specific task in cell culture management with the smallest possible quantity of a required medium.

[0024] This problem is solved by the present invention with a wobble device comprising the receiving device and the features of claim 1. According to the invention, the wobble device for the cell culture management device for the efficient use of liquid media in a cell culture container comprises: the receiving device for receiving a cell culture container, an inner frame which supports the receiving device, an outer frame which can be mounted on a stationary base frame by means of at least one bearing element, an outer drive to drive the outer frame to a movement relative to its bearing elements, an inner drive to drive the inner frame to a movement relative to its bearing elements, and a control device to control the operation of the inner drive and the outer drive.

[0025] The inner frame is pivotally mounted on the outer frame about a first pivot axis. The outer frame is pivotally movable relative to its at least one bearing element about a second pivot axis extending transversely to the first pivot axis. The inner drive and the outer drive can be driven independently of each other by the control device.

[0026] This design allows a large surface area of ​​a cell culture container mounted on the wobble device to be wetted with a relatively small amount of medium introduced into the cell culture container, due to the independent movement of the cell culture container around each of the two pivot axes.

[0027] The terms "inner" and "outer" drive do not refer to spatial relationships, but rather to functional relationships with the frames they drive, which share the same attribute. Furthermore, the term "frame" should not be understood literally, but rather in the sense of a structure or support, although the inner and / or outer frame can also be a physical structure surrounding a spatial or surface area.

[0028] To ensure the most widespread distribution of a medium introduced into a cell culture container, a cell culture management device includes a tumbling device on which at least one cell culture container is pivotably mounted about two axes transverse to each other. Preferably, the cell culture container is mounted on the tumbling device such that its largest or second-largest inner surface is arranged parallel to at least one of the axes, and particularly preferably parallel to both axes, of the tumbling device. This allows even a quantity of medium significantly less than the capacity of the cell culture container to be distributed and wetted across the entire large inner surface of the cell culture container by a tumbling motion.The wobbling motion can be achieved by simultaneously swiveling the cell culture container mounted on the wobbling device back and forth around both axes.

[0029] To avoid complicated and therefore difficult-to-control movements of the cell culture container, as well as to avoid forces resulting from such movements, according to a preferred embodiment, the inner frame is pivotably mounted on the outer frame only about the first pivot axis. Additionally or alternatively, the outer frame can be pivotably movable relative to its at least one bearing element only about the second pivot axis, which runs transversely to the first pivot axis.

[0030] Preferably, the axes of the wobble device are orthogonal to each other, so that the cell culture container mounted on it can be pivoted gimbal-style.

[0031] Preferably, the cell culture container is mounted on the tumbling device such that a dispensing opening of the cell culture container, to which the container's tubing assembly is connected, is positioned at a distance from one of the axes of the tumbling device. This allows the cell culture container to be tilted to facilitate the removal of medium, such that the medium contained within flows by gravity towards the dispensing opening and collects there, where it can be extracted via the tubing assembly. Preferably, this axis, which facilitates the emptying of the cell culture container, is orthogonal to the virtual flow path of the tubing of a cell culture container mounted on the tumbling device.

[0032] To facilitate fluid-transferring coupling of the cell culture container, mounted on the wobble device, to a connection structure, such as the aforementioned container-side valve block, the receiving device can be movably supported by the inner frame. This relative mobility of the receiving device relative to the inner frame can be rotational and / or translational. Since this relative mobility is particularly important for the automated establishment of a fluid-transferring connection between the cell culture container and the connection structure, the following options are available:In order to support a conveying channel section formed in the connection structure, which is particularly easy to produce and separate by a translational, especially rectilinear, movement, the relative mobility of the receiving device relative to the inner frame is preferably a translational, especially a rectilinear, relative movement.

[0033] Preferably, the wobble device includes a pre-tensioning device that pre-tensions the receiving device, and thus indirectly the cell culture container held therein, relative to the inner frame in one of the two opposite directions of movement of the receiving device. Alternatively or additionally, the receiving device can be pre-tensioned relative to the inner frame in one of the two opposite directions of movement of the receiving device by gravity. This pre-tensioning or pre-loading fundamentally ensures a secure connection between the container piping assembly and the container-side connection structure, in particular the container-side valve block. In this case, the pre-tensioning or pre-loading acts in the direction of the container-side connection structure.

[0034] For this purpose, the wobble device can have a slide movable relative to the inner frame, which carries the receiving device and thus, during operation, the cell culture container. The slide can be mechanically preloaded and consequently pre-tensioned by a spring, pneumatically by a gas spring, magnetically, or by gravity in a preload direction described above.

[0035] The translational path of the receiving device can be oriented on the wobble device such that, at least in one relative position of the inner frame to the outer frame, it runs parallel or coaxial to the second pivot axis. This allows the receiving device to be moved translationally along the second pivot axis in this relative position.

[0036] To accommodate various cell culture containers with different physical designs, the receiving device can have an interchangeable adapter structure, which is designed to hold the cell culture container. Depending on the cell culture container currently in use, a suitable adapter structure can be selected from a number of available options and attached to the receiving device. The receiving device can have a support structure, such as a mounting plate, to secure the interchangeable adapter structure. The interchangeable adapter structure can be easily and conveniently mounted on this plate, which can optionally be designed as a support plate.

[0037] To facilitate the aforementioned creation of a fluid-transmitting connection between the container-side connection structure, in particular the container-side valve block, and a cell culture container held in the receiving device by means of the relative movement of the receiving device and the inner frame, according to a further development of the present invention, the container-side connection structure, which has a container-side conveying channel section formed in the container-side connection structure, can be connected to the inner frame for common movement. In this way, the relative movement between the container-side connection structure and the cell culture container held in the receiving device can be combined with the relative movement between the receiving device and the inner frame, which advantageously has only one translational degree of freedom.The cell culture container held by the receiving device can be easily connected to and disconnected from the connection structure and its container-side conveying channel section via fluid transfer thanks to this relative movement. For this purpose, the cell culture container or its container valve can have a coupling configuration, and the container-side receiving device can have a mating coupling configuration matching the coupling configuration. To ensure that the receiving device can be moved towards and away from the container-side connection structure independently of its pivoting movement about at least one of its two pivot axes, the wobble device can have a third drive unit that drives the receiving device to move relative to the inner frame. The third drive unit is preferably also controllable by the aforementioned control device, independently of the inner and outer drives.

[0038] To avoid requiring the third drive to be continuously energized to hold the receiving device in a once-achieved advantageous position, the third drive is preferably designed as a self-locking drive. For this reason, the inner and / or outer drive(s) can also each be a self-locking drive. A self-locking drive is a drive whose output element cannot be used as an input element in reverse kinematic terms, as is the case, for example, with a screw drive, spindle drive, worm gear drive, or a hydraulic piston-cylinder arrangement with a piston that can be locked by a valve arrangement, to name just a few examples.

[0039] In principle, the cell culture container, which usually needs to be replaced between cultivation or management cycles, can be detachably attached to the tumbling device in any desired manner. A cell culture container can be attached to the receiving device by clamping, which is particularly quick and secure. Therefore, according to a preferred embodiment, the tumbling device includes a clamping device for securing the cell culture container to the receiving device.

[0040] The clamping device can include a clamping bracket to transmit a desired clamping force. Preferably, in a locking position where it secures the cell culture container to the receiving device, the clamping bracket spans the cell culture container; more preferably, the clamping bracket extends beyond the cell culture container on at least one, or even better, on two opposite sides. The clamping bracket is preferably adjustable between a release position, in which the cell culture container is not secured to the receiving device, and a locking position, in which the cell culture container is secured to the receiving device. To avoid a continuously energized clamping device drive, which is necessary to transmit a desired clamping force from the clamping bracket to the cell culture container and the receiving device, the clamping bracket is preferably pre-tensioned in the locking position.By selecting a suitable force device to pre-tension the clamping bracket into the locking position, the clamping force exerted by the clamping bracket on the cell culture container and the receiving device can be precisely adjusted.

[0041] Depending on the cells being cultivated, cell culture containers may require specific ambient temperatures to promote optimal cell culture. For this purpose, the tumbling device can include a heating element for heating and / or temperature-controlling the cell culture container mounted on the device. The heating element is preferably an electric heating element with a heat output that can be precisely adjusted.

[0042] The present invention also relates to a cell culture management device for managing cell cultures in at least one cell culture container. The cell culture management device envisaged in this context comprises at least one tumbling device as described and further developed in the present application. Preferably, the cell culture management device comprises several tumbling devices of the type described in the present application, each of which carries at least one cell culture container, preferably exactly one cell culture container, and each of which can be driven independently to move the cell culture container.

[0043] Regarding the nomenclature used in the present application:

[0044] The term "media line" is used in the present application as a collective term for a line suitable for conveying fluid media, irrespective of its assignment to a source or a destination. A media line can therefore be a supply line, a container line, a disposal line, or any other line of the line arrangement subsequently mentioned in the preferred embodiments of the present invention.

[0045] The term "line valve" is used in the present application as a collective term for any valve of the line valve arrangement, irrespective of the valve's assignment to a specific media line and irrespective of the source, destination, or purpose of the media line on or in which the line valve is arranged. A storage valve, a disposal valve, a container valve, and further valves of the line valve arrangement subsequently mentioned in preferred embodiments of the present invention are each a line valve within the meaning of the present application.

[0046] In this application, the term "fluid medium" refers to a gaseous or liquid medium, or a medium in a two-phase state, regardless of the specific state of matter of the medium in question. Without a specific specification of an associated state of matter in any individual case, a medium mentioned below is to be understood as a fluid medium.

[0047] When the present application states that a media line is "fluid-transmittingly connected" to the valve block assembly or another structure, this means that the media line in question is connected to the said structure in such a way that, in principle, the transmission of a fluid medium to the connected structure is possible through the media line, regardless of the operating state of a line valve arranged on or in the media line, in particular an intermediate valve. A line valve arranged on or in a media line in its closed state therefore does not alter the fact that the media line is fluid-transmittingly connected to the said structure. A media line fluid-transmittingly connected to a structure terminates at the structure or at the specified outlet of the media line in or on the structure.The term "media supply" refers to a quantity of a fluid medium from which the supply device can draw for circulation through the piping system. Preferably, the media supply is provided in a media reservoir. In the case of air as a possible fluid medium of the supply device, described in more detail below, the atmosphere itself can be the media supply, which is made available through a corresponding intake opening in the piping system and a supply line dedicated to conveying air. Gas, particularly air, can also be provided as compressed gas, or compressed air, in a media reservoir or storage container.

[0048] The term "intermediate arrangement of a line valve" indicates that the respective line valve is positioned on the affected media line at a connection point between the media line and another flowable structure in such a way that it can either block or allow the flow of media from the source of the media line to the structure connected to the media line via the intermediate arrangement of the line valve. The intermediate arrangement of a line valve does not alter the direct connection between the media line supporting the line valve and the structure. A channel formed within the line valve and closable by the valve body is therefore part of the media line that supports or forms the valve.On a media line connected to a structure via an intermediate arrangement of a line valve, the line valve is arranged in the area of ​​the connection of the media line to the structure, preferably as part of a coupling component of a line coupling that can be released as intended.

[0049] The term "pipe coupling" refers to a connection structure between two sections of a media line that is designed to be non-destructively detachable, including a connection structure between a media line and a downstream structure, such as a valve block assembly. A pipe coupling often has a male and a female coupling component, which can be coupled together in a media-tight manner to create a pipe connection. In a simple case, the coupling components can be directly coupled by friction alone. In a preferred embodiment, the coupling components, especially the male and female coupling components, are secured against unintentional detachment from one another, for example by cleavage, screwing, or other positive locking, such as a bayonet lock, or by using a screwable, stainless steel, or otherwise positively locking component.Another way to secure a coupling connection of the coupling components of a pipe coupling is to create and disconnect a coupling connection by moving at least one coupling component towards and away from the other, into and out of a coupling position, by means of a self-locking displacement device, such as a worm gear drive or a spindle drive with appropriately selected material pairings and thread pitches of the components in screw engagement, or by preloading by means of a preloading device comprising at least one preloading component or force device made of a mechanical spring, elastomeric spring, gas spring, magnet, or by gravity towards each other.

[0050] In principle, any device which is designed and intended to block or allow the flow of a media line in the line arrangement shall be considered a line valve within the meaning of the present application.

[0051] Preferably, the piping arrangement of a cell culture container comprises exactly one piping section. Equally preferably, this piping section comprises exactly one valve, located at its end region closest to the valve block on the container side.

[0052] Likewise, exactly one disposal line is connected to a container-side valve block in a fluid-transferring manner, preferably with exactly one disposal valve at the end area of ​​the disposal line that is closer to the container-side valve block.

[0053] Preferably, a valve block on the container side is connected to exactly one cell culture container, wherein the detachable line coupling, in a particularly simple and therefore preferred embodiment, is a plug connection of a line head carrying the container valve at the longitudinal end of the container line of the cell culture container furthest from the container, to a receiving recess formed in the valve block on the container side. Preferably, the line head is simply inserted into the receiving recess for quick changing of the cell culture container, without being directly fixed to the receiving recess or the valve block on the container side, or otherwise positively coupled.If the container piping arrangement includes separate container lines for supplying and discharging media into and out of the cell culture container, each detachable pipe coupling of the container lines of a cell culture container preferably has a plug connection, preferably according to the embodiment described above, with the container-side valve block. The portion of the detachable pipe coupling provided by the container piping arrangement preferably comprises a pipe head with a container valve at each longitudinal end of a container line furthest from the cell culture container. Preferably, the valve body of a pipe head detached from the container-side valve block is exposed. However, it can also be covered by a cap to protect it from dust.

[0054] The plug connection between the container piping assembly and the container-side valve block can be secured against unintentional loosening, as described above, by pre-tensioning at least one pipe head and / or the container piping assembly and / or the cell culture container towards the container-side valve block. For this purpose, a suitable pre-tensioning device can be arranged in the cell culture management device, such as a movable component, like a slide or a swivel arm, pre-tensioned towards the container-side valve block by a force device such as a spring, a gas spring, a magnet, and the like, and / or pre-loaded by gravity.

[0055] Each container pipe runs along a virtual flow path, through which media can flow. The pipe head preferably has a circumferential surface that is closed around the virtual flow path of the container pipe supporting it. When the plug connection is made, this circumferential surface is surrounded by a closed counter-surface of the receiving recess of the container-side valve block. A sealing effect between the circumferential surface and the counter-surface is not required. A seal between the pipe coupling of a container pipe and the container-side valve block is preferably achieved at the end face of the pipe head by means of a soft, elastic support component already present on the container valve, on which the valve body of the container valve rests in the closed position of the container valve.

[0056] To increase the effectiveness of the cell culture management device, the device can additionally include a second cell culture container. The aforementioned at least one cell culture container is then referred to as the first cell culture container.

[0057] Preferably, the cell culture management device then has a second tank-side valve block with a second tank-side valve block housing and a second tank-side conveying channel section for managing the second cell culture container. The tank-side valve block described above is then a first tank-side valve block. The reservoir-side valve block and the second tank-side valve block are fluid-transferringly connected to each other by means of a second connecting line arrangement. A second connecting valve arrangement and a second conveying pump are arranged in the second connecting line arrangement to control the media flow through the second connecting line arrangement. The aforementioned connecting line arrangement and its connecting valve arrangement are then a first connecting line arrangement and a first connecting valve arrangement.

[0058] The second cell culture container is fluid-transmittingly connected to the second container-side valve body by means of a second container line arrangement with an intermediate arrangement of a second container valve arrangement via a second line coupling that can be released as intended.

[0059] The above statements regarding the first tank-side valve block, the first cell culture tank, the first connecting pipe assembly, the first connecting valve assembly, and the first feed pump apply mutatis mutandis equally to the second tank-side valve block, the second cell culture tank, the second connecting pipe assembly, the second connecting valve assembly, and the second feed pump. This applies in particular to the connection of the second cell culture tank to the second tank-side valve block and the connection of the second tank-side valve block to the reservoir-side valve block.

[0060] Preferably, the first and second cell culture containers are identical in design. Preferably, the first and second container-side valve blocks are identical in design. Preferably, the first and second connecting pipe assemblies are identical in design. Preferably, the first and second connecting valve assemblies are identical in design. Preferably, the first and second feed pumps are identical in design. This allows for the stocking of essentially identical components for maintenance and repair, which can then be used as needed in the management system. The second connecting pipe assembly is part of the pipe assembly. The second connecting valve assembly is part of the pipe valve assembly.

[0061] The cell culture management device preferably includes a control device for controlling the operation and the individual components of the cell culture management device. The control device preferably comprises at least one integrated circuit and a data storage device and is particularly preferably designed as a computer or microcomputer with an operating program and utility stored in the data storage device. The data storage device can store volatile data for retrieval by the at least one integrated circuit during the operation of the cell culture management device.

[0062] The present invention is explained in more detail below with reference to the accompanying drawings. It illustrates:

[0063] Fig. 1 is a rough schematic representation of the structure of an embodiment of a cell culture management device according to the invention of the present application, Fig. 2A is a longitudinal sectional view of a first embodiment of a dimensionally stable media container of Fig. 1 in bottle shape,

[0064] Fig. 2B shows a second embodiment of a shape-labile media container from Fig. 1 in bag form,

[0065] Fig. 3 shows a perspective view of the supply-side valve block with a line valve switching device from Fig. 1.

[0066] Fig. 4 shows a longitudinal sectional view of the supply-side valve block of Fig. 1 along a section plane containing the virtual supply-side flow path of the supply-side conveying channel section and the virtual flow paths of the end sections of the supply lines leading into the supply-side conveying channel section.

[0067] Fig. 5 shows a longitudinal sectional view of the first tank-side valve block of Fig. 1 along a section plane containing the virtual first tank-side flow path of the first tank-side conveying channel section and the virtual flow paths of the end sections of the media lines opening into the first tank-side conveying channel section, and

[0068] Fig. 6 shows a perspective view of the first wobble device of Fig. 1 as an embodiment of a wobble device according to the invention.

[0069] The figures are not to scale.

[0070] Figure 1 shows a rough schematic representation of the structural design of a cell culture management device of the present application, which is generally designated by 10.

[0071] The cell culture system 10 comprises, as its core component for cultivating living cells, a first cell culture container 12 and a substantially identical second cell culture container 14. For the cell culture containers 12 and 14, the cell culture system 10 includes, as media reservoirs 16 in Figure 1, from left to right: atmosphere A, in which the cell culture system 10 is located and which serves as an air reservoir and thus as a reservoir of a gaseous rinsing medium; a water reservoir 18, containing sterile demineralized water as a liquid rinsing medium; and, to the right of the water reservoir 18 in Figure 1, a pipe cleaning media reservoir 20 containing peracetic acid, adjacent to which is a cell cleaning media reservoir 22 containing phosphate-buffered saline, abbreviated "PBS" for "phosphate-buffered saline".

[0072] To the right of the cell cleaning media reservoir 22, as shown in Fig. 1, is a cell nutrient media reservoir 24, which contains a liquid nutrient medium for supplying living cells in the cell culture containers 12 and 14.

[0073] A cell harvesting medium 26 is arranged as the far right media reservoir, comprising an endopeptidase, in particular trypsin or trypsin-EDTA ("EDTA" stands for "ethylenediaminetetraacetic acid"). The liquid harvesting medium serves to detach harvestable adherent cells from their culture surfaces in the respective cell culture containers 12 and 14, to which they adhere during their cultivation phase, in order to subsequently remove the harvestable cells from the cell culture containers 12 and 14.

[0074] The liquid media supplies 16, namely supplies 18, 20, 22, 24 and 26, are each stored in a media container 28. For the sake of clarity, not all media containers 28 are labeled with a reference symbol in Figure 1.

[0075] The media supplies 16 are connected to the cell culture containers 12 and 14 for the passage of media via a conduit arrangement 30.

[0076] The pipe arrangement 30 comprises supply lines 32 of a supply line arrangement 34. Each supply line 32 leads from the respective media reservoir 16 to a reservoir-side valve block 36. The reservoir-side valve block 36 is also part of the pipe arrangement 30.

[0077] The supply line assembly 34 with its supply lines 32 is connected to the supply-side valve block 36 via an intermediate supply valve assembly 38 with supply valves 40. For the sake of clarity, not all supply valves 40 are labeled with a reference numeral.

[0078] A liquid sensor 42, known per se, is arranged on each of the supply lines 32 of the liquid media reservoirs 18, 20, 22, 24, and 26. This sensor detects whether liquid is present in or flowing through the supply line 32 assigned to the respective liquid sensor 42 by its physical arrangement. For clarity, only some of the liquid sensors 42 are identified by reference numerals. These liquid sensors 42 are connected to a control device 44, which will be described in more detail below. The control device 44 receives signals from the liquid sensors 42 and can issue an error message based on a comparison of the actual and target states. For this purpose, the control device 44 can cooperate with an output or display device 46 of the management device 10.

[0079] In the supply line 32, which conveys air as a gaseous rinsing medium from the atmosphere A towards the cell culture containers 12 and 14, a filter 48 with a preferred mesh size of 0.2 pm is arranged, which cleans the aspirated air during its flow through it.

[0080] The supply-side valve block 36 comprises a supply-side valve block housing 50. In the valve block housing 50, which is preferably designed in multiple parts for ease of assembly, a supply-side delivery channel section 52 is formed through which fluid media can flow. This section extends along a straight, virtual supply-side flow path 54. In the schematic representation of Figure 1, the horizontal dashed line symbolizes both the supply-side delivery channel section 52 and its virtual supply-side flow path 54. The supply lines 32 open into the supply-side delivery channel section 52. In the exemplary embodiment, the line arrangement 30 comprises a first connecting line arrangement 56 with exactly one first connecting line 58 and a second connecting line arrangement 57 with exactly one second connecting line 60.The first connecting line 58 connects the reservoir-side valve block 36 to a first container-side valve block 62, which is connected to the first cell culture container 12. The second connecting line 60 connects the reservoir-side valve block 36 to a second container-side valve block 64, which is connected to the second cell culture container 14. Since the two container-side valve blocks 62 and 64 are essentially identical in design to each other, as are the two cell culture containers 12 and 14, only the first container-side valve block 62 will be described in detail below, and its description can also be used to explain the second container-side valve block 64.

[0081] The first tank-side valve block 62 comprises a first tank-side valve block housing 66, preferably designed in multiple parts for ease of assembly, in which a first tank-side conveying channel section 68 is formed, which runs along a first virtual tank-side flow path 70.

[0082] The storage valve arrangement 38 is part of a line valve arrangement 72, which also includes a first connecting valve arrangement 74 and a second connecting valve arrangement 76. The first connecting valve arrangement 74 comprises two connecting valves 78 and 80, of which the storage-side connecting valve 78 is arranged in the area of ​​the opening of the first connecting line 58 into the storage-side conveying channel section 52, and the tank-side connecting valve 80 is arranged in the area of ​​the opening of the first connecting line 58 into the first tank-side conveying channel section 68.

[0083] The same applies mutatis mutandis to the second connecting valve arrangement 76, under whose intermediate arrangement the second connecting line arrangement 57 is connected both to the supply-side valve block 36 and to the second container-side valve block 64, in an analogous manner to how the first connecting line arrangement 56 is connected under the intermediate arrangement of the first connecting valve arrangement 74 to the supply-side valve block 36 and the first container-side valve block 62.

[0084] Liquid sensors 42 in the first connecting line 58 and in the second connecting line 60, which are connected to the control device 44 via signal transmission, supply the control device 44 with a signal indicating whether there is liquid in the respective connecting line or whether liquid is flowing through the connecting line.

[0085] A first pump 84, preferably configured as a peristaltic pump and acting on the first connecting line 58 (designed as a flexible hose), pumps the respective fluid medium present in the supply-side delivery channel section 52 from the supply-side delivery channel section 52 to the first tank-side valve block 62. Likewise, a second pump 86, preferably configured as a peristaltic pump and particularly preferably essentially identical to the first pump 84, pumps a respective fluid medium present in the supply-side delivery channel section 52 from the supply-side delivery channel section 52 to the second tank-side valve block 64.

[0086] The operation of the feed pumps 84 and 86 is preferably controlled by the control device 44, which is connected to the feed pumps 84 and 86 via signal transmission.

[0087] Likewise, the control device 44, which for this purpose comprises one or more integrated circuits and one or more data storage devices for storing an operating program and for storing volatile data during operation, and which is preferably designed as a microcomputer, controls the line valves of the line valve arrangement 72. This will be explained below by way of example using the reservoir valves 40. The description given here also applies to the other line valves of the line valve arrangement 72.

[0088] The storage valves 40 of the storage valve arrangement 38 are adjusted between their closed and open positions by a storage-side line valve switching device 88. The storage-side line valve switching device 88 is controlled by the control device 44.

[0089] The supply-side line valve switching device 88 comprises movable switching magnets 90, mounted in switching magnet carriers 89. Preferably, exactly one switching magnet 90 in exactly one switching magnet carrier 89 is assigned to each supply valve 40, the supply-side connecting valve 78, and the supply-side connecting valve of the second connecting valve arrangement 76. The dashed line in the switching magnets 90 in Figure 1 indicates the boundary between the two magnetic poles of the switching magnets 90; that is, preferably, the polarization direction of the switching magnets 90 corresponds to the displacement direction of the switching magnets 90 towards and away from the line valve 40 or 78 they switch. For clarity, not all switching magnet carriers are provided with the reference numeral 89.

[0090] Each switching solenoid 90 can be brought close to and removed from the line valve it controls by its own drive, such as an electric motor 92, for example via a spindle drive 94. The supply valves 40 and the supply-side connecting valve 78, as well as all other line valves of the line valve arrangement 72, are, in the embodiment shown here, magnetically biased internal line valves in their closed position. They have a permanent magnet in a valve seat through which the medium in the respective media line flows and a permanent magnet valve body wettable by the same medium. As the switching solenoid 90 approaches the respective supply valve 40, the permanent magnet valve body is attracted to it by the stronger magnetic field of the switching solenoid 90 compared to the permanent magnet in the valve seat and lifted from the valve seat.In the exemplary illustration in Figure 1, the reservoir valve 40 of the liquid rinsing media reservoir 18 containing sterile demineralized water and the reservoir-side connecting valve of the second connecting valve assembly 76 are open. All other line valves 40 and 78 housed in the reservoir-side valve block 36 are in the closed position according to their magnetic preload. With the reservoir-side line valve switching device 88 in this position, the second pump 86 can pump demineralized water from the liquid rinsing media reservoir 18 into the second tank-side valve block 64.

[0091] A disposal line assembly 102 is also flushed by the cleaning media used. Except during the harvesting of cultured cells, any other fluid medium is discharged from the line assembly 30 via the disposal line assembly 102 into a disposal container 116.

[0092] A line valve switching device, constructed and functioning identically (mutatis mutandis), is also provided on each tank-side valve block. There, the switching magnets 90 are only symbolically indicated by horseshoe symbols.

[0093] In contrast to the illustration in the exemplary embodiment, at least those line valves of the line valve arrangement 72 which are arranged for controlling the media flow on media lines that are permanently connected to a structure, such as the reservoir-side valve block 36, the first tank-side valve block 62, or the second tank-side valve block 64, and the like, can be formed by line valves not shown externally in the figures. External line valves are line valves whose valve seat is not exposed to the medium in the associated media line and whose valve body is not wetted by the medium in the associated media line. A pinch valve, known per se, is a possible external line valve.

[0094] The first cell culture container 12 is connected to the first container-side valve block 62 by a container line arrangement 95 firmly connected to the first cell culture container 12, preferably with exactly one bidirectionally flowing container line 96 and an intermediate container valve arrangement 98 with exactly one container valve 100.

[0095] In Figure 1, two switching magnet symbols are assigned to the container valve 100. This indicates that the switching magnet 90 assigned to the container valve 100 can not only be moved towards and away from the container valve 100 as described above, but that the switching magnet 90 of the container valve 100 can also be displaced transversely to its approach and removal direction along the first virtual container-side flow path 70 of the first container-side valve block 62 in the area of ​​the opening of the container line 96, in order to assist a flow coming from the first connecting line 58 from the area of ​​the first container-side conveying channel section 68 located to the left of the container line 100 in Figure 1 into the first cell culture container 12 by displacing the valve body of the container valve 100 to the right in Figure 1.Likewise, by a targeted displacement of the valve body of the container valve 100 in Figure 1 to the left, a flow exiting from the first cell culture container 12 into the area of ​​the first container-side conveying channel section 68 located to the right of the container line 100 in Figure 1 can be supported.

[0096] Alternatively, for the container valve 100, two switching magnets 90 could be arranged, offset along the first virtual container-side flow path 70 with respect to the opening of the container line 96 into the first container-side conveying channel section 68, one of which each sets the container valve 100 to the open position, depending on between which of the aforementioned areas of the first container-side conveying channel section 68 and the first cell culture container 12 a medium is to flow. Along the first virtual container-side flow path 70, the opening of the container line 96 in the embodiment with two switching magnets for the container valve 100 is located between the two switching magnets of the container valve 100.

[0097] While the first connecting line 58 along the first virtual tank-side flow path 70 is an outermost media line opening into the first tank-side conveying channel section 68 at a longitudinal end region, the disposal line arrangement 102, already mentioned above, opens into the first tank-side conveying channel section 68 at the longitudinal end region opposite the first virtual tank-side flow path 70, with a first disposal line 104 as the outermost media line along the first virtual tank-side flow path 70. The disposal line arrangement 102 is also part of the line arrangement 30.

[0098] Part of the line valve assembly 72 is a disposal valve assembly 106 with a first disposal valve 108 and a second disposal valve 110. The disposal line assembly 102 is connected to the first and second container-side valve blocks 62 and 64, respectively, via the disposal valve assembly 106. Specifically, in Figure 1, the first disposal line 104 is connected to the first container-side valve block 62 via the first disposal valve 108. A liquid sensor 42 detects liquid or a liquid flow in the first disposal line 104.

[0099] In the common branch 112 of the disposal line assembly 102, a further fluid pump 114 is arranged as a disposal fluid pump. This disposal fluid pump 114 is also preferably a peristaltic pump. Particularly preferably, the disposal fluid pump 114 is essentially identical to the first feed pump 84 and / or the second feed pump 86. The disposal fluid pump 114 can discharge medium from the conveying channel sections on the container side and, with a suitable valve position, also from the cell culture containers 12 and 14, respectively. The disposal line assembly 102 terminates at its end furthest from the container-side valve blocks 62 and 64 at or within the disposal container 116 mentioned above.

[0100] The arrangement of flow spaces of the fluid media shown allows the entire pipeline, comprising the supply-side conveying channel section 52, the connecting line arrangements 56 and 57, and the tank-side conveying channel sections 68 and 69, to be completely flushed with cleaning medium and neutralized or rinsed clean with rinsing medium.

[0101] Along the first virtual tank-side flow path 70 between the outlets of the first connecting line 58 and the first tank line 96, a transfer line arrangement 118, comprising exactly one transfer line 120 in the illustrated embodiment, opens into the first tank-side conveying channel section 68. The transfer line arrangement 118 is part of the line arrangement 30.

[0102] The transfer line assembly 118 opens into the second container-side conveying channel section 69 at the appropriate point between the outlet of the second connecting line 60 and the container line of the second cell culture container 14. A transfer pump 122, arranged on the transfer line assembly 118 or its single transfer line 120, serves to generate a pressure differential in the transfer line assembly 118 and thereby convey a medium between the first container-side conveying channel section 68 and the second container-side conveying channel section 69, or preferably between the first cell culture container 12 and the second cell culture container 14. This enables the transfer of media and, in particular, cells between the cell culture containers 12 and 14, or even just between the container-side valve blocks 62 and 64.

[0103] The line valve arrangement 72 comprises a transfer valve arrangement 124 with one transfer valve 126 and one 128 at each outlet of the transfer line arrangement 118 into one of the two tank-side conveying channel sections 68 and 69. The transfer valve arrangement 124 can also be switched between its open position and its closed position by the control device 44 via a tank-side line valve switching device. This applies individually to each of the transfer valves 126 and 128.

[0104] A cell singulation device 130, such as that known, for example, from WO 2017 / 137472 A1, the disclosure of which is fully incorporated into and referenced in the present application, can be arranged upstream and / or downstream of the transfer pump 122 in the transfer line assembly 118. The cell singulation device 130 gently breaks up cell clusters by means of turbulence in the medium flowing through it, without damaging the cells forming the clusters, thus advantageously allowing cells to be conveyed individually between the cell culture containers 12 and 14. For taking samples, such as from the cells cultivated in the cell culture containers 12 and 14, the line assembly 30 can include a sampling line assembly 132.The sampling line arrangement 132 can comprise a first sampling line 134 connected to the first container-side valve block 62 via fluid transfer and a second sampling line 136 connected to the second container-side valve block 64.

[0105] In the sampling lines 134 and / or 136, a fluid pump can again be arranged in a manner known per se and already described above, in order to generate a pressure difference between the cell culture containers 12 and 14 on the one hand and a section of the line located downstream of the fluid pump in the sampling direction, and thereby pump medium from the respective cell culture container 12 or 14 to a sampling end of the respective sampling line 134 or 136. This at least one fluid pump of the sampling line arrangement 132 is also controlled for operation by the control device 44. Preferably, the at least one fluid pump in the sampling line 134 and / or 136 is essentially identical to at least one of the fluid pumps already mentioned above.

[0106] Furthermore, the line valve arrangement 72 can include a sampling valve arrangement 138, which either blocks or allows flow through the sampling line arrangement 132 depending on its operating position. Analogous to the functional line arrangements 34, 56, 57, 102, and 118 described above, the sampling line arrangement 132 is connected to the tank-side valve blocks 62 and 64 via the sampling valve arrangement 138. More precisely, the first sampling line 134 is fluid-transmitting to the first tank-side valve block 62 via a first sampling valve 140, and the second sampling line 136 is connected to the second tank-side valve block 64 via a second sampling valve 142. The first sampling line 134 flows into the first container-side conveying channel section 68 between the first tank line 96 and the first disposal line 104.The same applies mutatis mutandis to the second sampling line 136 on the second container-side valve block 64.

[0107] All media lines in Figure 1, which are accompanied by a directional arrow parallel to the respective media line, carry fluid flow only in the direction indicated by the arrow, due to the operation of the fluid pump directly or indirectly cooperating with the respective media line, which is initiated by the control device 44. This also applies to the supply lines 32, which run from the liquid media reservoirs 18, 20, 22, 24, and 26 to the reservoir-side valve block 36. These media lines 32 are simply too short to show a directional arrow next to them in Figure 1. The reservoir-side delivery channel section 52 also carries fluid flow only in one direction, since the connecting line arrangements 56 and 57 likewise carry fluid flow only in one direction.

[0108] The cultivation device 10 comprises a first tumbling device 144, to which the first cell culture container 12 is fixed during a cultivation phase, and a similarly constructed second tumbling device 146, to which the second cell culture container 14 is similarly fixed during a cultivation phase. The description of the first tumbling device 144 given in the present application therefore also applies to the second tumbling device 146. The operation of the tumbling devices 144 and 146 is also controlled by the control device 44. Preferably, the first tumbling device 144 and the second tumbling device 146 can be controlled independently of one another to perform a movement, in particular a tumbling movement.

[0109] The first tumbling device 144 is pivotable simultaneously, but with section-wise different angular velocities, about two mutually perpendicular, in particular orthogonal, axes S1 and S2 between two end positions per axis S1 and S2, in order to gently wet as large an internal surface area as possible of the first cell culture container 12, which is fixed to the first tumbling device 144 and contains medium, by means of a tumbling motion imposed on the first cell culture container 12 by the first tumbling device 144, without excessive splashing. The first container-side valve block 62 is pivotable together with the first tumbling device 144, so that during a tumbling pivoting motion of the first cell culture container 12 by the first tumbling device 144, no relative movement induced by the tumbling pivoting motion occurs between the first cell culture container 12 and the first container-side valve block 62.

[0110] At least one of the mutually orthogonal pivot axes S1 and S2 of a wobbling device 144 or 146 is preferably oriented parallel to the largest or at least the second largest wettable inner planar surface of the cell culture container 12 or 14 mounted on the wobbling device 144 or 146. In Figure 1, the plane of Figure 1 is parallel to a planar surface of a support plate (see support plate 721 in Figure 6) supporting the respective cell culture container in its neutral position, and thus parallel to the orthogonal pivot axes S1 and S2 of the wobbling device 144 or 146 in their undisplaced neutral position. The first pivot axis S1 of the first wobbling device 144 runs parallel to the first container-side conveying channel section 68 and can pass through the first container-side valve block 62 and preferably the first container-side conveying channel section 68.The second pivot axis S2 of the first wobble device 144 preferably runs parallel to the first container line 96 and optionally coaxially to the first container line 96. The same applies mutatis mutandis to the second wobble device 146.

[0111] Cell culture containers 12 and 14 can be pivoted about their respective first pivot axis S1 to extract a medium, particularly a liquid, from the respective cell culture container 12 or 14, such that the liquid medium inside the cell culture container 12 or 14 flows by gravity to the respective container line. The majority or all of the volume of the respective cell culture container is then located geodetically above the respective conveying channel section 68 or 69 on the container side.

[0112] The number of cell culture containers that can be managed by the management device 10 using the media reservoirs A, 18, 20, 22, 24 and 26 can be increased in various ways. In the simplest case, one or more further connecting line arrangements can be fluid-transferred to the reservoir-side valve block 36, with further connecting valves and a fluid pump in between, leading to further container-side valve blocks with at least one cell culture container connected to them for fluid transfer.

[0113] Alternatively or additionally, for example, a sampling line on the first and / or second container-side valve block 62 or 64, or optionally on at least one further container-side valve block, can be replaced by a transfer line, which can be fluid-transferred to a further or further container-side valve block. In this case, no culture sample can be taken from at least one cell culture container during the cultivation phase. Instead, more than two cell culture containers 12 and 14 can be managed from a single reservoir-side valve block 36. The at least one additional transfer line can be configured like the transfer line 120 of Fig. 1. Further cell culture containers can be connected in parallel or in series with those shown in Fig. 1, preferably using one container-side valve block per additional cell culture container.The cell culture containers 12 and 14 shown in Figure 1 are connected via at least two transfer lines. Preferably, each cell culture container is assigned exactly one container-side valve block for fluid transfer to it, and vice versa.

[0114] Alternatively or additionally, two or more supply lines 32 can extend from a media reservoir, each of which is fluid-transferring to a different reservoir-side valve block. The two or more supply lines can originate directly from the respective media container. Alternatively, a single supply line extending from a media container can branch into two or more branches at a distance from the media container. One, two, or more container-side valve blocks can then be fluid-transferring to the additional reservoir-side valve block supplied in this way. Figure 2A schematically shows a longitudinal sectional view of a first embodiment of a media container 28 for the media reservoirs 16 for liquid media.

[0115] The generally bottle-shaped media container 28 of Fig. 2A comprises a dimensionally stable container body 200, made of, for example, bias-molded plastic, with a receiving volume 202 in which a liquid medium for cultivating cell cultures is contained. A container neck 204 extends from the container body 200, onto which a two-part container lid 206 is screwed. The container lid 206 comprises a cap nut 208 that can be screwed onto an external thread of the container neck 204 and a functional lid 212 that is clamped by the cap nut 208 against an annular end face 210 of the container neck. The functional lid 212 and the cap nut 208 can, contrary to the illustration in Fig. 2A, be formed in one piece or be permanently connected to each other.

[0116] Two channel nozzles 214 and 216 protrude from the functional cover towards the container body 200. Channel nozzle 214 serves to equalize pressure in the receiving volume 202 in the event of liquid medium being drawn from the container body 200. A further union nut 218 is screwed onto an external thread of channel nozzle 214, which clamps a bracket 220 for a pressure equalization hose 222 with an air filter 224 against the end face of channel nozzle 214.

[0117] The channel nozzle 216 also carries a union nut 226, which is identical in design to the union nut 218. The union nut 226 is penetrated by a flexible hose 228, which forms a supply line 32 of Fig. 1. The hose 228 extends with its longitudinal end 228a on the container side to the bottom 230 of the container body 200 in order to empty the media container 28 as completely as possible. At its longitudinal end 228b on the far side of the container, the hose 228 has a supply valve 40 of Fig. 1. A dashed line marks the course of a virtual flow path 230, conceived as passing centrally along the length of the hose 228, through the supply line 32 and thus also through the supply valve 40. The supply valve 40, which, with the minor exception of the container valve 100, is essentially identical in construction to all other line valves in Fig.The assembly comprises a central valve structure 300, which is completely penetrated by a flow channel 302. A virtual flow path 304 of the storage valve 40, conceived as centrally penetrating the flow channel 302, runs coaxially with the flow path 230 of the hose 228. The virtual flow paths 230 and 304 are coaxially linear within the extent of the storage valve 40.

[0118] The central valve structure 300 has a Christmas tree formation 306 onto which the flexible hose 128 is pushed. Alternatively, the hose 128 can be permanently connected to the central valve structure, for example by a material bond, in particular by welding, especially preferably by ultrasonic welding.

[0119] The central valve structure 300 also has a circumferential radial projection 308, against which the hose 228, pushed onto the fir-tree formation 306, rests at its end face, and against which a valve union nut 310, surrounding the longitudinal end 228b furthest from the container and the fir-tree formation 306, rests with a circumferential axial projection 312. The valve union nut 310 is not present on the container valve 100.

[0120] The valve union nut 310 has a skirt section 311 extending coaxially to the virtual flow path 304 and having an internal thread.

[0121] At its longitudinal end opposite the fir tree formation 306 of the central valve structure 300, an end piece 314 is received on the central valve structure 300, preferably by snapping the end piece 314 with the central valve structure 300 after it has been pushed onto the longitudinal end of the central valve structure 300 along the virtual flow path 304 of the upstream valve 40.

[0122] In a central, flowable recess of the end piece 314, a flowable, annular permanent magnet 316 is received as a preloading component, which is radially covered on the outside by a soft, elastic, annular, flowable support component 318. A spherical permanent magnet valve body 320 rests on the annular support component 318 and is held by the annular permanent magnet 316 against the valve seat 322 formed by the end piece 314, the annular permanent magnet 316, and the support component 318, and is preloaded into the closed position shown in Fig. 2A, in which the valve body 320 blocks flow through the flow channel 302 and thus through the flexible hose 228.

[0123] Unless otherwise stated in the present application, all line valves of the management device 10 shown in Fig. 1 correspond in construction to the storage valve 40 described in Fig. 2A.

[0124] The reservoir valve 40 forms a male coupling assembly 324, which can be coupled to a female coupling assembly of a line coupling 330 (see Figs. 3 and 4) as described in connection with Fig. 4 to form a fluid-transmitting connection. The valve union nut 310 is a locking component for securing a coupling connection with a female coupling component once it has been established. The internal thread of the valve union nut 310 can then be detachably screwed into an external thread on the female coupling assembly to prevent the fluid-transmitting connection of the line coupling 330 from unintentionally loosening.

[0125] For the storage of a liquid medium by the media container 28 before its coupling to the storage-side valve block 36, the valve body 320 can be exposed to the outside environment or can be covered by a cap which is pushed onto the end piece 314. However, because of the possibility of flushing the pipe assembly as described above, a cover by a cap is not absolutely necessary.

[0126] Figure 2B shows a second embodiment of a media container 28' in the form of a flexible bag 250. The bag 250, made of flexible film, does not require a pressure equalization device, since, due to the flexibility of the bag 250, liquid withdrawn from the receiving volume 252 of the bag 250 does not need to be replaced by a corresponding volume of gas to prevent an undesirable negative pressure inside the bag 250. Instead, when liquid medium is withdrawn from it, the bag 250 can simply decrease its volume due to the essentially constant ambient pressure.

[0127] The bag 250 has an eyelet 254 for hanging and positioning the bag 250 in the management device 10. Therefore, it is sufficient to position the container-side longitudinal end 228a of the flexible hose 228 at the lowest geodetic point of the bag 250 suspended from the eyelet 254, since the liquid collected in the bag 250 then flows by gravity towards the container-side longitudinal end 228a and the hose opening inevitably present there, thus facilitating the most complete possible emptying of the bag 250.

[0128] Fig. 3 shows a perspective view of the reservoir-side valve block 36 from Fig. 1. The reservoir-side valve block housing 50, which is preferably made of a stiffer material, i.e., a material with a higher modulus of elasticity than a flexible hose 228, is formed in two parts in the illustrated example, with a housing base body 50a and a housing cover 50b covering the housing base body 50a. Locking elements 50c at both longitudinal ends of the elongated reservoir-side valve block housing 50 secure the housing cover 50b to the housing base body 50a.

[0129] The housing body 50a and the housing cover 50b are preferably made of metal, for example aluminum or stainless steel, with aluminum being preferred for reasons of lower weight. It is also possible to make the components of the valve block housing 50 from plastic components, for example injection-molded or machined plastic components.

[0130] Fig. 3 shows how the valve union nuts 310 of the individual supply lines 32, as well as the first connecting line 58 and the second connecting line 60, are connected to the supply-side valve block 36 by screwing them together, acting as a locking component for the line couplings 330 with female coupling configurations. The connecting lines 58 and 60 are also preferably made of flexible hose material, the same material used for the hoses 228 of the supply lines 32. The supply line 32 on the far left in Fig. 3 leads to the atmosphere A. The supply line 32 adjacent to the leftmost supply line 32 in Fig. 3 leads to the reservoir 18 of sterile demineralized water. The first connecting line 58 is shown on the far right of the supply-side valve block 36.

[0131] Fig. 3 further shows how switching magnet carriers 89, which carry switching magnets (not shown in Fig. 3), are guided in their movement towards and away from the respective line valves by guides 91. The switching magnet carriers 89 are each mounted on a holder arrangement 93 guided on a guide 91 and connected to the spindle drive 94 for common translational movement via a connecting rod 95.

[0132] Instead of an electric motor 92 with a spindle drive 94, a linearly movable armature in an electromagnetic actuator can be used to relocate the switching magnets 90.

[0133] In a different embodiment, the switching magnets can be ring magnets whose central ring opening is penetrated by the spindle of the spindle drive 94, so that the ring-shaped switching magnets completely surround the spindle in at least part of their operating positions.

[0134] Fig. 4 shows the reservoir-side valve block 36 in a longitudinal section, the longitudinal section plane containing the parallel virtual flow paths 304 of the flow channels 302 in the central valve structures of the depicted line valves: reservoir valves 40, first reservoir-side connecting valve 78, and reservoir-side connecting valve of the second connecting valve arrangement 76, as well as the virtual flow path 54 of the reservoir-side delivery channel section 52. In Fig. 4, the rightmost reservoir line 32 is that of the gaseous purge media reservoir, i.e., atmosphere A. The first connecting line 58 is located on the reservoir-side valve block 36 at the far left in Fig. 4. All line connections to the reservoir-side valve block 36 and all line valves arranged therein are of the same design. Therefore, it suffices to reproduce the valve design at the two outermost line valves 40 and 78 in Fig. 4, which has already been explained in principle in connection with Fig. 2A.4. To be provided with reference signs of formations already explained.

[0135] In the reservoir-side valve block housing 50, between the base housing 50a and the housing cover 50b, a reservoir-side cavity 400 is formed, in which a reservoir-side insert component 402 is received. The reservoir-side insert component 402 can be an injection-molded part and, depending on the complexity of its shape, can be manufactured in one piece or from several sub-components. The reservoir-side insert component 402 can alternatively or additionally be manufactured by machining. Like the reservoir-side valve block housing 50 and its components 50a and 50b, the reservoir-side insert component 402, unlike the hoses 228, is a dimensionally stable component that retains its shape essentially under its own weight and also under moderate external loads.

[0136] The storage-side insert component 402, preferably designed as a shell component, incorporates the storage-side conveying channel section 52. Its straight, virtual storage-side flow path 54 is conceived as passing centrally through the length of the storage-side conveying channel section 52. Radially projecting webs 404, which may partially or completely encircle the storage-side conveying channel section 52, position the storage-side insert component 402 within the storage-side cavity 400. Not all webs 404 of the storage-side insert component 402 are labeled with reference numerals in Fig. 4.

[0137] The reservoir-side insert component 402 also has female coupling formations 406 projecting radially outward from the reservoir-side conveying channel section 52 on the valve block side, into which the male coupling formations 324 on the media line side are inserted. An external thread is formed on the female coupling formations 406 on the valve block side as a locking element, to which the internal thread of the skirt 311 of the valve union nut 310 is screwed. A male coupling formation 324 and a female coupling formation 406 together form a line coupling 330. The line coupling 330 can be quickly disconnected by hand without tools by loosening the screw connection of the valve union nut 310 with the female coupling formation 406 on the valve block side and by pulling the line valve 40 or 78 out of the female coupling formation 406 on the valve block side.As long as the screw connection of the valve union nut 310 with the valve block-side female coupling formation 406 exists, a fluid-transmitting connection between the respective media line and the supply-side delivery channel section 52 is reliably established.

[0138] Figure 5 shows a longitudinal section through the first container-side valve block 62. The longitudinal section includes the first cell culture container 12, which is connected to the first container-side valve block 62 via fluid transfer. The second container-side valve block 64, with the second cell culture container 14 connected to it via fluid transfer, appears identical in the same longitudinal section, so the description of Figure 5 also applies to the second container-side valve block 64 and the second cell culture container 14 connected to it via fluid transfer.

[0139] Analogous to the reservoir-side valve block 36, the first tank-side valve block housing 66 comprises a base housing 66a and a housing cover 66b, which enclose a first tank-side cavity 500 in which a first tank-side insert component 502 is received. The first tank-side conveying channel section 68 is formed in the first tank-side insert component 502, which runs along the straight first virtual tank-side flow path 70. Like the reservoir-side insert component 402, the first tank-side insert component 502 is preferably a shell-shaped component.

[0140] The first tank-side insert component 502, like the reservoir-side insert component 402, can be an injection-molded part and, depending on the complexity of its shape, can be manufactured in one piece or from several sub-components. The first tank-side insert component 502 can alternatively or additionally be manufactured by machining. Unlike the hoses mentioned above, the first tank-side insert component 502, like the first tank-side valve block housing 66 and its components 66a and 66b, is a dimensionally stable component that retains its shape essentially under its own weight and also under moderate external loads.

[0141] The first virtual tank-side flow path 70 is conceived as passing centrally through the first tank-side conveying channel section 68 lengthwise. Radially projecting webs 504 from the first tank-side conveying channel section 68, which may partially or completely encircle the first tank-side conveying channel section 68, position the first tank-side insert component 502 in the first tank-side cavity 500. Not all webs 504 of the first tank-side insert component 502 are labeled with reference numerals in Fig. 5.

[0142] Securing elements 66c secure the housing cover 66b to the housing base 66a.

[0143] The line valves on the first tank-side valve block 62, namely the connecting valve 80, the transfer valve 126, the first withdrawal valve 140, and the first disposal valve 108, are identical and correspond to the supply valve 40 shown in Figures 2A and 2B and described above. Any differences in the graphic representation of the line valves in Figure 5 compared to Figure 4 or Figures 2A and 2B are solely due to the schematic nature of the illustrations. Components and component sections of the line valves in Figure 5, already explained in connection with the supply valve 40 in Figures 2A and 2B, are provided in Figure 5 with the previously established reference numerals. For the sake of clarity, not all components and component sections of the line valves 80, 126, 140, and 108 in Figure 5 are provided with a reference numeral.

[0144] The first tank-side insert component 502, analogous to the reservoir-side insert component 402, has female valve block-side coupling formations 506 projecting radially away from the first tank-side conveying channel section 68. The female valve block-side coupling formations 506 of the first tank-side insert component 502 are identical in shape and function to the female valve block-side coupling formations 406 of the reservoir-side insert component 402.

[0145] The male couplings 324 of the line valves 80, 126, 140 and 108 on the media line side are inserted into the female coupling assemblies 506 on the valve block side. An external thread is formed on the female coupling assemblies 506 on the valve block side as a locking element, to which the internal thread of the skirt 311 of the valve union nut 310 is screwed. A male coupling assembly 324 and a female valve block-side coupling assembly 506 together form the line coupling 330 described above on the first tank-side valve block 62. The line coupling 330 can be quickly disconnected by hand without tools by loosening the screw connection of the valve union nut 310 with the valve block-side female coupling assembly 506 and by pulling out one of the line valves 80, 126, 140 and 108 from the valve block-side female coupling assembly 506.As long as the screw connection of the valve union nut 310 with the valve block-side female coupling formation 506 exists, a fluid-transferring connection between the respective media line and the first container-side conveying channel section 68 is safely established.

[0146] Unlike the female coupling assemblies 506 for connecting the male coupling assemblies 324 of the line valves 80, 126, 140, and 108, the radial projection length of a female coupling socket 507, which is integrally formed on the insert component 502 and projects radially from the first tank-side conveying channel section 68, for connecting the tank valve assembly 98 or the tank valve 100, is shorter than that of the female coupling assemblies 506 and has no external thread or other locking feature. Instead, the recess 510 in the first tank-side valve block housing 66 or in its housing base 66a, described below, together with the female coupling socket, contributes to forming a two-part female coupling assembly for the fluid-transmitting connection of the tank line 96 with the first tank-side valve block 62.The container valve assembly 98, and thus the container valve 100, has an identical valve seat 322 as the previously discussed line valves 40, 80, 126, 140, and 108. However, unlike the male coupling assemblies 324, the male coupling assembly 624 of the container valve 100 does not have a union nut with an internal thread as a locking element. In the illustrated preferred embodiment, the valve seat 322 is therefore the male coupling assembly 624.

[0147] In contrast, the end piece 314 is simply inserted into the cylindrical or conical recess 510 in the device housing 66, particularly on the housing base 66a, and is held there essentially by preloading the cell culture container 12 onto the container-side valve block 64. A circumferential surface 314a of the end piece 314, which runs around the straight virtual flow path 97 of the container line arrangement 95 and thus around the container line 96, is surrounded by a corresponding inner circumferential surface 510a of the recess 510 in the device housing 66. Preferably, the inner circumferential surface 510a of the recess 510 is designed to be at least partially complementary to the circumferential surface 314a.

[0148] As a further difference between the container valve 100 and the previously described line valves 40, 80, 126, 140 and 108, the valve structure 600 supporting the end piece 314 of the container valve 100 is designed differently from the previously described central valve structures 300.

[0149] The valve structure 600 of the container valve 100, which forms at least a section of the container line assembly 95 and thus of the container line 96, is integrally formed with a container lid 604 that can be screwed onto a neck 602 of the first cell culture container 12. The locking mechanism securing the end piece 314 to the valve structure 600 is identical to that of the previously described line valves, so that only a single embodiment of an end piece 314 is used to form the entire line valve assembly 72. The neck 602 is part of a container body 606, which encloses a container volume 610 into which the container line 96 leads.

[0150] Cross-hatching marks the cross-section of a culture area 608 in the container body 606, to which adherent cells to be cultivated can attach in order to subsequently multiply.

[0151] The female coupling socket 507 of the container line assembly 95, together with the male coupling assembly 624 of the first cell culture container 12, forms a line coupling 530. The coupling connection is established by inserting and withdrawing the male coupling assembly 624 into the recess 510 and the female coupling socket 507, respectively, via a self-locking drive train of a slide 720 (see Fig. 6) carrying the first cell culture container. The coupling is held in the coupled state and then released. This enables a quick and reliable, at least automated, exchange of cell culture containers at the first container-side valve block 62. The coupling between the female coupling socket 507 and the coupling assembly 624 is sealed by the support component 318 of the respective valve. This applies particularly to the line coupling 530 in conjunction with the container valve 100.

[0152] As explained above, the switching magnets 90, when approaching their associated valve bodies 320, cause the valve bodies 320 to lift from their respective valve seats 322. In Fig. 5, the valve body lifted from the valve seat of the first extraction valve 140 is shown with dashed lines. When the valve body is in the position shown with dashed lines, the first extraction valve 140 is in its open position.

[0153] As explained above, the switching magnet of the container valve 100 is movable along the virtual flow path 70 of the first container-side conveying channel section 68, so that the valve body 320 of the container valve 100 can not only be lifted from its valve seat 324, but also displaced along the virtual flow path 70. An adjustment range 512 of the first container-side conveying channel section 68, in which the container line 96 opens into the first container-side conveying channel section 68, has a larger diameter, so that the illustrated preferred valve ball, rather than the valve body 320, can move along the virtual flow path 70 in the adjustment range 512.

[0154] On either side of the adjustment range 512, a line section 514a or 514b of the first tank-side conveying channel section 68 connects to it. The cross-sectional area of ​​these lines is smaller than the largest cross-section of the valve body 320, so that the valve body 320 cannot leave the adjustment range 512 except in the direction away from the female coupling socket 507. Section 514a of the first tank-side conveying channel section 68 is the section into which the first connecting line 58 and the transfer line 120 open. Section 514b of the first tank-side conveying channel section 68 is the section into which the first sampling line 134 and the first disposal line 104 open.

[0155] In Fig. 5, the two possible positions of the valve body 320 of the container valve 100 are shown in the adjustment range 512 with dashed lines when the container valve 100 is in the open position. When media from area 514a are to flow into the first cell culture container 12, the container valve 100 can be adjusted to the open position such that the valve body 320, lifted from the valve seat 322, blocks the inactive area 514b from flowing through it, so that no medium can flow from area 514a into area 514b and vice versa. If, on the other hand, medium is to be taken from the first cell culture container 12 via the area 514b, the valve body 320 can be moved into the lower dashed position in Fig. 5, where it blocks the area 514a from flowing through, thus preventing any exchange of media between the areas 514a and 514b.

[0156] The female coupling socket 507 of the insert component 502 in the first tank-side valve block 62 projects from the first tank-side conveying channel section 68 to the opposite side than the female coupling formations 506 of the line couplings 330. This creates space for movement of the switching magnet of the tank valve 100. In contrast, all female coupling formations 406 on the supply-side valve block 36 project to the same side.

[0157] At the first valve block 62 on the vessel side, the virtual flow paths 304 of the line valves 80, 126, 140 and 108 preferably lie in one plane and are particularly preferably parallel to each other. Furthermore, the virtual flow path 97 of the vessel line 96 preferably runs parallel to at least one virtual flow path 304 of the line valves 80, 126, 140 and 108 and is particularly preferably located in the same plane as it.

[0158] Fig. 6 shows the first wobble device 144 in perspective. The first wobble device 144 and the second wobble device 146 are identical, so the following description of the first wobble device 144 also applies mutatis mutandis to the second wobble device 146.

[0159] The first wobble device 144 has a multi-part frame 700. The multi-part frame 700 comprises an outer frame 702 and an inner frame 704. The multi-part frame 700 is mounted on a frame (not shown in Fig. 6) via two substantially identical bearing elements 706. The frame can, for example, be part of an incubator cabinet or the like.

[0160] An external drive 708, positioned relative to the frame or bearing elements 706 (not shown), drives the outer frame 702 via a first belt drive 710 to a pivoting movement about the pivot axis S2. The outer frame 702 is pivotably mounted about the axis S2 on the bearing elements 706 via a drive shaft 712 and a bearing shaft 714 coaxial with the drive shaft 712.

[0161] All drives used on the first wobble device 144 of the exemplary embodiment are rotary electric motors.

[0162] The inner frame 704 is pivotably mounted on the outer frame 702 via the drive shaft 716 and a bearing shaft, which is concealed by the first cell culture container 12 in Fig. 6 and is coaxial with the drive shaft 716, about the pivot axis S1. The outer frame 702 and the inner frame 704 thus form a multi-part gimbal frame construction.

[0163] An inner drive 718, fixed to the outer frame 702 and movable together with the outer frame 702, drives the inner frame 704 via a belt drive 719 to pivot about the axis S1 independently of the rotational position of the outer frame 702.

[0164] The inner frame 704 carries a slide 720 which moves translationally along the track SP and thus towards and away from the first valve block 62 on the container side. The slide 720 is guided for translational movement relative to the inner frame 704 by guide rods (only one guide rod 722 is visible in Fig. 6). The track SP is shown as an extension of the section of the guide rod 722 visible in Fig. 6. In one position of the inner frame 704 relative to the outer frame 702, the track SP is parallel to the pivot axis S2.

[0165] By means of the translational movement of the slide 720 relative to the inner frame 704, a fluid-transferring connection of the container line 96 with the first container-side valve block 62 can be established, held and released again.

[0166] An adapter structure 724 is mounted on the carriage 720, which accommodates the first cell culture container 12. The adapter structure 724 comprises a support plate 726 and a receiving element 728 for a substantially play-free reception of the container lid 604 of the first cell culture container 12 along the container line 96. Due to the inclined neck 602 of the container body 606 in the exemplary embodiment, the support plate 726 is inclined such that the container line 96 of a cell culture container mounted on the adapter structure 724 runs substantially parallel to the carriage track SP and is aligned with the recess 510 in the first container-side valve block 62. In the case of a straight container neck, a correspondingly different adapter structure would be selected, the support plate of which is not inclined.The receiving element 728 has an upwardly open U-shape which surrounds a container lid 604 received therein along a wrap angle of at least 120°, preferably 180°. The first cell culture container 12 can thus be placed onto the adapter structure 724 from above and its position is essentially fixed by a positive fit between the container lid 604 and the receiving element 728. Since, as can be seen from the description of Fig. 5 above, the male coupling element 624 of the first cell culture container 12 is supported by the container lid 604 by means of the valve structure 600 formed integrally with the container lid 604, the male coupling element 624 is also fixed in its position relative to the slide 720 and thus relative to the first container-side valve block 62 and its recess 510.

[0167] The use of adapter structure 724 has the advantage that, by exchanging adapter structure 724 for another suitable adapter structure, a large number of differently designed cell culture containers can be used on the first tumbling device 144. It is even conceivable that different cell culture containers could be used on the first tumbling device 144 and on the second tumbling device 146, whereby only 146 different adapter structures are required on the two tumbling devices 144, while the remaining structure of the tumbling devices 144 and 146 remains identical.

[0168] To facilitate the mounting of additional functional assemblies, a mounting plate 721 of the slide 720 can already have a hole pattern with prepared mounting openings 730.

[0169] Then, when the slide 720 is advanced to the first container-side valve block 62, which is fixed immovably relative to the inner frame 704, and the first cell culture container 12 is in fluid-conveying connection with the first container-side valve block 510, the first cell culture container 12 is advantageously held on the adapter structure 724 by a clamping device 732. The clamping device 732 comprises a clamping bracket 734, which is pivotally movable about a clamping axis PB parallel to the pivot axis S1. In Fig. 6, the clamping bracket 734 is shown in its release position, in which the first cell culture container 12 can be removed or replaced by another cell culture container.

[0170] The clamping bracket 734 comprises two substantially identical pivot arms 736, which are arranged offset from each other along the clamping axis PB. A clamping rod 738 at the longitudinal end of the pivot arms 736, which in the exemplary embodiment are roughly S-shaped, connects the distant longitudinal ends of the pivot arms 736. In a locking position, which differs from the release position shown in Fig. 6 and in which the clamping device 732 secures the first cell culture container 12 to the adapter structure 724 and thus to the first wobble device 144 against removal, the clamping rod 738 rests against the upper surface 612 of the first cell culture container 12 and forms a physical blockage against lifting the first cell culture container 12 from the first wobble device 144.

[0171] The clamping rod 738 can be rubberized or otherwise coated to protect the cell culture container 12, which has a lower modulus of elasticity compared to the clamping rod 738 and is therefore more deformable under the same external load than the clamping rod 738.

[0172] A third drive 740, which is mounted immovably on the inner slide 704 relative to it, serves to move both the slide 720 and the first cell culture container 12 mounted on it along the slide track SP towards and away from the first container-side valve block 62 in order to bring the first cell culture container 12 into fluid-transferring contact with the first container-side valve block 62, to maintain this fluid-transferring connection, and to disconnect it again. A slip clutch in the drive train of the slide 720 can prevent overloading of the third drive 740 when the slide 720 reaches an end position, particularly when a fluid-transferring connection has been established between the first cell culture container 12 and the first container-side valve block 62.

[0173] The clamping bracket 734 can be fixed or otherwise held in the release position shown in Fig. 6, being pre-tensioned into the locking position by a pre-tensioning device, for example comprising a spring. As the slide 720 approaches the first container-side valve block 62, the slide 720 or a component connected to it, such as an actuating nose or the like, can release the retaining device or, more generally, the mounting that holds the clamping bracket 734 in the release position, so that the clamping bracket 734, driven by its pre-tension, moves into its locking position and, under the influence of the pre-tension, rests against the top surface 612 of the first cell culture container 12. In this way, the first cell culture container 12 can be clamped to the adapter structure 724 without requiring the third drive 740 to be continuously energized.

[0174] Instead of the aforementioned rusting, the third drive 740 can be designed to be self-locking, for example as a threaded drive, such as in the form of a spindle drive or worm gear drive.

[0175] By moving into the locking position, a driver of the clamping device 732, which is connected to the clamping bracket 734 for at least partial common movement, can come into engagement with the slide 720 in such a way that, during its movement away from the first container-side valve block 62, the slide 720, utilizing the driving force of the third drive 740, moves the clamping bracket 734 back into the release position against the preload force acting on the clamping bracket 734, where a renewed locking or retaining or self-locking mechanism holds the clamping bracket 734 in the release position and relieves the third drive 740.

[0176] The third drive 740 is kinematically coupled to the slide 720 via a belt drive 742 and a self-locking spindle drive (not shown). Further motion transmissions or reductions can be implemented under the slide 720 by means of gears and / or linkages in order to provide the necessary adjusting torques, adjusting forces and adjustment travels for the slide 720 and the clamping bracket 734, based on the drive torque supplied by the third drive 740.

[0177] All drives 708, 718 and 740 on the first wobble device 144 can be controlled by the control device 44 mentioned and described in connection with Fig. 1.

Claims

Claims 1. A wobble device (144) for a cell culture management device (10) for the efficient use of liquid media in a cell culture container, comprising: a receiving device (721, 724, 728) for receiving a cell culture container (12), an inner frame (704) which supports the receiving device (721, 724, 728), an outer frame (702) which can be mounted on a stationary base frame by means of at least one bearing element (706), an outer drive (708) for driving the outer frame (702) to a movement relative to its bearing elements (706), an inner drive (718) for driving the inner frame (704) to a movement relative to its bearing elements (706), and a control device (44) for controlling the operation of the inner drive (708) and the outer drive (708), wherein the inner frame (704) pivots about a first pivot axis (S1) is pivotably mounted on the outer frame (702),wherein the outer frame (702) is pivotably movable relative to its at least one bearing element (706) about a second pivot axis (S2) extending transversely to the first pivot axis (S1), wherein the inner drive (718) and the outer drive (708) can be driven to movement independently of each other by the control device (44).

2. Wobble device (144) according to claim 1 , characterized in that the inner frame (704) is pivotably mounted on the outer frame (702) only about the first pivot axis (S1 ) and / or that the outer frame (702) is pivotably movable relative to its at least one bearing element (706) only about the second pivot axis (S2) extending transversely to the first pivot axis (S1 ).

3. Wobble device (144) according to claim 1 or 2, characterized in that the first pivot axis (S1 ) and / or the second pivot axis (S2) are orthogonal to each other.

4. Wobble device (144) according to one of the preceding claims, characterized in that the receiving device (721 , 724, 728) is movably supported by the inner frame (704) relative to the inner frame (704).

5. Wobble device (144) according to claim 4, characterized in that the receiving device (721 , 724, 728) is supported translationally movable from the inner frame (704) relative to the inner frame (704).

6. Wobble device (144) according to claim 4 or 5, characterized in that the receiving device (721 , 724, 728) is preloaded relative to the inner frame (704) in one of its opposite directions of movement by a preloading device and / or by gravity.

7. Wobble device (144) according to one of claims 5 or 6, including claim 5, characterized in that a translational movement path (SP) of the receiving device (721 , 724, 728) in a relative position of the inner frame (704) relative to the outer frame (702) runs parallel or coaxial to the second pivot axis (S2).

8. Wobble device (144) according to one of the preceding claims, characterized in that the receiving device (721 , 724, 728) has an interchangeable adapter structure (724) which is designed to receive the cell culture container (12).

9. Wobble device (144) according to one of the preceding claims, characterized in that the inner frame (704) carries a container-side connection structure (62) connected to the inner frame (704) for common movement, with a container-side conveying channel section (68) formed in the connection structure (62), wherein the cell culture container received on the receiving device (721 , 724, 728) can be connected to and separated from the connection structure (62) and its container-side conveying channel section (68) by means of fluid transfer.

10. Wobble device (144) according to one of the preceding claims, including claim 4, characterized in that the wobble device (144) has a third drive (740) by which the receiving device (721 , 724, 728) can be driven to move relative to the inner frame (704).

11. Wobble device (144) according to claim 10, characterized in that the third drive (740) is designed as a self-locking drive.

12. Wobble device (144) according to one of the preceding claims, characterized in that the wobble device (144) has a clamping device (732) for clamping the cell culture container (12) to the receiving device (721 , 724, 728).

13. Wobble device (144) according to claim 12, characterized in that the clamping device (732) has a clamping bracket (734) which is adjustable between a release position in which the cell culture container (12) is not fixed to the receiving device (721 , 724, 728) and a locking position in which the cell culture container (12) is fixed to the receiving device (721 , 724, 728), wherein the clamping bracket (734) is biased into the locking position.

14. Tumble device (144) according to one of the preceding claims, characterized in that the tumble device (144) has a heating device for heating and / or tempering the cell culture container (12) received on the tumble device (144).

15. Cell culture management device (10) for managing cell cultures in at least one cell culture container, characterized in that the cell culture management device (10) comprises at least one tumbling device (144), preferably a plurality of tumbling devices (144, 146), according to one of the preceding claims.

Images