Sterile connector for the sterile transfer of a liquid medium

Description

[0001] The invention relates to a sterile connector for the sterile transfer of a liquid, in particular biological, medium according to the preamble of claim 1, a coupling device of a sterile connector according to the preamble of claim 14, a packaging arrangement with a packaging and at least one such coupling device or sterile connector packaged therein according to claim 15, as well as the use of such a sterile connector, such a sterile coupling device and / or such a packaging arrangement according to claim 17.

[0002] A bioprocessing facility is generally understood to be a device that can be used to carry out or support biotechnological processes. Bioreactors, in which microorganisms or tissue cells are cultivated under specified conditions, are merely examples. Such a facility typically comprises a container containing a biological reaction medium consisting of the substances intended for a biotechnological process, e.g., microorganisms or tissue cells, and a corresponding nutrient medium, in order to carry out the respective biotechnological process step, such as fermentation or cultivation.

[0003] One example of such a bioreactor is a production bioreactor, i.e., a relatively large, production-scale bioreactor with a working volume of, for example, several hundred or several thousand liters, for the industrial production of microbial or cellular products, particularly biopharmaceuticals. Such a bioreactor produces a fermentation broth as its product, which is usually further treated in a so-called downstream process to obtain a product from the cells or the culture supernatant. Another example is a laboratory bioreactor, i.e., a relatively small, laboratory-scale bioreactor with a working volume of, for example, less than 10 liters.Such a laboratory bioreactor is used, for example, to produce ATMPs (Advanced Therapy Medical Products) and / or to perform cell expansion, which allows the generation of a sufficient number of cells, particularly tissue cells or microbial cells, for the respective application. One application is the proliferation of human cells, for example, T cells (T lymphocytes), which are taken from the patient, subsequently expanded ex vivo, and then reinfused into the patient.

[0004] Especially in the production of ATMPs using a laboratory bioreactor, but also in principle in a production bioreactor, the sterile addition of the individual liquid, for example, biological, media into the respective bioreactor is particularly important. Since many ATMPs cannot be sterile filtered or finally sterilized, the production of such medicinal products takes place in a sterile manner in cleanrooms of the appropriate cleanroom classes. The addition of a liquid medium to a bioreactor or the transfer of a liquid medium between two culture vessels and / or bioreactors inherently carries a risk of contamination, which is why such handling steps are usually carried out in a cleanroom class A (GMP Guideline Annex 1) or ISO 5 (ISO 14644-1). However, the production of medicinal products in such cleanrooms is very cost-intensive due to high monitoring requirements, complex clothing procedures, etc.

[0005] For this reason, there is a demand for closed systems for the cultivation or expansion of cells, particularly in the field of ATMP production, which allows the use of cleanrooms of lower cleanroom classes, such as cleanroom class D (GMP Guide Annex 1) or ISO 8 (ISO 14644-1). However, one challenge is adding a liquid medium to such a closed system as simply as possible. Various connection systems, such as Luer connectors and Luer-Lock connectors, are known (US 2009 / 182309 A1), for example, to connect a small-volume liquid container such as a syringe or vial to a closed system.However, there is a risk of contamination at the coupling point where the two coupling devices of the connector—in the case of a Luer connector, the male Luer connector and the female Luer connector—are connected. Therefore, particular attention must be paid to sterile conditions during the connection process (US 2016 / 022979 A1). US 2019 / 011070 A1 discloses another prior art connector.

[0006] The invention is based on the problem of designing and developing a sterile connector for the sterile transfer of a liquid medium from a liquid container into a bioprocessing system in such a way that sterile conditions can be easily created during the transfer of the medium.

[0007] The above problem is solved in a sterile connector for the sterile transfer of a liquid, in particular biological, medium according to the preamble of claim 1 by the features of the characterizing part of claim 1.

[0008] The fundamental idea is to create a sterile connector with two coupling devices that are to be connected to one another for the liquid transfer from a liquid container, which is for example a minimum quantity liquid container, into a bioprocessing system, which is in particular a bioreactor, in which the coupling devices are initially provided in a state in which contamination of the preferably sterile parts that are relevant for the liquid transfer by the user is not easily possible, since in this state they are covered in the coupling device and thus protected from contact.

[0009] In this state, the channel of the respective coupling device, as well as at least the outlet opening of one coupling device and at least the corresponding inlet opening of the other coupling device, are in a preferably sterile, protected from contamination position. Once the two coupling devices have been connected to each other as intended, they can each be brought into a state in which the parts relevant for fluid transfer are moved out of the protected, preferably sterile, position and connected to each other and aligned with each other so that fluid transfer can take place.In this state, which enables the transfer, the previously protected and still sterile outlet opening of one coupling device and the previously protected and still sterile inlet opening of the other coupling device are arranged in such a way that the liquid medium can flow from one coupling device to the other. In this state, the liquid medium in the area of ​​the transition from one coupling device to the other only comes into contact with the previously protected and still sterile sections of the coupling devices. Areas that were previously unprotected and therefore exposed to a potential risk of contamination are spaced away from the fluid-flowing area so that no germs or other media can enter the liquid medium.

[0010] It is particularly preferred if, before the two coupling devices are connected to one another, the liquid container from which the medium is to be dispensed and / or the bioprocessing system into which the medium is to be added are sterilely connected to the respective associated coupling device. This particularly preferably takes place on the manufacturer's side. It is thus conceivable for the manufacturer of the liquid container to already provide it with the associated coupling device of the sterile connector, with the liquid container particularly preferably already being filled by the manufacturer at this point in time, with the liquid container and the coupling device preferably being made available to the user in the intended state connected to one another, in particular as single-use components.The same applies to the bioprocessing system, where it is also conceivable that the manufacturer of the system already provides it with the associated coupling device of the sterile connector, possibly even with several such coupling devices, whereby the bioprocessing system and the respective coupling device are preferably made available to the user in the intended connected state, in particular as single-use components.

[0011] In this way, the two coupling devices of the sterile connector cannot be contaminated at any point relevant for fluid transfer, preferably a sterile one, before the connection is established, since a sterile connection already exists in the area where the medium flows from the fluid container into the connected coupling device, as well as in the area where the medium flows from the other coupling device into the bioprocessing system. The sections of the coupling devices through which the medium is intended to flow from the coupling device associated with the fluid container into the other coupling device are only moved away from the protected, preferably sterile, area of ​​the respective coupling device and brought together after the two coupling devices have been connected to each other.In particular, these two sections are brought together directly without coming into contact with other, contaminated sections of the coupling devices or with the user during their movement from the protected area to their intended end position. Since the still sterile parts of the coupling devices are only aligned and brought into contact with each other as intended after the two coupling devices have been connected, and contamination of the parts is not possible during this movement, the proposed sterile connector can be used to establish a sterile connection between a liquid container and a bioprocessing system in a particularly simple manner.

[0012] In detail, it is now proposed that in the initial position the respective channel extends into an area of ​​the housing interior that is hermetically sealed from the surroundings of the housing.

[0013] A "housing" is generally understood here to mean a component that surrounds the actuating element at least partially, preferably essentially completely, in at least one circumferential direction. If the actuating element is one that is rotatably mounted, as will be explained below, this actuating element is partially or essentially completely surrounded by the housing, at least in the radial direction relative to the axis of rotation. The latter is particularly preferred when the actuating element inlet openings and outlet openings point radially outward relative to the axis of rotation. In principle, however, it is also conceivable for the actuating element inlet openings and outlet openings to point parallel to the axis of rotation, in which case the actuating element is preferably surrounded by the housing at least partially or essentially completely in the axial direction.In principle, the actuating element can also be movable linearly, in which case the housing preferably surrounds the actuating element at least partially or substantially completely on the sides parallel to the direction of movement, in which case the actuating element inlet openings and the actuating element outlet openings of the actuating elements are directed in a direction transverse to the direction of movement.

[0014] "Substantially complete" means that the housing is completely closed in the respective direction with the exception of the fluid inlet and the fluid outlet.

[0015] In any case, the housing is designed such that, in the initial position of the actuating element, it protects the actuating element inlet opening and the actuating element outlet opening and thus keeps them sterile, and, in the operating position of the actuating element, it enables the actuating element outlet opening of one coupling device, which is in particular assigned to the liquid container, and the actuating element inlet opening of the other coupling device, which is in particular assigned to the bioprocessing system, to be brought into overlap with one another.

[0016] "Overlap" here means a partial or complete overlap of the two respective openings in a direction parallel to the central axes of the openings.

[0017] Claims 2 to 7 specify particularly preferred possibilities for arranging the preferably sterile actuating element inlet openings and the preferably sterile actuating element outlet openings in the housings in the initial position so as to be optimally protected from the environment and from contamination, and for arranging these in relation to one another while maintaining sterility in the operating position. For this purpose, a hermetically sealed area, which is preferably already sterile in the delivery state, is provided in the respective housing, in which area the channel running through the actuating element extends in the initial position of the actuating element. Only when the actuating element moves from its initial position to its operating position would the channel and, accordingly, its actuating element inlet opening or actuating element outlet opening enter a non-sterile area.However, when the sterile connector is used as intended, the two coupling devices are previously connected to each other in such a way that the movement of the actuating element from the initial position to the operating position cannot lead to contact between the actuating element inlet opening, the actuating element outlet opening and the channel with the environment.

[0018] In this context, "hermetically sealed" or "hermetically sealed" means that a seal is provided that prevents the penetration of contaminants, especially germs. In another embodiment, "hermetically sealed" or "hermetically sealed" refers to a sterile and / or contamination-protected area of ​​the sterile connector. In a particularly preferred embodiment, the terms "hermetically sealed" or "hermetically sealed" also include the term "sterile" and are thus interchangeable.

[0019] Claim 8 relates to particularly preferred alignments of all fluid-flowing parts in the operating position of the respective actuating element. Particularly preferably, the two fluid inlets of the housings, the two fluid outlets of the housings, and the two channels of the actuating elements extend coaxially to one another. However, other configurations are also conceivable.

[0020] The further preferred embodiments in claims 9 to 11 relate to the adjustment movement of the respective actuating element between the initial position and the operating position. In particular, the adjustment movement of one actuating element is accompanied by a corresponding adjustment movement of the other actuating element, i.e., both actuating elements move synchronously and are simultaneously in their initial position and in their operating position. This is preferably enabled by a transmission, in particular a gear transmission. The transmission can be actuated by the user from outside the housing, thereby effecting the adjustment movements of both actuating elements.

[0021] According to the particularly preferred embodiment according to claim 12, the fluid inlet of one housing and the fluid outlet of the other housing are connectable or connected by a hose or tube. As already explained above, it is particularly preferred if the liquid container is already connected by the manufacturer to the respective associated coupling device and the bioprocessing system is already connected to the respective associated coupling device, which can also be done via a corresponding hose or tube.

[0022] Claim 13 defines preferred possibilities for connecting the two housings to each other.

[0023] According to a further teaching according to claim 14, which has independent significance, a coupling device of a sterile connector, in particular a proposed sterile connector, is claimed for the sterile transfer of a liquid, in particular biological, medium from a liquid container into a bioprocessing system, in particular into a bioreactor. Given that the proposed sterile connector has two coupling devices, reference may be made to all relevant statements regarding the first-mentioned teaching.

[0024] According to a further teaching according to claim 15, which also has independent significance, a packaging arrangement is claimed comprising a package and at least one, preferably exactly one, sterilely packaged, proposed coupling device or sterile connector according to the invention. Given that the proposed packaging arrangement comprises a proposed sterile connector or a proposed coupling device, reference may be made to all relevant statements regarding the first and second teachings.

[0025] According to claim 16, either a liquid container or a bioprocessing system can also be sterilely packaged in the packaging, wherein the liquid container or the bioprocessing system is already fluidically coupled to the coupling device in the packaging.

[0026] According to a further teaching according to claim 17, which also has independent significance, the use of a sterilely packaged, proposed sterile connector, a sterilely packaged, proposed coupling device, and / or a proposed packaging arrangement for the sterile transfer of a liquid, in particular biological, medium from a liquid container into a bioprocessing system, in particular into a bioreactor, is claimed. Given that the proposed use concerns the use of a proposed sterile connector, a proposed coupling device, and / or a proposed packaging arrangement, reference may be made to all relevant statements regarding the aforementioned teachings.

[0027] With the proposed packaging arrangement and the proposed use, it has been recognized that with the proposed sterile connector or with the proposed coupling devices, a liquid medium can be supplied to a closed system, in particular a bioreactor, particularly easily without any significant risk of contamination, in that the coupling devices keep the parts relevant for the liquid transfer in a sterile state, namely in the said initial position, until the liquid transfer, namely in the said operating position, actually takes place.

[0028] In the particularly preferred embodiment according to claim 18, individual components of the mentioned components, in particular the proposed coupling device, in particular both coupling devices, preferably also the liquid container and / or the bioprocessing system and / or the hose(s) or tube(s) are preferably designed as single-use components, wherein the components are preferably made of a plastic material.

[0029] In the following, the invention is explained in more detail with reference to a drawing which merely represents an exemplary embodiment. In the drawing, Fig. 1 in a perspective view a proposed sterile connector connecting its two coupling devices, Fig. 2 in a perspective view of the two coupling devices in the connected state a) in the initial position of the two control elements and b) in the operating position of the two control elements, Fig. 3 in a sectional view of the two coupling devices in the connected state a) in the initial position of the two control elements and b) in the operating position of the two control elements and Fig. 4 in a perspective view, a proposed packaging arrangement with a proposed coupling device and a liquid container connected thereto, as well as a proposed packaging arrangement with a further proposed coupling device and a bioprocessing system connected thereto.

[0030] The one in the Figures 1 to 4The proposed sterile connector 1 shown serves for the sterile transfer of a liquid, in particular biological, medium from a liquid container 2, here a low-volume liquid container, i.e., a liquid container with a small capacity of, for example, a maximum of 30 ml, into a bioprocessing system 3, here a bioreactor. The proposed sterile connector 1 has two mechanically and fluidically connectable coupling devices 4a, 4b, of which one coupling device 4a is assigned to the liquid container 2 and the other coupling device 4b to the bioprocessing system 3. "Assigned" means that the coupling device 4a is connectable or connected to the liquid container 2, and the coupling device 4b is connectable or connected to the bioprocessing system 3.Particularly preferably, the liquid container 2 has already been connected by the manufacturer, in a sterile state, to the coupling device 4a assigned thereto and the bioprocessing system 3 to the coupling device 4b assigned thereto.

[0031] The bioprocessing system 3, in particular the bioreactor, forms a closed system or is integrated into a closed system. The bioreactor is designed, for example, as a laboratory bioreactor, i.e., as a bioreactor that, in contrast to a production bioreactor, has a relatively small working volume (maximum available filling volume) of a maximum of 10 liters. Such a bioreactor is used to carry out a biotechnological process, which here and preferably serves to produce an advanced therapy medicinal product (ATMP). For example, the biotechnological process can also be a cell expansion process for T cells. In any case, a biological reaction medium is provided in the bioreactor, which in particular contains tissue cells or microbial cells as well as a nutrient medium. In this case, it is necessary to add the liquid media to the closed system under sterile conditions.

[0032] The coupling devices 4a, 4b each comprise a housing 5a, 5b with a preferably sterile housing interior 6a, 6b and a preferably sterile actuating element 8a, 8b adjustably mounted in the housing interior 6a, 6b and forming a channel 7a, 7b. The channel 7a, 7b extends through the actuating element 8a, 8b from an actuating element inlet opening 9a, 9b to an actuating element outlet opening 10a, 10b. Furthermore, it is essential that the housing 5a of one coupling device 4a is mechanically connectable to the housing 5b of the other coupling device 4b. It is also essential that the respective housing 5a, 5b has a fluid inlet 11a, 11b and a fluid outlet 12a, 12b, which connect the housing interior 6a, 6b with the surroundings of the respective housing 5a, 5b, wherein in the mechanically connected state of the housings 5a, 5b, the fluid outlet 12a of one housing 5a and the fluid inlet 11b of the other housing 5b overlap with each other.Finally, it is also essential that when the housings 5a, 5b are mechanically connected to one another, the adjusting elements 8a, 8b each move from an initial position (. Fig. 2a ), Fig. 3a )), in which a fluid connection between channel 7a, 7b and actuator inlet opening 9a, 9b on the one hand and between channel 7a, 7b and actuator outlet opening 10a, 10b on the other hand is blocked, into an operating position ( Fig. 2b ), Fig. 3b )), in which the control element inlet opening 9a, 9b is in fluid communication with the fluid inlet 11a, 11b and the control element outlet opening 10a, 10b is in fluid communication with the fluid outlet 12a, 12b, in particular completely, are adjustable.

[0033] It is now essential that in the initial position the respective channel 7a, 7b extends into an area of ​​the housing interior 6a, 6b that is hermetically sealed from the surroundings of the housing 5a, 5b.

[0034] In the proposed sterile connector 1 or the proposed coupling devices 4a, 4b to be connected to one another, it is therefore provided that the actuating elements 8a, 8b can be moved from an initial position into an operating position, wherein in the initial position the parts relevant for fluid transfer, namely the channel 7a, 7b, the actuating element inlet opening 9a, 9b and / or the actuating element outlet opening 10a, 10b, are in a sterile state. The sterile state is ensured by the fact that the parts relevant for fluid transfer are preferably sterile in the initial position of the actuating element 8a, 8b and are covered from the surroundings of the housing 5a, 5b and accordingly protected from contamination. Once the two coupling devices 4a, 4b are connected to one another as intended, the actuating elements 8a, 8b can be moved into the operating position, in which the transfer of the liquid medium can then take place.In the operating position, the said parts relevant for the fluid transfer remain sterile, since the two coupling devices 4a, 4b or the two housings 5a, 5b were previously connected to each other, i.e. before the movement from the initial position to the operating position, in such a way that the parts relevant for the fluid transfer could not come into contact with the environment at any time.

[0035] In the embodiment illustrated here and preferred in this respect, the respective channel 7a, 7b extends in the initial position into an area of ​​the housing interior 6a, 6b that is already sterile compared to the surroundings of the housing 5a, 5b in the delivery state. Here and preferably, it is further the case that in the initial position, the adjusting element inlet opening 9a, 9b and the adjusting element outlet opening 10a, 10b each point towards the housing inner wall 13a, 13b of the respective housing 5a, 5b.

[0036] The respective adjusting element 8a, 8b is here and preferably one that is rotatably mounted and, as Fig. 3shows, has a substantially round cross-section. Accordingly, the respective actuating element 8a, 8b has a substantially cylindrical circumference which runs around the rotational axis xa, xb of the actuating element 8a, 8b, wherein the respective actuating element inlet opening 9a, 9b and the respective actuating element outlet opening 10a, 10b are arranged here and preferably on the circumference and point in the radial direction relative to the rotational axes xa, xb. The channel 7a, 7b connecting the respective actuating element inlet opening 9a, 9b with the respective actuating element outlet opening 10a, 10b has here and preferably a straight course. The channel runs centrally through the respective actuating element 8a, 8b, and thus also through the rotational axis xa, xb of the respective actuating element 8a, 8b. The actuator inlet opening 9a, 9b and the actuator outlet opening 10a, 10b of the respective actuator 8a, 8b are here and preferably diametrically opposite each other.In an alternative embodiment not shown here, it is also conceivable for the actuating element inlet opening and / or actuating element outlet opening of the actuating element 8a, 8b to be directed laterally, i.e., parallel to the rotation axis xa, xb. Additionally or alternatively, in a further embodiment not shown here, it is also conceivable to provide a linearly movable actuating element instead of a rotatable actuating element 8a, 8b. The explanations given here for the preferably rotatable actuating elements 8a, 8b also apply accordingly and equally to differently designed or adjustable actuating elements, in particular also linearly adjustable actuating elements.

[0037] The fluid inlet 11a of one housing 5a and the fluid outlet 12b of the other housing 5b are channel-shaped here, i.e., designed as an inlet or outlet channel leading from the outside into the housing interior 6a, 6b, whereas the fluid outlet 12a of one housing 5a and the fluid inlet 11b of the other housing 5b are designed here as an opening that directly connects the housing interior 6a, 6b with the environment. In an exemplary embodiment, the cross-section of the fluid inlet 11a of one housing 5a and the fluid outlet 12b of the other housing 5b is smaller than the cross-section of the fluid outlet 12a of one housing 5a and the fluid inlet 11b of the other housing 5b. The "cross-section" always refers to a section transverse to the flow direction.The longitudinal extent of the fluid inlet 11a of one housing 5a and the fluid outlet 12b of the other housing 5b is also greater than the longitudinal extent of the fluid outlet 12a of one housing 5a and the fluid inlet 11b of the other housing 5b. The latter is almost zero. The "longitudinal extent" is always relative to the flow direction.

[0038] Here, and preferably, it is further the case that, in the initial position, a section, in particular a circumferential section Ua 1 , Ub 1 , of the respective actuating element 8a, 8b hermetically seals the fluid inlet 11a, 11b of the respective housing 5a, 5b. Additionally or alternatively, it is further preferably provided that, in the initial position, a further section, in particular a further circumferential section Ua 2 , Ub 2 , of the respective actuating element 8a, 8b hermetically seals the fluid outlet 12a, 12b of the respective housing 5a, 5b.

[0039] Furthermore, it is preferably the case here that, in the initial position, a section extending around the actuating element inlet opening 9a, 9b, in particular a circumferential section Ua 3 , Ub 3 , of the respective actuating element 8a, 8b rests hermetically sealed against the housing inner wall 13a, 13b of the respective housing 5a, 5b. Additionally or alternatively, it is preferably provided here that, in the initial position, a section extending around the actuating element outlet opening 10a, 10b, in particular a circumferential section Ua 4 , Ub 4 , of the respective actuating element 8a, 8b rests hermetically sealed against the housing inner wall 13a, 13b of the respective housing 5a, 5b.

[0040] Furthermore, it is here and preferably the case that in the initial position a section Aa 1 of the housing 5a of the coupling device 4a, which is assigned here to the liquid container 2, which section runs around the fluid inlet 11a and / or a section Ab 2 of the housing 5b of the coupling device 4b, which is assigned here to the bioprocessing system 3, which section runs around the fluid outlet 12b, lies hermetically sealed against the respective actuating element 8a, 8b, namely the section Aa 1 on the actuating element 8a and the section Ab 2 on the actuating element 8b.Here and preferably it is further provided that in the initial position a section Aa 2 of the housing 5a of the coupling device 4a, which is assigned here to the liquid container 2, running around the fluid outlet 12a and / or a section Ab 1 of the housing 5b of the coupling device 4b, which is assigned here to the bioprocessing system 3, running around the fluid inlet 11b, rests hermetically sealed against the respective actuating element 8a, 8b.

[0041] As in particular the Figures 3a) and b) show, the actuating element 8a of one housing 5a and the actuating element 8b of the other housing 5b, in the mechanically connected state of the housings 5a, 5b, lie against each other under prestress, at least when both actuating elements 8a, 8b are in their operating position, here and preferably also when both actuating elements 8a, 8b are in their initial position. Here and preferably, the two actuating elements 8a, 8b constantly lie against each other under prestress. This is achieved in particular by the actuating elements 8a, 8b being designed, either entirely or at least only in the area of ​​their mutual contact, from a comparatively soft plastic, in particular from an elastomer, in particular from a silicone material. In this way, the actuating elements 8a, 8b can deform elastically in the area of ​​mutual contact. As Fig. 3shows, it is here and preferably the case that in the mechanically interconnected state of the housings 5a, 5b, when both actuating elements 8a, 8b are in their operating position, a section running around the actuating element outlet opening 10a, in particular circumferential section Ua 4 , of one actuating element 8a and a section running around the actuating element inlet opening 9b, in particular circumferential section Ub 3 , of the other actuating element 8b lie against one another in a hermetically sealing manner along the respective channel 7a, 7b towards the respective housing 5a, 5b.

[0042] As mentioned, an elastomer is provided, in particular, for the purpose of hermetic sealing. Particularly preferably, the actuating element 8a, 8b is constructed in sections or entirely from such an elastomer, in particular from a silicone material. The respective housing 5a, 5b can also be constructed, at least in sections, from an elastomer, in particular from a silicone material, although it is preferred that the housing 5a, 5b be constructed from a plastic with as little elasticity as possible, preferably from a plastic with lower elasticity, in particular a thermoplastic or Vero material.According to a particularly preferred embodiment, it is provided that the respective actuating element 8a, 8b is designed in sections or completely from an elastomer, in particular from a silicone material, in particular in the section, here circumferential section Ua 1 , Ub 1 , which hermetically seals the fluid inlet 11a, 11b, and / or in the section, here circumferential section Ua 2 , Ub 2 , which hermetically seals the fluid outlet 12a, 12b, and / or in the section running around the actuating element inlet opening 9a, 9b, here circumferential section Uas, Ub 3 , and / or in the section running around the actuating element outlet opening 10a, 10b, here circumferential section Ua 4 , Ub 4 .Additionally or alternatively, it can be provided that the respective housing 5a, 5b is designed in sections, in particular in the section Aa 1 , Ab 1 running around the fluid inlet 11a, 11b and / or in the section Aa 2 , Ab 2 running around the fluid outlet 12a, 12b, from an elastomer, in particular from a silicone material, and preferably otherwise from a plastic with a lower elasticity, in particular a thermoplastic or Vero material.

[0043] How Fig. 3b) further illustrates, in the mechanically connected state of the housings 5a, 5b, when both actuating elements 8a, 8b are in their operating position, the fluid inlet 11a, 11b and the actuating element inlet opening 9a, 9b on the one hand and / or the fluid outlet 12a, 12b and the actuating element outlet opening 10a, 10b on the other hand, in the coupling devices 4a, 4b are in overlap with each other. In particular, these are aligned coaxially with each other. At the same time, the fluid outlet 12a of one housing 5a and the fluid inlet 11b of the other housing 5b are also in overlap with each other. These are also aligned here and preferably coaxially with each other. Particularly preferred here are, as Fig. 3b ), the two fluid inlets 11a, 11b, the two fluid outlets 12a, 12b and the two channels 7a, 7b are aligned coaxially with each other.

[0044] The Fig. 3a) The adjustment movement of one actuating element 8a between its initial position and its operating position, represented by a circulating arrow, is here and preferably accompanied by a corresponding adjustment movement of the other actuating element 8b. This applies here and preferably exclusively to the mechanically connected state of the housings 5a, 5b, as shown in the Figures 2 and 3 For this purpose, a gear 14 is preferably provided, which, as shown in Fig. 2shown, is particularly preferably a gear transmission. The transmission 14 has at least two transmission components, preferably each in the form of a gear and / or gear segment 14a, 14b. As the gear segment 14a, 14b, for example, a toothed circumferential section of a circular disk is provided here, whereby instead of a completely circumferential disk as here, this can also only have the shape of a circular section, with the toothing then extending along the circular arc. Here and preferably, two gear segments 14a, 14b are provided as transmission components. When the housings 5a, 5b are mechanically connected to one another, the transmission 14 effects a synchronous adjustment of the two actuating elements 8a, 8b between their initial position and their operating position.Here, and preferably, a transmission component of the transmission 14, in particular a gear or gear segment 14b of the transmission 14, is or can be connected in a rotationally fixed manner to an actuating element 15 for manually actuating the transmission 14. The actuating element 15 can be a lever, a crank, or the like.

[0045] The adjustment movement of the respective actuating element 8a, 8b between the initial position and the operating position is, as previously indicated, here and preferably a rotational movement, i.e., the actuating element 8a, 8b is here in each case a rotatable actuating element. The respective actuating element 8a, 8b is adjusted here and preferably between the initial position and the operating position at an angle of less than 45 degrees, preferably less than 40 degrees, more preferably less than 35 degrees, more preferably less than 30 degrees. In principle, in an alternative embodiment not shown here, a linear movement of the respective actuating element is also conceivable as an adjustment movement.

[0046] The adjustment movement of the respective actuating element 8a, 8b can be limited in one or both directions, i.e. towards the initial position and / or the operating position. Here and preferably, this is ensured in both directions by at least one gear component, here both gear components, being or are a gear segment 14a, 14b, so that an adjustment movement is only possible in the toothed circumferential section, i.e., for example, only in an angular range of less than 45 degrees, preferably less than 40 degrees, more preferably less than 35 degrees, more preferably less than 30 degrees. Additionally or alternatively, as in the Figures 3a) and b) is shown merely by way of example, the adjustment movement in the initial position can be limited by a stop 16a, 16b and / or in the operating position by a stop 17a, 17b. The respective stop 16a, 16b and / or the respective stop 17a, 17b can be provided inside the housing 5a, 5b, as here, or outside the housing 5a, 5b.

[0047] In this way, the initial position can first be set as a defined position, particularly by the manufacturer, thus reliably ensuring that the parts critical for fluid transfer are located in the protected and, in particular, sterile area. Subsequently, the operating position can be set as a defined position, particularly by the user, thus reliably ensuring that the respective control element inlet opening 9a, 9b overlaps with the respective associated fluid inlet 11a, 11b and the respective control element outlet opening 10a, 10b overlaps with the respective associated fluid outlet 12a, 12b.

[0048] The Figures 1 and 2further show that here and preferably the fluid inlet 11a of one housing 5a and the fluid outlet 12b of the other housing 5b are each connectable or connected to a hose 18a, 18b or tube, in particular via a plug connection. Here and preferably the fluid inlet 11a of one housing 5a is coupled to the liquid container 2 via a hose 18a or a tube. Additionally or alternatively, as the Figures 1 and 2 also show, the fluid outlet 12b of the other housing 5b is fluidically coupled to the bioprocessing system 3, here the bioreactor, via a hose 18b or a tube.

[0049] Furthermore, the Figures 1 to 3It can be seen that the housings 5a, 5b can be connected to one another in a form-fitting manner. Here, they can only be plugged together, for example via a dovetail connection or the like. In principle, however, it is also conceivable for the housings 5a, 5b to be lockable to one another. The only important thing is that the housings 5a, 5b are held securely together when the adjusting movement of the adjusting elements 8a, 8b is carried out. Since the adjusting elements, at least in the operating position, preferably bear against one another under prestress, the form-fitting connection preferably also exists in the direction of the prestress. Here and preferably, the form-fitting connection between the housings 5a, 5b exists in the flow direction of the liquid medium during its transfer.

[0050] According to a further teaching of independent significance, the respective coupling device 4a, 4b, i.e., here the coupling device 4a assigned to the liquid container 2 and / or the coupling device 4b assigned to the bioprocessing system 3, is claimed as such. In particular, the coupling device 4a, 4b is a coupling device of the proposed sterile connector 1.

[0051] Such a coupling device 4a comprises a housing 5a with a housing interior 6a and an adjusting element 8a adjustably mounted in the housing interior 6a and forming a channel 7a, wherein the channel 7a extends through the adjusting element 8a from an adjusting element inlet opening 9a to an adjusting element outlet opening 10a. The housing 5a of the coupling device 4a is mechanically connectable to the housing 5b of a further coupling device 4b. With regard to the design of the further coupling device 4b, reference may be made to the explanations regarding the proposed first coupling device 4a.The housing 5a has a fluid inlet 11a and a fluid outlet 12a, which connect the housing interior 6a to the environment. In the mechanically connected state of the housings 5a, 5b, the fluid outlet 12a of the housing 5a of the proposed coupling device 4a and the fluid inlet 11b of the housing 5b of the further coupling device 4b can be brought into overlap with one another. In the mechanically connected state of the housings 5a, 5b, the actuating element 8a can be adjusted from an initial position, in which a fluid connection between the channel 7a and the actuating element inlet opening 9a, on the one hand, and between the channel 7a and the actuating element outlet opening 10a, on the other hand, is blocked, into an operating position, in which the actuating element inlet opening 9a is in fluid communication with the fluid inlet 11a and the actuating element outlet opening 10a is in fluid communication with the fluid outlet 12a.

[0052] It is now essential that in the initial position the respective channel 7a, 7b extends into an area of ​​the housing interior 6a, 6b that is hermetically sealed from the surroundings of the housing 5a, 5b.

[0053] In this respect, reference may be made to all statements relating to the proposed sterile connector 1.

[0054] According to a further teaching, which also has independent significance, a packaging arrangement 19, 21 is claimed with a packaging 20, 22 and with at least one, preferably exactly one, sterilely packaged, proposed coupling device 4a, 4b or a sterilely packaged, proposed sterile connector 1 is claimed. Reference may be made to all statements regarding the proposed sterile connector 1 and the proposed coupling device 4a.

[0055] According to one embodiment, a packaging arrangement 19 as shown in Fig. 4As shown above, it is provided with a packaging 20 and a coupling device 4a according to the invention packaged therein in a sterile manner, as well as a liquid container 2 packaged therein in a sterile manner, in particular filled, here already filled by the manufacturer. The liquid container 2 is fluidically coupled to the coupling device 4a according to the invention of the sterile connector 1, i.e. already in the packaged state, and the control element 8a of the coupling device 4a is in its initial position.

[0056] According to a further embodiment, a packaging arrangement 21 as shown in Fig. 4shown below, with a packaging 22 and a sterilely packaged, proposed coupling device 4b as well as a sterilely packaged bioprocessing system 3, here a bioreactor. The bioprocessing system 3 or the bioreactor is fluidly coupled to the proposed coupling device 4b of the sterile connector 1, i.e. in the packaged state, and the actuating element 8b of the coupling device 4b is in its starting position. Here and preferably, the packaging arrangement 21 additionally also has an actuating element 15, which later serves in the assembled state of the sterile connector 1, i.e. when the housings 5a, 5b are connected to one another as described, for manually actuating the gear 14 and correspondingly for adjusting the actuating elements 8a, 8b from the starting position to the operating position.

[0057] In an alternative embodiment not shown here, a packaging arrangement with a package is also conceivable in which only a proposed sterile connector 1, comprising the two coupling devices 4a, 4b, is sterilely packaged. In principle, it is also conceivable to provide a packaging arrangement in which only the respective coupling device 4a, 4b is sterilely packaged.

[0058] According to yet another teaching, which also has independent significance, a use of a sterilely packaged, proposed sterile connector 1, a sterilely packaged proposed coupling device 4a, 4b, and / or a proposed packaging arrangement 19, 21 for the sterile transfer of a liquid, in particular biological, medium from a liquid container 2 into a bioprocessing system 3, in particular into a bioreactor, is claimed as such. With regard to the claimed use, reference may also be made to all statements regarding the proposed sterile connector 1, the proposed coupling device 4a, 4b, and the proposed packaging arrangement 19, 21.

[0059] According to the Fig. 4In the embodiment shown, after unpacking the unit comprising the coupling device 4a and the liquid container 2 on the one hand, and after unpacking the unit comprising the coupling device 4b and the bioprocessing system 3 on the other hand, each with the hoses 18a, 18b or tubes establishing the connection, one coupling device 4a is connected to the other coupling device 4b as described. Subsequently, the actuating elements 8a, 8b are moved, in particular synchronously, from their initial position to their operating position, so that the transfer of the liquid medium from the liquid container 2 via the coupling device 4a and the coupling device 4b into the bioprocessing system 3 can then take place.

[0060] In a particularly preferred embodiment, at least the proposed coupling device 4a or the proposed coupling device 4b, in particular both coupling devices 4a, 4b, preferably also the liquid container 2 and / or the bioprocessing system 3 and / or the hose(s) 18a, 18b or tube(s), are each a single-use component. The respective component, i.e. the respective coupling device 4a, 4b, the liquid container 2, the bioprocessing system 3 and / or the respective hose 18a, 18b or the respective tube, is at least partially, preferably at least predominantly, made of a plastic material. Suitable plastics for the individual components include, in particular, a silicone material and / or a polymer material, in particular an elastomer and / or thermoplastic and / or Vero material.Examples include PE (polyethylene), PP (polypropylene), PTFE (polytetrafluoroethylene), PBT (polybutylene terephthalate), PSU (polysulfone), PESU (polyethersulfone), PC (polycarbonate).

Claims

1. Sterile connector for the sterile transfer of a liquid medium, in particular a biological medium, from a liquid container (2) to a bioprocess engineering system (3), in particular to a bioreactor, wherein the sterile connector (1) has two coupling devices (4a, 4b), wherein the coupling devices (4a, 4b) each have a housing (5a, 5b) having a housing interior (6a, 6b) and a control element (8a, 8b) which is adjustably mounted in the housing interior (6a, 6b) and forms a channel (7a, 7b), wherein the channel (7a, 7b) extends through the control element (8a, 8b) from a control element inlet opening (9a, 9b) to a control element outlet opening (10a, 10b), wherein the housing (5a) of one coupling device (4a) is able to be mechanically connected to the housing (5b) of the other coupling device (4b), wherein each housing (5a, 5b) has a fluid inlet (11a, 11b) and a fluid outlet (12a, 12b) which connect the housing interior (6a, 6b) to the surroundings, wherein, in the mechanically connected state of the housings (5a, 5b), the fluid outlet (12a) of one housing (5a) and the fluid inlet (11b) of the other housing (5b) overlap, wherein, in the mechanically connected state of the housings (5a, 5b), the control elements (8a, 8b) are each adjustable from a starting position, in which a fluid connection between the channel (7a, 7b) and the control element inlet opening (9a, 9b) on the one hand and between the channel (7a, 7b) and the control element outlet opening (10a, 10b) on the other hand is blocked, into an operating position, in which the control element inlet opening (9a, 9b) is fluidically connected to the fluid inlet (11a, 11b) and the control element outlet opening (10a, 10b) is fluidically connected to the fluid outlet (12a, 12b), characterized in that, in the starting position, each channel (7a, 7b) extends in a region of the housing interior (6a, 6b) that is hermetically sealed with respect to the surroundings of the housing (5a, 5b).

2. Sterile connector according to claim 1, characterized in that, in the starting position, the control element inlet opening (9a, 9b) and the control element outlet opening (10a, 10b) each face the housing inner wall (13a, 13b) of the respective housing (5a, 5b).

3. Sterile connector according to claim 1 or 2, characterized in that, in the starting position, a portion, in particular a circumferential portion (Ua1, Ub1), of the respective control element (8a, 8b) closes the fluid inlet (11a, 11b) and / or a portion, in particular a circumferential portion (Ua2, Ub2), of the respective control element (8a, 8b) closes the fluid outlet (12a, 12b) of the respective housing (5a, 5b) in a hermetically tight manner, and / or in that, in the starting position, a portion, in particular a circumferential portion (Ua3, Ub3), of the respective control element (8a, 8b) extending around the control element inlet opening (9a, 9b) and / or a portion, in particular a circumferential portion (Ua4, Ub4), of the respective control element (8a, 8b) extending around the control element outlet opening (10a, 10b) is in contact in a hermetically sealing manner with the housing inner wall (13a, 13b) of the respective housing (5a, 5b), and / or in that, in the starting position, a portion (Aa1, Ab1) of the respective housing (5a, 5b) extending around the fluid inlet (11a, 11b) and / or a portion (Aa2, Ab2) of the respective housing (5a, 5b) extending around the fluid outlet (12a, 12b) is in contact in a hermetically sealing manner with the respective control element (8a, 8b).

4. Sterile connector according to any one of the preceding claims, characterized in that the control element (8a) of one housing (5a) projects from the housing interior (6a) through the fluid outlet (12a) of the housing (5a), and / or in that the control element (8b) of the other housing (5b) projects from the housing interior (6b) through the fluid inlet (11b) of the housing (5b).

5. Sterile connector according to any one of the preceding claims, characterized in that the control element (8a) of one housing (5a) and the control element (8b) of the other housing (5b), in the mechanically connected state of the housings (5a, 5b), at least when the two control elements (8a, 8b) are in their operating position, preferably also when the two control elements (8a, 8b) are in their starting position, more preferably always, are in contact with one another under preload, preferably in that the contact elements (8a, 8b) deform elastically in the region of mutual contact.

6. Sterile connector according to any one of the preceding claims, characterized in that, in the mechanically connected state of the housings (5a, 5b), when the two control elements (8a, 8b) are in their operating position, a portion, in particular a circumferential portion (Ua4), of one control element (8a) extending around the control element outlet opening (10a) and a portion, in particular a circumferential portion (Ub3), of the other control element (8b) extending around the control element inlet opening (9b) are in contact with one another in such a manner that the respective channel (7a, 7b) is hermetically sealed with respect to the respective housing (5a, 5b).

7. Sterile connector according to any one of the preceding claims, characterized in that each control element (8a, 8b) is produced in part or completely, in particular in the portion that closes the fluid inlet (11a, 11b) in a hermetically tight manner, and / or in the portion that closes the fluid outlet (12a, 12b) in a hermetically tight manner, and / or in the portion extending around the control element inlet opening (9a, 9b) and / or in the portion extending around the control element outlet opening (10a, 10b), from an elastomer, in particular from a silicone material, and / or in that each housing (5a, 5b) is produced in part, in particular in the portion extending around the fluid inlet (11a, 11b) and / or in the portion extending around the fluid outlet (12a, 12b), from an elastomer, in particular from a silicone material, and preferably for the rest from a plastics material with relatively low elasticity, in particular from a thermoplastic.

8. Sterile connector according to any one of the preceding claims, characterized in that, in the mechanically connected state of the housings (5a, 5b), when the two control elements (8a, 8b) are in their operating position, in the case of both coupling devices (4a, 4b) in each case the fluid inlet (11a, 11b) and the control element inlet opening (9a, 9b) and / or the fluid outlet (12a, 12b) and the control element outlet opening (10a, 10b) overlap, in particular are oriented coaxially with one another, and the fluid outlet (12a) of one housing (5a) and the fluid inlet (11b) of the other housing (5b) overlap, in particular are oriented coaxially with one another, preferably in that, in the mechanically connected state of the housings (5a, 5b), when the two control elements (8a, 8b) are in their operating position, the two fluid inlets (11a, 11b), the two fluid outlets (12a, 12b) and the two channels (7a, 7b) are oriented coaxially with one another.

9. Sterile connector according to any one of the preceding claims, characterized in that, in the mechanically connected state of the housings (5a, 5b), an adjusting movement of one control element (8a, 8b) between its starting position and its operating position is accompanied by a corresponding adjusting movement of the other control element (8b, 8a), preferably in that there is provided a transmission (14), in particular a gear train, which, in the mechanically connected state of the housings (5a, 5b), effects a synchronous adjustment of the two control elements (8a, 8b) between their starting position and their operating position, more preferably in that a transmission component of the transmission (14), in particular a gear wheel or gear wheel segment of the transmission (14), is connected or is able to be connected in a rotationally fixed manner to an actuating element (15).

10. Sterile connector according to any one of the preceding claims, characterized in that the adjusting movement of each control element (8a, 8b) between its starting position and its operating position is a rotational movement or a linear movement.

11. Sterile connector according to any one of the preceding claims, characterized in that the adjusting movement of each control element (8a, 8b) between its starting position and its operating position is limited in the starting position and / or operating position via a stop (16a, 16b, 17a, 17b).

12. Sterile connector according to any one of the preceding claims, characterized in that the fluid inlet (11a) of one housing (5a) and the fluid outlet (12b) of the other housing (5b) is able to be connected or is connected, in particular via a plug-in connection, to a flexible tube (18a, 18b) or a pipe, preferably in that the fluid inlet (11a) of one housing (5a) is fluidically coupled via the flexible tube (18a) or the pipe with a liquid container (2), in particular with a minimum-quantity liquid container, for the delivery of a liquid medium, in particular a biological medium, and / or in that the fluid outlet (12b) of the other housing (5b) is fluidically coupled via the flexible tube (18b) or the pipe with a bioprocess engineering system (3), in particular a bioreactor.

13. Sterile connector according to any one of the preceding claims, characterized in that the two housings (5a, 5b) are able to be connected together in a form-fitting manner, in particular are able to be pushed together or latched together.

14. Coupling device of a sterile connector (1) for the sterile transfer of a liquid medium, in particular a biological medium, from a liquid container (2) to a bioprocess engineering system (3), in particular to a bioreactor, in particular a sterile connector (1) according to any one of the preceding claims, wherein the coupling device (4a, 4b) has a housing (5a, 5b) having a housing interior (6a, 6b) and a control element (8a, 8b) which is adjustably mounted in the housing interior (6a, 6b) and forms a channel (7a, 7b), wherein the channel (7a, 7b) extends through the control element (8a, 8b) from a control element inlet opening (9a, 9b) to a control element outlet opening (10a, 10b), wherein the housing (5a, 5b) of the coupling device (4a, 4b) is able to be mechanically connected to the housing (5b, 5a) of a further coupling device (4b, 4a) of the sterile connector (1), wherein the housing (5a, 5b) has a fluid inlet (11a, 11b) and a fluid outlet (12a, 12b) which connect the housing interior (6a, 6b) to the surroundings, wherein, in the mechanically connected state of the housings (5a, 5b), the fluid outlet (12a, 12b) of the housing (5a, 5b) of the coupling device (4a, 4b) and the fluid inlet (11b, 11a) of the housing (5b, 5a) of the further coupling device (4b, 4a) are able to be brought to overlap, wherein, in the mechanically connected state of the housings (5a, 5b), the control element (8a, 8b) is adjustable from a starting position, in which a fluid connection between the channel (7a, 7b) and the control element inlet opening (9a, 9b) on the one hand and between the channel (7a, 7b) and the control element outlet opening (10a, 10b) on the other hand is blocked, into an operating position, in which the control element inlet opening (9a, 9b) is fluidically connected to the fluid inlet (11a, 11b) and the control element outlet opening (10a, 10b) is fluidically connected to the fluid outlet (12a, 12b), characterized in that, in the starting position, each channel (7a, 7b) extends in a region of the housing interior (6a, 6b) that is hermetically sealed with respect to the surroundings of the housing (5a, 5b).

15. Packaging arrangement having a packaging (20, 22) and having at least one, preferably exactly one, coupling device (4a, 4b) according to claim 14 sterile packaged therein or a sterile connector (1) according to any one of claims 1 to 13 sterile packaged therein.

16. Packaging arrangement according to claim 15, characterized in that the control element (8a, 8b) of the coupling device (4a, 4b) sterile packaged in the packaging (20, 22) is in its starting position, and in that there is additionally sterile packaged in the packaging (20, 22) a liquid container (2), in particular a filled liquid container, which is fluidically coupled with the coupling device (4a), or there is sterile packaged a bioprocess engineering system (3) which is fluidically coupled with the coupling device (4b).

17. Use of a sterile packaged sterile connector (1) according to any one of claims 1 to 13, of a sterile packaged coupling device (4a, 4b) according to claim 14 and / or of a packaging arrangement (19, 21) according to claim 15 or 16 for the sterile transfer of a liquid medium, in particular a biological medium, from a liquid container (2) to a bioprocess engineering system (3), in particular to a bioreactor.

18. Use according to claim 17, characterized in that at least one coupling device, in particular both coupling devices (4a, 4b), preferably also the liquid container (2) and / or the bioprocess engineering system (3) and / or the flexible tube(s) (18a, 18b) or the pipe(s), in particular as a single-use component, are produced at least in part, preferably at least predominantly, from a plastics material.