Cell culture management device with media conveyance between cell culture containers and method for media transfer between cell culture containers

Abstract

In a cell culture management device (10), a valve block arrangement (36, 62) comprises a supply-side valve block (36) having a supply-side valve block housing (50) and a supply-side conveying channel portion (52) extending along a virtual supply-side flow path (54), and a container-side valve block (62) formed separately from the supply-side valve block (36) and having a container-side valve block housing (66) formed separately from the supply-side valve block housing (50) and a container-side conveying channel portion (68) extending along a virtual container-side flow path (70), wherein a supply line arrangement (34) feeds into the supply-side conveying channel portion (68) and wherein a discharge line arrangement (102) and a container line arrangement (95) feed into the container-side conveying channel portion (68), wherein the supply-side valve block (36) and the container-side valve block (64) are fluidically connected to one another by means of a connection line arrangement (56) with a connection valve arrangement (74) and a feed pump (84).

Description

[0001] Cell culture management device with media transfer between cell culture containers and method for media transfer between cell culture containers

[0002] Description

[0003] The present invention relates to a cell culture management device for managing cell cultures in at least one cell culture container. The cell culture management device is intended to 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 will hereinafter also be 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 comprises 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 explicitly stated otherwise in a specific case. In its reference state, the cell culture management device comprises: a piping arrangement for conveying fluid media, including,

[0005] + a valve block arrangement with a valve block housing and with a conveying channel formed in the valve block housing, wherein the valve block arrangement has at least one first valve block with a first valve block housing and with a first conveying channel section of the conveying channel formed in the first valve block housing,

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

[0007] + a first 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, a first 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 first 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 fluid-transferringly connected to the valve block assembly via the reservoir line arrangement, with the reservoir valve arrangement interposed. Furthermore, in the operational reference state, the first cell culture container is fluid-transferringly connected to the first valve block via the first container line arrangement, with the first container valve arrangement interposed, and a first line coupling that can be released as intended. Additionally, in the operational reference state, the disposal line arrangement is fluid-transferringly connected to the valve block assembly. The disposal valve arrangement is located within the disposal line arrangement, such that the disposal line arrangement, or at least one disposal line thereof, can be selectively blocked or opened for media flow by the disposal valve arrangement.The disposal line arrangement can be fluid-transferred to the valve block arrangement via an intermediate disposal valve arrangement.

[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 these cases, a distinction between the valve seat and valve body is sometimes not possible or not practical. 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 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] 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] Although the above-mentioned cell culture management devices enable the management of several cell culture containers by successively connecting and disconnecting the valve block arrangement disclosed therein to a cell culture container, because the valve block arrangement can be cleaned by rinsing with cleaning fluid after being connected to a new cell culture container, there is still a theoretical risk of contamination from the use of one and the same valve block arrangement in conjunction with several cell culture containers between sowing an initial cell culture base in the cell culture containers at the beginning of a cultivation phase and harvesting the propagated cell cultures in the cell culture containers at the end of a cultivation phase.

[0021] The object of the present invention is to further develop a cell culture management device in such a way that it enables very efficient cultivation of living cells while simultaneously providing high protection against contamination.

[0022] The present invention solves this problem with a cell culture management device having the features of claim 1. According to the invention, the valve block arrangement comprises a second valve block with a second valve block housing and with a second conveying channel section. Additionally, the cell culture management device comprises at least one second cell culture container.

[0023] The at least one second cell culture container is, in the reference state, fluid-transmittingly connected to the second valve block via a second container piping arrangement with an intermediate second container valve arrangement and a second, detachable line coupling. This enables controlled media supply to and from the at least one second cell culture container. Like the first container piping arrangement, the second container piping arrangement also has at least one container line. Likewise, the second container valve arrangement has at least one valve which, depending on its operating state, opens or closes the second container piping arrangement to allow media flow.

[0024] The piping arrangement includes a transfer line arrangement with at least one transfer line for a direct media-transferring connection between the first and second valve blocks. The piping valve arrangement includes a transfer valve arrangement with at least one transfer valve to control the flow through the transfer line arrangement. The cell culture management device includes at least one transfer pump to drive the media flow in the transfer line arrangement.

[0025] The transfer valve assembly and the transfer delivery pump are arranged in the transfer line assembly.

[0026] The transfer line arrangement connects the first and second valve blocks to each other in a fluid transfer manner, with the transfer line arrangement opening into both the first and the second conveying channel section.

[0027] The above design makes it fundamentally possible to pump a fluid medium between the first and second valve blocks. This also applies to fluid media, especially liquids, containing living cells, i.e., so-called cell suspensions.

[0028] According to the invention, the valve block arrangement of the management device comprises a multi-part valve block. This multi-part valve block preferably 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.

[0029] In case of doubt, the virtual flow path on the supply side is conceived as running centrally along the length of the volume of fluid media through which the supply-side conveying channel section can flow. Similarly, in case of doubt, the virtual flow path on the tank side is conceived as running centrally along the length of the volume of fluid media through which the tank-side conveying channel section can flow.

[0030] In contrast to the supply line arrangement, the disposal line arrangement and the first container line arrangement preferably terminate in the container-side conveying channel section. This allows the first 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.

[0031] To supply the at least one cell culture vessel connected to the valve block assembly with media from the media reserves, the piping arrangement comprises a connecting piping arrangement with at least one connecting line. The piping valve arrangement comprises a connecting valve arrangement with at least one connecting valve. The at least one connecting valve is also a piping valve in the sense described above, comprising as a valve component a valve seat and a valve body that is displaceable relative to the valve seat. At least one valve component of the at least one connecting valve is accommodated in or on the multi-part valve block housing of the valve block assembly.

[0032] The supply-side valve block and the tank-side valve block are fluid-transferring via the connecting pipe assembly. The connecting pipe assembly houses the connecting valve assembly and the feed pump. This allows media to be selectively and controllably transferred from the supply-side valve block to the tank-side valve block by the feed pump and the connecting valve assembly. Likewise, unwanted flow or backflow of a medium between the supply-side and tank-side valve blocks can be prevented, or a desired backflow can be selectively controlled to advantageously reduce the amount of media in the dead volume of a pipe run. The dead volume of a pipe run is the unusable pipe volume between a supply valve at the beginning of the pipe run and the tank valve at the end of the pipe run.After introducing a desired quantity of a medium into at least one cell culture container, the medium in the dead volume was indeed removed from the respective media supply, but does not reach the cell culture container and is disposed of with the next cleaning or rinsing process without further measures.

[0033] In principle, the connecting valve assembly can be located at any point in the connecting pipe assembly. The connecting valve assembly can be fluid-transferred to the supply-side valve block and / or the tank-side valve block via an intermediate connecting valve assembly. This is particularly advantageous if the connecting pipe assembly is intended to be detachably connected to at least one of the valve blocks by means of a pipe coupling. In this case, the connecting valve assembly or a connecting valve can be part of the pipe coupling.

[0034] The connecting pipe arrangement preferably opens at one end into the supply-side conveying channel section and at the other end into the tank-side conveying channel section.

[0035] The advantage of the presented cell culture management device compared to the prior art is that, in principle, a single feed pump arranged between the reservoir-side and the container-side valve block is sufficient to introduce media from all media reservoirs connected to the reservoir-side valve block into the cell culture container connected to the container-side valve block via the reservoir-side valve block.

[0036] In a preferred embodiment, this pump can, for example, be a peristaltic pump which, in a manner known per se, flexes a flexible hose of the connecting line arrangement to pump a fluid medium, the point of maximum hose deformation achieved during flexing shifting along the deformable hose in the desired pumping direction. However, any pump suitable for pumping the media used can be employed. A separate pump for each media supply is therefore unnecessary and preferably not present. As will be shown below with reference to preferred embodiments of the present invention, the pump in question need not be the only pump in the management device. However, at a minimum, the pump in question must be present.

[0037] In the case of a valve block arrangement with a reservoir-side valve block and a tank-side valve block, the tank-side valve block can be the aforementioned first valve block. The reservoir-side valve block can be the second valve block, to which the second cell culture tank is connected via the second tank piping arrangement. The connecting piping arrangement is then the transfer piping arrangement, and the feed pump is the transfer-feed pump. The connecting valve arrangement is the transfer valve arrangement.

[0038] Preferably, however, no cell culture container is directly connected to the reservoir valve block. The reservoir valve block is preferably reserved for the media supply lines and the connecting line arrangement. This allows the reservoir valve block to be positioned and moved independently of the cell culture containers it supplies.

[0039] In the latter preferred case, the tank-side valve block is then a first tank-side valve block and the first valve block mentioned above. The tank-side valve block housing of the first tank-side valve block is a first tank-side valve block housing. The virtual tank-side flow path is a first virtual tank-side flow path. The tank-side conveying channel section extending along the first virtual tank-side flow path is a first tank-side conveying channel section.

[0040] The valve block arrangement then comprises a second, tank-side valve block, designed separately from the first, tank-side valve block, as the second valve block mentioned above. The second, tank-side valve block has a second valve block housing designed separately from the first, tank-side valve block housing and a second tank-side conveying channel section extending along a second virtual, tank-side flow path.

[0041] In this preferred embodiment, the connecting line assembly is designed and arranged separately from the transfer line assembly. Likewise, the transfer pump is designed and arranged separately from the fluid pump of the connecting line assembly. Finally, the connecting valve assembly is designed and arranged separately from the transfer valve assembly.

[0042] Preferably, the first and second valve blocks on the container side are identical in design, so that the cell culture management system can be built with as many identical parts as possible. This simplifies inventory management for assembly and repair.

[0043] Finally, it should not be excluded that the cell culture management device has a third valve block on the container side with a third cell culture container connected to it via fluid transfer. Just as what has been said in the present application regarding the first valve block on the container side preferably applies to the second valve block on the container side, this also preferably applies to the third valve block on the container side and, if applicable, to any further valve blocks on the container side.

[0044] Preferably, the third valve block on the tank side, and optionally each further valve block on the tank side, is connected to another valve block on the tank side via its own transfer line arrangement. The further transfer line arrangement of the third or further valve block on the tank side corresponds in its design to the transfer line arrangement between the first and second valve blocks. Accordingly, each further transfer line arrangement preferably comprises at least one transfer line, a further transfer valve arrangement with at least one transfer valve, and a further transfer pump.According to an advantageous embodiment of the present invention, the reservoir-side valve block and the second tank-side valve block can be fluid-transferred to one another by means of a second connecting line arrangement, in which a second connecting valve arrangement and a second feed pump are housed. Media from the media reservoirs can then be conveyed directly from the reservoir-side valve block to the first and / or the second tank-side valve block. Furthermore, media can be conveyed through the transfer line between the first and the second tank-side valve blocks.

[0045] In a less preferred, but fundamentally possible, embodiment, only the first tank-side valve block can be fluid-transferred to the reservoir-side valve block via the connecting line arrangement. Media can then only be conveyed serially from the reservoir-side valve block via the first tank-side valve block and the transfer line to the second reservoir-side valve block, and from there optionally to a further reservoir-side valve block.

[0046] For the reasons mentioned above, the supply line arrangement preferably leads into the supply-side conveying channel section, and especially preferably only into the supply-side conveying channel section.

[0047] Preferably, a cell culture container is assigned exactly one container-side valve block for transferring fluid media into and out of the cell culture container. Therefore, according to an advantageous embodiment, the first container piping arrangement opens into the first container-side conveying channel section, particularly preferably only into the first container-side conveying channel section. Likewise, according to this embodiment, the second container piping arrangement opens into the second container-side conveying channel section, particularly preferably only into the second container-side conveying channel section.

[0048] In principle, it may suffice if the disposal line arrangement terminates in only one tank-side conveying channel section consisting of the first and second tank-side conveying channel sections, since the transfer line arrangement allows for the direct conveying of media between the tank-side valve blocks. However, it is preferable for the disposal line arrangement to terminate in both the first and second tank-side conveying channel sections. In this case, each tank-side valve block, consisting of the first and second tank-side valve blocks, has its own connection to the disposal line arrangement. This advantageously enables short disposal paths and thus short wetting distances of the channel lumens in the tank-side valve blocks due to the consumed medium.

[0049] Sometimes it can be advantageous to be able to take samples from a cell culture container to monitor the cultivation process. In a further advantageous embodiment, the piping arrangement can include a sampling line arrangement. The first valve block on the container side can then be fluid-transferred to a first sampling line of the sampling line arrangement. Alternatively or additionally, the second valve block on the container side can be fluid-transferred to at least one second sampling line of the sampling line arrangement. Here, too, it is advantageous to achieve the shortest possible flow paths if each valve block on the container side has its own sampling line.

[0050] The line valve assembly can include a sampling valve assembly, which cooperates with the sampling line assembly to block or allow media flow through the sampling line assembly. The sampling valve assembly has at least one sampling valve for this purpose. In principle, the sampling valve assembly can be located at any point within the sampling line assembly. A clearly defined separation of the sampling line assembly from the respective tank-side valve block can be achieved by having the sampling line assembly open into the first and / or second tank-side conveying channel section via the intermediate sampling valve assembly. Naturally, the sampling line assembly can also be used for the complete removal of the contents of a cell culture tank during a cell culture harvest.

[0051] The transfer line arrangement preferably opens into the first container-side conveying channel section and / or into the second container-side conveying channel section between the connecting line arrangement and the container line arrangement of the respective conveying channel section, i.e. preferably into that area of ​​a container-side conveying channel section in which, during operation, either fresh medium or cleaning medium flows, but not used medium taken from a cell culture container for disposal.

[0052] The aforementioned problem is also solved by a method for managing cell cultures, in particular with a cell culture management device as described and further developed above. The method comprises the step of conveying a liquid medium from a first cell culture container into a second cell culture container. Preferably, the liquid medium can be conveyed bidirectionally between the receiving volumes of the first cell culture container and the second cell culture container.

[0053] A particular advantage is that the liquid medium can contain living cells, so that, for example, cells can be seeded from a first cell culture container into the second or, if necessary, into several further cell culture containers.

[0054] The advantageous further developments of the cell culture management device mentioned in the present application also include further developments of the process.

[0055] Regarding the nomenclature used in the present application:

[0056] 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.

[0057] 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, a transfer valve, and a withdrawal valve, as well as any further valves of the line valve arrangement that may be mentioned subsequently in preferred embodiments of the present invention, are each a line valve within the meaning of the present application.

[0058] 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.

[0059] 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 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 passage through the piping system. Preferably, a 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, in particular air, can also be provided as compressed gas, or compressed air, in a media reservoir.

[0060] 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.

[0061] 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 comprises 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, particularly 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 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.

[0062] If the present application refers only to a container-side valve block without assigning it an ordinal number, the statement made regarding the container-side valve block applies to both the first and the second container-side valve block. The same applies to statements regarding the cell culture container, the container piping arrangement, the container valve arrangement, and the container-side conveying channel section, even if these are not further specified by an ordinal number. Such statements also then apply to the first and the second cell culture container, the first and the second container piping arrangement, the first and the second container valve arrangement, and the first and the second conveying channel section, respectively.

[0063] In principle, any device designed and intended to block or allow the flow of media through a line of the piping arrangement is considered a line valve within the meaning of this application. Different types of line valves can be provided on the piping arrangement. However, for reasons of simplified manufacturing and assembly, at least a plurality of line valves, preferably all line valves, are identical in design. Therefore, preferably all line valves of the piping arrangement, including those mentioned later in connection with preferred embodiments of the present invention, have a valve seat and a valve body movable relative to the valve seat. Optionally, all line valves of the piping arrangement have identical valve seats and identical valve bodies.

[0064] For reliable cleaning of a line valve in a media line, which, compared to other media lines, is frequently separated from and connected to the valve block assembly, while simultaneously ensuring reliable sealing of the media line against flow of medium, the line valve is preferably designed as an internal line valve. Its valve seat is designed and positioned to allow flow of the medium from the respective media line. Likewise, the valve body of an internal line valve is preferably arranged in the media line containing the respective internal line valve so that it can be wetted by the flowing medium. This also allows for short adjustment travel of the line valve between the closed and open positions, enabling the internal line valve to be advantageously adjusted quickly between these positions.

[0065] Media lines that frequently need to be disconnected from and connected to the valve block assembly include the at least one supply line of the supply line assembly and the at least one reservoir line of the reservoir line assembly. This is because, during operation, emptied media reservoirs must be exchanged for full ones, and the at least one cell culture reservoir is replaced by one or more new cell culture reservoirs after a cultivation cycle for a subsequent new cultivation cycle. Therefore, preferably at least the at least one supply valve of the supply valve assembly and the at least one reservoir valve of the first and second reservoir valve assemblies are designed as the described internal line valve.

[0066] Preferably, a single line valve is used; more preferably, a plurality of line valves is used; and even more preferably, all line valves are pre-tensioned in their closed position. The pre-tension can be applied mechanically, electromagnetically, or magnetically. Preferably, the pre-tension is applied magnetically without current, as this enables reliable pre-tensioning in the closed position with the fewest possible components and without generating heat through current.

[0067] In a preferred embodiment, the valve seat of an internal inlet valve is permanently magnetized and comprises a permanently magnetized preload element. To ensure the most homogeneous magnetic field acting on the valve body, the valve seat, through which the medium of the associated media line flows, preferably comprises a permanent magnet ring magnet as the preload element. More preferably, the preload element is permeable to the medium in the respective media line. Particularly preferably, the preload element is formed as a closed loop around a virtual flow path that centrally penetrates the media line supporting the respective internal inlet valve. The valve body is preferably also permanently magnetized. Alternatively, the valve body can be soft-magnetized, i.e., not permanently magnetized, but magnetizable.Alternatively, the valve body can be permanent magnet and the preload component soft magnet.

[0068] To ensure a tight, gap-free seal between the valve body and the valve seat and to prevent undesirably harsh impacts when the valve body is seated on the valve seat, the flow-through valve seat preferably comprises a soft, elastic support structure compared to the material of the preloading component, for example, made of a polymer, in particular an elastomer such as rubber, especially silicone rubber, or more generally a polysiloxane or a polyorganosiloxane. The support structure, against which the valve body preferably bears directly in the closed position of the inner line valve, is preferably arranged between the valve body and the preloading component.

[0069] The valve body of an internal line valve is preferably predominantly, and even more preferably entirely, made of metal, particularly a ferromagnetic metal, with respect to its mass. Preferably, the valve body, which is wettable by the medium, is permanently magnetized. It can therefore be made of at least one rare earth element in addition to or instead of metal. The preloading component is preferably also made of a ferromagnetic, and especially preferably permanently magnetized, metal and / or of at least one rare earth element.

[0070] A preferred design of an internal line valve, which is also preferably used in the cell culture management device of the present application, is described in WO 2014 / 114610 A1, WO 2016 / 008636 A1, and WO 2017 / 216237 A1. Valves of a design that can also preferably be used in the cell culture management device discussed here are also described in WO 2008 / 037430 A and WO 2009 / 117995 A. The disclosure of permanently magnet-preloaded line valves in the closed position in the five aforementioned publications is expressly also a disclosure relating to the preferred line valves of the cell culture management device discussed here and is expressly incorporated into the present application.

[0071] Preferably, the cell culture management device includes a line valve switching device by which a plurality of the existing internal line valves, preferably all internal line valves, of the line valve arrangement can be switched between the closed position and the open position. Such a line valve switching device is also described in WO 2014 / -114610 A1, WO 2016 / 008636 A1, and WO 2017 / 216237 A1. The disclosure of a line valve switching device contained in these publications is also a disclosure of the line valve switching device of the present application and is expressly incorporated into the present application. Preferably, the line valve switching device comprises a permanent magnet, which can be brought close to and removed from the respective internal line valve to be switched, as a switching magnet.The use of movable permanent magnets instead of electromagnets to generate a changing magnetic field in the receiving area of ​​the inner valve, in order to displace the valve body relative to the valve seat, advantageously avoids heat sources near the media lines. This means that a medium flowing in a media line is preferably not thermally stressed by either the inner valve of the media line or the valve switching device. The switching magnet of an inner valve can be driven towards and away from the inner valve in any desired manner, for example, by an electric motor (such as a worm gear or spindle drive), pneumatically, or electromagnetically, to name just a few.

[0072] Preferably, at least one switching magnet is not only arranged in the control device, and in particular in the valve switching device, in a way that allows it to approach and move away from the inner valve it switches between the closed and open positions along a switching path, but is also movable relative to the inner valve that can be switched by the switching magnet along a deflection path that runs transversely, in particular orthogonally, to the switching path. This allows the valve body of the associated inner valve not only to be adjusted between a closed and an open position, but also to be selectively moved from the closed position to the open position to one of two sides of the virtual flow path along which the flow passes through the inner valve.By shifting the flow to a specific side outside the virtual flow path of the inner valve, the flow between a conveying channel section and a branching media line can be enhanced. This effectively removes the valve body from the path, preventing it from being obstructed by the branching media flow, or minimizing the obstruction. This is particularly relevant for the at least one switching solenoid of a container valve switching solenoid assembly, which switches the container valve assembly between the closed and open positions, since media are both introduced into and discharged from the at least one fluid-transferring cell culture container.Preferably, the media is introduced into the at least one cell culture container relative to the container valve arrangement from a region of the conveying channel section located on one side of the container valve arrangement, into which the container line arrangement opens, and the media is discharged from the at least one cell culture container into the respective other region of the conveying channel section located on the other side of the container valve arrangement relative to the container valve arrangement.

[0073] By deflecting the valve body into an open position of the respective inner valve, the valve body can not only open its media line for flow, but also block a section of the piping arrangement, particularly a conveying channel section, that is not intended for media flow at that time. For this purpose, it is sufficient if the valve body has a larger maximum cross-sectional area than the section of the piping arrangement, particularly the conveying channel section, that is to be blocked in the open position. Therefore, the valve body of an inner valve is preferably spherical, and the mounting structure at the inlet to the section of the piping arrangement to be blocked is circular. Then, in the open position of its inner valve, the valve body can be brought into a blocking position against the mounting structure.

[0074] Preferably, the deflection path runs along the conveying channel section into which the container piping assembly empties, and particularly preferably parallel to the flow path of the conveying channel section. The deflection path can be curved if the relevant switching magnet is pivotally mounted transversely to the switching path. The deflection path can also be straight. Likewise, the switching path can be curved, for example, in the case of pivoting movement for approaching and moving away from an internal line valve, or, preferably, it can be straight.

[0075] Preferably, each switchable internal line valve is assigned exactly one switching solenoid. Equally preferably, each line valve, in particular each internal line valve, is arranged to be switchable between the closed and open positions independently of every other line valve, in particular every other internal line valve. The inherent independent switchability can be partially overridden by a control device, for example, to prevent line valves, which must never open simultaneously, from being in the open position at the same time.

[0076] 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.

[0077] In addition to the aforementioned internal line valves, external line valves can also be used in the line valve arrangement to reduce contamination risks and for cost reasons. The components of the external line valves are neither exposed to nor wetted by the medium flowing in the associated line. One possible design of an external line valve is a pinch valve, which, in the closed position, compresses the associated line to a flow cross-section of 0 by applying force to the outside of the line, and, in the open position, allows a flow-through cross-section.

[0078] An external line valve can be used with a media line that is permanently, i.e., inseparably, connected to a structure for fluid transfer. For such media lines, the cleaning effort is reduced or even eliminated due to the lack of separation and re-establishment of a fluid-transferring connection, compared to line couplings intended for separating and connecting media line sections. Since the valve block assembly is at least two-part, the line valve switching device is preferably also at least two-part, comprising a supply-side line valve switching device and a tank-side line valve switching device, so that the line valves arranged on each valve block of the valve block assembly can be reliably switched.

[0079] Preferably, all supply lines of the supply line arrangement are directly connected to the supply-side valve block and open into the supply-side delivery channel section. Preferably, therefore, none of the supply lines are directly connected to the tank-side valve block and its valve block housing. Thus, all media taken directly from a media supply, which have never been in a cell culture tank, can flow as fresh media through the supply-side delivery channel section and thus through the supply-side valve block housing.

[0080] Preferably, all container lines and all disposal lines of the container line assembly are directly connected to the first and / or second container-side valve block and open into the first and / or second container-side conveying channel section. This means that preferably no container line or disposal line is directly connected to the reservoir-side valve block. Thus, all media flowing out of the at least one cell culture container through the container line assembly and all media discharged from the line assembly through the disposal line assembly can be discharged via the container-side valve block housing without ever reaching the reservoir-side valve block housing.

[0081] If the connecting line arrangement is at least partially or preferably completely made of flexible material, for example, at least one flexible hose, the reservoir-side and container-side valve blocks can advantageously be moved relative to each other. Furthermore, separating the valve block arrangement into a reservoir-side and a container-side valve block ensures that the reservoir-side valve block and the container-side valve block can each be located in differently conditioned environments, for example, in higher-level containers such as cabinets, with different temperatures or temperature profiles and / or different atmospheres with regard to composition and / or humidity, and the like.For example, at least one cell culture container with the container-side valve block connected by means of its container piping arrangement may be housed in an incubator, while the media supplies may be housed in one or more other containers and / or without a receiving container in a laboratory room.

[0082] To ensure, particularly during cleaning processes of the piping arrangement, that media from the media reservoirs always flow advantageously in the same direction through the reservoir-side conveying channel section towards the at least one cell culture container, all outlets of the reservoir piping arrangement into the reservoir-side conveying channel section are preferably located on the same side along the virtual reservoir-side flow path relative to all outlets of the connecting piping arrangement into the reservoir-side conveying channel section. This means that the outlets of the connecting piping arrangement into the reservoir-side conveying channel section are preferably not located between outlets of the reservoir piping arrangement into the reservoir-side conveying channel section along the virtual reservoir-side flow path.

[0083] In principle, the supply-side conveying channel section and / or the tank-side conveying channel section can be a closed, circumferential ring channel section, although this is not preferred in order to prevent media from different media supplies from flowing into the connecting pipe arrangement in different directions. Preferably, the supply-side conveying channel section and / or the tank-side conveying channel section is a channel section extending from a defined channel section beginning to a defined channel section end, and particularly preferably a channel section extending in a straight line between the respective channel section beginning and end. By avoiding unnecessary changes in the flow direction of a medium flowing through a conveying channel section, the flow resistance of the conveying channel section can be advantageously kept low.Furthermore, this allows the number of pump cycles required to convey a predetermined quantity of media through a conveying channel section to be kept advantageously low.

[0084] Especially during the period between removing a cell culture container from the container-side valve block and connecting a new or different cell culture container to the container-side valve block, the remaining pipework, reduced by the container pipework, is open to its external environment.Thanks to the design of the present management device with at least one container-side valve block separately formed from at least one supply-side valve block, and in particular its supply line arrangement connected to the at least one supply-side valve block in a fluid-transferring manner, and its line valve arrangement, a remaining line arrangement that is temporarily open to its external environment can be readily accepted, since it can be sufficiently cleaned by rinsing after a cell culture container is reconnected, before media are introduced from the remaining line arrangement into the container line arrangement of the new cell culture container, which is connected to the container-side valve block in a fluid-transferring manner, and thus into the new cell culture container.

[0085] In particular, if the feed pump located between the supply-side and the tank-side valve block is a peristaltic pump, the feed pump can draw in not only liquids but also gas and deliver it to the tank-side valve block.

[0086] Preferably, each media reservoir is connected via its own supply line to the reservoir-side valve block and thus to the reservoir-side conveying channel section, so that a supply line up to its supply valve is advantageously only permeable to a single medium. In contrast, the reservoir-side conveying channel section, the connecting line arrangement, the tank line arrangement, and the disposal line arrangement are permeated by different media during operation.

[0087] In principle, to interrupt a fluid flow between the supply-side and the respective tank-side valve block, it may be sufficient if the connecting line arrangement transferring fluid between these two structures is equipped with a line valve somewhere in the connecting line arrangement or only at one of its two end regions.A particularly advantageous, clean separation of the connecting pipe arrangement from each of the valve blocks from the storage-side and the tank-side valve block without leakage or spillage of the medium contained therein can be achieved if the connecting pipe arrangement is fluid-transferringly connected to the storage-side and tank-side valve blocks, both at its storage-side end region opening into the storage-side conveying channel section and at its tank-side end region opening into the tank-side conveying channel section, by means of at least one connecting valve.

[0088] Although the connecting line arrangement may have more than one connecting line between the supply-side and the tank-side valve block, it is preferred, to avoid unnecessary manufacturing and assembly effort, if the connecting line arrangement has exactly one connecting line between the aforementioned valve blocks of the valve block arrangement. Accordingly, each connecting line preferably has at least one, and particularly preferably exactly one, line valve at one end.

[0089] For the reasons already explained above for the supply-side conveying channel section, the tank-side conveying channel section is also a conveying channel section with a defined channel section beginning and a defined channel section end. Since the tank-side conveying channel section is cleaned by a cleaning medium conveyed from the supply-side valve block to the tank-side valve block, preferably no pipe outlet is formed upstream of the opening of the connecting pipe arrangement and no pipe outlet is formed downstream of the opening of the disposal pipe arrangement in a flow direction from the opening of the connecting pipe arrangement to the opening of the disposal pipe arrangement.This ensures that a cleaning medium introduced into the tank-side conveying channel section via the connecting pipe arrangement cleans a maximum length of the conveying channel before being discharged via the disposal pipe arrangement, and also reaches and thus cleans every other outlet of a media line in the tank-side conveying channel section.

[0090] For this reason, the container piping arrangement preferably terminates at the container-side valve block between the connecting piping arrangement and the disposal piping arrangement, leading into the container-side conveying channel section. Thus, the used medium discharged from the at least one cell culture container, and therefore requiring disposal, does not flow towards the connecting piping arrangement and therefore does not contaminate a section of the container-side conveying channel located between the connecting piping arrangement and the container piping arrangement, which is traversed by fresh medium.

[0091] For the disposal of a cleaning medium that flows through the reservoir valve block, the connecting pipe assembly, and the tank-side valve block to clean the piping system and is discharged from the piping system via the discharge pipe assembly, the pump described above, located between the reservoir and tank-side valve blocks, is generally sufficient. For the safe discharge of medium from the at least one cell culture container without involving the flow chambers of the connecting pipe assembly and the reservoir valve block, it is advantageous if the cell culture management device includes a discharge pump located in the discharge pipe assembly.The disposal pump is preferably designed to discharge a medium from the at least one cell culture container via the disposal line arrangement to a medium sink, such as a disposal container or disposal system. Preferably, the container line arrangement of a cell culture container comprises exactly one container line. Equally preferably, this container line comprises exactly one container valve, located at its end section closest to the valve block on the container side.

[0092] 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.

[0093] 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 cell culture container, with 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.

[0094] The plug connection between the container piping assembly and the container-side valve block can be secured against unintentional loosening 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.

[0095] 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 push-fit 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. Sealing of the pipe coupling between a container pipe and the container-side valve block is preferably achieved at the end face of the pipe head by means of the soft elastic support component already present on the container valve.

[0096] According to an advantageous embodiment of the present invention, the sampling line arrangement is provided that the container-side valve block opens into the container-side conveying channel section between the container line arrangement and the disposal line arrangement.

[0097] According to a preferred embodiment, in the reference state, a plurality of the lines of the line arrangement, in particular the supply line arrangement, which open into the conveying channel, are connected to the valve block arrangement by means of a fluid quick-release coupling in the form of a plug-in coupling, a bayonet coupling, or a screw coupling as a line coupling. This connection is intended to be detachable but secured against unintentional detachment. The conveying channel comprises the supply-side conveying channel section and the tank-side conveying channel sections. The supply-side valve block and / or at least one tank-side valve block, preferably all tank-side valve blocks, can be configured as follows: the essentially rigid valve block housing can be multi-part and can include an insert component forming the respective conveying channel section.The insert component can be made of one or more pieces, for example in the form of an injection-molded component, which may be joined or built from several components, in particular injection-molded sub-components, due to the physical complexity of the insert component.

[0098] Valve block-side coupling elements of fluid quick-release couplings preferably have a thread. For easier access, the valve block-side coupling elements preferably project outwards from the valve block housing. End sections of a media line, in particular a supply line, preferably have a media line-side coupling element of a fluid quick-release coupling, which can be coupled to a valve block-side coupling element and secured against loosening by means of a threaded connection between the media line-side coupling element and the threaded connection of the valve block-side coupling element.

[0099] Preferably, a media line, in particular a supply line, has a line valve at its connectable end section with the media line-side coupling assembly. This line valve is part of the media line-side coupling assembly and can be inserted into the valve block-side coupling assembly of the valve block housing. To allow for automated cleaning of the valve body at the media line-side coupling assembly after a fluid-transmitting connection has been established between the media line and the valve block-side coupling assembly, the valve body is preferably exposed at the connectable longitudinal end of the media line.

[0100] One thread on the valve block housing-side coupling assembly and one on the media line-side coupling assembly are external threads, while the other thread is internal. It has proven advantageous for the valve block housing-side coupling assembly to have an external thread and the media line-side coupling assembly to have a union nut with an internal thread. The union nut can be screwed onto the valve block housing-side coupling assembly by securing the media line to the valve block housing, and in the tightened state, it can largely or completely shield the coupling assembly to which it is connected.

[0101] The above description applies to both the reservoir-side and the tank-side valve blocks. Alternatively, the connecting pipe assembly can also be permanently connected to one or both valve blocks via a fluid transfer mechanism, for example by welding, particularly ultrasonic welding, or bonding.

[0102] The valve body is preferably a valve ball, so that a rotational orientation of the valve body is not important for the valve to function.

[0103] The above statements regarding the tank-side valve block, the cell culture tank, the connecting pipe assembly, the connecting valve assembly, the tank-side conveying channel section, and the conveying pump apply mutatis mutandis to both the first and second tank-side valve blocks, both the first and second cell culture tanks, both the first and second connecting pipe assemblies, both the first and second connecting valve assemblies, and both the first and second conveying pumps. 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.

[0104] 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.

[0105] In principle, the transfer valve assembly can be located at any point in the transfer line assembly. A clearly defined separation of the transfer line assembly from the first and / or second tank-side valve block can be achieved by connecting the transfer line assembly to the first and / or second tank-side valve block via an intermediate transfer valve assembly. The transfer line assembly terminates in both the first and second tank-side conveying channel sections. Like the connecting line assembly, the transfer line assembly can have a transfer valve assembly at each of its end sections that can be connected to a tank-side valve block for fluid transfer.

[0106] Preferably, the transmission line arrangement comprises exactly one transmission line and the transmission valve arrangement has exactly one transmission valve, in particular at each longitudinal end of the transmission line.

[0107] The transfer line assembly can also be connected to any of the tank-side valve blocks via a fluid quick-release coupling as described above, and secured against unintentional disconnection. Alternatively, the transfer line assembly can also be permanently connected to one or both tank-side valve blocks in a fluid-transferring manner, for example by welding, particularly ultrasonic welding, or bonding. Accordingly, at least one transfer valve of the transfer valve assembly can be designed as an external line valve. Preferably, to facilitate manufacturing and assembly, a plurality of the transfer valves, and particularly preferably all transfer valves, are designed identically to the transfer valve assembly, whether as internal or external line valves. The present invention is explained in more detail below with reference to the accompanying drawings. It illustrates:

[0108] Fig. 1 shows a rough schematic representation of the structure of an embodiment of a cell culture management device according to the invention of the present application,

[0109] Fig. 2A shows a longitudinal sectional view of a first embodiment of a dimensionally stable media container of Fig. 1 in bottle shape,

[0110] Fig. 2B shows a second embodiment of a shape-labile media container from Fig. 1 in bag form,

[0111] Fig. 3 shows a perspective view of the supply-side valve block with a line valve switching device from Fig. 1.

[0112] 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.

[0113] 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

[0114] Fig. 6 is a perspective view of the first wobble device from Fig. 1.

[0115] The figures are not to scale. Figure 1 shows a rough schematic representation of the structural design of a cell culture management device of the present application, generally designated by 10.

[0116] The management device 10 comprises, as the core component of a living cell cultivation system, a first cell culture container 12 and an essentially identical second cell culture container 14.

[0117] For the management of cell culture containers 12 and 14, the management device 10 comprises, as media reservoirs 16 in Figure 1, from left to right: atmosphere A, in which the management device 10 is located and which serves as an air reservoir and thus as a reservoir of a gaseous rinsing medium. The media reservoirs 16 further comprise a water reservoir 18, which contains sterile demineralized water as a liquid rinsing medium. To the right of the water reservoir 18 in Figure 1 is a pipe cleaning media reservoir 20, which contains peracetic acid, and adjacent to this is a cell cleaning media reservoir 22 with phosphate-buffered saline solution, abbreviated "PBS" for "phosphate-buffered saline".

[0118] 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.

[0119] 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.

[0120] The liquid media supplies 16, namely supplies 18, 20, 22, 24, and 26, are each stored in a media container 28. For clarity, not all media containers 28 are labeled in Figure 1. The media supplies 16 are connected to the cell culture containers 12 and 14 via a conduit arrangement 30 for the transfer of media.

[0121] 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.

[0122] 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.

[0123] 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 it by 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.

[0124] 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.

[0125] The supply-side valve block 36 comprises a supply-side valve block housing 50. For ease of assembly, the valve block housing 50 preferably has multiple parts and incorporates a supply-side delivery channel section 52 through which fluid media can flow. This delivery channel 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.

[0126] 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, via fluid transfer, the reservoir-side valve block 36 to a first container-side valve block 62, which is connected, via fluid transfer, to the first cell culture container 12. The second connecting line 60 connects, via fluid transfer, the reservoir-side valve block 36 to a second container-side valve block 64, which is connected, via fluid transfer, to the second cell culture container 14.Since the two container-side valve blocks 62 and 64 are essentially identical 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 more detail below, the description of which can also be used to explain the second container-side valve block 64.

[0127] 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.

[0128] 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.

[0129] 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.

[0130] 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.

[0131] 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 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 the 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.

[0132] 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.

[0133] 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.

[0134] 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.

[0135] 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.

[0136] 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 of 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 arrangement 76 are open. All other line valves 40 and 78 included in the reservoir-side valve block 36 are in the closed position according to their magnetic preload.

[0137] Under this switching position of the supply-side line valve switching device 88, the second feed pump 86 can pump demineralized water from the liquid rinsing media supply 18 into the second tank-side valve block 64.

[0138] 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.

[0139] 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.

[0140] 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.

[0141] 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.

[0142] 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.

[0143] 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.

[0144] 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 of the first tank-side conveying channel section 68, 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.

[0145] The disposal line order 102 is also part of the line order 30.

[0146] 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.

[0147] 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.

[0148] 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.

[0149] 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 with, in the illustrated embodiment, exactly one transfer line 120 opens into the first tank-side conveying channel section 68. The transfer line arrangement 118 is part of the line arrangement 30.

[0150] 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.

[0151] 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.

[0152] A cell singulation device 130, such as that known, for example, from WO 2017 / 137472 A1, the disclosure of which relating to the cell singulation device 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 arrangement 118. The cell singulation device 130 gently breaks up cell clusters due to turbulence of the medium flowing through it, without damaging the cells forming the clusters, advantageously allows cells to be conveyed singly between the cell culture containers 12 and 14.

[0153] For taking samples, for example from the cells cultivated in cell culture containers 12 and 14, the piping arrangement 30 can include a sampling line arrangement 132. The sampling line arrangement 132 can comprise a first sampling line 134, which is fluid-transferred to the first container-side valve block 62, and a second sampling line 136, which is connected to the second container-side valve block 64.

[0154] 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.

[0155] 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.

[0156] 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 directional 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.

[0157] 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.

[0158] 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.

[0159] 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.

[0160] 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 container-side conveying channel section 68 or 69.

[0161] 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.

[0162] 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.

[0163] Alternatively or additionally, two or more supply lines 32 can extend from a media reservoir, each of which is fluid-transferred 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-transferred to the additional reservoir-side valve block supplied in this way.

[0164] Fig. 2A schematically shows a longitudinal section view of a first embodiment of a media container 28 for the media reserves 16 for liquid media.

[0165] 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.

[0166] Two channel nozzles 214 and 216 project 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.

[0167] 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 as shown in 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 as shown in 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.

[0168] The storage valve 40, which, with the minor exception of the reservoir valve 100, is essentially identical in construction to all other line valves in Fig. 1, 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 collinear within the extent of the storage valve 40.

[0169] 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.

[0170] 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.

[0171] The valve union nut 310 has a skirt section 311 extending coaxially to the virtual flow path 304 and having an internal thread.

[0172] At the longitudinal end of the central valve structure 300 opposite the fir-tree formation 306, an end piece 314 is received on the central valve structure 300, preferably by snapping the end piece 314 into place with the central valve structure 300 after it has been slid onto the longitudinal end of the central valve structure 300 along the virtual flow path 304 of the upstream valve 40. 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 at the valve seat 322 formed by the end piece 314, the annular permanent magnet 316 and the support component 318, and is inserted into the position shown in Fig.2A shown in the pre-tensioned locking position, in which the valve body 320 blocks a flow through the flow channel 302 and thus through the flexible hose 228.

[0173] 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.

[0174] 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 explained 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 coming loose.

[0175] For storing a liquid medium in 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. 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 removed from the receiving volume 252 of the bag 250 does not need to be replaced by a corresponding volume of gas within the bag 250 to prevent an undesirable negative pressure inside the bag 250.Instead, when liquid medium is removed from the bag, the 250 can simply decrease its volume due to the essentially constant ambient pressure.

[0176] 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 located there, thus facilitating the most complete possible emptying of the bag 250.

[0177] 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.

[0178] 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. 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 as a locking element for the line couplings 330 with female coupling formations, in a fluid-transmitting manner. The connecting lines 58 and 60 are also preferably made of flexible hose material, from which the hoses 228 of the supply lines 32 are also made. The supply line 32 on the far left in Fig. 3 leads to the atmosphere A.The leftmost supply line 32, adjacent to the supply line 32, leads to the reservoir 18 of sterile demineralized water. On the far right in Fig. 3, the first connecting line 58 is shown at the reservoir-side valve block 36.

[0179] 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.

[0180] 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.

[0181] 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.

[0182] 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 illustrated 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 reservoir line 32 on the far right is that of the gaseous purge media reservoir, i.e., atmosphere A. On the far left in Fig. 4, the first connecting line 58 is arranged on the reservoir-side valve block 36.

[0183] All line connections to the supply-side valve block 36 and all line valves arranged therein are of the same design. It is therefore sufficient to provide the valve arrangement, already explained in connection with Fig. 2A, at the two outermost line valves 40 and 78 in Fig. 4 with reference numerals of previously explained configurations.

[0184] 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.

[0185] The reservoir-side insert component 402, preferably designed as a shell component, incorporates the reservoir-side conveying channel section 52. Its straight, virtual reservoir-side flow path 54 is conceived as passing centrally through the reservoir-side conveying channel section 52 lengthwise. Radially projecting webs 404, which may partially or completely encircle the reservoir-side conveying channel section 52, position the reservoir-side insert component 402 within the reservoir-side cavity 400. Not all webs 404 of the reservoir-side insert component 402 are labeled with reference numerals in Fig. 4. The reservoir-side insert component 402 also features radially projecting female valve block-side coupling formations 406, into which the media line-side male coupling formations 324 are inserted.The female coupling assemblies 406 on the valve block side have an external thread 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 coupling assembly 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 assembly 406 on the valve block side and by pulling out the line valve 40 or 78 from the female coupling assembly 406 on the valve block side. As long as the screw connection of the valve union nut 310 with the female coupling assembly 406 on the valve block side remains, a fluid-transmitting connection between the respective media line and the supply channel section 52 on the reservoir side is reliably established.

[0186] 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.

[0187] 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 component. The first tank-side insert component 502 can, like the reservoir-side insert component 402, be an injection-molded component 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.The first container-side insert component 502, like the first container-side valve block housing 66 and its components 66a and 66b, is, unlike the hoses mentioned above, a dimensionally stable component which retains its shape essentially not only under the load of its own weight but also under moderate external load.

[0188] 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.

[0189] Securing elements 66c secure the housing cover 66b to the housing base 66a.

[0190] 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.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.

[0191] 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.

[0192] 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.

[0193] 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.

[0194] 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.

[0195] 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.

[0196] 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 formed integrally with a container lid 604 that can be screwed onto a neck 602 of the first cell culture container 12. However, 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.

[0197] The neck 602 is part of a container body 606, which encloses a container volume 610 into which the container line 96 leads.

[0198] 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.

[0199] 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.

[0200] 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 withdrawal valve 140 is shown with dashed lines. When the valve body is in the position shown with dashed lines, the first withdrawal valve 140 is in its open position. As also explained above, the switching magnet of the reservoir valve 100 is movable along the virtual flow path 70 of the first reservoir-side conveying channel section 68, so that the valve body 320 of the reservoir 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, is designed with a larger diameter, so that the illustrated preferred valve ball can move as the valve body 320 in the adjustment range 512 along the virtual flow path 70.

[0201] 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.

[0202] 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.

[0203] 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.

[0204] 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.

[0205] 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.

[0206] 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.

[0207] A first 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. All drives used in the first wobble device 144 of the exemplary embodiment are rotary electric motors.

[0208] 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.

[0209] A second 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.

[0210] 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.

[0211] 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.

[0212] 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.

[0213] The receiving element 728 has an upwardly open LI 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.

[0214] 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.

[0215] 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. 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-transmitting 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.

[0216] The clamping device 732 comprises a clamping bracket 734, which is pivotably 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.

[0217] 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.

[0218] 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.

[0219] 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.

[0220] 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 the need to continuously energize the third drive 740.

[0221] 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.

[0222] 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.

[0223] 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.

[0224] 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. Cell culture management device (10), wherein the cell culture management device (10) in an operational reference state of the cell culture management device (10) comprises: a piping arrangement (30) for conveying fluid media, comprising, + a valve block arrangement (36, 62, 64) with a valve block housing (50, 66) and with a conveying channel (52, 68) formed in the valve block housing (50, 66), wherein the valve block arrangement (36, 62, 64) has at least one first valve block (62) with a first valve block housing (66) and with a first conveying channel section (68) formed in the first valve block housing (66), + a supply line arrangement (34) with at least one supply line (32), + a first container piping arrangement (95) with at least one container piping (96) and + a disposal line arrangement (102) with at least one disposal line (104), a plurality of media reservoirs (16) which provide different fluid media for their introduction into the line arrangement (30), a first cell culture container (12), a line valve arrangement (72), comprising + a storage valve arrangement (38) with at least one storage valve (40), + a disposal valve arrangement (106) with at least one disposal valve (108, 110) and + a first container valve arrangement (98) with at least one container valve (100), and a feed pump (84) for conveying fluid media in the line arrangement (30), wherein in the operational reference state a plurality of media reserves (16) are drawn from the plurality of media reserves (16) by means of the reservoir- The line arrangement (34) is fluid-transferringly connected to the valve block arrangement (36, 62, 64) via the intermediate arrangement of the storage valve arrangement (38), wherein the first cell culture container is fluid-transferringly connected to the first valve block (62) via the first container line arrangement (95) via a first line coupling (660) that can be released as intended, and wherein the disposal line arrangement (102), in which the disposal valve arrangement (106) is arranged, is fluid-transferringly connected to the valve block arrangement (36, 62, 64), wherein a plurality of line valves of the line valve arrangement (72) each have a valve seat (322) and a valve body (320) that can be displaced relative to the valve seat (322) as valve components, wherein the operating state of each line valve can be changed between a closed state in which the line valve blocks a flow,and a flow state in which the line valve permits flow, wherein the conveying channel (52, 68) of the valve block arrangement (36, 62, 64) has openings, wherein in the reference state the supply line arrangement, the container line arrangement (95) and the disposal line arrangement (102) each open into the conveying channel (52, 68) at at least one opening, and wherein in the reference state at least one valve component (320) is received in or on the valve block housing (50, 66) of the plurality of line valves, characterized in that the valve block arrangement (36, 62, 64) has a second valve block (64) with a second valve block housing and a second conveying channel section (70), wherein the cell culture management device (10) additionally has at least one second cell culture container (14),wherein the second cell culture container (14) is fluid-transmittingly connected to the second valve block (64) by means of a second container line arrangement with an intermediate second container valve arrangement via a second line coupling that can be released as intended, wherein the line arrangement (30) has a transfer line arrangement (118) with at least one transfer line (120), wherein the line valve arrangement (72) has a transfer valve arrangement (124) with at least one transfer valve (126, 128), wherein the cell culture management, Device (10) has at least one transfer pump (122), wherein the transfer line arrangement (118), in which the transfer valve arrangement (124) and the transfer pump (122) are arranged, connects the first and second valve blocks (62, 64) to each other in a fluid-transferring manner, wherein the transfer line arrangement (118) opens into both the first and the second delivery channel section (68, 69).

2. Cell culture management device (10) according to claim 1, characterized in that the valve block arrangement (36, 62, 64) comprises a storage-side valve block (36) with a storage-side valve block housing (50) and a storage-side conveying channel section (52) extending along a virtual storage-side flow path (54), as well as a container-side valve block (62) formed separately from the storage-side valve block (36) with a container-side valve block housing (66) formed separately from the storage-side valve block housing (50) and a container-side conveying channel section (68) extending along a virtual container-side flow path (70), wherein the supply line arrangement (34) opens into the storage-side conveying channel section (68) and wherein the disposal line arrangement (102) and the first container line arrangement (95) open into the container-side conveying channel section (68) flow into,wherein the line arrangement (30) comprises a connecting line arrangement (56) with at least one connecting line (58), wherein the line valve arrangement (72) comprises a connecting valve arrangement (74) with at least one connecting valve (78, 80), wherein the supply-side valve block (36) and the tank-side valve block (62) are fluid-transferringly connected to each other by means of the connecting line arrangement (56) in which the connecting valve arrangement (74) and the feed pump (84) are accommodated.

3. Cell culture management device (10) according to claim 2, characterized in that the supply-side valve block (36) is the second valve block and that the container-side valve block (62) is the first valve block, wherein the connecting line arrangement (56) is the transfer line arrangement, and wherein the feed pump (84) is the transfer feed pump. and wherein the connecting valve arrangement (74) is the transfer valve arrangement.

4. Cell culture management device (10) according to claim 2, characterized in that the container-side valve block (62) is a first container-side valve block (62) and the first valve block, wherein the container-side valve block housing (66) of the first container-side valve block (62) is a first container-side valve block housing (66), wherein the virtual container-side flow path (70) is a first virtual container-side flow path (70), wherein the container-side conveying channel section (68) extending along the first virtual container-side flow path (70) is a first container-side conveying channel section (68), wherein the valve block arrangement (36, 62,64) as the second valve block (64) comprises a second tank-side valve block (64) formed separately from the first tank-side valve block (62) with a second valve block housing formed separately from the first tank-side valve block housing (66) and a second tank-side delivery channel section (69) extending along a second virtual tank-side flow path, wherein the connecting line arrangement (56) is formed and arranged separately from the transfer line arrangement (118), wherein the transfer delivery pump (122) is formed and arranged separately from the fluid pump (84), and wherein the connecting valve arrangement (74) is formed and arranged separately from the transfer valve arrangement (124).

5. Cell culture management device (10) according to claim 4, characterized in that the supply-side valve block (36) and the second container-side valve block (64) are connected to each other by means of a second connecting line arrangement (57) in which a second connecting valve arrangement (76) and a second feed pump (86) are accommodated, in a fluid-transferring manner.

6. Cell culture management device (10) according to one of the preceding claims, characterized in that the supply line arrangement (34) opens into the supply-side conveying channel section (68).

7. Cell culture management device (10) according to claim 4 or 5, or according to claim 6, incorporating claim 4 or 5, characterized in that the first container line arrangement (95) opens into the first container-side conveying channel section (68), that the second container line arrangement opens into the second container-side conveying channel section (69), and that the disposal line arrangement (102) opens into the first container-side conveying channel section (68) and / or into the second container-side conveying channel section (69).

8. Cell culture management device (10) according to one of claims 4 to 7, including claim 4 or 5, characterized in that the line arrangement (30) has a sampling line arrangement (132), wherein the first container-side valve block (62) is fluid-transmittingly connected to a first sampling line (134) of the sampling line arrangement (132) and / or wherein the second container-side valve block (64) is fluid-transmittingly connected to at least a second sampling line (136) of the sampling line arrangement (132), wherein the line valve arrangement (72) has a sampling valve arrangement (138) with at least one sampling valve (140), wherein the sampling valve arrangement (138) is received in the sampling line arrangement (132).

9. Cell culture management device (10) according to one of claims 4 to 8, including claim 4 or 5, characterized in that the transfer line arrangement (118) is connected to the first container-side conveying channel section (68) and / or to the second container-side conveying channel section (69) between the connecting line- arrangement (56, 57) and the container pipe arrangement (95) of the respective conveying channel section (68, 69) leads into.

10. A method for managing cell cultures, in particular with a cell culture management device according to any of the preceding claims, comprising the step of conveying a liquid medium from a first cell culture container (12) into a second cell culture container (14) or vice versa.

11. The method according to claim 10, characterized in that the liquid medium contains living cells.

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