Patent Application
20220260189
The invention concerns a sterile connector for the sterile transfer of a liquid, in particular biological medium, according to the preamble of claim 1, a packing arrangement with a packing and at least one first or second coupling device of such a sterile connector packed in sterile fashion therein, or such a sterile connector packed in sterile fashion therein according to claim 26, and the use of such a sterile connector packed in sterile fashion, a first or second such coupling device packed in sterile fashion, and/or such a packing arrangement according to claim 28.
An application example for the sterile connector is the sterile transfer of a liquid, in particular biological medium, into a bioprocess-technical system. A bioprocess-technical system here generally means a device with which biotechnological processes can be carried out or supported. Purely as an example, bioreactors are cited here, in which microorganisms or tissue cells are cultivated under predefined conditions. Such a device regularly comprises a container containing a biological reaction medium which is composed of the substances provided for a biotechnological process, e.g. microorganisms or tissue cells on one side and a corresponding nutrient medium on the other, in order to be able to perform the respective biotechnological process step, for example fermentation or cultivation.
An example of such a bioreactor is firstly a production bioreactor, i.e. a relatively large bioreactor on production scale with a working volume of for example several hundred or several thousand liters, for industrial production of microbial or cellular products, in particular biopharmaceuticals. Such a bioreactor forms as a product a fermentation broth which is normally processed further in a so-called downstream process in order to obtain a product from the cells or the culture supernatant. Another example is a laboratory bioreactor, i.e. a relatively small bioreactor on laboratory scale with a working volume of for example less than 10 liters. Such a laboratory bioreactor serves for example for production of ATMPs (Advanced Therapy Medical Products) and/or for performance of cell expansion, by means of which a sufficient number of cells for the respective application, in particular tissue cells or microbial cells, can be produced. One application for this is the multiplication of human cells, for example T-cells (T-lymphocytes) which are taken from the patient then expanded ex vivo and re-infused into the patient.
In particular in the manufacture of ATMPs with a laboratory bioreactor, but in principle also in a production bioreactor, particular importance is laid on a sterile addition of the individual liquid, e.g. biological, media to the respective bioreactor. Since many ATMPs cannot be filtered in sterile fashion or later sterilized, such medicaments are manufactured in sterile fashion in clean rooms of a corresponding clean room class. Thus the addition of a liquid medium to a bioreactor or the transfer of a liquid medium between two culture vessels and/or bioreactors in principle carries a risk of contamination, for which reason such handling steps are usually carried out in a clean room of clean room class A (GMP guideline Annex 1) or ISO 5 (ISO 14644-1). The production of medicaments in such clean rooms is however very cost-intensive because of the high monitoring requirements, complex clothing procedures etc.
For this reason, there is a demand for closed systems for cultivation or expansion of cells, in particular in the field of manufacture of ATMPs, whereby clean rooms of a lower clean room class may be used, for example clean rooms of clean room class D (GMP guideline Annex 1) or ISO 8 (ISO 14644-1). One challenge however is the addition of liquid medium to such a closed system as simply as possible. Various connecting systems are known such as Luer connectors, Luer lock connectors etc., in order for example to be able to couple a small capacity liquid container, such as a syringe or vial, to a closed system. At the coupling point at which the two coupling devices of the connector are connected together—for a Luer connector, the male Luer terminal and the female Luer terminal—there is a risk of contamination, for which reason particular attention must be paid to sterile conditions in the creation of the connection.
The invention is based on the problem of designing or refining a sterile connector for the sterile transfer of a liquid medium from a liquid container to a fluid chamber, for example of a bioprocess-technical system, such that sterile conditions can easily be created on transfer of the medium.
The above problem is solved with a sterile connector for the sterile transfer of a liquid, in particular biological medium according to the preamble of claim 1, with the features of the characteristic part of claim 1.
An essential feature is the fundamental consideration of creating a sterile connector with two coupling devices to be coupled together for the liquid transfer from a liquid container, which is for example a minimal quantity liquid container, to a fluid chamber, in which the coupling devices are initially provided in a state in which contamination of the parts decisive for the liquid transfer by the user is simply not possible, since in this state they are concealed within the coupling device and thereby protected from contact. The fluid chamber in which the liquid medium is filled from the liquid container via the sterile connector may be formed by a bioprocess-technical system, in particular a bioreactor. In principle however, it is also possible that the fluid chamber forms part of the second coupling device, i.e. the coupling device facing away from the liquid container. In the latter case, the fluid chamber is preferably closed apart from a fluid passage via which the liquid medium is conducted into the fluid chamber. The fluid chamber may however also open into a further fluid outlet which is or can be fluidically connected to a bioprocess-technical system, in particular a bioreactor.
With the sterile connector as proposed, a first preferably sterile cannula of a first coupling device assigned to the liquid container, in any case with its front end forming a fluid outlet, is initially in a position protected from contamination. In a further second coupling device, a first septum is arranged which axially covers and/or closes the fluid passage in this coupling device and thereby also protects this from contamination. The first septum is then pierced by the first cannula in an activation process which creates a fluidic connection through the entire sterile connector, whereby then the liquid medium can pass via the first cannula through the fluid passage. In order to be able to come into contact with the first septum, firstly access must be created through a second septum, which takes place automatically by a coupling process in which the two coupling devices are correctly connected together. During this coupling process, a second, preferably sterile cannula, in or into which the first cannula is movable, pierces said second septum. Until piercing of the second septum, the second cannula may still be arranged in a sealing envelope which is also pierced thereby on piercing of the second septum. In an activation process following the coupling process, now the first cannula may be guided through the second cannula up to the first septum and then pierce this. Until piercing of the first septum, the first cannula may still be arranged in a sealing envelope which is also pierced thereby during piercing of the first septum. The proposed cannulas are preferably made of metal for optimal piercing of the respective septum, but in principle may also be made of a plastic material. Particularly preferably, at their end facing the respective septum, the cannulas are pointed, but in principle may also be blunt.
Contamination of the first cannula in the region of the fluid outlet, i.e. in the region of its front end, is thus not possible until the time at which the first cannula comes into contact with the first septum. The first septum also cannot be contaminated until this time, since in the initial state of the sterile connector, i.e. before performance of the coupling process, it is arranged in a preferably sterile region protected from contamination. Also, the fluid passage in the second coupling device is sterile and protected from contamination until the time at which the first cannula punctures the first septum. This ensures that no germs or other media can reach the liquid medium during the transfer.
It is particularly preferred that before interconnection of the two coupling devices, i.e. before the coupling process, the liquid container from which medium is to be extracted, and/or a bioprocess-technical system to which the medium is to be added, are connected in sterile fashion to the respective assigned coupling device. Particularly preferably, this takes place by the manufacturer. Thus it is conceivable that the manufacturer of the liquid container already provides this with the assigned first coupling device of the sterile connector, wherein the liquid container particularly preferably is already filled by the manufacturer at this time, wherein the liquid container and the first coupling device are preferably made available to the user in a correctly interconnected state, in particular as a single-use component. The same also applies to the bioprocess-technical system, wherein it is also conceivable that the manufacturer of the system has already provided this with the assigned second coupling device of the sterile connector, in some cases with several such coupling devices, wherein the bioprocess-technical system and the second coupling device are preferably made available to the user in the correctly interconnected state, in particular a single-use components.
In this way, the two coupling devices of the sterile connector cannot be contaminated at any point decisive for the liquid transfer before creation of the connection, since there is already a sterile connection in the region in which the medium passes from the liquid container to the first coupling device connected thereto, and in the region in which the medium passes from the further second coupling device into the bioprocess-technical system. The portions or elements of the coupling devices, via which the liquid medium passes correctly from the coupling device assigned to the liquid container into the respective other coupling device, are also protected from contamination until the time of liquid transfer. In this way, via the sterile connector as proposed, in a particularly simple fashion, a sterile connection may be created between a liquid container and a fluid chamber, in particular a bioprocess-technical system.
It should be pointed out again that the liquid chamber need not necessarily be part of a bioprocess-technical system, but may also be part of the second coupling device and in particular may be closed with the exception of the fluid passage through which the liquid medium enters the fluid chamber.
In detail, it is now proposed that the first coupling device has a fluid inlet and a fluid outlet fluidically connected thereto, wherein the first coupling device comprises a first, preferably sterile cannula having an end which faces away from the fluid inlet and forms the fluid outlet; the second coupling device has a fluid passage which, in an initial state of the sterile connector, is axially covered by a first septum; in the initial state of the sterile connector, the fluid outlet formed by the first cannula is arranged in an in particular sterile region of the first coupling device which is hermetically sealed against the environment of the first coupling device, and the surface of the first septum axially facing away from the fluid passage is arranged in an in particular sterile region of the second coupling device which is hermetically sealed against the environment of the second coupling device; and in a fluidic connection process, starting from the initial state of the sterile connector, a fluidic connection can be created between the fluid inlet of the first coupling device and the fluid passage of the second coupling device, in that the end of the first cannula forming the fluid outlet in any case pierces the first septum of the second coupling device.
The terms “hermetically tight” or “hermetically sealed” in this context mean that a seal is provided which prevents a penetration of contaminants, in particular germs. In a further embodiment, the terms “hermetically tight” or “hermetically sealed” refer to a sterile and/or contamination-protected region of the sterile connector. In a particularly preferred embodiment, the terms “hermetically tight” or “hermetically sealed” also comprise the term “sterile” and are therefore interchangeable.
Claims 2 and 3 define in more detail the fluidic connection process in which a fluidic connection is created between the fluid inlet of the first coupling device and the fluid passage of the second coupling device. Thus the fluidic connection process is firstly a coupling process in which the first coupling device is mechanically connected to the second coupling device (claim 2), and secondly an activation process in which the first coupling device is adjusted relative to the second coupling device from a starting position into an operating position (claim 3). The adjustment comprises preferably a relative linear movement and in some cases also a relative rotational movement of the two coupling devices relative to one another. The coupling process here serves in particular exclusively to create a mechanical connection, whereas the activation process serves in particular exclusively to create a fluidic connection.
Claims 4 to 10 concern the coupling process and describe preferred embodiments and action mechanisms of the elements of the sterile connector which cooperate during the coupling process. Particularly preferably, here the region of the second coupling device which in the initial state is hermetically sealed, is delimited at least partially, preferably completely, by the first septum and a second septum (claim 4). Via a second, preferably sterile cannula of the first coupling device (claim 5), then the coupling process creates access for the first cannula to the hermetically sealed region of the second coupling device. Particularly preferably here, in the initial state, the second cannula is surrounded by a first sealing envelope, in particular in the form of a bellows, which the second cannula pierces during the coupling process (claim 8), in particular directly before piercing the second septum. The movement which causes the piercing of the second septum and in particular of the first sealing envelope by the second cannula may be transmitted to the second cannula by a cannula holder, which is mounted so as to be axially movable in the first coupling device (claim 9).
Claims 11 to 14 concern the activation process and describe preferred embodiments and action mechanisms of the elements of the sterile connector which cooperate during the activation process. The first coupling device here preferably has a second sealing envelope, which in any case surrounds the portion of the first cannula which during the activation process pierces the first septum (claim 11). The second sealing envelope is here preferably arranged together with the first cannula inside the second cannula, wherein during the coupling process, the second cannula can be moved axially relative to the first cannula and the second sealing envelope, so that the front end of the first cannula and the second sealing envelope protrude axially from the second cannula, however preferably only after the second cannula has pierced the second septum. The activation process may cause an axial cannula portion of the first cannula, which in particular surrounds the front cannula end or fluid outlet, to pierce the second sealing envelope (claim 12), wherein the first cannula then, preferably immediately afterwards, pierces the first septum. To perform the activation process, at least one actuation element may be provided on the cannula holder (claim 13), by means of which the cannula holder and accordingly the second cannula, together with the second coupling device mechanically connected thereto, can be moved linearly and in particular also rotationally.
Claim 15 concerns a fluid chamber of the second coupling device into which the fluid passage of the second coupling device opens. This fluid chamber may be fluidically connected to a fluid outlet of the second coupling device or otherwise closed. The term “otherwise closed” means that the fluid chamber has no further opening other than the fluid passage and to this extent forms a further liquid container. Liquid media may also be stored and/or mixed in such a liquid container, as in a bioprocess-technical system. Preferably, the fluid chamber of the second coupling device is however merely a component through which the liquid medium is conducted as it flows via the first coupling device from the liquid container connected thereto through the fluid passage of the second coupling device, in particular to a bioprocess-technical system, for example a bioreactor.
Claims 16 to 25 concern the fluidic connection process of a further embodiment of the sterile connector, and describe preferred embodiments and action mechanisms of the elements of the sterile connector which cooperate during the coupling process and the activation process. The adjustment during the activation process here again comprises a relative linear movement, but in contrast to the embodiment described above, preferably has no relative rotational movement of the two coupling devices relative to one another (claim 16).
Particularly preferably, in this further embodiment of a sterile connector, the region of the second coupling device which is hermetically sealed in the initial state is delimited by the first septum and by a first sealing envelope, in particular in the form of a bellows (claim 17). Via a second, preferably sterile cannula of the second coupling device (claim 18), the coupling process may then provide access for the first cannula to the first septum (claim 20). Particularly preferably, an axial cannula portion of the second cannula which pierces the second septum during the coupling process, is surrounded in the initial state by the first sealing envelope (claim 21), and in particular immediately before piercing of the second septum.
According to a further embodiment in claim 25, in the further embodiment a mechanism is provided for indication, in particular haptic indication, of at least one defined axial position of the first coupling device relative to the second coupling device. Preferably, in the respective defined axial position, an axial form fit is created, in particular via a catch mechanism, between the first coupling device and the second coupling device. A defined axial position in particular corresponds to the starting position in coupled state, and/or a defined axial position corresponds to the operating position in coupled state, i.e. the state after completion of the activation process.
According to a further teaching in claim 26, which has independent significance, a packing arrangement is claimed with a packing and with, packed in sterile fashion therein, at least one, preferably precisely one, first or second coupling device of a sterile connector as proposed, or with, packed in sterile fashion therein, a sterile connector as proposed. In view of the fact that the packing arrangement as proposed comprises a sterile connector as proposed or a coupling device of a sterile connector as proposed, reference may be made to all statements of the aforementioned teaching in this respect.
According to claim 27, the packing may also contain, packed in sterile fashion, either a liquid container or a bioprocess-technical system, wherein the liquid container or the bioprocess-technical system is already fluidically connected to the respective coupling device in the packing.
According to a further teaching in claim 28, which also has independent significance, the use is claimed of a sterile connector as proposed, packed in sterile fashion, a coupling device, packed in sterile fashion, of a sterile connector as proposed, and/or a packing arrangement as proposed, for the sterile transfer of liquid, in particular biological medium from a liquid container into a fluid chamber, preferably of a bioprocess-technical system, in particular a bioreactor, or into a fluid chamber of the second coupling device. In view of the fact that the use as proposed concerns the use of a sterile connector as proposed, a coupling device of a sterile connector as proposed, and/or a packing arrangement as proposed, reference may be made to all statements of the aforementioned teaching in this respect.
With the packing arrangement as proposed and the use as proposed, it has been found that, with the sterile connector as proposed or with the coupling devices of the sterile connector as proposed, which according to the proposal are also claimed as such, a liquid medium can be supplied particularly simply without significant risk of contamination to a closed system, in particular a bioreactor, in that the coupling devices keep the parts decisive for the liquid transfer, in particular said first cannula and the fluid passage, in a sterile state, namely in the coupled state in said starting position, until the liquid transfer actually takes place, namely in the operating state established by the activation process.
In the particularly preferred embodiment according to claim 29, individual ones of said components are preferably configured as single-use components, wherein the components are preferably made of a plastic material.
The invention is explained in more detail below with reference to a drawing showing merely one exemplary embodiment. The drawing shows:
The sterile connector 1 as proposed, shown in
The bioprocess-technical system 4, in particular the bioreactor, here forms a closed system or is integrated in a closed system. The bioreactor is for example designed as a laboratory bioreactor, i.e. as a bioreactor which, in contrast to a production bioreactor, has a relatively small working volume (maximum fill volume available) of maximum 10 liters. Such a bioreactor serves for performance of a biotechnological process, which here and preferably serves for production of advanced therapy medical products (ATMP). For example, the biotechnological process may also be a cell expansion process for T-cells. In any case, a biological reaction medium is provided in the bioreactor which in particular comprises tissue cells or microbial cells and a nutrient medium. Here, it is necessary to add the liquid media to the closed system in sterile state.
It is now essential that the first coupling device 5 has a fluid inlet 7 and a fluid outlet 8 fluidically connected thereto, wherein the first coupling device 5 has a first, preferably sterile cannula 9 which has an end facing away from the fluid inlet 7 and forming the fluid outlet 8; that the second coupling device 6 has a preferably sterile fluid passage 10 which in the initial state of the sterile connector 1 is covered axially at the front, i.e. away from the fluid passage 10, by the first septum 11; that in the initial state of the sterile connector 1, the fluid outlet 8 formed by the first cannula 9 is arranged in an in particular sterile region of the first coupling device 5 which is hermetically sealed against the environment of the first coupling device 5, and the surface 11a of the first septum 11 pointing away from the fluid passage 10 is arranged in an in particular sterile region of the second coupling device 6 which is hermetically sealed against the environment of the second coupling device 6; and that starting from the initial state of the sterile connector 1, in a fluidic connection process, a fluidic connection can be created between the fluid inlet 7 of the first coupling device 5 and the fluid passage 10 of the second coupling device 6, in that the end of the first cannula 9 forming the fluid outlet 8 in any case pierces the first septum 11 of the second coupling device 6.
A “septum”, also known as a puncture membrane, generally means a membrane separating two chamber portions from one another. It has the general effect that any adhesions on the outside of a cannula are stripped off during piercing of the septum. Preferably, it is made of a plastic material, further preferably an elastomer, in particular silicone material. Such a septum may have any form. In particular, a septum such as the first septum 11 here may be disk-like, or like the second septum 12 described below, may be pot-like. In the preferred case that—as here—a first septum 11 and a second septum 12 are provided, these may have different or the same forms (disk-like, pot-like), wherein preferably—as here—only one septum 11, 12, in particular the second septum 12, or alternatively (not shown here) both the first and the second septums 11, 12, is/are pot-like. The term “pot-like” means that a chamber portion is delimited by radial walls and an axial wall. The terms “axial” and “radial”, and the term “in the circumferential direction” as used below, here always relate to a longitudinal axis X of the sterile connector along which the two coupling devices 5, 6 extend during correct transfer of the liquid medium.
The first exemplary embodiment will now be described below.
As
The second coupling device 6 also has two housing parts 14a, 14b which are preferably made of a thermoplastic, in particular PC (polycarbonate), of which the housing part 14a is here and preferably also configured so as to be substantially cylindrical with a cylinder axis coaxial to the longitudinal axis X of the sterile connector. The first septum 11 and the second septum 12, to be described below, are arranged in the first housing part 14a, wherein the first septum 11 covers the preferably sterile fluid passage 10 axially towards the front, and thus here also the preferably sterile outlet channel 16, and thereby here and preferably hermetically closes the fluid passage 10. The term “axially towards the front” means in the direction from which the first coupling device 5 is supplied during the connection process, i.e. the direction towards the first coupling device 5.
The first septum 11 guarantees the sterility of the fluid passage 10 until this is punctured, as will be described below, in that it protects the fluid passage 10 from contact by the user or other components.
The second housing part 14b forms a fluid chamber 3′ which extends in particular along the longitudinal axis X of the sterile connector from the fluid passage 10 of the second coupling device 6 to the fluid outlet 15 of the second coupling device 6. The fluid passage 10 thus here too opens into a fluid chamber 3′ of the second coupling device 6 which has a fluid outlet 15 fluidically connected to the fluid passage 10, and to this extent forms an outlet channel 16. In an alternative embodiment (not shown here), the fluid chamber 3′ may also be otherwise closed, with the exception of the fluid passage 10, i.e. forming a further liquid container. In both alternatives, the second housing part 14b of the second coupling device 6 is connected in particular axially and rotationally fixedly to the first housing part 14a of the second coupling device 6, and preferably formed integrally.
During the fluidic connection process illustrated schematically in
The coupling process is illustrated in
In this way, the sterile connector 1 is brought from the initial state shown in
The coupling process is followed by an activation process which is illustrated firstly in
As
Now the individual elements, which cooperate with one another, of the first coupling device 5 and the second coupling device 6 of the first exemplary embodiment and their function will be explained in more detail.
In the initial state, as
Since the second septum 12 protects the first septum 11 from contact by the user or other components, this guarantees the sterility of the first septum 11 until the coupling process, and in particular until the second septum 12 is pierced, as will be described below.
The coupling process, in particular the linear movement of the coupling process, as shown in
The coupling process, in particular the linear movement of the coupling process, now causes a cannula portion of the second cannula 17 to pierce the second septum 12, and thus create the access for the first cannula 9 into the preferably sterile region of the second coupling device 6 which is hermetically sealed in the initial state, and/or creates an access for the first cannula 9 to the first septum 11. Here it is provided that the first cannula 9 and the second septum 12 do not touch one another before, during and after the coupling process. Contamination of the first cannula 9 by the second septum 12 can thus be excluded.
In order to delimit the hermetically sealed, preferably sterile region of the first coupling device 5 from the environment, the first coupling device 5 has at least one sealing envelope. Thus initially a first sealing envelope 18 is provided, here and preferably in the form of a bellows, which in the initial state radially and at the front end surrounds the axial cannula portion of the second cannula 17 which pierces the second septum 12 during the coupling process. Here, in the initial state, the first sealing envelope 18 or the bellows, as shown in
The first sealing envelope 18 is here and preferably fixed to a cannula holder 19 for the second cooler 17, which will be described in more detail below. The first sealing envelope 18 is hermetically tightly connected to the cannula holder 19. According to an alternative embodiment (not shown here), it is also conceivable that the first sealing envelope 18 lies hermetically tightly on and/or is fixed to an axial cannula portion of the second cannula 17 and/or a wall portion of the first coupling device, in particular of the housing part 13b.
The first sealing envelope 18 guarantees the sterility of the axial cannula portion of the second cannula 17 until penetration into the second septum 12, in that it protects the second cannula 17 from contact by the user or other components. The second cannula 17 pierces the first sealing envelope 18 preferably only during the coupling process, when the first sealing envelope 18 comes to rest axially on the second septum 12. Preferably, the second cannula 17 penetrates into the second septum 12 immediately after piercing the first sealing envelope 18, and then pierces this septum completely.
In the case when, as shown in
As stated, in the exemplary embodiment depicted here and to this extent preferred, the second cannula 17 is fixed to a cannula holder 19 which is preferably made of a thermoplastic, in particular PC (polycarbonate). The cannula holder 19 is mounted so as to be axially movable in the first coupling device 5. Because of the coupling process here, now the second coupling device 6, in particular the housing part 14a, comes to rest axially on the cannula holder 19. Particularly preferably, the coupling process creates the axial and/or radial connection of the second coupling device 6 or the housing part 14a to the cannula holder 19 by form fit or force fit. In the exemplary embodiment shown here, the second coupling device 6 or the housing part 14a is latched onto the cannula holder 19. Thus an axial and/or radial displacement of the cannula holder 19 in the first coupling device 5, or relative to the housing part 13b, causes the relative movement of the first cannula 9 inside the second cannula 17, and finally the piercing of the first septum 11 by the first cannula 9 during the activation process.
In order to guarantee a defined relative movement between the first coupling device 5 and the second coupling device 6 in the coupling process, here and preferably also a guide device 20 is provided. This achieves axial guidance of the first coupling device 5 relative to the second coupling device 6 during the coupling process. Thus a protrusion or axially running web 21 and/or an axially running groove may be provided on a wall portion of the first coupling device 5, in particular on the housing part 13b, preferably on the inside, and a corresponding counter-piece 22 provided on a wall portion of the second coupling device 6, in particular on the housing part 14a, preferably on the outside. The counter-piece 22 is for example an axially running groove corresponding to the protrusion or axially running web 21 of the first coupling device 5, or a protrusion or axially running web corresponding to the axially running groove of the first coupling device 5. The protrusion or web 21 or the groove of the first coupling device 5, and the corresponding counter-piece 22 of the second coupling device 6, then together form the guide device 20. In the exemplary embodiment shown here, two such guide devices 20 are provided opposite one another on the radial sides of the sterile connector 1.
As
As
The second sealing envelope 23 is here and preferably fixed to the housing part 13a. The second sealing envelope 23 is hermetically tightly connected to the housing part 13a. According to an alternative embodiment (not shown here), it is also conceivable that the second sealing envelope 23 rests hermetically tightly against and/or is fixed to an axial cannula portion of the first cannula 9 and/or the housing part 13b.
This second sealing envelope 23 guarantees the sterility of the axial cannula portion of the first cannula 9 surrounding the fluid outlet 8 until penetration of the first cannula 9 into the first septum 11, in that it protects the first cannula 9 from contact by the user or other components. The first cannula 9 preferably only pierces the second sealing envelope 23 when the latter rests axially on the first septum 11. Preferably immediately after piercing the second sealing envelope 23, the first cannula 9 penetrates into the septum 11.
In order to be able to perform the activation process manually after the coupling process, which mechanically connects the first coupling device 5 to the second coupling device 6, here and preferably an actuation element 24 is provided on the cannula holder 19 for manual actuation of the cannula holder 19. By means of the actuation element 24, the cannula holder 19 together with the second cannula 17 and the second coupling device 6 can be moved generally linearly and here also rotationally relative to the first coupling device 5 during the activation process. Here and preferably, two such actuation elements 24 are provided on opposite radial sides of the sterile connector 1 or first coupling device 5 or cannula holder 19. Here and preferably, the actuation element 24 extends radially outward from the cannula holder 19 through a guide opening 25 which is provided in a wall portion of the first coupling device 5, in particular in the housing part 13b.
The actuation element 24 is here and preferably mounted in the guide opening 25 so as to be axially and here also rotationally displaceable during the activation process. Here, during the activation process, the actuation element 24 is displaceable in the guide opening 25 initially in the circumferential direction (
The illustration of the actuation element 24 in dotted lines shows an intermediate position into which the actuation element 24 is moved by its displacement in the circumferential direction, and out of which then the actuation element 24 is moved linearly. The solid lines indicate the respective end positions of the actuation element 24 in the guide opening 25, wherein
It should be pointed out that
Now the second exemplary embodiment will be explained in more detail.
As
The second coupling device 6 also has two housing parts 14a, 14b, of which the housing part 14a is here and preferably also configured so as to be substantially cylindrical with a cylinder axis coaxial to the longitudinal axis X of the sterile connector. The first septum 11 and a first sealing envelope 18—to be described in more detail below—are arranged in the first housing part 14a, wherein the first septum 11 covers the fluid passage 10 and hence here also the outlet channel 16 axially to the front, and thereby here and preferably hermetically closes the fluid passage 10. The term “axially to the front” means in the direction from which the first coupling device 5 is supplied during the connection process, i.e. the direction towards the first coupling device 5.
The first septum 11 guarantees the sterility of the fluid passage 10 until this is pierced, as will be described below, in that it protects the fluid passage 10 from contact by the user or other components.
The second housing part 14b forms a fluid chamber 3′ which extends in particular along the longitudinal axis X of the sterile connector, from the fluid passage 10 of the second coupling device 6, to a fluid outlet 15 of the second coupling device 6. The fluid passage 10 thus here opens into a fluid chamber 3′ of the second coupling device 6 which has a fluid outlet 15 fluidically connected to the fluid passage 10, and to this extent forms an outlet channel 16. In an alternative embodiment (not shown here), the fluid chamber 3′ may also be otherwise closed with the exception of the fluid passage 10, i.e. forming a further liquid container. In both alternatives, the second housing part 14b of the second coupling device 6 is connected in particular axially and rotationally fixedly to the first housing part 14a of the second coupling device 6, and preferably formed integrally.
The fluidic connection process illustrated schematically in
The coupling process is illustrated in
In this way, the sterile connector 1 is brought from the initial state shown in
The coupling process is followed by an activation process which is illustrated firstly in
As
Now the individual elements, which cooperate with one another, of the first coupling device 5 and second coupling device 6 of the second exemplary embodiment, and their function will be explained in more detail.
In the initial state, as
Since the first sealing envelope 18 protects the first septum 11 and a second cannula 17 (presented in more detail below), in which the first septum 11 is arranged in particular axially fixedly, from contact by the user or other components, the first sealing envelope 18 guarantees the sterility of the first septum 11 and the second cannula 17 until the coupling process.
The coupling process, in particular the linear movement of the coupling process, as shown in
In the exemplary embodiment shown here and to this extent also preferred, the second cannula 17 is connected axially fixedly and in particular rotationally fixedly to the housing part 14a of the second coupling device 6.
In order for the first cannula 9 of the first coupling device 5 to be able to come into contact with the first septum 11 of the second coupling device 6, firstly an access thus be created through a second septum 12 in the first coupling device 5. This is achieved in that because of the coupling process, in particular the linear movement of the coupling process, an axial cannula portion of the second cannula 17 of the second coupling device 6 pierces the second septum 12 of the first coupling device 5, and thus creates an access for the first cannula 9 in the region of the second coupling device 6 which is hermetically sealed in the initial state, and/or an access for the first cannula 9 to the first septum 11. It is provided here that the first cannula 9 and the second septum 12 do not touch one another before, during and/or after the coupling process. Contamination of the first cannula 9 by the second septum 12 can thus be excluded.
In order to delimit the hermetically sealed, preferably sterile region of the first coupling device 5 against the environment in the initial state of the sterile connector 1, the first coupling device 5 comprises, as well as the second septum 12, here also a second sealing envelope 23, in particular in the form of a hose closed at one end, which surrounds the first cannula 9 radially and at the front end forming the fluid outlet 8.
The first sealing envelope 18 is here and preferably fixed to the housing part 14a. Here, the first sealing envelope 18 is hermetically tightly connected to the housing part 14a. According to an alternative embodiment (not shown here), it is also conceivable that the first sealing envelope 18 lies hermetically tightly against and/or is fixed to an axial cannula portion of the second cannula 17.
The first sealing envelope 18 guarantees the sterility of the axial cannula portion of the second cannula 17 until its penetration into the second septum 12, in that it protects the second cannula 17 from contact by the user or other components. The second cannula 17 pierces the first sealing envelope 18 preferably only during the coupling process, when the first sealing envelope 18 comes to rest axially on the second septum 12. Preferably, the second cannula 17 penetrates into the second septum 12 immediately after piercing of the first sealing envelope 18, and then completely pierces said septum.
In the case when, as shown in
As
The second sealing envelope 23 is here and preferably fixed to the housing part 13a. The second sealing envelope 23 is hermetically tightly connected to the housing part 13a. According to an alternative embodiment (not shown here), it is also conceivable that the second sealing envelope 23 rests hermetically tightly against and/or is fixed to an axial cannula portion of the first cannula 9 and/or the housing part 13b.
This second sealing envelope 23 guarantees the sterility of the axial annular portion of the first cannula 9 surrounding the fluid outlet 8 until penetration of the first cannula 9 into the first septum 11, in that it protects the first cannula 9 from contact by the user or other components. The first cannula 9 preferably only pierces the second sealing envelope 23 when this rests axially on the first septum 11. Preferably immediately after piercing the second sealing envelope 23, the first cannula 9 penetrates into the septum 11.
Finally, here and preferably, as a combined view of
It is pointed out that in
According to a further teaching which has independent significance, a packing arrangement 27, 28 is claimed with a packing 29, 30 and at least one, preferably precisely one first or second coupling device 5, 6, packed in sterile fashion therein, of a sterile connector 1 as proposed, or with a sterile connector 1 as proposed packed in sterile fashion therein (
According to one exemplary embodiment, a packing arrangement 27 is proposed, as shown at the top in
According to a further exemplary embodiment, a packing arrangement 28, as shown at the bottom in
In an alternative exemplary embodiment (not shown here), a packing arrangement is conceivable with a packing in which only a sterile connector 1 as proposed, comprising the two coupling devices 5, 6, is packed in sterile fashion. In principle, it is also conceivable to provide a packing arrangement in which only the first coupling device 5 or the second coupling device 6 of the sterile connector 1 as proposed is packed.
According to yet a further teaching which also has independent significance, a use is claimed of a sterile connector 1 as proposed, packed in sterile fashion, a first or second coupling device 5, 6, packed in sterile fashion, of a sterile connector 1 as proposed, and/or a packing arrangement 27, 28 as proposed, for the sterile transfer of a liquid, in particular biological medium, from a liquid container 2 to a fluid chamber 3, in particular of a bioprocess-technical system 4, for example a bioreactor. Also with respect to the claimed use, to this extent reference may be made to all statements relating to the sterile connector 1 as proposed and to the packing arrangement 27, 28 as proposed.
According to the packing arrangements 27, 28 shown in
In a particularly preferred embodiment, at least the first coupling device 5 or second coupling device 6 of the sterile connector 1 as proposed, in particular both coupling devices 5, 6, preferably also the liquid container 2 and/or the bioprocess-technical system 4 and/or the hose(s) 26 or tube(s), are each single-use components. The respective components, i.e. the respective coupling device 5, 6, the liquid container 2, the bioprocess-technical system 4 and/or the respective hose 26 or tube, are made at least partly and preferably at least mainly of a plastic material. Suitable plastics for the individual components are in particular a silicone material and/or a polymer material, in particular an elastomer and/or thermoplastic. Examples of these are PE (polyethylene), PP (polypropylene), PTFE (polytetrafluoroethylene), PBT (polybutylene terephthalate), PSU (polysulfone), PESU (polyethersulfone) or PC (polycarbonate).
| Number | Date | Country | Kind |
|---|---|---|---|
| 10 2019 116 970.4 | Jun 2019 | DE | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/065686 | 6/5/2020 | WO |
