Method for performing biotreatment of cell culture

Abstract

The invention relates to a method for carrying out a biological treatment on a cell culture, in which the biological treatment is carried out on an integrated biological treatment system (1), in which the integrated biological treatment system (1) delivers a culture medium, in particular a cell culture, used in the biological treatment through a tube when the biological treatment is carried out, wherein the integrated biological treatment system (1) comprises a tube connection system (2) for connecting tubes of the integrated biological treatment system (1) as required by welding, and wherein a first tube (4), a first tube holder (7) and a first fluid structure (12) for receiving and / or providing a culture medium are carried by a movable first carrier (10), wherein the first tube (4) is held by a first tube holder (7) and fluidly connected to a first fluid structure (12), and wherein the first carrier (10) and the first tube (4) carried by the first carrier, the first tube holder (7) and the first fluid structure (12) are conveyed to a welding location within the integrated biological treatment system (1), a tube connection system (2) connects the first switch (4) and the second tube (5), thereby forming a tube connection (3) through which the integrated biological treatment system (1) delivers the medium from or to the first fluid structure (12) of the first carrier (10) after welding.

Description

Technical Field

[0001] The present invention relates to a method for performing a bioprocess on a cell culture according to claim 1, an integrated bioprocessing system for performing a bioprocess on a cell culture according to claim 7, an integrated bioprocessing system for performing a bioprocess on a cell culture according to claim 17, a sealing unit according to claim 18, and a device for a delivery tube according to claim 19. Background Art

[0002] The term "bioprocess" encompasses processes in the broad field of biotechnology, such as in the field of cell and gene therapy, including processes for the allogeneic or autologous production of genetically modified immune cells. In bioprocessing, living cell cultures are extracted from patients, particularly generated, modified, and / or used to obtain specific desired products. The desired products can be the cells themselves and / or products produced by the cells. For example, if a corresponding product is to be obtained, specific cell cultures can be generated and modified such that the product is subsequently produced and obtained. Generally, different types of cell cultures may produce different types of products. In the context of the present application, the term "bioprocess" must be understood broadly such that it indeed includes partial processes, such as the generation or modification of cell cultures or the use of cell cultures to obtain products, as well as the entire processing of cell cultures. An example of a typical bioprocess is the manufacture of autologous T cells modified to express a chimeric antigen receptor (CAR). These cells can be used to treat various types of blood malignancies, including different types of leukemia (blood cancer). Other cell therapies based on primary cells (especially stem cells and their derivatives) also fall within the scope of interest.

[0003] For bioprocessing involving the use of cell cultures (especially for cell and gene therapy), processing flexibility is particularly important because the operations of bioprocessing must be adjusted and carried out individually according to different environments. For this purpose, currently, such bioprocessing is typically performed in an integrated bioprocessing system that is flexible and has a certain level of automation.

[0004] WO2021 / 212124A1 discloses an example of an integrated bioprocessing system for performing bioprocessing. Here, a method for modularizing and parallelizing the processing of cell cultures on an integrated bioprocessing system is disclosed.

[0005] Another integrated bioprocessing system is known from WO2023 / 281257A1. In such an integrated bioprocessing system, tubes are held by a retainer and welded by a tube welding system. Generally, the movement of components such as tubes and the tube welding system is performed by a robotic mechanism. Handling flexible tubes is very challenging. Controlling the end of a robotic manipulator and detecting the position of the tube with sufficiently low tolerances to grasp the tube requires very complex control and sensing capabilities. Therefore, it is necessary to reduce the degrees of freedom of the integrated bioprocessing system, and in particular, a way needs to be found to completely remove the robotic manipulator or at least increase the tolerances that the position of the end of the robotic manipulator may have relative to the tube, such that the robotic manipulator can reliably grasp the tube.

[0006] During bioprocessing, different kinds of operations can be performed, and thus different kinds of culture media are required, such as the cell culture itself or other fluids, especially liquids, such as culture media for cell expansion, activation reagents, viral vector compositions, washing buffers, magnetic bead solutions, etc. Since when bioprocessing is performed by using an integrated bioprocessing system, the operations of the bioprocessing can be performed at different positions within the integrated bioprocessing system or by using different components of the integrated bioprocessing system, the transfer of the corresponding one or more culture media is mandatory. Therefore, known integrated bioprocessing systems generally include tubes that are linked to enable the transfer of one or more culture media. The linked tubes form tube connections.

[0007] Even though the methods for connecting different components to tubes are generally well-established in the art, the tube connections within known integrated bioprocessing systems are either pre-linked, for example, by using a set of tubes, or manually linked by an operator, for example, before or during the bioprocessing to be performed. However, while pre-linked tube connections limit the flexibility of the integrated bioprocessing system, manually linked tube connections increase the risk of cell culture contamination since the transfer of one or more culture media is to some extent pre-determined. For this reason, known methods of bioprocessing cell cultures by using an integrated bioprocessing system are limited in terms of the flexibility of the performance of the bioprocessing itself or in terms of providing sterility. Summary of the Invention

[0008] Therefore, the present invention is based on the problem of providing a method for performing bioprocessing on a cell culture by using an integrated bioprocessing system that is improved in terms of flexibility without compromising the sterility of the cell culture.

[0009] The above object is solved by the features of claim 1.

[0010] The main objective achieved by the present invention is that using welding to connect tubes to an integrated bioprocessing system is a simple way to form any number of tube connections, so as to flexibly convey culture media through the integrated bioprocessing system. During bioprocessing, different culture media (especially cell cultures) can be automatically conveyed between different receptacles, devices, cartridges or containers. Sealed fluid structures can be formed and connected as needed. At the same time, the tube connections formed by welding are sterile, minimizing any risk of contamination of the cell culture, especially if the welding procedure is automated. In addition, due to the simpler operation of tubes in the integrated bioprocessing system, using a carrier for carrying the tubes and a holder for holding the tubes enables a higher degree of automation of the entire bioprocessing.

[0011] Compared with known robotic welding mechanisms, the present application proposes various ways to operate the tube positions by means other than a robotic manipulator to reduce the degrees of freedom of the integrated bioprocessing system. A robotic manipulator (such as a robotic mechanism) can still be used for welding, but even so, since the tubes are also operated by other means, the control of the robotic manipulator will be easier. In some embodiments, no robotic manipulator is used for tube welding.

[0012] A method for performing a bioprocess on a cell culture is proposed, wherein the bioprocess is performed on an integrated bioprocessing system. When performing the bioprocess, the integrated bioprocessing system conveys culture media, especially cell cultures, used in the bioprocess through tubes. The integrated bioprocessing system includes a tube connection system for connecting the tubes of the integrated bioprocessing system by welding as needed. A first tube, a first tube holder and a first fluid structure for receiving and / or providing culture media are carried by a movable first carrier. The first tube is held by the first tube holder and is fluidly connected to the first fluid structure. The first carrier and the first tube, the first tube holder and the first fluid structure carried by it are transported to a welding position within the integrated bioprocessing system. At the welding position during the welding procedure, the tube connection system connects the first tube and the second tube, thereby forming a tube connection. After welding, the integrated bioprocessing system conveys the culture media from the first fluid structure of the first carrier or conveys the culture media to the first fluid structure through the tube connection.

[0013] According to an advantageous embodiment of claim 2, the welding procedure includes different stages to be performed, namely a placement stage, a trimming stage and a welding stage. Each stage itself or a combination of these stages provides a simple sequence, which, when included in the welding procedure, results in a tube connection between the first tube and the second tube, especially a sterile tube connection.

[0014] Claim 3 also details the trimming phase and the welding phase. During the advantageous heating step of the trimming phase, the blade is heated to a specific temperature by the blade heater of the tube cutting unit. At this time, on the one hand, the blade itself is sterilized so that contamination can be avoided when cutting the tube. On the other hand, the heated blade can also make the cutting of the tube smooth because these tubes are usually made of plastic materials, and when cut, these plastic materials fuse at a certain temperature. During the advantageous alignment step of the trimming phase, the tube cutting unit is aligned so that the tube cutting unit is positioned relative to the first tube and / or the second tube, and this positioning can ensure proper cutting of the tube. During the advantageous cutting step of the trimming phase, the first tube and / or the second tube are cut by the tube cutting unit. During the advantageous contact step of the welding phase, the tubes can be axially aligned to achieve proper tube connection when the tubes are welded. Alternatively or additionally, during the contact step, the tube cutting unit can be moved at least partially so that the tubes can be easily contacted, and the movement of the tube cutting unit enables the tubes to be contacted. Alternatively or additionally, during the contact step, the tubes can be contacted by the axial movement of at least one of the tubes, where the tubes fuse together, especially if the material of the tubes is also heated due to the cutting process. In particular, if the tubes have been axially aligned, the movement of the tubes only in the axial direction prevents improper tube connection.

[0015] An advantageous embodiment according to claim 4 relates to a disconnection procedure which, if necessary, enables the tubes to be disconnected. The disconnection procedure is carried out by a tube disconnection device. The disconnection procedure can include a sealing phase in which at least one tube is sealed so that the fluid connection between the tubes is interrupted. The disconnection procedure can include a disconnection phase in which the tubes are cut so that the physical connection between the tubes is interrupted.

[0016] According to a preferred embodiment of claim 5, the method includes performing an integrity test procedure. Here, the integrity of the tube connection formed by welding can be tested so that if the integrity of the tube connection is not verified, an emergency procedure for preserving the cell culture can be initiated. The emergency procedure can include ensuring the sterility of the tubes and / or notifying the user and / or initiating a disconnection procedure and / or initiating another welding procedure.

[0017] According to claim 6, the first tube can be connected to a third tube so as to form an additional tube connection in the welding procedure. This advantageous embodiment enables the first tube to be connected to different tubes as needed, so that the provided method offers further flexibility.

[0018] According to another aspect, when the carrier carries the first tube holder, the first fluid structure, and the first tube and the first tube holder holds the first tube, the carrier carrying the first tube holder, the first fluid structure, and the first tube is inserted into and / or removed from the integrated bioprocessing system. This allows for pre-configuration of the carrier with the fluid structure. In particular, the carrier enters and exits the integrated bioprocessing system together with the fluid structure without the need for reconfiguration of the fluid structure (except for tube welding) within the integrated bioprocessing system.

[0019] According to another aspect, before the first tube holder enters the integrated bioprocessing system, the first tube is placed in the first tube holder outside the integrated bioprocessing system, particularly manually. The entry into and / or exit from the integrated bioprocessing system can be defined by the housing of the integrated bioprocessing system, which may include one or more defined interfaces for the carrier to enter and / or exit the integrated bioprocessing system.

[0020] According to a second equally important teaching of claim 7, it relates to an integrated bioprocessing system for performing a bioprocess on a cell culture, wherein during the performance of the bioprocess, a culture medium for the bioprocess, particularly the cell culture, can be conveyed by the integrated bioprocessing system through a pipeline. The integrated bioprocessing system includes a first tube for conveying the culture medium and a second tube for conveying the culture medium, wherein the first tube is held by a first tube holder and is fluidly connected to a first fluid structure for receiving and / or providing the culture medium. The integrated bioprocessing system further includes a movable first carrier, wherein the first tube, the first tube holder, and the first fluid structure are carried by the first carrier, and wherein the first carrier and the first tube, the first tube holder, and the first fluid structure carried thereby can be transported to a welding position within the integrated bioprocessing system. The integrated bioprocessing system further includes a tube connection system for connecting the first tube and the second tube at the welding position during a welding procedure to form a tube connection by welding, wherein after welding, the culture medium can be conveyed from or to the first fluid structure of the first carrier through the tube connection.

[0021] The proposed integrated bioprocessing system can perform the proposed method, so all the features and explanations given regarding the proposed method are fully applicable to the proposed integrated bioprocessing system, and vice versa.

[0022] Claim 8 defines an advantageous embodiment that enables simple positioning and simple operation of the second tube within the integrated bioprocessing system.

[0023] Claim 9 details the tube connection system of the integrated bioprocessing system. The tube connection system includes: a tube arrangement unit for arranging a first tube and a second tube relative to each other at least in the axial direction of the first tube and / or the second tube during the arrangement phase of the welding process, such that the first tube and the second tube can be cut; and a tube cutting unit for cutting the first tube and the second tube during the finishing phase of the welding process, wherein the tube arrangement unit is designed such that during the welding phase of the welding process, the first tube and the second tube are brought into contact and fused together to form a tube connection.

[0024] According to claim 10, the tube arrangement unit may include a first tube holder and a second tube holder. The tube holders enable the manipulation of the tubes, especially during the welding process. The tube arrangement unit may further include a first holder moving device and / or a second holder moving device, which are capable of moving the first tube holder and / or the second tube holder respectively, such that the first tube and / or the second tube can be moved indirectly accordingly, especially for arrangement, alignment, manipulation, etc. Advantageously, the first holder moving device includes a first holder guide and / or a first holder drive unit, and the first holder guide is particularly designed as a first track unit. Alternatively or additionally, the second holder moving device includes a second holder guide and / or a second holder drive unit, and the second holder guide is particularly designed as a second track unit. The first holder guide and / or the second holder guide enable the first tube holder and / or the second tube holder to perform predetermined movements precisely and especially in a space-saving manner. The first drive unit and / or the second drive unit can drive the movement of the first tube holder and / or the second tube holder, especially on rails. In particular, the combination of the corresponding holder guides and drive units can result in an economical, highly precise and especially space-saving movement system for moving the corresponding tube holders.

[0025] Claim 11 details a further option for moving the first tube and / or the second tube. While the foregoing embodiments mainly achieve the indirect movement of the tubes by moving the tube holders that hold the tubes, according to an advantageous embodiment of claim 10, the first tube and / or the second tube can be moved in a direct manner. This can result in a further degree of mobility such that the first tube and / or the second tube can be moved in at least a further direction. The tube arrangement unit may include a first tube drive unit and / or a second tube drive unit for driving the movement of the corresponding tube.

[0026] In claim 12, the first drive unit and the second drive unit are further advantageously specified in detail. By means of the respective drive rollers, a structurally simple but equally effective option can be provided for moving the respective tube, in particular in the axial direction of the tube. By means of the respective drive locking elements, the drive rollers can be locked, thereby preventing further movement of the respective tube, in particular movement in the axial direction of the tube. By means of the respective passive rollers, the respective tube can be positioned in the drive unit such that the tube is in contact with the drive rollers. By means of the pre-tensioning device, the clamping of the drive rollers on the tube can be improved by pre-tensioning the tube on the drive rollers and vice versa.

[0027] In order to provide higher flexibility for the relative movement of the tube and the tube cutting unit, the tube connection system advantageously comprises a tube connection head according to claim 13. The first tube holder and / or the second tube holder can be designed separately from the tube connection head. Here, the tube connection head can comprise a tube cutting unit such that the tube cutting unit can move relative to the first tube holder and / or the second tube holder and thus relative to the first tube held by the first tube holder and / or the second tube held by the second tube holder. In a preferred embodiment, the tube connection head comprises a first tube receiver and / or a second tube receiver. Here, the first tube receiver and / or the second tube receiver can be designed as a gripper of the tube connection head such that the first tube and / or the second tube can be gripped by the first tube receiver and / or the second tube receiver. Alternatively, the first tube receiver and / or the second tube receiver can be designed as a tube holder having one or more features of the first tube holder and the second tube holder. The tube cutting unit can be part of the tube connection head or can be designed separately, where in both cases the tube can move relative to the tube cutting unit via the tube connection head.

[0028] According to an embodiment of claim 14, the first tube and / or the second tube (in particular during movement) can be guided. Since tubes are generally flexible, the first guiding means and / or the second guiding means can prevent the first tube and / or the second tube from bending and thus result in more precise movement of the respective tube. Advantageously, the first guiding means comprises a first funnel and / or the second guiding means comprises a second funnel, where the respective funnel provides a structurally easy but reliable and stable guiding scheme for the respective tube. Due to the respective funnel, the guided tube can be guided along the axis of the funnel.

[0029] An advantageous embodiment according to claim 15 relates to position determination within a tube connection system. In particular, due to the highly flexible movement of the tubes, tube retainers, and / or tube connectors (especially due to one or more carriers), when the tube connection system is operating, the position determination device can result in higher precision. The position determination device can include one or more position sensors, which are widely known in the art for numerous applications, such that these position sensors can be utilized at a relatively cost-effective development cost.

[0030] According to an embodiment of claim 16, the tube connection system includes a robotic mechanism. The robotic mechanism carries a tube connector such that the tube connector can move in at least one direction. According to another embodiment of claim 16, the tube connection system additionally or alternatively includes a transfer mechanism, wherein the first carrier and / or the second carrier can be moved by the transfer mechanism. For example, if the first carrier, the first tube, the first tube retainer, and the first fluid structure are part of a cartridge with which unit operations can be performed, and the second carrier, the second tube, the second tube retainer, and the second fluid structure are part of a container for transporting a cell culture, the transfer mechanism enables the direct movement of the cartridge and / or the container. The corresponding tubes, corresponding tube retainers, and corresponding fluid structures are moved indirectly since they are carried by the corresponding carriers. In particular, the combination of the robotic mechanism and the transfer mechanism can result in an efficient tube connection system, especially for an integrated bioprocessing system.

[0031] According to a third equally important teaching according to claim 17, it relates to an integrated bioprocessing system for performing a bioprocess on a cell culture, wherein during the performance of the bioprocess, the culture medium used in the bioprocess, especially the cell culture, can be conveyed by the integrated bioprocessing system through a pipeline. The integrated bioprocessing system includes a first tube for conveying the culture medium and a second tube for conveying the culture medium, wherein the first tube and the second tube are connected by a tube connection portion and are in a disconnected position within the integrated bioprocessing system, wherein the first tube is held by a first tube retainer and is fluidly connected to a first fluid structure for receiving and / or providing the culture medium via the first tube. The integrated bioprocessing system further includes a movable first carrier, wherein the first tube, the first tube retainer, and the first fluid structure are carried by the first carrier. The integrated bioprocessing system further includes a tube disconnecting device for disconnecting the first tube and the second tube at the disconnected position during a disconnection procedure such that the first tube and the second tube are fluidly and / or physically disconnected, and wherein the first carrier and the first tube, the first tube retainer, and the first fluid structure carried by it are conveyed from the disconnected position after the first tube and the second tube are disconnected.

[0032] Using the proposed integrated bioprocessing system, the proposed method can be implemented. Therefore, all the features and explanations given for the proposed method are fully applicable to the proposed integrated bioprocessing system according to claim 17, and vice versa. In addition, all the features and explanations regarding the proposed integrated bioprocessing system according to claim 7 are fully applicable to the proposed integrated bioprocessing system according to claim 17, and vice versa.

[0033] Equally important, a fourth teaching relates to a tube disconnecting device for disconnecting a first tube and a second tube of an integrated bioprocessing system during a disconnection procedure such that the first tube and the second tube are fluidly and / or physically disconnected. The tube disconnecting device includes a sealing unit for sealing the first tube and / or the second tube during a sealing phase, thereby forming a first seal and / or a second seal. The sealing unit includes at least one sealing surface designed to crimp the first tube and / or the second tube along an axial direction of the respective tube such that the first tube and / or the second tube achieves self-sealing.

[0034] The proposed tube disconnecting device can be used in the proposed method. Therefore, all the features and explanations given for the proposed method are fully applicable to the proposed tube disconnecting device, and vice versa. The proposed tube disconnecting device can be used in the proposed integrated bioprocessing system according to claim 7 and / or the proposed integrated bioprocessing system according to claim 17. Thus, all the features given regarding the integrated bioprocessing system are fully applicable to the proposed tube disconnecting device, and vice versa.

[0035] Equally important, a fifth teaching according to claim 18 relates to a sealing unit, particularly a sealing unit of a tube disconnecting device in an integrated bioprocessing system, for sealing a first tube and / or a second tube during a sealing phase, thereby forming a seal. The sealing unit includes at least one sealing surface designed to crimp the first tube and / or the second tube along an axial direction of the respective tube such that the first tube and / or the second tube achieves self-sealing.

[0036] The proposed sealing unit can be used in the proposed method. Therefore, all the features and explanations given for the proposed method are fully applicable to the proposed sealing unit, and vice versa. The proposed sealing unit can be used in the proposed tube disconnecting device, the proposed integrated bioprocessing system according to claim 7, and / or the proposed integrated bioprocessing system according to claim 17. Thus, all the features given are fully applicable to the proposed sealing unit, and vice versa.

[0037] The equally important sixth teaching according to claim 19 relates to a device for a delivery tube, in particular for a delivery tube within an integrated bioprocessing system, wherein the device comprises a carrier, a tube, a tube holder and a fluid structure, wherein the carrier bears the tube, the tube holder and the fluid structure such that the tube, the tube holder and the fluid structure can be transported together with the carrier, and wherein the tube holder holds the tube in a defined position.

[0038] The proposed device relates to the proposed method, the proposed integrated bioprocessing system according to claim 7, the proposed integrated bioprocessing system according to claim 17, the proposed tube disconnecting device according to claim 18 and the proposed sealing unit, and thus all the features and explanations given apply fully to the proposed tube holder and vice versa.

[0039] According to the equally important seventh teaching, a method for performing a bioprocess on a cell culture is proposed, wherein the bioprocess is performed on an integrated bioprocessing system, wherein while the bioprocess is being performed, the integrated bioprocessing system conveys a culture medium, in particular a cell culture, used in the bioprocess through a tube, wherein the integrated bioprocessing system comprises a tube connection system for connecting the tubes of the integrated bioprocessing system by welding as required, wherein a first tube, a first tube holder and a first fluid structure for receiving and / or providing the culture medium are part of the integrated bioprocessing system, wherein the first tube is held by the first tube holder and is fluidly connected to the first fluid structure, wherein the first tube holder is positioned at a welding position by a positioning mechanism separate from the tube connection system, wherein at the welding position during a welding procedure, the tube connection system connects the first tube and a second tube, thereby forming a tube connection, and wherein the integrated bioprocessing system conveys the culture medium from the first fluid structure of the first carrier or conveys the culture medium to the first fluid structure through the tube connection after welding.

[0040] All the explanations given with respect to any other teaching can apply and vice versa.

[0041] If the tube is positioned (in particular only roughly) at the welding position (in particular at a predefined welding position for a number of welding procedures), the tube connection system can interact with the tube by aiming generally at the known welding position, which can be defined relative to the integrated bioprocessing system and is independent of the actual position of the tube, and the tube connection system can be positioned at the welding position in a repeatable process.

[0042] In one embodiment, the first carrier is positioned at the welding location so as to position the first retainer at the welding location. In another embodiment, subsequently, the first retainer is further repositioned such that it is positioned more precisely at the welding location. In another embodiment, only after the above repositioning is completed does the tube connection system interact with the tube. In another embodiment, only at this time does the tube connection system further reposition the tube, in particular by repositioning the tube retainer or without repositioning the tube retainer, for welding.

[0043] Over time, the tube connection system can interact with several, possibly dozens or hundreds, of tube retainers at the same welding location, since the carrier and the tube retainer can be changed as frequently as described.

[0044] According to one embodiment, the positioning mechanism can position the tube retainer in one or completely only in two-dimensional space, in particular in a space parallel to the ground. If the first tube retainer is positioned along the gravity dimension, preferably, the positioning mechanism includes a separate mechanism for positioning the first tube retainer along the gravity dimension and orthogonal to the gravity dimension. Preferably, the positioning mechanism is configured to move the first tube retainer in no more than two dimensions, preferably no more than one dimension, simultaneously. Exemplarily, the positioning mechanism can be a transporter that moves the carrier or an orbital unit that moves the tube retainer.

[0045] According to an equally important eighth teaching, a method for performing a bioprocess on a cell culture is provided, wherein the bioprocess is performed on an integrated bioprocessing system, wherein while the bioprocess is being performed, the integrated bioprocessing system conveys, through a tube, a culture medium, in particular a cell culture, used in the bioprocess, wherein the integrated bioprocessing system includes a tube connection system for connecting, as needed, the tubes of the integrated bioprocessing system by welding, wherein a first tube, a first tube retainer, and a first fluid structure for receiving and / or providing the culture medium are part of the integrated bioprocessing system, wherein the first tube is held by the first tube retainer and is fluidly connected to the first fluid structure, wherein the first tube retainer fluidly closes (in particular clamps) the first tube, in particular reversibly, wherein at the welding location during a welding procedure, the tube connection system connects the first tube and a second tube, thereby forming a tube connection, and wherein the integrated bioprocessing system conveys the culture medium from the first fluid structure of the first carrier or conveys the culture medium to the first fluid structure through the tube connection after welding. By providing additional safety against incorrect welding, the tube retainer can be used for further functions in this way. After the welding has been verified, the closure can be released. If the welding is not verified, the user can, for example, remove the fluid structure from the integrated bioprocessing system while the tube is still closed.

[0046] All explanations given with respect to any other teaching can apply, and vice versa.

[0047] A method for performing a bioprocess on a cell culture is proposed according to the equally important ninth teaching, wherein the bioprocess is performed on an integrated bioprocessing system, wherein while the bioprocess is being performed, the integrated bioprocessing system conveys, via a tube, a culture medium, in particular a cell culture, used in the bioprocess, wherein the integrated bioprocessing system includes a tube connection system for connecting the tubes of the integrated bioprocessing system by welding as needed, wherein a first tube, a first tube holder, and a first fluid structure for receiving and / or providing the culture medium are part of the integrated bioprocessing system, wherein the first tube is held by the first tube holder and fluidly connected to the first fluid structure, wherein the first tube holder extrudes the first tube into the tube connection system, in particular before any interaction between the first tube and the tube connection system, wherein at a welding location during a welding procedure, the tube connection system connects the first tube and a second tube, thereby forming a tube connection, and wherein the integrated bioprocessing system conveys the culture medium from the first fluid structure or conveys the culture medium to the first fluid structure via the tube connection after welding. This is another way to operate the tubes by means other than the tube connection system to reduce the complexity of the tube connection system.

[0048] All explanations given with respect to any other teaching can apply, and vice versa.

[0049] According to the equally important tenth teaching, a method for performing a biological treatment on a cell culture is proposed, wherein the biological treatment is performed on an integrated biological treatment system, wherein during the performance of the biological treatment, the integrated biological treatment system conveys a culture medium, in particular a cell culture, used in the biological treatment through a tube, wherein the integrated biological treatment system includes a tube connection system for connecting the tubes of the integrated biological treatment system by welding as needed, wherein a first tube, a first tube holder, and a first fluid structure for receiving and / or providing the culture medium are part of the integrated biological treatment system, wherein the first tube is held by the first tube holder and fluidly connected to the first fluid structure, wherein before any interaction between the first tube and the tube connection system, the first tube holder holds the first tube at a predetermined angle and angular range defined relative to the following parts: the integrated biological treatment system itself and / or the tube connection system and / or a second tube, wherein at the welding position during the welding procedure, the tube connection system connects the first tube and the second tube, thereby forming a tube connection, wherein the integrated biological treatment system conveys the culture medium from the first fluid structure of the first carrier or conveys the culture medium to the first fluid structure through the tube connection after welding. If an angle or an angular range is defined and thus the direction of the tube is at least partly defined, the tube connection system can more easily interact with the tube. It is even possible that the tube connection system cannot be rotated perpendicular to the ground or cannot be rotated at all, such that a predetermined orientation of the tube is necessary. For example, moving the tube connection system to a plurality of predetermined welding positions in the Cartesian direction without rotating the tube connection system greatly simplifies the control of the tube connection system.

[0050] All explanations given with respect to any other teaching are applicable, and vice versa.

[0051] The eleventh teaching relates to a method for welding a tube, in particular a sealed tube, at least partly along the extension of the tube, in particular in an integrated biological treatment system.

[0052] All explanations given with respect to any other teaching are applicable, and vice versa.

[0053] All features described herein can be incorporated into further teachings, and all features of all teachings can be combined. Any device, component, method step, etc. described is a preferred embodiment of any combination. In particular, the carrier is not a necessary feature in all embodiments of the present invention. Also preferred are other ways of improving the operation of the tube and tube welding as described herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Hereinafter, embodiments of the present invention will be explained with reference to the drawings. In the drawings:

[0055] Figure 1 is a schematic view of the provided integrated biological treatment system with an enlarged view of the tube connection.

[0056] Figure 2 a) to Figure 2 e) are top views of the welding procedure,

[0057] Figure 3 a) to Figure 3 d) are according to Figure 2 a) to Figure 2 e) are schematic views of the tube connection system provided in the welding procedure,

[0058] Figure 4 a) to Figure 4 d) are top views of the disconnection procedure,

[0059] Figure 5 is a top view of an embodiment of the provided tube holder, wherein the enlarged view of the tube holder is a cross-sectional view, and a first guiding device and a second guiding device are arranged at the tube holder,

[0060] Figure 6 is another embodiment of the provided tube connection system,

[0061] Figure 7 is a schematic view of the integrity test procedure,

[0062] Figure 8 a) and Figure 8 b) are schematic views of the provided tube disconnection device during the disconnection procedure, particularly during the sealing phase,

[0063] Figure 9 is an embodiment of the provided tube connection system, which has first and second guiding devices as part of the tube connection head. Detailed Description

[0064] A method for performing a bioprocess on a cell culture is provided. The bioprocesses performed can be the same, but particularly can be different and / or unique bioprocesses. However, each bioprocess can include at least one unit operation (i.e., basic step) that is performed to achieve a certain physical or chemical effect. The cell cultures on which the bioprocesses are performed can be of the same or different types. Preferably, the bioprocesses can be performed at least partially simultaneously.

[0065] Preferably here, the cell culture is a liquid immune cell culture or a primary cell culture.

[0066] The term "liquid immune cell culture" should be understood in a broad sense and refers to a culture of at least one type of immune cells contained as particles suspended in any type of liquid. As will be explained below, a liquid immune cell culture may contain other cell types that are not immune cells. Thus, the term "liquid immune cell culture" refers to a liquid immune cell culture at any stage during a biological process. Thus, during the application of a biological process, as certain immune cells are enriched or depleted from the liquid immune cell culture and / or the immune cells are genetically modified, the types and proportions of the immune cells present in the liquid immune cell culture will change.

[0067] The term "immune cell" generally refers to different types of white blood cells. Thus, the term "immune cell" includes a variety of cells, such as but not limited to dendritic cells, T lymphocytes (also known as T cells), B lymphocytes, natural killer cells, macrophages, etc. Immune cells may also include subtypes of immune cells, such as tumor infiltrating lymphocytes or different types of T cells. Subtypes of certain types of immune cells can be classified based on the type of antigen present on the cell surface. Thus, the term immune cell can refer, for example, to a T cell containing the surface antigen CD4 ("CD4+ T cell"). Generally, a certain type of immune cell (such as a T cell), preferably a certain subtype of immune cell (such as a CD4+ T cell), will be selectively enriched by a biological process, while other immune cells (such as macrophages) and / or other cell types that are not immune cells (such as red blood cells) and / or other subtypes of immune cells (such as CD8+ T cells) will be depleted from the liquid immune cell culture. The immune cells to be enriched are referred to as target immune cells, and all other components depleted from the liquid immune cell culture are referred to as "impurities". In addition, as described above, the target immune cells can be genetically modified.

[0068] The term "primary cell" refers to a cell that can still differentiate into different target cell types. In particular, stem cells and their derivatives are primary cells before they are fully differentiated into a specific cell type. The term also includes primary immune cells.

[0069] The term "liquid" should also be understood in a broad sense and refers to any liquid and / or particulate-containing liquid that is processed within an integrated biological processing system. Thus, the term liquid can refer to a culture medium, waste, liquid immune cell culture, by-products obtained during a biological process, samples, and / or an initial immune cell culture.

[0070] In Figure 1 an exemplary preferred embodiment of the proposed integrated biological processing system 1 is shown. The provided method can be performed using the proposed integrated biological processing system 1 that is respectively applicable.

[0071] The term "integrated bioprocessing system" refers to a system capable of performing several bioprocesses, where the bioprocesses are preferably performed at least partly simultaneously. The integrated bioprocessing system 1 can be provided with a central electronic process control device to control the execution of all bioprocesses. The integrated bioprocessing system 1 can also be provided with shared infrastructure elements, such as conveying elements, medium supply units, supply units for consumables, and / or dedicated unit operation stations 1a for performing at least one unit operation, several unit operations, or all unit operations of each bioprocess.

[0072] When performing bioprocesses, especially when performing one or more operations on a cell culture, the integrated bioprocessing system 1 conveys one or more media used in the bioprocess via tubes 4, 5. The medium can in particular be the cell culture on which the corresponding bioprocess is to be performed.

[0073] Thus, within the integrated bioprocessing system 1, a number of tube connections 3 can be provided for conveying the medium (especially the cell culture) within the integrated bioprocessing system 1. For example, the medium can be received and conveyed by a container 1b, which can be moved from or to different unit operation stations 1a. At the unit operation station 1a, one or more unit operations can be performed. The unit operations themselves can be performed by using a cartridge 1d, which is individually adapted according to the unit operation to be performed. In order to convey the corresponding medium from one of the containers 1b to one of the cartridges 1d, or from one of the cartridges 1d to one of the containers 1b, the container and the cartridge should be fluidly connected. This connection can be provided by connectable tubes 4, 5 of the container 1b and the cartridge 1d. However, within the integrated bioprocessing system 1, there can be a number of other tube connections 3 for fluidly connecting components, such that all kinds of media, especially fluids, such as liquids, for example liquid cell cultures, reagents, culture media, buffers, mixtures thereof, etc., can be conveyed.

[0074] Currently, the connection of components (especially via tubes) is usually carried out manually, which poses a risk of contamination and a risk of incorrect connection due to the mixing of tubes, or the connection is usually pre-configured, which limits the flexibility of known systems.

[0075] It is proposed that the integrated bioprocessing system 1 includes a tube connection system 2 for connecting (especially aseptically connecting) the tubes of the integrated bioprocessing system 1 by welding as needed. Thus, for example, if a separate unit operation is to be performed, welding is carried out as needed. The tubes to be connected can have a circular cross-section.

[0076] The integrated bioprocessing system 1 includes a first tube 4, a first tube holder 7, and a first fluid structure 12 for receiving and / or providing a culture medium via the first tube 4. The first tube 4 is held in a defined position by the first tube holder 7 and is in fluid connection with the first fluid structure 12 such that fluid (in particular, the culture medium) can be guided through the first tube 4 to and from the first fluid structure 12. The first fluid structure 12 can contain a culture medium (in particular, a cell culture) and / or can perform unit operations on the culture medium (in particular, a cell culture).

[0077] The term "fluid structure" includes all types of fluid structures capable of receiving and / or providing a culture medium (in particular, a cell culture). The fluid structure can be designed as a reservoir in which the culture medium can be stored, or as an operating structure in which unit operations can be performed.

[0078] The first tube 4, the first tube holder 7, and the first fluid structure 12 are carried by a movable first carrier 10. The first carrier 10 can be designed as a receptacle, where in particular the first fluid structure is part of the receptacle, or can be designed as a carrier on which the first tube 4, the first tube holder 7, and the first fluid structure 12 are arranged (in particular, attached), as exemplarily depicted in Figure 1 The first tube 4 is carried integrally by the first carrier 10 in particular. The first carrier 10 can enable the first tube 4 to be transported to a welding position independently of the tube cutting unit 9 and / or the tube connector 43.

[0079] In particular, due to the first carrier 10, the transport within the integrated bioprocessing system 1 is simplified. The first carrier 10 and the first tube 4, the first tube holder 7, and the first fluid structure 12 carried thereby are transported to a welding position within the integrated bioprocessing system 1. Welding is performed at this welding position. The integrated bioprocessing system 1 can include a number of welding positions at which welding can be performed by the tube connection system 2. The transport of the first carrier 10 together with the first tube 4, the first tube holder 7, and the first fluid structure 12 can be automatically performed by the integrated bioprocessing system 1, specifically by a robotic mechanism 52 or preferably by a transfer mechanism 53.

[0080] At the welding position, in a welding procedure, the tube connection system 2 connects the first tube 4 and the second tube 5 such that a tube connection 3 (in particular, a sterile tube connection) is formed by welding. The second tube 5 can be part of a device for performing unit operations, which device includes a second fluid structure 13 and an optional second tube holder 8. Alternatively, the second tube 5 can be carried by a second carrier 11. As Figure 1 exemplarily depicted in, the second carrier 11 can also carry the second tube holder 8 and the second fluid structure 13 in addition to the second tube 5.

[0081] After welding, the integrated bioprocessing system 1 conveys the culture medium from the first fluid structure 12 of the first carrier 10 or conveys the culture medium into the first fluid structure 12 through the tube connection 3. In this way, the previously unconnected tubes 4, 5 (in particular the unconnected fluid structures 12, 13) can be connected particularly automatically while keeping them sterile.

[0082] The tube connection 3 is used to perform bioprocessing. Preferably, several tube connections 3 are used to perform the corresponding bioprocessing. More preferably, as will be described below, different unit operations of the corresponding bioprocessing are performed, and the tube connection 3 is formed and / or disconnected between the unit operations. Exemplarily, a unit operation can be performed, then the tube connection 3 can be formed, particularly to convey the cell culture to the location for the next unit operation, then the culture medium (in particular the cell culture) can be conveyed through the tube connection 3, the tube connection 3 can be disconnected, and then another unit operation can be performed, particularly a unit operation on the cell culture, for example through the fluid structure 13 connected to one of the tubes 4, 5. Between two unit operations, the tubes 4, 5 can be transported within the integrated bioprocessing system 1, particularly by moving the corresponding carriers 10, 11.

[0083] As Figure 1 exemplarily shown, and preferably, the first tube 4 and the second tube 5 are connectable to form the tube connection 3. The tube connection 3 fluidly connects components of the integrated bioprocessing system 1, such as the first fluid structure 12 and the second fluid structure 13. Via the tube connection 3, the culture medium (in particular a fluid, such as a liquid, preferably a cell culture) can be conveyed.

[0084] In the preferably exemplary embodiment shown, the first carrier 10, the first tube 4, the first tube holder 7 and the first fluid structure 12 are part of the container 1b. In the container 1b, particularly in the first fluid structure 12, the culture medium and other fluids can be transported within the integrated bioprocessing system 1. Here and preferably, the second carrier 11, the second tube 5, the second tube holder 8 and the second fluid structure 13 are part of the cartridge 1d. In the cartridge 1d, particularly in the second fluid structure 13, unit operations can be performed on the culture medium (in particular the cell culture). Here and preferably, the first tube 4 and the second tube 5 are designed as flexible tubes. Further preferably, the first tube 4 and the second tube 5 are designed equally, particularly with respect to the tube diameter, the tube wall thickness and / or the tube material and / or the circular cross-section.

[0085] However, the term "tube" in the context of the present application must be understood in a broad sense. Thus, "tube" includes flexible tubes as well as rigid tubes (such as pipelines), but also includes tube elements of different designs (such as tube connectors, etc.) through which fluids can be conveyed. Generally, a tube can be any medium-conducting element, preferably an elongated and more preferably a cylindrical element. Preferably, the tube is made of a plastic material, preferably a thermoplastic material, and more preferably a thermoplastic elastomer.

[0086] It should generally be noted that in the context of the present application, the combination of the term "second" with the corresponding components of the integrated bioprocessing system 1 (such as "second tube 5", etc.) or the tube connection system 2 does not necessarily have to be understood as the embodiment including at least two of the corresponding components. In addition, the term "second" is chosen for reasons of distinction, for example, to distinguish the first tube 4 from the second tube 5. For this purpose, the integrated bioprocessing system 1 may include a second component, but not the corresponding first component. The same applies to the term "third".

[0087] Advantageously, the welding procedure is at least partially automatically performed by the tube connection system 2. The automatically performed welding procedure or the phases of the automatically performed welding procedure may or may not require manual input, action, or interaction from the user. Thus, the risk of contamination can be reduced and the entire bioprocess can be further automated. Preferably, the welding procedure is performed completely automatically.

[0088] The welding procedure may include different phases, namely a placement phase, a trimming phase, and / or a welding phase. Figure 2 a) to Figure 2 e) are exemplarily shown in detail for the welding procedure. The different phases may be performed simultaneously, preferably at least partially simultaneously and / or sequentially. Particularly preferably, the welding phase is directly performed after the trimming phase.

[0089] In a preferred embodiment, the welding procedure includes a placement phase. During the placement phase, the first tube 4 and the second tube 5 are arranged relative to each other at the welding position. Generally, the relative arrangement of the first tube 4 and the second tube 5 can be performed by the direct or indirect movement of at least one of the tubes 4, 5. The direct movement can be performed by the pushing or retracting of the corresponding tube. The indirect movement can be performed by the movement of the corresponding tube holders 7, 8 or by the movement of the first carrier 10 and / or the second carrier 11 together with the corresponding tubes 4, 5. Here and preferably, the first tube 4 and / or the second tube 5 are particularly only moved in the axial direction of the first tube 4 and / or the second tube 5.

[0090] As Figure 2As exemplarily shown in a), preferably, during the arrangement phase, the first tube 4 is particularly automatically moved in its axial direction (preferably pushed out or retracted), and / or the second tube 5 is particularly automatically moved in its axial direction (preferably pushed out or retracted). The axial directions of the first tube 4 and the second tube 5 are preferably opposite to each other, especially when the first tube 4 is in the first cutting position and the second tube 5 is in the second cutting position. In Figure 2 a), the tubes 4, 5 are moved in the x dimension, where the first tube 4 is moved in a direction opposite to the direction of movement of the second tube 5. Preferably, and as Figure 2 shown in a), during the arrangement phase, the first tube 4 is held by the first tube holder 7, and the second tube 5 is held by the second tube holder 8.

[0091] Furthermore, it is possible that the first tube 4 is moved in the transverse direction of its axis (especially in the orthogonal direction), and / or the second tube 5 is moved in the transverse direction of its axis (especially in the orthogonal direction). In Figure 2 a), the orthogonal direction of the axes of the first tube 4 and the second tube 5 is within the y dimension.

[0092] The arrangement phase can be performed at least in part by the tube arrangement unit 6, which particularly includes the first tube holder 7 and / or the second tube holder 8. The movement of the first tube 4 and / or the second tube 5 can be performed directly, i.e., by directly moving the corresponding tube, for example, by pushing out and / or retracting the corresponding tubes 4, 5 by the tube moving devices 27, 28, and / or indirectly, i.e., by moving the corresponding tube holders 7, 8 (e.g., by the holder moving devices 21, 22), such that the corresponding tubes 4, 5 move along the axial direction and / or the transverse direction of the corresponding tubes 4, 5 together with the tube holders. Before the first tube 4 and / or the second tube 5 are moved in the axial direction by the tube moving devices 27, 28, the first tube 4 and / or the second tube 5 can be moved transversely by the corresponding tube holders 7, 8. Thus, the corresponding tubes 4, 5 can be roughly positioned.

[0093] During the arrangement phase, the first tube 4 and / or the second tube 5 can be moved to the first cutting position and / or the second cutting position, respectively. In Figure 2 b), the first tube 4 and the second tube 5 are in their respective cutting positions. Preferably, if the first tube 4 is in the first cutting position and the second tube 5 is in the second cutting position, the first tube 4 and the second tube 5 are arranged adjacent to each other, especially parallel. Preferably, if the tubes 4, 5 are in the corresponding cutting positions, the first tube 4 and the second tube 5 at least partially overlap each other. The first tube 4 and the second tube 5 can be arranged side by side in the corresponding cutting positions.

[0094] Preferably, the reaching of the respective cutting position is verified by a sensor. Exemplarily, the tube connection system 2 may include one or more sensors that sense the position of the tubes 4, 5, especially in the case where the tubes 4, 5 are in their respective cutting positions. The one or more sensors may indicate whether the pushing or retracting of the tubes 4, 5 has successfully started. Suitable sensors (such as optoelectronic sensors) are well known in the art.

[0095] Furthermore, it is preferred that the method includes temporarily closing the first tube 4 and / or the second tube 5 before performing the welding procedure. The first tube 4 and / or the second tube 5 may be temporarily closed by one or more closing elements 60 (such as clamps, etc.). Preferably, one tube closing element 60 is mounted at either of the tubes 4, 5. Preferably, the tube closing elements 60 are mounted such that the tube connection 3 is formed between the tube closing elements 60. In this case, preferably, each tube closing element 60 is mounted between the tube connection 3 and the respective tube holders 7, 8.

[0096] The tube closing elements 60 for closing the first tube 4 and / or the second tube 5 may be provided by the first tube holder 7 and / or the second tube holder 8 respectively. Preferably, the first tube holder 7 and / or the second tube holder 8 may respectively include the closing elements 60. Alternatively, one or more closing elements 60 may be designed separately, for example, designed as separate clamps, etc., and may be installed during the welding procedure, for example, by a robotic mechanism 52, preferably after the tubes 4, 5 are in their respective cutting positions.

[0097] Preferably, after performing the welding procedure, an integrity test procedure is performed to verify the integrity of the tube connection 3. This verification check enables determination of whether the tube connection 3 formed by welding is intact or unsafe. Intact means that the inside of the tube is kept isolated from the external atmosphere, thus maintaining the sterility of the liquid inside the tube. Unsafe means that the tubes are not properly connected, especially the inside of the tube is not completely sealed against the external atmosphere. If the seal is not complete, potential contaminants may enter the tube from the external atmosphere, which will compromise the sterility of the liquid to be conveyed to the tube. Preferably, after the welding procedure, preferably after the integrity test procedure is performed and the integrity of the tube connection 3 is detected, the temporary closure is released. If the welding fails, the temporary closure maintains the sterility of the closed sections of the tubes 4, 5. In this case, a disconnection procedure can be performed, as described in more detail below. Here and preferably, the sealing phase of the disconnection procedure is performed before removing the closing element 60. In this case, preferably, the first tube 4 and / or the second tube 5 is sealed between the first tube holder 7 and the respective closing element 60 and / or between the second tube holder 8 and the respective closing element 60. In this way, the sterility of the tubes 4, 5 can be ensured.

[0098] The integrity test procedure can be performed by the welding verification device 49, which will be explained in detail below.

[0099] Preferably, based on the results of the integrity test procedure, if the integrity of the tube connection is verified, the temporary closure of the first tube and / or the second tube is released. At this time, the culture medium can then be transferred from the first tube to the second tube or from the second tube to the first tube via the tube connection 3. However, if the integrity of the tube connection 3 is not verified, an emergency procedure for preserving the cell culture is initiated. In the emergency procedure, the temporary closure is not released, so that contamination of the cell culture via the unsafe tube connection 3 can be prevented. Therefore, the sterility of the tubes can be ensured, and thus the sterility of the liquid inside the tubes and the liquids connected to the tubes can be ensured. The emergency procedure can include reporting a notification to the user and / or initiating a disconnection procedure and / or initiating a disconnection procedure for subsequently performing another welding procedure. It is particularly possible that the parts of the first tube 4 and / or the second tube 5 that are potentially exposed to the external environment are kept closed by one or more closing elements 60, for example by clamping. In addition, it is possible that the parts of the first tube 4 and / or the second tube 5 that are potentially exposed to the external environment are sealed and particularly cut off, for example by performing a disconnection procedure. After sealing the tubes 4, 5 in the disconnection procedure (which will be described in detail below), one or more closing elements 60 can be removed. After performing the disconnection procedure, another welding procedure can be performed.

[0100] Alternatively or additionally, the welding procedure includes a trimming phase. During the trimming phase, the first tube 4 and the second tube 5 are cut at the welding position. Preferably, the trimming phase is after the arrangement phase, so that the tubes 4, 5 are cut at their cutting positions. Preferably, the tubes 4, 5 are cut by using a high-temperature cutting process. The trimming phase can be at least partially performed by the tube cutting unit 9, which particularly includes a blade 9a, a blade holder 9b, and / or a blade heater 9c.

[0101] Preferably, the tube connection system 2 includes a tube cutting unit 9, where the tube cutting unit 9 includes a blade 9a and preferably includes a blade heater 9c.

[0102] In the case of the trimming phase, preferably, the trimming phase includes a heating step, during which the blade heater 9c heats the blade 9a to the cutting temperature. This high-temperature cutting process provides decontamination during the welding procedure, where high temperature means higher than 150 °C, preferably higher than 250 °C, and further preferably higher than 350 °C. In addition, the cutting of the tubes 4, 5 can be simplified because the tubes 4, 5, which are preferably plastic tubes, are melted by the heated blade 9a during cutting.

[0103] Here and preferably, the trimming stage comprises an alignment step, in which the tube cutting unit 9 is aligned relative to the first tube 4 and / or the second tube 5. The alignment of the tube cutting unit 9 relative to the first tube 4 and / or the second tube 5 can be achieved such that the tube cutting unit 9 is moved and / or such that the first tube 4 and / or the second tube 5 is moved. Preferably, when the alignment step is performed, the first tube 4 is in the first cutting position and / or the second tube 5 is in the second cutting position. Here, the tube cutting unit 9 can be moved for the alignment. Preferably, the alignment step is after the heating step, or the heating step is after the alignment step, or the alignment step is performed at least partially simultaneously with the heating step, or the heating step is performed at least partially simultaneously with the alignment step.

[0104] exist Figure 2 b), the heating step and the alignment step of the trimming stage are exemplarily shown in a preferred embodiment. The first tube 4 and the second tube 5 are in the first cutting position or the second cutting position, respectively. The tubes 4, 5 are held by tube holders 7, 8. See Figure 2 b) with Figure 2 a), the tube cutting unit 9 is aligned relative to the tubes 4, 5, wherein the tube cutting unit 9 itself is moved during the alignment step. The tube cutting unit 9 is aligned such that the blade 9a is oriented transversely, in particular orthogonally, relative to the first tube 4 and / or the second tube 5. During the heating step, the blade 9a is heated by a blade heater 9c of the tube cutting unit 9. Figure 3 Another example of an alignment step is shown in a), where Figure 3 The tube cutting unit 9 is moved relative to the tubes 4 , 5 , as exemplarily indicated by the arrows in a). Figure 3 b) exemplarily shows a heating step, wherein the blade 9a is heated by a blade heater 9c.

[0105] Further preferably, in the case of a trimming phase, the trimming phase comprises a cutting step, wherein the first tube 4 (in particular in the first cutting position) and / or the second tube 5 (in particular in the second cutting position) is cut by the tube cutting unit 9 (in particular by the blade 9a). During the cutting step, the tubes 4, 5 are cut. Preferably, the first tube 4 and the second tube 5 are cut at least partially, preferably completely, simultaneously. Preferably, the cutting step follows the heating step and / or the alignment step. Further preferably, during the cutting step, the blade 9a is heated to a certain temperature by the blade heater 9c. The tubes 4, 5 may be at least partially melted during the cutting step. During the trimming phase, the first tube 4 and / or the second tube 5 may be extruded in the extrusion direction, and the cutting may be performed in the transverse direction (in particular orthogonal to the extrusion direction). In this way, the cutting may be optimized and simplified. Since the tubes 4, 5 are extruded, the cross section of the respective tube 4, 5 temporarily comprises a short side and a long side, whereby the cutting may be simplified by cutting along the long side.

[0106] In Figure 2 c), the cutting step of the trimming phase is exemplarily shown in a preferred embodiment. The heated blade 9a cuts the first tube 4 and the second tube 5 at least partially simultaneously. During the cutting step, the first tube 4 and the second tube 5 are typically open on one side, but the blade 9a blocks the openings of the tubes 4, 5 towards the surrounding atmosphere. As a result, contamination can be prevented, in particular due to the temperature of the blade 9a. Another example of the cutting step is shown in Figure 3 c), where the blade 9a cuts through the tubes 4, 5. As can be seen and preferably, the tube cutting unit 9 includes a cutting table 9d facing the blade 9a. The cutting table 9d can support the cutting process of the blade 9a.

[0107] In addition to or as an alternative to the trimming phase, the welding procedure includes a welding phase. During the welding phase, the first tube 4 and the second tube 5 come into contact and fuse together at the welding position, thereby forming the tube connection 3. The welding phase preferably occurs after the arrangement phase and / or the trimming phase. In particular, the welding phase directly follows the trimming phase, such that after the first tube 4 and the second tube 5 are cut within the trimming phase, the first tube 4 and the second tube 5 come into contact and fuse together within the welding phase. The welding phase is specifically partially performed by the tube arrangement unit 6 and the tube cutting unit 9. The contact and fusion of the tubes 4, 5 are preferably performed by the first tube holder 7 and / or the second tube holder 8, and the first tube holder 7 and / or the second tube holder 8, for example, squeeze the first tube 4 and / or the second tube 5 so that they come into contact. The welding phase is exemplarily shown in Figure 2 c), Figure 2 d) and Figure 2 e).

[0108] In the case of the welding phase, advantageously, the welding phase includes a contact step. Preferably, during the contact step, the first tube 4 and the second tube 5 are axially aligned. The axial alignment of the tubes 4, 5 can be carried out along the tube cutting unit 9, particularly along the blade 9a. Here, the openings of the cut tubes 4, 5 can be covered by the blade 9a. Preferably, the first tube 4 and the second tube 5 are axially aligned respectively by the movement of the first tube holder 7 and / or the second tube holder 8, particularly by the movement of the first tube holder moving device 21 and / or the second tube holder moving device 22. The first tube holder 7 and / or the second tube holder 8 can move independently of the tube connector 43 and the tube cutting unit 9.

[0109] Alternatively or additionally, during the contacting step, the tube cutting unit 9 is moved at least partially (in particular laterally, preferably orthogonally) towards the tubes 4, 5 so that the first tube 4 and the second tube 5 can come into contact. Preferably, the blade 9a is moved in particular laterally (preferably orthogonally) towards the tubes 4, 5 so that the first tube 4 and the second tube 5 can come into contact. Preferably, this movement of the tube cutting unit 9 is carried out after the axial alignment of the tubes 4, 5. Additionally or alternatively, during the contacting step, the first tube 4 and the second tube 5 come into contact, in particular by axially moving the first tube 4 and / or the second tube 5 preferably by means of the first tube moving device 27 and / or the second tube moving device 28. This can be carried out after the axial alignment of the tubes 4, 5 and / or after the movement of the tube cutting unit 9. Preferably, the axial movement of the first tube 4 is effected by moving the first tube holder 7 and / or the movement of the second tube 5 is effected by moving the second tube holder 8. Alternatively and equally preferably, the axial movement of the first tube 4 is effected by the first tube holder 7 such that the first tube 4 is pushed out and / or retracted, and / or the axial movement of the second tube 5 is effected by the second tube holder 8 such that the second tube 5 is pushed out and / or retracted. During the contacting step, the first tube 4 and the second tube 5 come into contact and fuse together, in particular because the tubes 4, 5 are heated by the heating blade 9a during the trimming phase. During the contacting step, a tube connection 3 is formed, in particular a sterile one.

[0110] In Figure 2 c), Figure 2 d) and Figure 2 e), the welding phase is depicted by way of example. See Figure 2 Compared with Figure 2 d), here and preferably, the first tube 4 and the second tube 5 are axially aligned by a particular horizontal movement of the first tube holder 7 and / or the second tube holder 8. The movement of the first tube holder 7 and / or the second tube holder 8 can be carried out transversely (in particular orthogonally) to the axis of the first tube 4 and / or the second tube 5. During the axial alignment, the blade 9a remains in place such that the first tube 4 and / or the second tube 5 move along the blade 9a and in particular come into contact with the blade 9a during this movement. In particular, after the axial alignment, the blade 9a is moved relative to the tubes 4, 5 (in particular laterally, in particular orthogonally) so that the tubes 4, 5 can be contacted. In Figure 2 d), the blade moves upwards in the vertical direction. In Figure 2 e), the first tube 4 and the second tube 5 are brought into contact and fused together by an axial movement of at least one of the tubes 4, 5. Thus, the tube connection 3 is formed. In Figure 3 c) and Figure 3 d), the welding phase is further depicted by way of example.

[0111] The pipe connection part 3 can be opened after welding is performed. The pipe connection part 3 can be opened by an external force applied at the pipe connection part 3 on the outer surfaces of the first pipe 4 and the second pipe 5. This external force can be applied by the pipe cutting unit 9 or the pipe welding head 43 or another robot, etc. The external force can be applied perpendicular to the axes of the pipes 4, 5. Alternatively, the pipe connection part 3 can be opened by applying an internal pressure to the pipes 4, 5. This can be achieved by the pumping device 54.

[0112] Furthermore, it is preferred that the method includes temporarily closing the first pipe 4 and / or the second pipe 5 before performing the welding procedure or before performing the welding phase. The first pipe 4 and / or the second pipe 5 can be closed by a fixture, especially a fixture designed independently of the pipe connection head 43, etc. Preferably, as Figure 7 exemplarily shown, after performing the welding procedure or after performing the welding phase, an integrity test procedure for verifying the integrity of the pipe connection part is performed. This verification check enables determination of whether the pipe connection part 3 formed by welding is intact or unsafe. According to the result of the integrity test procedure, if the integrity of the pipe connection part is verified, the temporary closing of the first pipe 4 and / or the second pipe 5 is released. Then, the culture medium can be conveyed through the pipe connection part 3. However, if the integrity of the pipe connection part 3 is not verified, an emergency procedure for preserving the cell culture is initiated. Here, the temporary closing is not released, so that contamination of the cell culture via the unsafe pipe connection part 3 can be prevented. The emergency procedure can include reporting a notification to the user and / or initiating a disconnection procedure and / or initiating another welding procedure.

[0113] Furthermore, preferably, the pipe connection system 2 includes a pipe disconnection device 14. The pipe disconnection device 14 preferably includes a sealing unit 15 and / or a disconnection unit 17.

[0114] In another preferred embodiment, the method includes a disconnection procedure in which the first pipe 4 and the second pipe 5 are disconnected. By the disconnection procedure, the pipes 4, 5 can be disconnected fluidly and / or physically. "Disconnected fluidly" means that fluid cannot be conveyed through the pipes 4, 5 because, for example, the pipes 4, 5 are sealed. "Disconnected physically" means that the pipes 4, 5 are completely disconnected and can be manipulated independently of each other, such as moved. The disconnection procedure can be performed by the pipe disconnection device 14 of the pipe connection system 2.

[0115] Preferably, the disconnection procedure includes a sealing phase in which, in particular, the currently connected first pipe 4 and / or the second pipe 5 is sealed, thereby forming a first seal 56 and / or a second seal 57. This is shown in Figure 4is exemplarily depicted. Preferably, during the sealing phase, the first tube 4 and / or the second tube 5 are sealed by compression and heating. Here, the first tube 4 and / or the second tube 5 are compressed, in particular transversely to the respective tube axis, and heated such that the first tube 4 and / or the second tube 5 are partially melted and sealed, in particular self-sealed. The sealing phase can be carried out by the tube disconnecting device 14, in particular by the sealing unit 15 of the tube disconnecting device 14. The sealing unit 15 can include a sealing surface 16 for compression and heating. The sealing unit 15 can be designed independently of the tube cutting unit 9. The sealing surface 16 can be designed independently of the disconnecting blade 18.

[0116] Advantageously, the disconnecting procedure includes a disconnecting phase in which the first tube 4 and / or the second tube 5 are cut, in particular between the first seal 56 and the second seal 57. The first tube 4 or the second tube 5 can also be cut within the respective seal 56, 57 itself. Thus, the tubes 4, 5 are physically disconnected. The disconnecting phase can be carried out by the tube disconnecting device 14, in particular by the disconnecting unit 17 of the tube disconnecting device 14.

[0117] Figure 4 a), Figure 4 b), Figure 4 c) and Figure 4 d) exemplarily show the disconnecting procedure. As Figure 4 exemplarily depicted in a), here and preferably, the first tube 4 and the second tube 5 are first physically and fluidly connected. Preferably, for example, as Figure 4 shown in b), during the disconnecting procedure, the first tube 4 and the second tube 5 are at least partially simultaneously sealed by the sealing unit 15 of the tube disconnecting device. However, the sealing can also be carried out sequentially, i.e., one after the other. As Figure 4 exemplarily shown in c), the sealing unit 15 includes two sealing surfaces 16 which compress the tubes 4, 5 and are heated such that the tubes 4, 5 achieve self-sealing. As a result, a first seal 56 and a second seal 57 are produced. As Figure 4 exemplarily shown in c), after sealing the tubes 4, 5 in the sealing phase, in the disconnecting phase, the tubes 4, 5 are cut by the disconnecting unit 17, in particular by the disconnecting blade 18. Preferably, the disconnecting blade 18 is heated to simplify the cutting. Here and preferably, the sealing phase is carried out before the disconnecting phase. Alternatively, for example, if the disconnecting blade 18 cuts the tubes 4, 5 and temporarily seals the resulting openings, the sealing phase can also be carried out after the disconnecting phase. Here and preferably, the disconnecting blade 18 cuts the first tube 4 and the second tube 5 in a cutting plane which is perpendicular to the axis of the tubes 4, 5. This cutting plane can be oriented transversely to the sealing surface 16 and / or the first seal 56 and / or the second seal 57.

[0118] Preferably, the method further includes connecting, via the pipe connection system 2, the first pipe 4 or the second pipe 5 of the integrated bioprocessing system 1 to the third pipe 19, thereby forming another pipe connection portion 20, wherein the another pipe connection portion 20 is formed during a welding procedure. The welding procedure can be performed as described previously in the case of the pipe connection portion 3 of the first pipe 4 and the second pipe 5. In particular, the same pipe connection system 2 is used to connect the first pipe 4 or the second pipe 5 to the third pipe 19. The first pipe 4 or the second pipe 5 can be welded to different pipes 4, 5, 19 multiple times during the welding procedure. This is an advantage of using the welding system because if there is sufficient pipe length, the pipes 4, 5, 19 can be easily cut and welded multiple times.

[0119] The third pipe 19 can be carried by a third carrier. The third carrier can carry a third pipe holder and a third fluid structure. The third carrier, the third pipe 19, the third pipe holder, and the third fluid structure can be part of the container 1b or the cartridge 1d.

[0120] The different pipes 4, 5, 19 can come from different cartridges 1d and / or different containers 1b. Thus, it is possible that the cartridges 1d can be connected to different containers 1b, particularly one after another. In addition, the containers 1b can be connected to (preferably one after another) different cartridges 1d. Further, the cartridge 1d can also include multiple pipes 4, 5, 19 that are connected to the pipes 4, 19 of the container 1b or the pipes 4, 5, 19 of multiple containers 1b. Here, the cartridge 1d can be connected to the container 1b via multiple pipe connection portions 3, 20, or can be connected to multiple containers 1b via multiple pipe connection portions 3, 20.

[0121] For example, the cartridge 1d includes pipes 4, 5, 19 that are connected to the pipes 4, 5, 19 of the container 1b, thereby forming pipe connection portions 3, 20. The culture medium or multiple culture media can be conveyed via the pipe connection portions 3, 20, and unit operations can be performed on the cartridge 1d. Thereafter, the pipes 4, 5, 19 can be disconnected, particularly by performing a disconnection procedure. Then, the cartridge 1d and / or the container 1b can be transported to another location of the integrated bioprocessing system 1, particularly another welding location. Then, by connecting the pipes 4, 5, 19 of the cartridge to another pipe 4, 5, 19 of the container 1b or to another pipe 4, 5, 19 of another container 1b, particularly by performing a welding procedure, another pipe connection portion 3, 20 can be formed.

[0122] First, use the first set of tube holders 7, 8 to connect the first container 1b containing the liquid immune cell culture to the cartridge 1d, and connect the tubes 4, 19 of the first container 1b to the tubes 5, 19 of the cartridge 1d. The first container 1b may include a first fluid structure 12 that initially contains a culture medium, particularly a cell culture. The cartridge 1d (particularly the fluid structure 13 of the cartridge) may receive the culture medium from the first container 1b. Then, it is possible that, for example, in order to perform countercurrent centrifugation in the fluid structure 13 of the cartridge 1d, the tubes 4, 19 of the second container 1b having another fluid structure including a buffer may be connected to the cartridge 1d using the second tubes 5, 19 located in different holders 8 of the cartridge 1d.

[0123] Alternatively, when the tube connections 3, 20 between the first container 1b and the cartridge 1d are subsequently disconnected, the tubes 4, 19 of the second container 1b may be connected to the first tubes 5, 19 of the cartridge 1d. After performing the unit operation, the liquid immune cell culture may be transferred from the second fluid structure 13 of the cartridge 1d to the third container 1b, particularly to an additional fluid structure of the third container 1b, while the waste may be transferred from the cartridge 1d to the fourth container 1b. Here, it may also be the case that two or more holders 8 are arranged on the same track. The container 1b may also include a plurality of tubes 4, 19 that are connected one by one to the tubes 5, 19 of the cartridge 1d. Thus, the container 1b may include, for example, different culture media accommodated in different vessels of the fluid structure, and these culture media may be transferred to the cartridge 1d through different tubes 4, 19. Exemplarily, the container 1b may include a first vessel containing a liquid (e.g., a buffer for cell washing) and a second vessel for receiving a liquid (e.g., waste from a cell washing step). In this case, each vessel may include a tube 4, 19, and each tube 4, 19 may be located in the holder 7. Two holders may be arranged on the same track of the container 1b. In the first step, the buffer may be transferred from the first vessel to the centrifugation unit of the fluid structure 13 located in the cartridge 1d by using the first tube 5, 19 of the cartridge 1d. After or during centrifugation, the waste from centrifugation may be transferred from the cartridge 1d by using the second tube 5, 19. This second tube 5, 19 may be connected to the tube 4, 19 belonging to the second vessel of the container 1b.

[0124] Preferably, the plurality of tube connections 3, 20 are formed by a plurality of welding procedures, where, particularly within the integrated bioprocessing system 1, one (particularly the same) or more tube connection systems 2 perform the welding procedures. The welding procedures are preferably performed before, during, and / or after the execution of the bioprocess.

[0125] It is particularly preferred that the welding procedure is performed at least once during the bioprocessing of the cell culture, preferably at least once for each unit operation performed on the cell culture. During the welding procedure, the box 1d and the container 1b can be connected, in particular via the tube connection 3. Preferably, after performing the welding procedure, at least one unit operation of the bioprocessing is performed, in particular on the box 1d. The container 1b can include a culture medium, in particular a liquid immune cell culture, which is used for the bioprocessing (in particular for the unit operation) and is therefore transferred to the box 1d. After performing at least one unit operation, a disconnection procedure is performed, so that in particular the box 1d and the container 1b are disconnected. Thereafter, the box 1d and / or the container 1b can be moved within the integrated bioprocessing system 1. The container 1b, which exemplarily includes a liquid immune cell culture, can be moved to another unit operation station 1a, in particular by performing another unit operation on the liquid immune cell culture using a different box 1d.

[0126] Typically, it is also possible that the tube connection 3 is formed to extend the first tube 4. In this case, the second tube 5 is designed as an extension tube, which is welded to the first tube 4 as described above. It is also possible that the tube connection 3 is formed to extend the second tube 5. In this case, the first tube 4 is designed as an extension tube, which is welded to the second tube 5 as described above. However, in one embodiment, the tubes 4 and 5 can be extended during the disconnection procedure. To this end, before disconnection, the position of the tube connection 3 is changed, in particular by the tube holders 7 and 8, so that one of the tubes 4 and 5 is extended by a section of the other tube in the tubes 4 and 5. Therefore, the other tube in the tubes 4 and 5 is shortened. The integrated biological treatment system 1 may include a welding planning unit, which includes the steps of shortening and extending the tubes 4 and 5 by continuous welding and disconnection, thereby maintaining the target length interval of the tubes 4 and 5.

[0127] As a second teaching, it is provided that Figure 1 The integrated biological treatment system 1 exemplarily depicted in FIG. Since the integrated biological treatment system 1 is suitable for performing the provided method, all the explanations and features given above are fully applicable. Vice versa, all the following explanations and features are fully applicable to the proposed method.

[0128] The integrated bioprocessing system 1 is suitable for (in particular automatically) performing a bioprocessing on a cell culture, wherein when performing the bioprocessing, a culture medium (in particular a cell culture) used in the bioprocessing can be conveyed by the integrated bioprocessing system 1 through tubes 4, 5. The bioprocessing system 1 comprises a first tube 4 for conveying a culture medium (in particular a fluid), and a second tube 5 for conveying a culture medium (in particular a fluid). The first tube 4 is held by a first tube holder 7 and is fluidically connected to a first fluid structure 12 for receiving and / or providing a culture medium. Preferably, the first tube holder 7 holds a single tube 4.

[0129] The integrated bioprocessing system 1 includes a movable first carrier 10, wherein the first tube 4, the first tube holder 7, and the first fluid structure are carried by the first carrier 10. The first carrier 10 and the first tube 4, the first tube holder 7, and the first fluid structure carried thereby are transported to a welding position within the integrated bioprocessing system 1. The first carrier thus serves as a transport means for the first tube 4, and the integrated bioprocessing system 1 includes a tube connection system 2 for connecting the first tube 4 and the second tube 5 at the welding position during a welding procedure such that a particularly sterile tube connection 3 is formed by welding, wherein after welding, the culture medium can be transferred through the tube connection 3 to or from the first fluid structure 12 of the first carrier 10. Here and preferably, as part of a bioprocess or multiple bioprocesses, the culture medium is transferred through the tubes 4, 5, and the tube connection 3.

[0130] Preferably, the integrated bioprocessing system 1 includes a robotic mechanism 52. The robotic mechanism 52 can be part of the tube connection system 2. The robotic mechanism 52 can be involved in the welding procedure, but can particularly be involved in other actions within the integrated bioprocessing system 1.

[0131] Preferably, the second tube 5 is held by a second tube holder 8 and is fluidly connected to a second fluid structure 13 for receiving and / or providing the culture medium. Preferably, the second tube holder 8 holds a single tube 5. After welding, the culture medium can be transferred through the tube connection 3 to or from the second fluid structure 13 of the second carrier. When the first tube 4 and the second tube 5 are connected, the culture medium can be transferred between the first fluid structure 12 and the second fluid structure 13.

[0132] The second tube 5 can be part of a device for performing a unit operation. In this case, the second tube 5 can be held by a second tube holder 8, which is for example arranged on or attached to the device. The device can include a second fluid structure 13. However, more preferably, the integrated bioprocessing system 1 includes a movable second carrier 11, wherein the second tube 5, the second tube holder 8, and the second fluid structure 13 are carried by the second carrier 11. The second carrier 11, the second fluid structure 13, the second tube 5, and the second tube holder 8 can be part of a container 1b or particularly a cartridge 1d. The second carrier 11 and the second tube 5, the second tube holder 8, and the second fluid structure carried thereby can be transported to the welding position. The second carrier 11 can be transported independently of the first carrier 10 and / or the tube connector 43 and / or the tube cutting unit 9.

[0133] In addition, it is possible that the integrated bioprocessing system 1 includes a transfer mechanism 53. The transfer mechanism 53 can be part of the pipe connection system 2. The transfer mechanism 53 can involve a welding procedure, but can also involve other actions in the integrated bioprocessing system 1. The transfer mechanism 53 can convey the first carrier 10 and / or the second carrier 11 and / or the cartridge 1d or multiple cartridges 1d and / or the container 1b or multiple containers 1b within the integrated bioprocessing system 1, in particular to a welding position.

[0134] Alternatively or additionally, the robotic mechanism 52 is designed to convey the cartridge 1d or multiple cartridges 1d and / or the container 1b or multiple containers 1b within the integrated bioprocessing system 1. In particular, the robotic mechanism 52 can manipulate the cartridge 1d or multiple cartridges 1d and / or the container 1b or multiple containers 1b by picking up, moving, and releasing. The robotic mechanism 52 can be designed as an orbital robotic mechanism 52 that includes different moving axes or shafts for one-dimensional, two-dimensional, or three-dimensional linear motion (Cartesian robotic mechanism). As an alternative, the robotic mechanism 52 can be designed as a robotic arm.

[0135] The pipe connection system 2 of the integrated bioprocessing system 1 preferably includes a pipe arrangement unit 6 for arranging the first pipe 4 and the second pipe 5 relative to each other at least in the axial direction of the first pipe 4 and / or the second pipe 5 during the arrangement phase of the welding procedure, such that the first pipe 4 and the second pipe 5 can be cut. Preferably, the first pipe 4 and the second pipe 5 are arranged in a one-dimensional or two-dimensional manner during the arrangement phase. Preferably, the first pipe 4 and / or the second pipe 5 are moved at least in the axial direction of the first pipe 4 and / or the second pipe 5. Preferably, such arrangement is performed automatically. The pipe connection system 2 further includes a pipe cutting unit 9 for cutting the first pipe 4 and the second pipe 5 during the trimming phase of the welding procedure. Preferably, the pipe arrangement unit 6 is designed such that during the welding phase of the welding procedure, the first pipe 4 and the second pipe 5 come into contact and fuse together to form a pipe connection 3.

[0136] In the context of the present application, "dimension" relates to a three-dimensional Cartesian coordinate system, such as the x, y, or z dimension. "One-dimensional", "two-dimensional", and "three-dimensional" in the case of movement mean that one-dimensional, two-dimensional, or three-dimensional movement can be taken.

[0137] The tube connection system 2 connects the first tube 4 and the second tube 5 of the integrated bioprocessing system 1 during a welding process, wherein the tube connection 3 is formed by welding. The tube connection system 2 includes a tube arrangement unit 6 which arranges the first tube 4 and the second tube 5 relative to each other at least in the axial direction of the first tube 4 and / or the second tube 5 during the arrangement phase of the welding process, such that the first tube 4 and the second tube 5 can be cut. Furthermore, the tube connection system 2 includes a tube cutting unit 9 which cuts the first tube 4 and the second tube 5 during the finishing phase of the welding process. The tube arrangement unit 6 brings the first tube 4 and the second tube 5 into contact and fuses them together during the welding phase of the welding process, thereby forming the tube connection 3. Preferably, the tube arrangement unit 6 is designed separately from the tube cutting unit 9. Thus, the arrangement of the tubes 4, 5 can be carried out independently of the tube cutting unit 9.

[0138] Preferably, the tube arrangement unit 6 and the tube cutting unit 9 are designed such that the welding process is carried out at least partly, preferably fully automatically. Thus, the risk of contamination can be reduced and the tube connection process can be further automated. Furthermore, if the provided tube connection system 2 is applied to the provided integrated bioprocessing system 1, the automatically executable welding process can provide advantages since the automation of the integrated bioprocessing system 1 can be improved. In particular, the first carrier 10 and / or the second carrier 11 can automatically convey the first tube 4 and / or the second tube 5 within the integrated bioprocessing system 1.

[0139] In a preferred embodiment, the tube arrangement unit 6 includes a first tube holder 7 for holding the first tube 4 and a second tube holder 8 for holding the second tube 5. The first tube holder 7 and / or the second tube holder 8 is part of the tube arrangement unit 6. As Figure 2 exemplarily shown in Figure 2 a) to e), and preferably, the first tube holder 7 holds the first tube 4 at least during the entire welding process. The same applies to the second tube holder 8 which holds the second tube 5 at least during the entire welding process. Generally, and preferably, the first tube holder 7 and the second tube holder 8 are designed such that the first tube 4 and the second tube 5 can be presented for carrying out the welding process on the tubes 4, 5 to form the tube connection 3. Since the first tube holder 7 is preferably arranged on or attached to the first carrier 10 and / or the second tube holder 8 is preferably arranged on or attached to the second carrier 11, the tube holders 7, 8 hold the tubes 4, 5 in the respective defined positions, especially before and after carrying out the welding process.

[0140] Preferably, the tube arrangement unit 6 further comprises a first holder moving device 21 for moving the first tube holder 7 preferably in one, two or three dimensions, more preferably transversely to, preferably orthogonally to the axial direction of the first tube. The first holder moving device 21 enables the first tube holder 7 to be moved, in particular horizontally, where the first tube 4 can be moved together with the first tube holder 7. Additionally or alternatively, the tube arrangement unit 6 comprises a second holder moving device 22 for moving the second tube holder 8 preferably in one, two or three dimensions, more preferably transversely to, preferably orthogonally to the axial direction of the second tube 5. As Figure 2 exemplarily depicted in c), the second holder moving device 22 enables the second tube holder 8 to be moved, in particular horizontally, where the second tube 5 can be moved together with the second tube holder 8.

[0141] Regarding the first holder moving device 21 and / or the second holder moving device 22, preferably, the first holder moving device 21 comprises a first holder guide 23 and / or the second holder moving device 22 comprises a second holder guide 24. The holder guides 23, 24 enable the respective tube holders 7, 8 to perform a predetermined guiding movement. The first holder guide 23 and / or the second holder guide 24 can be designed as track units respectively. As is Figure 1 and Figure 2 exemplarily visible in a) to Figure 2 e), and preferably, at least one of the tube holders 7, 8 is movably mounted on the holder guides 23, 24 designed as track units respectively, such that at least one of the tube holders 7, 8 can be moved horizontally in one dimension, for example see Figure 2 c). In the example according to Figure 2 c), the second tube holder 8 can be moved transversely to the second tube 5 in the y direction of the Cartesian coordinate system. The holder guides 23, 24 designed as track units can each comprise one or two tracks. The first tube holder 7 and / or the second tube holder 8 can be attached to the first carrier 10 via the first holder guide 23, or alternatively, the second holder guide 24 is attached to the second carrier 11. Thus, the holder guides 23, 24 can perform a dual function.

[0142] Preferably, the first retainer moving device 21 includes a first retainer driving unit 25 and / or the second retainer moving device 22 includes a second retainer driving unit 26. The retainer driving units 25, 26 drive the corresponding movement of the tube retainers 7, 8, particularly the movement on the retainer guides 23, 24. The first retainer driving unit 25 can be at least partially, particularly completely, arranged on the first tube retainer 7, and / or the second retainer driving unit 26 can be at least partially, particularly completely, arranged on the second tube retainer 8. Thus, the tube retainers 7, 8 can be self-driven. Alternatively, in another preferred embodiment, the first retainer driving unit 25 and / or the second retainer driving unit 26 is designed to be separate from the first tube retainer 7 and / or the second tube retainer 8. The first retainer driving unit 25 and / or the second retainer driving unit 26 can be temporarily connected to the corresponding tube retainers 7, 8 such that the first tube retainer 7 and / or the second tube retainer 8 can be driven, particularly such that the corresponding tube retainers 7, 8 can move on the retainer guides 23, 24. The first retainer driving unit 25 and / or the second retainer driving unit 26 can be particularly sent to the first tube retainer 7 and / or the second tube retainer 8 by a robotic mechanism 52 as needed. In another embodiment, the first retainer driving unit 25 and / or the second retainer driving unit 26 can be part of the robotic mechanism 52 such that the first tube retainer 7 and / or the second tube retainer 8 is moved by the robotic mechanism 52.

[0143] Particularly preferably, the first retainer driving unit 25 and / or the second retainer driving unit 26 can be used to drive a number of different first tube retainers 7 and / or a number of different second tube retainers 8 within the integrated bioprocessing system 1. The different first tube retainers 7 and / or the different second tube retainers 8 can be part of different cartridges 1d and / or different containers 1b.

[0144] Generally, a single second carrier 11 can carry a plurality of second tube retainers 8. A single cartridge 1d can also include a plurality of second tube retainers 8. Each second tube retainer 8 can hold the second tube 5 such that the second carrier 11 carries or rather the cartridge 1d includes a plurality of second tubes 5. Generally, it is also possible that a single first carrier 10 carries a plurality of first tube retainers 7, where each first tube retainer 7 holds the first tube 4. It is also possible that a single container 1b includes a plurality of first tube retainers 7, where each first tube retainer 7 holds the first tube 4. Thus, a plurality of first tubes 4 and / or a plurality of second tubes 5 can be connected one after another to convey a culture medium, such as a liquid immunocyte culture, a washing buffer, waste, etc.

[0145] Generally, a plurality of tube connection portions 3 can be formed as needed. The plurality of tube connection portions 3 can be formed simultaneously, partially simultaneously, or one by one. The tube connection portion 3 can be formed between different first tubes 4 and different second tubes 5, and the first tube 4 and the second tube 5 are particularly held by different first tube holders 7 and different second tube holders 8. The different first tubes 4 can be carried on a single first carrier 10. In particular, the different first tubes 4 can each have different functions, such as medium inlet and medium outlet, etc. The different second tubes 5 can be carried on a single second carrier 11. In particular, the different second tubes 5 can each have different functions, such as medium inlet and medium outlet functions, etc.

[0146] In addition to the movable design of the tube holders 7, 8, it has proven advantageous if the tube arrangement unit 6 (in particular the first tube holder 7) includes a first tube moving device 27 for moving the first tube 4 held by the first tube holder 7 at least one-dimensionally (in particular in the axial direction of the first tube). Preferably, the first tube 4 held by the first tube holder 7 can be moved relative to the first tube holder 7 and the first carrier 10. Alternatively or additionally, the tube arrangement unit 6 (in particular the second tube holder 8) includes a second tube moving device 28 for moving the second tube 5 held by the second tube holder 8 one-dimensionally (preferably in the axial direction of the second tube), wherein preferably, the second tube 5 held by the second tube holder 8 is moved relative to the second tube holder 8 and the second carrier 11. Preferably, the first tube 4 can be pushed out and / or retracted by the first tube moving device 27, and / or the second tube 5 can be pushed out and / or retracted by the second tube moving device 28. For example, as Figure 2 a) and Figure 4 d) depict, and preferably, the first tube 4 is horizontally pushed out or retracted by the first tube holder 7. In an embodiment, as Figure 2 a) and Figure 4 d) show, the first tube 4 is pushed out or retracted one-dimensionally in the x-direction of the Cartesian coordinate system. The second tube 5 is horizontally pushed out or retracted by the second tube holder 8. In Figure 2 a), Figure 4In the embodiment shown in d), the second tube 5 is pushed out or retracted one-dimensionally in the x-direction of the Cartesian coordinate system. In order to drive this movement of the corresponding tubes 4, 5, preferably, the first tube moving device 27 includes a first tube driving unit 29, and / or the second tube moving device 28 includes a second tube driving unit 30. The first tube moving device 27 and / or the second tube moving device 28 can be automatically operated. In addition, the first tube driving unit 29 and / or the second tube driving unit 30 can be self-driven or powered from the outside, for example, by a robotic mechanism 52. The first tube driving unit 29 can be part of the first tube holder 7, and / or the second tube driving unit 30 can be part of the second tube holder 8.

[0147] Regarding the design of the tube driving units 29, 30, preferably, the first tube driving unit 29 includes a first driving roller 31 rotatably mounted, and / or the second driving unit 30 includes a second driving roller 32 rotatably mounted. The rotation of the corresponding driving rollers 31, 32 can cause the axial movement of the corresponding tubes 4, 5, in particular, pushing out or retracting. As Figure 5 exemplarily shown in and preferably, the corresponding tubes 4, 5 abut against the corresponding driving rollers 31, 32, such that the rotational movement of the driving rollers 31, 32 causes the axial movement of the tubes 4, 5. The rotational axes of the corresponding driving rollers 31, 32 are arranged vertically.

[0148] In a preferred embodiment, the tube driving units 29, 30 are self-driven. Here, the corresponding driving rollers 31, 32 can be rotated as needed, and the corresponding tubes 4, 5 can be pushed out or retracted accordingly. However, in another also preferred embodiment, the first tube driving unit 29 and / or the second tube driving unit 30 can be powered from the outside. Here, preferably, the first tube driving unit 29 is driven by a first tube driving unit driver 61, and / or the second tube driving unit 30 can be driven by a second tube driving unit driver 62. The first tube driving unit driver 61 and / or the second tube driving unit driver 62 can be designed to be separate from the corresponding tube driving units 29, 30 and can be temporarily connected to the corresponding tube driving units 29, 30 as needed. The first tube driving unit driver 61 and / or the second tube driving unit driver 62 can be conveyed to the first tube driving unit 29 and / or the second tube driving unit 30 by a robotic mechanism 52 within the integrated bioprocessing system 1. Particularly preferably, the first tube driving unit driver 61 and / or the second tube driving unit driver 62 can be used to drive a plurality of different tube driving units 29, 30, in particular, the tube driving units 29, 30 of different cartridges 1d and / or different containers 1b. The first holder driving unit driver and / or the second holder driving unit driver can be part of the tube connector 43.

[0149] Preferably, the first tube driving unit 29 includes a first driving locking member 33 for locking the first driving roller 31 such that the first tube 4 is immovable relative to the first tube driving unit 29. Additionally or alternatively, the second tube driving unit 30 includes a second driving locking member 34 for locking the second driving roller 32 such that the second tube 5 is immovable relative to the second tube driving unit 30. As Figure 2 a), Figure 2 as exemplarily shown in b), after the axial arrangement of the tubes 4, 5, the driving locking members 33, 34 can lock the driving rollers 31, 32.

[0150] Advantageously, the first tube driving unit 29 includes a first passive roller 35 rotatably mounted, and / or the second tube driving unit 30 includes a second passive roller 36 rotatably mounted. For example, as Figure 5 shown, and preferably, the respective passive rollers 35, 36 are arranged relative to the respective driving rollers 31, 32 such that the respective tubes 4, 5 are arranged between the passive roller and the driving roller. The rotational axes of the respective passive rollers 35, 36 are arranged vertically.

[0151] Furthermore, preferably, the first tube driving unit 29 includes a first pre-tensioning device 37 for pre-tensioning the first passive roller 35 against the first tube 4, and / or the second tube driving unit 30 includes a second pre-tensioning device 38 for pre-tensioning the second passive roller 36 against the second tube 5. The respective pre-tensioning devices 37, 38 can increase the grip of the respective driving rollers 31, 32 on the respective tubes 4, 5, and thus, can prevent the sliding of the respective tubes 4, 5. In Figure 5 the exemplary embodiment of, and preferably, the pre-tensioning devices 37, 38 include at least springs that pre-tension the respective passive rollers 35, 36 in the direction of the respective driving rollers 31, 32. As in the embodiment according to Figure 5 this, the spring can be a compression spring.

[0152] In another preferred embodiment, as Figure 5 depicted, the tube arrangement unit 6 includes a first guiding device 39 for guiding the first tube 4 and / or a second guiding device 40 for guiding the second tube 5. Since the tubes 4, 5 can be flexible, the guiding devices 39, 40 can improve the accuracy of the respective arrangements of the tubes 4, 5. Preferably, the first guiding device 39 is part of the first tube holder 7 and / or the second guiding device 40 is part of the second tube holder 8. As Figure 5As exemplarily depicted, particularly preferably, the first guiding device 39 includes a first funnel 41 and / or the second guiding device 40 includes a second funnel 42. The respective tubes 4, 5 can be pushed out and / or retracted through the respective funnels 41, 42. The first funnel 41 is preferably arranged on the first tube holder 7, and / or the second funnel 42 is preferably arranged on the second tube holder 8, wherein, further preferably, the first funnel 41 is arranged such that the first tube 4 can be moved through the first funnel 41, and / or the second funnel 42 is arranged such that the second tube 5 can be moved through the second funnel 42. The first funnel 41 and / or the second funnel 42 can be arranged such that the first tube 4 and / or the second tube 5 can be pushed out or retracted through the respective funnels 41, 42.

[0153] Alternatively, and as Figure 9 schematically depicted, the first guiding device 39 and the second guiding device 40 can also be part of a tube connector 43, in particular part of a first tube receiver 58 and a second tube receiver 59. The tube connector 43 is described in more detail below. Particularly preferably, the first guiding device 39 includes a first funnel 41 and / or the second guiding device 40 includes a second funnel 42. The respective tubes 4, 5 can be pushed out and / or retracted through the respective funnels 41, 42. Here and preferably, when the tubes 4, 5 are pushed out such that a welding procedure can be performed, the first funnel 41 and the second funnel 42 guide the first tube 4 and the second tube 5 into the tube connector 43. The first funnel 41 and the second funnel 42 can be arranged on the tube connector 43, wherein, further preferably, the first funnel 41 is arranged such that the first tube 4 can be moved through the first funnel 41 and / or the second funnel 42 is arranged such that the second tube 5 can be moved through the second funnel 42.

[0154] As described above, each of the funnels 41, 42 can include a sensor to verify the successful start of the tube push-out process and also indicate the successful retraction of the tube.

[0155] If the first guiding device 39 and the second guiding device 40 are part of the pipe connector 43, it is preferred that the first funnel 41 and the second funnel 42 include a first funnel opening and a second funnel opening, which extend along the axes of the respective funnels 41, 42 on the housing surfaces of the respective funnels 41, 42. Via the first funnel opening and the second funnel opening, the first pipe 4 and the second pipe 5 can be removed in a direction transverse to the funnels 41, 42, especially after forming the pipe connection 3 and the pipes 4, 5 are connected to each other. Alternatively, the first funnel 41 and the second funnel 42 can be designed as at least two parts respectively, such that the first pipe 4 and the second pipe 5 can be released from the funnels 41, 42, especially after forming the pipe connection 3. When the pipe connection 3 has been formed, the first funnel opening and the second funnel opening or the at least two-part funnels 41, 42 can enable the reception of the first pipe 4 and the second pipe 5. This can be beneficial if the welding process and the disconnection process are carried out by the pipe cutting unit 9 and the pipe disconnection device 14 of the pipe connection system 2 respectively.

[0156] Preferably and as Figure 1 exemplarily shown in, the first pipe holder 7 is an anchor point 1c, preferably a container anchor point or a cassette anchor point, and / or the second pipe holder 8 is an anchor point 1e, preferably a container anchor point or a cassette anchor point.

[0157] Preferably and as Figure 1 exemplarily shown in, the first pipe 4 is a transfer pipe, preferably a container transfer pipe or a cassette transfer pipe, and / or the second pipe is a transfer pipe, preferably a container transfer pipe or a cassette transfer pipe.

[0158] Advantageously, the pipe connection system 2 includes a pipe connector 43, which is preferably movable in one, two or three dimensions. Preferably, as Figure 3 shown in c) and Figure 3 d), the pipe arrangement unit 6 (especially the first pipe holder 7 and / or the second pipe holder 8) is designed to be movable separately and independently from the pipe connector 43. Alternatively, as Figure 6 exemplarily shown in, at least part of the pipe arrangement unit 6 (especially the first pipe receiver 58 and / or the second pipe receiver 59) can be arranged on the pipe connector 43. Here and preferably, the pipe receivers 58, 59 are designed as pipe holders having the same or at least partly the same features as the pipe holders 7, 8. Further preferably, as shown in, for example, Figure 3 c) and Figure 6 shown, the pipe cutting unit 9 is designed to be separated from the pipe connector 43, or at least part of the pipe cutting unit 9 is arranged on the pipe connector 43.

[0159] Figure 3 c) An exemplary preferred embodiment is shown, in which the tube connector 43 includes a tube cutting unit 9. The tube arrangement unit 6 (i.e., the first tube holder 7 and the second tube holder 8) is designed to be separated from the tube connector 43. The tube connector 43 can thus move relative to the tube holders 7, 8. Here, the tube cutting unit 9 can be moved to a certain position in the integrated bioprocessing system 1 to perform a welding procedure. A number of welding procedures can be performed to connect different tubes 4, 5 at different unit operation stations, for example.

[0160] On the other hand, Figure 6 Another exemplary preferred embodiment is shown, in which the tube connector 43 includes the tube cutting unit 9 and at least a part of the tube arrangement unit 6 (i.e., the first tube receiver 58 for receiving a tube, particularly the first tube 4, and the second tube receiver 59 for receiving a tube, particularly the second tube 5). Here, the first tube receiver 58 and the second tube receiver 59 can move together with the tube connector 43. The tube connector 43 can be moved to a certain position in the integrated bioprocessing system 1 to perform a welding procedure. Preferably, the welding procedure includes a lacing stage, in which the tubes 4, 5 are respectively laced or inserted into the tube receivers 58, 59. The first tube receiver 58 and / or the second tube receiver 59 can be designed as, for example, the tube holders 7, 8. The receivers 58, 59 can be particularly designed as the aforementioned tube holders 7, 8. Here, the arrangement stage can be performed at least in part by the movement of the tube connector 43.

[0161] Preferably, the tube cutting unit 9 includes a blade 9a for cutting the first tube 4 and / or the second tube 5, wherein the blade 9a is heatable. Preferably, the tube cutting unit 9 includes a blade heater 9c for heating the blade 9a and / or the blade seat 9b, wherein the blade 9a is particularly detachably and / or ejectably mounted in the blade seat 9b. After performing the welding procedure, the blade 9a can be automatically ejected by the blade seat 9b. Preferably, as Figure 3 c) and Figure 6 exemplarily shown, the blade 9a and / or the blade heater 9c and / or the blade seat 9b are arranged on the tube connector 43. Alternatively, the tube cutting unit 9 can also include an alternative cutting element for cutting the tubes 4, 5, such as a laser, etc. The cutting element can be disposable or reusable and / or non-contact.

[0162] For replacing the blade 9a, advantageously, the tube connection system 2 includes a blade compartment 44 for storing a plurality of blades 9a. Preferably, the blade compartment 44 includes a plurality of blades 9a that can be independently, and in particular fully automatically, mounted on the blade holder 9b. Since the blade 9a is preferably removably, and in particular ejectably, mounted in the blade holder 9b, the entire blade replacement process can be automatically performed, in which the used blade 9a is replaced with an unused blade 9a. Here, for example, after performing a welding procedure, the used blade 9a is separated by ejection, and an unused blade 9a that may be located in the blade compartment 44 is mounted.

[0163] Alternatively, the blade 9a can also be replaced by the operator. In this case, the tube cutting unit 9 can be moved to a position accessible to the operator of the integrated bioprocessing system 1.

[0164] In another preferred embodiment, the tube connection system 2 includes a tube identification device 45 for identifying the first tube 4 held by the first tube holder 7 and / or the second tube 5 held by the second tube holder 8. Preferably, the tube identification device 45 is at least partially arranged on the first tube holder 7 and / or at least partially arranged on the second tube holder 8 and / or at least partially arranged on the tube connector 43. Further preferably, the tube identification device 45 includes at least one, in particular optical, identification sensor 46. The tubes 4, 5 to be welded can be identified by the tube identification device 45. In an exemplary embodiment, the means for tube identification can be a coloring pattern or the like. The welding procedure can be performed according to the identified tubes 4, 5.

[0165] Preferably, the tube connection system 2 includes a position determination device 47 for determining the position of the first tube 4 and / or the second tube 5 and / or the first tube holder 7 and / or the second tube holder 8 and / or the tube connector 43 and / or the first carrier 10 and / or the second carrier 11. Determining the position of the respective components of the tube connection system 2 (especially in the integrated bioprocessing system 1) may be crucial for performing the welding process (especially in an automated manner). Particularly preferably, the position of the first tube 4 (especially in the integrated bioprocessing system 1) is determined by determining the position of the first carrier 10, and / or the position of the second tube 5 (especially in the integrated bioprocessing system 1) is determined by determining the position of the second carrier 11. Preferably, the position determination device 47 is at least partially arranged on the first tube holder 7, and / or at least partially arranged on the second tube holder 8, and / or at least partially arranged on the tube connector 43, and / or at least partially arranged on the first carrier 10 and / or the second carrier 11. Further preferably, the position determination device 47 includes at least one (especially optical or electrical) position sensor 48, or a plurality of (especially optical and / or electrical) position sensors 48.

[0166] For verification reasons, in another embodiment, preferably, the tube connection system 2 includes a welding verification device 49 for verifying the tube connection 3. The tube connection 3 can be verified by an integrity test procedure. The integrity test procedure can be performed according to the method proposed as described above. Preferably, the welding verification device 49 includes one or more tube closing elements 60 (such as clamps) for temporarily closing the first tube 4 and / or the second tube 5. The tube closing element 60 or the plurality of tube closing elements 60 can be part of the first tube holder 7 and / or the second tube holder 8. Preferably, the welding verification device 49 includes at least one verification sensor 50, especially an optical or pressure measurement verification sensor 50 or a plurality of verification sensors, especially optical and / or pressure measurement verification sensors 50. The welding verification device 49 preferably includes at least a tube pressure unit 51 for applying pressure to the first tube 4 and / or the second tube 5 especially after welding.

[0167] Further preferably, the welding verification device 49 includes a tube pressure unit 51. The tube pressure unit 51 can include one or more actuators, especially linear actuators, and each actuator compresses one of the tubes 4, 5. Compression at either side of the tube connection 3 is preferred. Preferably, the compression is performed by preferably applying pressure to the tubes 4, 5 by the tube pressure unit 51, especially by compressing the first tube 4 by one of the linear actuators and compressing the second tube 5 by the other linear actuator. It is possible to apply the compression according to a predefined compression pattern.

[0168] Preferably, the welding verification device 49 includes at least one verification sensor 50 (in particular for optical force or pressure measurement), or several verification sensors 50 (in particular for optical force or pressure measurement).

[0169] Preferably, the welding verification device 49 includes at least one verification sensor 50 on either side of the pipe connection 3 for verifying the integrity of the pipe connection 3. Preferably, the at least one verification sensor 50 is designed as a force measurement sensor, wherein the force measurement sensor is used to monitor the force required to compress each of the pipes 4, 5 to a certain extent. Preferably, the force measurement sensor or sensors are part of the pipe pressing unit 51. In particular, each linear actuator includes a force measurement sensor. Alternatively or additionally, each pipe holder 7, 8 may include a force measurement sensor.

[0170] Preferably, in order to check the integrity of the pipe connection 3, the sensor signals obtained over time during the compression of each of the pipes 4, 5 are compared with the sensor signals obtained for a pipe connection 3 known to be intact and / or the sensor signals obtained for a pipe connection 3 known to be insecure. For a given compression, the verification of the integrity of the pipe connection 3 can be performed, for example, by analyzing the peak force measured by any of the verification sensors 50, in particular by any of the force measurement sensors. Additionally or alternatively, multivariate data analysis methods (such as principal component analysis) or machine learning methods (such as neural networks) can be used to analyze the sensor signals and determine whether the pipe connection 3 is intact or insecure.

[0171] It has been found to be advantageous if the pipe connection system 2 includes a waste disposal device for disposing of waste during the cutting of the first pipe 4 and the second pipe 5. Preferably, the waste disposal device includes at least one waste disposal collector and / or at least one waste disposal suction unit. Further preferably, the waste disposal collector can be moved relative to the first pipe holder 7 and / or the second pipe holder 8, and / or the waste disposal suction unit is arranged on the pipe connection head 43. Alternatively, and preferably, the waste disposal collector can preferably be moved to a position where the waste disposal collector can preferably deposit the waste under automatic control using the same mechanism (such as the robotic mechanism 52) as the mechanism for moving the pipe connection system 2 for subsequent further processing, such as incineration.

[0172] Furthermore, it is preferred if the pipe connection system 2 includes a robotic mechanism 52, wherein the pipe connection head 43 is attached to the robotic mechanism 52 such that the pipe connection head 43 is preferably movable in one, two or three dimensions. The robotic mechanism 52 can be designed as a robotic arm, such as a multi-axis robot, or as a linear robot, having one, two (also called an x-y robotic mechanism) or three moving axes (also called a Cartesian robotic mechanism). Figure 1Among them, for example and preferably, the robotic mechanism 52 is designed as a linear robot with three moving axes, such that the robotic mechanism 52 can move the tube connector 43 in three dimensions, namely, in the x, y, and z directions.

[0173] Additionally or alternatively, the tube connection system includes a transfer mechanism 53, wherein the first carrier 10 and / or the second carrier 11 can be moved one-dimensionally, two-dimensionally, or three-dimensionally by the transfer mechanism 53. Generally, the robotic mechanism 52 can also be designed such that the first carrier 10 (especially the container 1b) and / or the second carrier 11 (especially the cassette 1d) can be moved by the robotic mechanism 52 within the integrated bioprocessing system 1. In Figure 1 Among them, for example and possibly, the transfer mechanism 53 can move the first tube 4 and the second tube 5 by moving the first carrier 10 (more precisely, the container 1b) and the second carrier 11 (more precisely, the cassette 1d) respectively within a horizontal plane, which horizontal plane is Figure 1 exemplarily depicted as being along the x and y directions.

[0174] In another preferred embodiment, the tube connection system 2 includes a tube disconnecting device 14 for disconnecting the first tube 4 and the second tube 5. The disconnection of the first tube 4 and the second tube 5 can be performed in a disconnection procedure as described previously in the context of the proposed method. Preferably, the tube disconnecting device 14 includes at least a sealing unit 15 and / or a disconnecting unit 17. Further preferably, the tube disconnecting device 14 is at least partially arranged on the tube connector 43. In Figure 4 b) and Figure 4 c), for example, a tube disconnecting device 14 having a sealing unit 15 and a disconnecting unit 17 is shown.

[0175] In this context, preferably, the sealing unit 15 includes two sealing surfaces 16, wherein the first tube 4 and / or the second tube 5 and / or the tube connection portion 3 can be arranged between the sealing surfaces 16 for sealing, and wherein the sealing surfaces 16 can move relative to each other for sealing. It is possible that at least one of the sealing surfaces 16 is heatable. With the sealing unit 15, a sealing phase can be performed. In Figure 4 b), for example, the sealing unit 15 includes four sealing surfaces 16 or more precisely two pairs of sealing surfaces 16. Here and preferably, the sealing surfaces 16 are respectively designed as flat surfaces that correspondingly produce planar seals 56, 57. Here and preferably, the planar seals 56, 57 are oriented transversely to the axes of the tubes 4, 5.

[0176] However, it is particularly preferred that the sealing unit 15 includes a sealing surface 63 which is designed to crimp the first tube 4 and / or the second tube 5 in the axial direction of the respective tubes 4, 5 such that the first tube 4 and / or the second tube 5 is self-sealing, especially if the sealing surface 63 is heated when the respective tubes 4, 5 are crimped. Figure 8 a), Figure 8 Examples of such an embodiment are shown in

[0177] Here and preferably, the sealing surface 63 includes a crimping element 64 which is designed as a pin 65, especially an elongate pin 65. As Figure 8 exemplarily shown in Figure 8 a), the elongate pin 65 is elongate in the axial direction of the tubes 4, 5 to be sealed. Preferably, as Figure 8 exemplarily depicted in

[0178] b), the sealing surface 63 forms a seal having a U-shaped cross-section (especially a cross-section along the main axis of the sealed tubes 4, 5). This cross-section can extend in the axial direction of the tubes 4, 5 for at least the length of the original diameter of the sealed tubes 4, 5, preferably for at least twice the length of the original diameter of the sealed tubes 4, 5. It is further possible that the cross-section of the seal includes at least one segment in an angular range of at least 180°, preferably at least 235°, within which the original diameter of the sealed tubes 4, 5 is maintained. As

[0179] Alternatively or additionally, the disconnect unit 17 includes a disconnect laser or in particular a heatable disconnect blade 18, wherein the first tube 4 and / or the second tube 5 and / or the tube connection 3 can be cut by the disconnect laser or the disconnect blade 18. Preferably, the disconnect blade 18 is in particular detachably and / or ejectably mounted on the blade seat 9b of the tube connector 43. By means of the disconnect blade 18 or the disconnect laser, a disconnect phase can be carried out. The disconnect blade 18 can in particular be the blade 9a included in the tube cutting unit 9. The tube cutting unit 9 can also be the disconnect unit 17. Generally, preferably, the tube disconnecting device 14 (in particular the disconnect unit 17) and the tube connection system 2 (in particular the tube cutting unit 9) share components such as the blades 9a, 18, the blade seat 9b and / or the blade compartment 44.

[0180] Furthermore, it may be advantageous if the tube connection system 2 includes a pumping device 54, wherein the pumping device 54 is designed such that a culture medium (in particular a fluid, preferably a liquid) can be conveyed through the first tube 4 and the second tube 5 after welding, and / or such that the culture medium in the first tube 4 and / or the second tube 5 can be squeezed to minimize the dead volume in the first tube 4 and / or the second tube 5. Preferably, the pumping device 54 includes a peristaltic pump and / or a pressure unit. The pumping device 54 can also evacuate the first tube 4 and / or the second tube 5 before welding (in particular before the welding phase).

[0181] In a preferred embodiment, the tube connection system 2 includes a data reporting unit 55 for reporting data on the following: the first tube 4 and / or the second tube 5 and / or the tube connection 3 and / or the first tube holder 7 and / or the second tube holder 8 and / or the tube connector 43 and / or the blade 9a and / or the blade heater 9c and / or the blade seat 9b and / or the blade compartment 44 and / or the robotic mechanism 52 and / or the transfer mechanism 53 and / or the tube disconnecting device 14 and / or the sealing unit 15 and / or the disconnect unit 17 and / or the welding and / or disconnecting of the ends of the first tube 4 and / or the ends of the second tube 5. The data is preferably movement data, position data, temperature data, time data and / or pressure data.

[0182] As a third teaching, an integrated bioprocessing system 1 for performing a bioprocess on a cell culture is provided, wherein during the performance of the bioprocess, the culture medium (in particular the cell culture) used in the bioprocess can be conveyed by the integrated bioprocessing system 1 through the tubes 4, 5. The integrated bioprocessing system 1 includes a first tube 4 for conveying the culture medium and a second tube 5 for conveying the culture medium, wherein the first tube 4 and the second tube 5 are connected by a tube connection 3 and are in a disconnect position within the integrated bioprocessing system 1. The disconnect position can be a welding position. The integrated bioprocessing system 1 can include several disconnect positions.

[0183] The first tube 4 is held by the first tube holder 7 and is fluidly connected to the first fluid structure 12 so as to receive and / or provide a culture medium via the first tube 4. In addition, the integrated bioprocessing system 1 includes a movable first carrier 10 that carries the first tube 4, the first tube holder 7, and the first fluid structure 12.

[0184] The integrated bioprocessing system 1 includes a tube disconnecting device 14 for disconnecting the first tube 4 and the second tube 5 at a disconnect position during a disconnect procedure such that the first tube 4 and the second tube 5 are fluidly and / or physically disconnected.

[0185] The first carrier 10 and the first tube 4, the first tube holder 7, and the first fluid structure 12 carried thereby are transportable from the disconnect position after the first tube 4 and the second tube 5 are disconnected.

[0186] With the proposed integrated bioprocessing system according to the third teaching, the proposed method can be carried out, and thus all features and explanations given with respect to the proposed method apply fully to the proposed integrated bioprocessing system according to the third teaching, and vice versa. In addition, all features and explanations with respect to the proposed integrated bioprocessing system according to the second teaching apply fully to the proposed integrated bioprocessing system according to the third teaching, and vice versa.

[0187] As a fourth teaching, there is provided a tube disconnecting device 14 for disconnecting the first tube 4 and the second tube 5, in particular the first tube 4 and the second tube 5 of the integrated bioprocessing system 1, during a disconnect procedure such that the first tube 4 and the second tube 5 are fluidly and / or physically disconnected, wherein the tube disconnecting device 14 includes a sealing unit 15 for sealing the first tube 4 and / or the second tube 5 during a sealing phase such that a first seal 56 and / or a second seal 57 is formed, wherein the sealing unit 15 includes at least one sealing surface 63 that is designed to crimp the first tube 4 and / or the second tube 5 along the axial direction of the respective tube 4, 5 such that the first tube 4 and / or the second tube achieves self-sealing.

[0188] The proposed tube disconnecting device 14 can be used in the proposed method, and thus all features and explanations given with respect to the proposed method apply fully to the proposed tube disconnecting device 14, and vice versa. The proposed tube disconnecting device 14 can be used in the integrated bioprocessing system 1 proposed according to the second teaching and / or the integrated bioprocessing system proposed according to the third teaching, and thus all features given with respect to the integrated bioprocessing system apply fully to the proposed tube disconnecting device 14, and vice versa.

[0189] As a fifth teaching, a sealing unit 15 is provided, in particular a sealing unit of a tube disconnection device 14 in an integrated bioprocessing system 1, for sealing a first tube 4 and / or a second tube 5 in a sealing stage, thereby forming a sealing portion 56, 57. The sealing unit 15 comprises at least one sealing surface 63, and at least one sealing surface 63 is designed to press the first tube 4 and / or the second tube 5 along the axial direction of the corresponding tube 4, 5, so that the first tube 4 and / or the second tube 5 achieves self-sealing.

[0190] An embodiment of the sealing unit 15 is Figure 8 a) and Figure 8 b) and previously described in the context of a tube disconnect device 14 of an integrated bioprocessing system. Therefore, all features are fully applicable.

[0191] The proposed sealing unit 15 can be used in the proposed method, and therefore all features and explanations given in relation to the proposed method are fully applicable to the proposed sealing unit 15, and vice versa. The proposed sealing unit 15 can be used in the integrated biotreatment system 1 proposed according to the second teaching and / or in the integrated biotreatment system proposed according to the third teaching and / or in the tube disconnection device 14 proposed according to the fourth teaching, and therefore all features given are fully applicable to the proposed sealing unit 15, and vice versa.

[0192] As a sixth teaching, a device for transporting tubes 4, 5 is provided, in particular for transporting tubes within an integrated bioprocessing system 1, wherein the device comprises carriers 10, 11, tubes 4, 5, tube holders 7, 8 and fluid structures 12, 13, wherein the carrier transports the tubes 4, 5, tube holders 7, 8 and fluid structures 12, 13, so that the tubes 4, 5, tube holders 7, 8 and fluid structures can be transported together with the carriers 10, 11, and wherein the tube holders 7, 8 hold the tubes 4, 5 in a defined position.

[0193] The device can be designed as a box 1d or a container 1b. The carrier 10, 11, the tube 4, 5, the tube holder 7, 8 and / or the fluid structure 12, 13 can be designed as described above. All the explanations and features given above are fully applicable. Vice versa, all the explanations and features about the device are fully applicable to the proposed method, the proposed integrated bioprocessing system 1, the proposed tube disconnection device 14 and the proposed sealing unit 15.

[0194] According to a seventh teaching, which is also important, it is proposed that the first tube holder 7 is positioned at the welding location by means of a positioning mechanism separate from the tube connection system 2 .

[0195] According to an equally important eighth teaching, it is provided that the first tube holder 7 fluidically closes (in particular clamps) the first tube 4, in particular reversibly,

[0196] According to the equally important ninth teaching, it is proposed that the first tube retainer 7 presses the first tube 4 into the tube connection system 2, especially before any interaction between the first tube 4 and the tube connection system 2.

[0197] According to the equally important tenth teaching, it is proposed that before any interaction between the first tube 4 and the tube connection system 2, the first tube retainer 7 holds the first tube 4 at a predetermined angle or angular range defined relative to the following parts: the integrated bioprocessing system 1 itself and / or the tube connection system 2 and / or the second tube 5. The defined angles of the first tube and the second tube 5 can be Figure 2 seen in. Figure 3 It shows how this angle facilitates the interaction with the tube connection system 2.

[0198] The eleventh teaching relates to a method of welding (especially sealing) a tube at least partially along the extension of the tube, especially in the integrated bioprocessing system 1.

Claims

1. A method for performing a bioprocess on a cell culture, wherein the bioprocess is performed on an integrated bioprocessing system (1), and wherein during the performance of the bioprocess, the integrated bioprocessing system (1) conveys a culture medium, in particular the cell culture, used in the bioprocess through a tube, and wherein the integrated bioprocessing system (1) includes a tube connection system (2) for connecting the tubes of the integrated bioprocessing system (1) by welding as needed, and wherein a first tube (4), a first tube holder (7), and a first fluid structure (12) for receiving and / or providing the culture medium are carried by a movable first carrier (10), and wherein the first tube (4) is held by the first tube holder (7) and is fluidly connected to the first fluid structure (12), and wherein the first carrier (10) and the first tube (4), the first tube holder (7), and the first fluid structure (12) carried thereby are transported to a welding position within the integrated bioprocessing system (1), and wherein at the welding position during a welding procedure, the tube connection system (2) connects the first tube (4) and a second tube (5) to form a tube connection (3), and wherein after welding, the integrated bioprocessing system (1) conveys the culture medium from the first fluid structure (12) of the first carrier (10) or conveys the culture medium to the first fluid structure (12) through the tube connection (3).

2. The method according to claim 1, characterized in that, The welding procedure includes an arrangement phase and / or a trimming phase and / or a welding phase. In the arrangement phase, the first tube (4) and the second tube (5) are preferably arranged relative to each other at least in the axial direction of the first tube (4) and / or the second tube (5). In the trimming phase, the first tube (4) and the second tube (5) are cut. In the welding phase, the first tube (4) and the second tube (5) come into contact and fuse together to form the tube connection (3).

3. The method according to claim 1 or 2, characterized in that, The tube connection system (2) includes a tube cutting unit (9), the tube cutting unit (9) includes a blade (9a) and preferably includes a blade heater (9c). Preferably, the trimming phase includes a heating step during which the blade heater (9c) heats the blade (9a) to a cutting temperature, and / or the trimming phase includes an alignment step in which the tube cutting unit (9) is aligned relative to the first tube (4), particularly at a first cutting position, and / or the tube cutting unit (9) is aligned relative to the second tube (5), particularly at a second cutting position, and / or the trimming phase includes a cutting step in which the first tube (4), particularly at the first cutting position, and / or the second tube (5), particularly at the second cutting position, is cut by the tube cutting unit (9), particularly by the blade (9a).

4. The method according to one of the preceding claims, characterized in that, The pipe connection system (2) comprises a pipe disconnecting device (14), preferably the pipe disconnecting device (14) comprises a sealing unit (15) and / or a disconnecting unit (17), and further preferably, the method comprises a disconnecting procedure in which the first pipe (4) and the second pipe (5) are disconnected, and further preferably, the disconnecting procedure comprises a sealing phase and / or a disconnecting phase, in the sealing phase, the first pipe (4) and / or the second pipe (5) are sealed by the sealing unit (15) to form a first seal (56) and / or a second seal (57), and in the disconnecting phase, the first pipe (4) and the second pipe (5) are cut by the pipe disconnecting unit (17), in particular between the first seal (56) and the second seal (57) by the pipe disconnecting unit (17).

5. The method according to one of the preceding claims, characterized in that, The method comprises temporarily closing the first pipe (4) and / or the second pipe (5) before performing the welding procedure or before performing the welding phase, performing an integrity test procedure after performing the welding procedure or after performing the welding phase to verify the integrity of the pipe connection (3), and, depending on the result of the integrity test procedure, if the integrity of the pipe connection (3) is verified, releasing the temporary closure of the first pipe (4) and / or the second pipe (5), and if the integrity of the pipe connection (3) is not verified, initiating an emergency procedure for preserving the cell culture.

6. The method according to one of the preceding claims, characterized in that, The method comprises connecting the first pipe (4) or the second pipe (5) of the integrated bioprocessing system (1) to a third pipe (19) through the pipe connection system (2) to form a further pipe connection (20), wherein the further pipe connection (20) is formed in a welding procedure.

7. An integrated bioprocessing system for performing a bioprocess on a cell culture, wherein during the performance of the bioprocess, a culture medium for the bioprocess, in particular a cell culture, can be conveyed by the integrated bioprocessing system (1) through a tube. The integrated bioprocessing system (1) includes a first tube (4) for conveying the culture medium and a second tube (5) for conveying the culture medium, a movable first carrier (10), and a tube connection system (2). The first tube (4) is held by a first tube holder (7) and is fluidly connected to a first fluid structure (12) for receiving and / or providing the culture medium. The first tube (4), the first tube holder (7), and the first fluid structure (12) are carried by the first carrier (10), and the first carrier (10) and the first tube (4), the first tube holder (7), and the first fluid structure (12) carried thereby can be transported to a welding position within the integrated bioprocessing system (1). The tube connection system (2) is used to connect the first tube (4) and the second tube (5) at the welding position during a welding procedure, thereby forming a tube connection portion (3) by welding. After welding, the culture medium can be conveyed from or to the first fluid structure (12) of the first carrier (10) through the tube connection portion (3).

8. The integrated biological treatment system according to claim 7, wherein The second tube (5) is held by a second tube holder (8) and is fluidly connected to a second fluid structure (13) for receiving and / or providing the culture medium. Preferably, the integrated bioprocessing system (1) includes a movable second carrier (11). The second tube (5), the second tube holder (8), and the second fluid structure (13) are carried by the second carrier (11), and the second carrier (11) and the second tube (5), the second tube holder (8), and the second fluid structure (13) carried thereby can be transported to the welding position.

9. The integrated biological treatment system according to claim 7 or 8, characterized in that The tube connection system (2) includes a tube arrangement unit (6) and a tube cutting unit (9). The tube arrangement unit is used to arrange the first tube (4) and the second tube (5) relative to each other at least in the axial direction of the first tube (4) and / or the second tube (5) during the arrangement stage of the welding procedure, such that the first tube (4) and the second tube (5) can be cut. The tube cutting unit (9) is used to cut the first tube (4) and the second tube (5) during the trimming stage of the welding procedure. Preferably, the tube arrangement unit (6) is designed to bring the first tube (4) and the second tube (5) into contact and fuse them together during the welding stage of the welding procedure, thereby forming the tube connection portion (3).

10. The integrated biological treatment system according to claim 9, wherein, The first tube holder (7) and / or the second tube holder (8) is / are part of the tube arrangement unit (6). Preferably, the tube arrangement unit (6) includes a first holder moving device (21) and / or a second holder moving device (22). The first holder moving device (21) is configured to move the first tube holder (7), particularly in a direction orthogonal to the axial direction of the first tube (4). The second holder moving device (22) is configured to move the second tube holder (8), particularly in a direction orthogonal to the axial direction of the second tube (5). More preferably, the first holder moving device (21) includes a first holder guide (23) for guiding the movement of the first tube holder (7) and / or the second holder moving device (22) includes a second holder guide (24) for guiding the movement of the second tube holder (8), and / or the first holder moving device (21) includes a first holder drive unit (25) and / or the second holder moving device (22) includes a second holder drive unit (26). Preferably, the first holder guide (23) is designed as a first track unit and / or the second holder guide (24) is designed as a second track unit.

11. The integrated biological treatment system according to claim 9 or 10, characterized in that, The tube arrangement unit (6), particularly the first tube holder (7), includes a first tube moving device (27) for moving the first tube (4) held by the first tube holder (7), particularly one-dimensionally and / or in the axial direction of the first tube (4). Preferably, the first tube (4) held by the first tube holder (7) is moved relative to the first tube holder (7), and / or the tube arrangement unit (6), particularly the second tube holder (8), includes a second tube moving device (28) for moving the second tube (5) held by the second tube holder (8) one-dimensionally, particularly in the axial direction of the second tube (5), and / or the first tube moving device (27) includes a first tube drive unit (29) and / or the second tube moving device (28) includes a second tube drive unit (30).

12. The integrated biological treatment system according to claim 11, characterized in that, The first tube driving unit (29) includes a rotatable first driving roller (31), and / or the second driving unit (30) includes a rotatable second driving roller (32), wherein when the first driving roller (31) rotates, it causes the first tube (4) to move in its axial direction, and / or when the second driving roller (32) rotates, it causes the second tube (5) to move in its axial direction. Preferably, the first tube driving unit (29) includes a first driving locking member (33) for locking the first driving roller (31) such that the first tube (4) is immovable relative to the first tube driving unit (29), and / or the second tube driving unit (30) includes a second driving locking member (34) for locking the first driving roller (31) such that the second tube (5) is immovable relative to the second tube driving unit (30), and / or the first tube driving unit (29) includes a rotatable first passive roller (35), and / or the second driving roller (36) includes a rotatable second passive roller (36). Preferably, the first tube driving unit (29) includes a first pre-tensioning device (37) for pre-tensioning the first passive roller (35) against the first tube (4), and / or the second tube driving unit (30) includes a second pre-tensioning device (38) for pre-tensioning the second passive roller (36) against the second tube (5).

13. The integrated biological treatment system according to any one of claims 7 to 12, characterized in that, The tube connection system (2) includes in particular a movable tube connector (43). Preferably, the tube connector (43) includes a first tube receiver (58) for receiving a tube, in particular the first tube (4), and / or a second tube receiver (59) for receiving a tube, in particular the second tube (5). Further preferably, at least a part of the tube cutting unit (9) is arranged on the tube connector (43).

14. The integrated biological treatment system according to any one of claims 7 to 13, characterized in that, The tube arrangement unit (6) includes a first guiding device (39) for guiding the first tube (4) and / or a second guiding device (40) for guiding the second tube (5). Preferably, the first guiding device (39) is part of the first tube holder (7) and / or the second guiding device (40) is part of the second tube holder (8), or the first guiding device (39) and the second guiding device (40) are part of the tube connector (43), in particular part of the first tube receiver (58) and the second tube receiver (59). More preferably, the first guiding device (39) includes a first funnel (41) and / or the second guiding device (40) includes a second funnel (42), wherein the first funnel (41) is arranged such that the first tube (4) can move through the first funnel (41) and / or the second funnel (42) is arranged such that the second tube (5) can move through the second funnel (42).

15. The integrated biological treatment system according to any one of claims 7 to 14, characterized in that, The pipe connection system (2) includes a position determination device (47) for determining the position of the first pipe (4) and / or the second pipe (5) and / or the first pipe holder (7) and / or the second pipe holder (8) and / or the pipe connection head (43) and / or the first carrier (10) and / or the second carrier (11). Preferably, the position determination device (47) includes at least one, in particular optical or electrical, position sensor (48) or a plurality of, in particular optical and / or electrical, position sensors (48), and the position sensors are at least partially arranged on the first pipe holder (7) and / or the second pipe holder (8) and / or the pipe connection head (43) and / or the first carrier (10) and / or the second carrier (11).

16. The integrated biological treatment system according to any one of claims 7 to 15, characterized in that The pipe connection system (2) includes a robotic mechanism (52), in particular an x-y robotic mechanism or a Cartesian robotic mechanism, wherein the pipe connection head (43) is attached to the robotic mechanism (52) such that the pipe connection head (43) can move at least one-dimensionally, preferably two-dimensionally or three-dimensionally, and / or the pipe connection system (2) includes a transfer mechanism (53), wherein the first carrier (10) and the first pipe holder (7) and / or the second carrier (11) and the second pipe holder (8) can move at least one-dimensionally, preferably two-dimensionally or three-dimensionally through the transfer mechanism (53).

17. An integrated bioprocessing system, in particular the integrated bioprocessing system according to any one of claims 7 to 16, for performing a bioprocess on a cell culture, wherein, During the execution of the bioprocess, the culture medium for the bioprocess, in particular a cell culture, can be conveyed by the integrated bioprocessing system (1) through pipes. The integrated bioprocessing system (1) includes a first pipe (4) for conveying the culture medium and a second pipe (5) for conveying the culture medium, a movable first carrier (10), and a pipe disconnecting device (14). The first pipe (4) and the second pipe (5) are connected through a pipe connection portion (3) and are at a disconnect position within the integrated bioprocessing system (1). The first pipe (4) is held by a first pipe holder (7) and is fluidly connected to a first fluid structure (12) for receiving and / or providing the culture medium via the first pipe (4). The first pipe (4), the first pipe holder (7), and the first fluid structure (12) are carried by the first carrier (10), and the pipe disconnecting device (14) is used to disconnect the first pipe (4) and the second pipe (5) at the disconnect position during a disconnect procedure such that the first pipe (4) and / or the second pipe (5) are fluidly and / or physically disconnected. After the first pipe (4) and the second pipe (5) are disconnected, the first carrier (10) and the first pipe (4), the first pipe holder (7), and the first fluid structure (12) carried by it can be conveyed from the disconnect position.

18. A sealing unit, in particular a sealing unit of a tube disconnecting device (14) in an integrated bioprocessing system (1), for sealing a first tube (4) and / or a second tube (5) during a sealing phase so as to form a seal (56, 57), wherein the sealing unit (15) comprises at least one sealing surface (63) which is designed to crimp the first tube (4) and / or the second tube (5) along the respective axial directions of the first tube (4) and the second tube (5) such that the first tube (4) and / or the second tube (5) is / are self-sealed.

19. A device for conveying pipes (4, 5), in particular for conveying pipes within an integrated bioprocessing system (1) according to claims 7 to 16, wherein, The device comprises carriers (10, 11), tubes (4, 5), tube holders (7, 8) and fluid structures (12, 13), wherein the carriers (10, 11) carry the tubes (4, 5), the tube holders (7, 8) and the fluid structures (12, 13) such that the tubes (4, 5), the tube holders (7, 8) and the fluid structures (12, 13) can be transported together with the carriers (10, 11), and wherein the tube holders (7, 8) hold the tubes (4, 5) in a defined position.

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