Multiple connector port

Abstract

To provide a multiple connector port, and a method for filling or drawing via the multiple connector port.SOLUTION: A multiple connector port comprises: an air connection part 430 for sterilized air; at least one access 410, 420 arranged for connection components 411, 421; and at least one line 412, 422 arranged for the connection components, wherein the access has a self closing diaphragm.EFFECT: In a bio reactor, automated sterilization work in a non-sterilized environment for filling or drawing a material is made possible. Then, an existing handling system in a non-sterilized environment and an existing bio reactor or container are used together with the multiple connector port to make it possible to perform drawing or filling with no contamination.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The present invention relates to a multi-connector port and a method for filling or withdrawing through a multi-connector port. [Background technology]

[0002] In laboratories, especially those involved in biological processes, there is an increasing need for automated dissolution solutions that improve reproducibility, allow for work with small volumes, and are simultaneously flexible in use. Currently, automated dissolution solutions for bioreactor systems fall into two groups: autosamplers and automated pipetting systems for small volumes or stand-alone individual dissolution. Autosamplers lack standardized connections and can only be used in specialized, sterile systems closed to the outside world. Furthermore, they are limited in sample collection, with dead volumes typically remaining in the sampler. In the field of biological processes, the residence time in the sampler can also affect the sample. Automated pipetting systems for small volumes or stand-alone individual dissolution generally have the disadvantage that they are only suitable for specific bioreactors or vessels, and work performed with these solutions must be performed at a workstation. Generally, neither of these systems can be used for single-use bioreactions. Summary of the Invention [Problem to be solved by the invention]

[0003] SUMMARY OF THE INVENTION The present invention therefore aims to provide an improved solution that addresses the above-mentioned problems. [Means for solving the problem]

[0004] According to a first aspect of the present invention, the above object is achieved by a multi-connector port comprising an air connection for sterile air, at least one connecting piece, at least one access arranged in the connecting piece, and at least one line arranged in the connecting piece, the access including a self-closing diaphragm.

[0005] The present invention is based on the recognition that automatic filling and withdrawal is possible in bioreactors and vessels, especially without the need to work in a sterile workstation or closed system. Furthermore, automatic filling and withdrawal is applicable to a wide variety of bioreactor and vessel embodiments, provided that the filling and withdrawal points are separate from the bioreactor and vessel. For this purpose, a multi-connector port is used between the bioreactor and the liquid handling device, which can be connected to the bioreactor via at least one line in a sterile and leak-tight manner, and which is penetrable by the tip of a device, providing closure to the outside, and thus providing access to the liquid handling device. It should be understood that the tip of a device refers not only to a sharp, hollow needle, but also to a relatively blunt tip, such as a pipette tip or a male connecting piece. In the context of the present invention, penetration refers not only to piercing, but also to pushing open a self-closing diaphragm. For example, swabable valves, also called wipeable valves or needleless diaphragm valves, involve pushing open with a blunt tip, such as a male connecting piece.

[0006] Thus, the present invention allows automated sterile operation in a non-sterile environment for filling or withdrawing material, for example in a bioreactor, and allows the use of existing handling systems in a non-sterile environment and existing bioreactors or vessels with multi-connector ports for contamination-free withdrawal or filling.

[0007] Furthermore, the present invention recognizes that if the multi-connector port can be purged by connecting it to sterile air, any liquid remaining in the connecting parts or lines of the multi-connector port can be transferred to a reactor or container, thereby preventing or minimizing dead volume or contamination caused by conventional filling or drawing processes. Therefore, sample utilization can be maximized, making it possible to work with very small sample or fill volumes. Thus, the multi-connector port and its use according to the present invention provide a dissolution that is flexible to use, does not require a sterile environment, and avoids dead volume.

[0008] The present invention also recognizes that the multi-connector port of the present invention enables multiple work steps that could not be integrated into a single dissolution in existing systems. Thus, the multi-connector port can be used to, for example, collect samples from a bioreactor, dispense samples into microreaction vessels for subsequent analysis, dispense samples into collection vessels, dispense samples into automated systems such as analytical instruments, bleed bioreactors (i.e., remove cells from a bioreactor to control cell concentration), and fill bioreactors with, for example, media or media cocktails. Furthermore, it allows for automated, time-controlled delivery of media or media cocktails for bioprocessing.

[0009] In one embodiment, the air connection further comprises an additional self-closing diaphragm and a sterile filter, in particular a sterile filter with a pore size of 0.22 μm or less. This air connection allows sterile air to be filled in a simple manner through the tip without the need to provide a structurally tailored connection between the multi-connector port and the sterile air supply. Alternatively, the air connection can be configured with a common air connection system.

[0010] The air connection can be designed as follows: sterile air is drawn through the air connection into the tip, for example the tip of the handling system; then the sterile air is released from the tip and into the at least one access; then the air connection is either disconnected so that it is no longer fluidly connected to said at least one access, or the air connection is directly fluidly connected to at least one connection part, which is then connected to said at least one access.

[0011] In one embodiment, the side of the sterile filter facing the opposite side of the self-closing diaphragm is in contact with outside air. In this embodiment, when the tip is inserted through the self-closing diaphragm and outside air is drawn in by the tip through the sterile filter, sterile air in the reservoir provided by the tip is then available for supply to at least one access. Therefore, it is possible to supply sterile air for purging operations in a relatively simple manner without having to maintain sterile air in an available state. Alternatively, if sterile air is present in the air connection of a typical air connection system, the sterile air can be provided or drawn into the reservoir through the tip.

[0012] In an alternative embodiment, the air connection is fluidly connected to the connecting piece, thereby fluidly connecting at least one access, the air connection, and at least one line to each other via the at least one connecting piece. In this way, the access, the connecting piece, and the line can be purged using air released into the air connection. Again, the air connection may be configured as a connection of the air connection system and may further include a self-closing diaphragm and a sterile filter, in particular a sterile filter with a pore size of 0.22 μm or less. In the latter case, air is provided, for example, through the diaphragm via the tip and filtered by the sterile filter before being supplied to the connecting piece.

[0013] In one embodiment, the multi-connector port comprises multiple accesses located on the connecting piece, for example, to allow for simultaneous loading of different media as well as simultaneous withdrawal of multiple samples.

[0014] In a further embodiment, the multi-connector port has each connecting part with exactly one access and exactly one line. In this embodiment, the media loaded and the media withdrawn via the access are completely separate from each other from the access to the connected container, e.g., bioreactor. This makes it possible to avoid, for example, mixing before entering the bioreactor. Particularly preferred is a multi-connector port with exactly two connecting parts, each with one access and one line. Even more preferred is one access for loading media and one access for withdrawing media. In this embodiment, samples can be withdrawn without the risk of contamination with previously loaded media.

[0015] In one embodiment, the multi-connector port has multiple accesses and connection components. In this embodiment, too, only one air connection is required, which can be used for purging all accesses. It is particularly advantageous here if the air connection is configured so that sterile air can be drawn into the tip through it. This embodiment is particularly advantageous because it can be used with multiple bioreactors simultaneously.

[0016] In a further embodiment, the respective accesses, the respective lines and the air connections are fluidly connected via respective connection pieces, so that purging can be performed at the two accesses via one air connection, while filling or withdrawing media is performed separately between the container and the accesses, thus avoiding mixing or contamination.

[0017] The multi-connector port advantageously has a locking device, which allows, for example, the connection parts to be mechanically connected to one another to improve handling as a self-contained component. However, it is also advantageous to use a locking device that is particularly configured to connect the multi-connector port to a handling system, in particular a processing robot. In this way, the multi-connector port can be accurately positioned and held in place, allowing automated devices such as processing robots to access it in an automated manner.

[0018] The multi-connector port is preferably designed to be sterilizable. Sterilization can preferably be accomplished using autoclaving, irradiation, or ethylene oxide. Thus, sterile access through the multi-connector port can be achieved by simple sterilization methods without the need to work in a closed system or workstation.

[0019] In one embodiment of the multi-connector port, at least one line has an airtight and liquid-tight connection at the end facing away from the connecting piece. Via this connection, the multi-connector port can be easily and safely connected, for example, to the head plate of a bioreactor. Standardized connections that are compatible with as many vessels or head plates as possible are particularly advantageous here. For example, Luer lock or screw connections may be included. In a very simple embodiment, at least one line is configured as a simple hose that can be plugged into a connection on the head plate of a bioreactor, for example.

[0020] It is further advantageous if the multi-connector port has a cap for covering at least one access and / or air connection, in this way the access and / or air connection can be protected from contamination while they are not in use.

[0021] In one embodiment, the self-closing diaphragm is configured as a pierceable septum. That is, even when pierced, it remains impermeable outside the piercing portion and forms a sealed closure with the piercing object. It is particularly preferred that the pierceable septum is impermeable to gases and liquids up to a pressure of 0.5 bar, even when pierced by a hollow needle or pipette tip, especially when pierced by a hollow needle or pipette tip with a diameter of less than 1.5 mm, and even after multiple piercings by such a hollow needle or pipette tip. In one embodiment, the pierceable septum has a piercing slot, especially a cross-shaped slot. The septum can be made, for example, from silicone; septa of this type are already known in the prior art.

[0022] However, in an alternative embodiment, the access can also be configured as a needleless diaphragm valve with a self-closing diaphragm, such valves being known for example from US Patent No. 5,368,801 A, US Patent No. 7,9497,032 B2 or International Application WO 2013 / 158756.

[0023] According to a second aspect, the present invention relates to a method for filling or withdrawing via a multi-connector port according to any one of the previous aspects, the method comprising: connecting at least one line of the multi-connector port to a vessel, in particular a bioreactor; cleaning the outer surface of at least one access and / or the outer surface of the air connection by wiping or rinsing with a cleaning agent, in particular containing isopropanol; - piercing the self-closing diaphragm of at least one access with a tip, in particular a hollow needle, a pipette tip or a male connection part; loading or withdrawing media into or from the container via the tip; withdrawing the tip; applying sterile air; Includes.

[0024] The step of applying sterile air preferably comprises: piercing an additional self-closing diaphragm of the air connection at the tip; Drawing ambient air through the tip and through a sterile filter into a reservoir connected to the tip; and withdrawing the tip from the additional self-closing diaphragm. piercing a self-closing diaphragm of at least one access of the multi-connector port with a distal end; applying air from a reservoir to the access; Includes.

[0025] This method, especially in combination with handling systems, can facilitate the use of sterile air for purging and avoid dead volumes without the need to keep sterile air available, meaning that work can be carried out more flexibly and independently from other infrastructure.

[0026] Alternatively, applying sterile air via the air connection is performed by applying sterile air via the air connection to at least one connection part that is fluidly connected to the air connection, where the sterile air is supplied from the outside via the air connection or from the outside via an additional self-closing diaphragm and a sterile filter to provide the at least one connection part and at least one line and at least one access arranged therein.

[0027] In a preferred embodiment, after applying sterile air, a final cleaning of the outer surface of at least one access and / or the outer surface of the air connection is performed. Preferably, the cleaning is performed using isopropanol or a similar cleaning liquid and / or disinfectant. The cleaning step facilitates working with the multi-connector port, even outside of a sterile environment, to ensure filling and withdrawal under sterile conditions. Preferably, the multi-connector port comprises at least one cap, which is removed before performing the cleaning and / or replaced after performing the final cleaning.

[0028] It is particularly advantageous to load the media via a different access and a different line than to withdraw the media.

[0029] In one embodiment of the method, if the tip is part of a handling system and has a locking device on the connecting part, the multi-connector port is accurately positioned relative to the handling system by the locking device before performing the cleaning, which facilitates automatic filling and withdrawal by the handling system.

[0030] According to a third aspect, the present invention relates to a system comprising a multi-connector port according to the first aspect of the invention and a handling system having at least one tip, in particular a hollow needle, a pipette tip or a male connection part. Such a system allows automatic, contamination-free filling and withdrawal of bioreactors or other containers, even without a sterile environment. Furthermore, the system according to the third aspect of the invention also shares the advantages of the multi-connector port and the method according to the further aspects of the invention.

[0031] Here, the handling system may in particular be a processing robot or an automated liquid handling system.

[0032] In one embodiment, the system further comprises a sealing device for encapsulating the tip against ambient air. Such a sealing device allows for more reliable withdrawal or filling, since the tip does not come into contact with ambient air and contamination is more effectively avoided. The sealing device may be designed in particular as a nozzle device for flowing sterile air around the tip, or as a self-closing casing.

[0033] In the case of a nozzle device for flowing sterile air around the tip, at least one nozzle is connected to an air connection for sterile air and is positioned near and facing the tip, so that sterile air flows around the tip and the tip does not come into contact with ambient air, at least over the maximum length that the tip can extend into at least one access or air connection. In this way, a sterile air curtain is formed by the nozzle device. Sterile air can flow around continuously, or at least until and as long as the tip does not penetrate completely.

[0034] The self-closing casing hermetically seals the tip when the tip is free, i.e., when the tip is not piercing anything. When the tip pierces, for example, a self-closing diaphragm, the casing is pressed in, and when the tip is withdrawn, the casing seals the tip again. Here, the self-closing casing, which can be made, for example, from silicone, has, for example, a cross-shaped slot extending over a predetermined length of the tip. When the tip is pressed into the self-closing diaphragm, the casing is also pressed in. This seals the tip, together with the self-closing diaphragm, against the ambient air. When the tip is withdrawn, the casing returns to its original shape and wraps around the tip. The self-closing casing can be designed, in particular, in the form of a cap, for example, a silicone cap with a cross-shaped slot.

[0035] In a further alternative, the air connection and / or at least one access comprises a cap that can be automatically attached to and detached from the tip.

[0036] Further embodiments are described below by way of example on the basis of the attached figures. [Brief explanation of the drawings]

[0037] [Figure 1] 1A and 1B show an embodiment of a multi-connector port according to a first aspect of the present invention; [Figure 2] 10A-10D show further embodiments of a multi-connector port according to the first aspect of the present invention; [Figure 3a] 10A-10D show further embodiments of a multi-connector port according to the first aspect of the present invention; [Figure 3b] 10A-10D show further embodiments of a multi-connector port according to the first aspect of the present invention; [Figure 4] 10A-10D show further embodiments of a multi-connector port according to the first aspect of the present invention; [Figure 5] FIG. 2 illustrates an embodiment of the method according to the second aspect of the present invention. [Figure 6] FIG. 2 illustrates an embodiment of a system according to a third aspect of the present invention. [Figure 7] FIG. 2 shows details of a portion of an embodiment of a system according to a third aspect of the present invention. [Figure 8] 5A and 5B show some details of an embodiment of two states of the system according to the third aspect of the invention; DETAILED DESCRIPTION OF THE INVENTION

[0038] FIG. 1 shows an embodiment of a multi-connector port 100 according to a first aspect of the present invention. In the embodiment shown, the multi-connector port 100 has two accesses 110, 120. Each of these accesses 110, 120 is disposed in a connecting piece 111, 112. Furthermore, in each case, one line 112, 122 is disposed in the respective connecting piece 112, 112. Each of the accesses 110, 120 has a self-closing diaphragm 115, 125. In the embodiment shown herein, the self-closing diaphragm 115, 125 of each access 110, 120 is configured as a pierceable septum. The septum may be, for example, a commercially available silicone septum that can be pierced by a tip, for example, in the form of a hollow needle or a pipette tip, and that remains leak-tightly sealed against the outside. In a preferred embodiment, the pierceable septum is configured as a slot, particularly a cross-shaped slot, through which the tip can penetrate, with the walls of the slot tightly pressed against the tip, thus closing the lumen below the septum in a leak-tight manner. In an alternative embodiment (not shown), the accesses 110, 120 can also be configured as needleless diaphragm valves. Apart from the accesses 110, 120, the multi-connector port 100 also has an air connection 130, which in the illustrated embodiment also includes an additional self-closing diaphragm 135 and a sterile filter 140. In the illustrated embodiment, the sterile filter has a pore size of 0.22 μm or less. In the illustrated embodiment, the air connection 130 is fluidly connected to the lines 112, 122 and the accesses 110, 120 via connecting pieces 111, 121. This embodiment of the air connection makes it easy to purge the connection parts 111, 121 and lines 112, 122 with sterile air by air introduced through an additional self-closing diaphragm via the tip and filtered by a sterile filter 140. The sterile air can then be connected to the multi-connector port without the need to keep the sterile air available along with the corresponding connection parts for its storage.Alternatively, a standardized air connection for sterile air can be provided at the multi-connector port. Lines 112, 122 lead to the head plate 155 of the bioreactor 150, and the multi-connector port 100 is used here for filling and withdrawing the bioreactor 150. However, the multi-connector port 100 can also be used for a large number of other containers and connection possibilities. The multi-connector port 100 can be flexibly combined with other systems. For this purpose, special connections for leak-tight connection to each container can be provided in the lines 112, 122. However, the lines 112, 122 can also be configured, for example, in the form of simple hoses inserted into existing septa on the head plate. The multi-connector port 100 allows simple and reliable filling and withdrawing of a large number of containers, with filling and withdrawing points separate from the containers themselves. Filling or withdrawing is performed via the accesses 110, 120. In the illustrated embodiment, it is particularly advantageous that one of the accesses (in this case, access 110) is used only for filling, and the other access (in this case, access 120) is used only for withdrawal. This ensures that samples taken from the container are not contaminated by media previously filled via access 110 and its connecting piece 111 and line 112. Access 120 and its connecting piece 212 and line 122 are fluidically isolated from access 110. The two parts of the multi-connector port are connected to each other only via an air connection, through which no liquid is exchanged. As already mentioned, air connection 130 is used to purge the connecting pieces and lines. Media present in connecting pieces 111, 121 or lines 112, 122 is forced into the reactor by filling with sterile air. Thus, the previously filled media is completely transferred to the reactor, leaving little or no dead volume in the connecting pieces or lines.In this way, it is possible to ensure that the predetermined amount of media actually reaches the bioreactor or other container. In the case of withdrawal access, the withdrawn media is forced back into the bioreactor or other corresponding container by purging with sterile air, so that the media is not left in the withdrawal line, which would expose the media to excessive conditions different from those inside the reactor. Therefore, if a sample is subsequently taken, it is guaranteed that the sample originates entirely from the interior of the bioreactor or other container and will not be contaminated by sample residues left in the lines or connecting parts for a relatively long period of time. The entire multiconnector port 100 is preferably designed to be sterilizable. It is further advantageous if all exterior surfaces of the multiconnector port, especially the diaphragm, can be easily sterilized, for example, by wiping with a cleaning liquid such as isopropanol or simply spraying or rinsing with such a cleaning liquid. These cleaning and sterilization procedures ensure that the multiconnector port 100 can be used to fill containers in a sterile manner, even outside of a sterile work environment. This reduces the cost of the work process while making the work involved in withdrawing or filling samples easier and more flexible in terms of location. As an additional protective measure not shown here, the multi-connector port 100 can include one or more caps for the accesses 110, 120 and the air connection 130. These caps are first removed before filling or withdrawing media and then reinstalled after the work is completed. This protects the accesses and air connections from contamination while they are not in use.

[0039] FIG. 2 shows a further embodiment of a multi-connector port 200 according to the first aspect of the present invention. The multi-connector port 200 has substantially the same structure as the multi-connector port 100 of FIG. 1. Therefore, further features will be described below, and reference is otherwise made to the description associated with FIG. 1. In the multi-connector port 200, components identical to those of the multi-connector port 100 are designated by the same reference numerals. The multi-connector port 200 is connected to a head plate 255 of a bioreactor 250. In the illustrated embodiment, the head plate is also disposed in a liquid handling system, thereby enabling automated filling and withdrawal. In the illustrated embodiment, the multi-connector port 200 includes a fixing device 260. The fixing device 260 is connected to and fixed in the handling system by a bracket 270 provided on the handling system, allowing a processing robot to easily and accurately move to the accesses 110, 120 of the multi-connector port 200. Here, an example is provided to show how a tip 285 of a processing robot 280 penetrates the self-closing diaphragm 115 of the access 110. As shown, the tip 285, configured here as a hollow needle, penetrates the diaphragm into the connecting piece, allowing liquid to be expelled into the connecting piece 110 and its adjacent line 112, thereby reaching the bioreactor 250. The multi-connector port 200 has an air connection 230 for connecting a sterile air line, which air connection 230 is configured by a screw thread. This connection makes it possible to use a sterile air reservoir or line to purge the multi-connector port 200 and force residues from the access, connecting piece, or line into the bioreactor 250. Here, the reservoir is already present in the respective workstation. The multi-connector port 200 otherwise shares the advantages described for the multi-connector port 100 of FIG. 1.

[0040] FIG. 3a shows a further embodiment of a multi-connector port 300 according to the first aspect of the present invention. This embodiment differs from the embodiment of FIGS. 1 and 2 in the following respects: In the embodiment shown in FIG. 3a, only one connecting piece 311 is provided, on which two accesses 310, 320 are arranged, each equipped with a self-closing diaphragm 315, 325. In this embodiment, an air connection 330 equipped with an additional self-closing diaphragm 335 and a sterile filter 340 is not fluidly connected to the connecting piece 311. In the illustrated embodiment, the sterile filter 340 is in contact with the outside air at its side 341 facing the opposite side of the additional self-closing diaphragm. When a tip is introduced from above through the self-closing diaphragm 330, air can be drawn through the tip, through the sterile filter 340, and transferred to a reservoir connected to the tip. The tip can then be introduced into one of the accesses 310, 320, and air can be applied to the connecting piece 311 and the line 312. This forces media present in the access, connection, or line from a previous filling or withdrawal process into the connected reaction vessel 350. The multi-connector port 300 has an air connection for sterile air 330, which has an additional self-closing diaphragm 335 and a sterile filter 340. Furthermore, the multi-connector port 300 has a locking device 360 for integration into a handling system. The illustrated embodiment can be used in particular when there is little space available for the multi-connector port 300 in the vessel or for the intended purpose, or when its use does not result in problematic contamination of the common lines, e.g., when the intended purpose involves only filling or only withdrawal. To further reduce the required space, it is also possible to provide only one access, e.g., access 310, so that the multi-connector port 300 can be implemented in a very small space.

[0041] The embodiment shown in Figure 3b differs from the embodiment of Figure 3a only in that the air connection 330 is not connected to the accesses 310, 320 by a fastening device 360. Here, the air connection 330 is configured separately. This is particularly advantageous in embodiments of the multi-connector port having multiple accesses (not shown here), since all of the multiple accesses can be purged by one air connection 330. These embodiments of the multi-connector port allow multiple bioreactors to be connected simultaneously.

[0042] FIG. 4 illustrates a further embodiment of a multi-connector port 400 according to the first aspect of the present invention. In the illustrated embodiment, access 410 and access 420 have completely separated paths. Connection pieces 411 and 421 are located in access 410 and access 420, respectively, and lines 412 and 422 are located in connection pieces 411 and 421, respectively. Access 410 and access 420 each have a self-closing diaphragm 415, 425, which in this embodiment are in the form of a pierceable silicone septum. To prevent contamination, access 410 is preferably provided for filling and access 420 for withdrawal. Multi-connector port 400 further includes a locking device 460, which allows for easy connection of multi-connector port 400 to a handling system. Locking device 460 is simultaneously mechanically connected to accesses 410, 420 and air connection 430. As already described in detail with respect to the multi-connector port 300 and its air connection 330, the fixture is equipped with a sterile filter 440 and an additional self-closing diaphragm. This allows ambient air to be drawn in through the air connection 430, sterilized in the filter 440, and then passed through one of the previously used accesses via a tip with a connected reservoir, so that it can be used for purging. In the embodiment shown, lines 412, 422 are plugged through the multi-connector port 400 into connections 456 on a head plate 455 of the bioreactor 450, allowing filling and sampling of the bioreactor 450.

[0043] 5 shows an embodiment of a method according to the second aspect of the invention for filling or withdrawing fluid through a multi-connector port. For preparation purposes, in step S1, at least one line of the multi-connector port is connected to a vessel, in particular a bioreactor. In the simplest case, the connection can be made, for example, by introducing a line configured as a hose into a diaphragm or septum in the head plate of the bioreactor. If the multi-connector port is used in combination with a handling system, this step also includes accurate positioning and optional fixation relative to the handling system, so that the tip and other parts of the handling system can be easily and accurately moved relative to the multi-connector port.

[0044] In optional step S2a, a cap placed on at least one access or air connection is removed. The cap is optionally pre-cleaned, for example with a cleaning agent and / or a disinfectant. Then, in step S2b, the outer surface of the at least one access and / or air connection is cleaned. This is preferably done by rinsing, spraying, or wiping with a cleaning agent and / or a disinfectant such as isopropanol. If the multi-connector port is integrated into a handling system, this step can be performed automatically, in particular by the handling system.

[0045] In step S3, the self-closing diaphragm of at least one access is pierced with a tip, in particular in the form of a hollow needle, a pipette tip or a male connecting part, and either the introduction of media into the container or the withdrawal of sample or media is carried out via the tip.

[0046] In step S4, sterile air is applied to the access of a previously used multi-connector port. This can be performed via a fluid connection between the air connection and the access, or in one embodiment, includes the substep of piercing an additional self-closing diaphragm of the air connection with the tip. Ambient air is then drawn through the tip through a sterile filter into a reservoir connected to the tip. The tip is then withdrawn from the additional self-closing diaphragm, and the tip pierces the self-closing diaphragm of at least one access of the multi-connector port. Finally, air is applied from the reservoir to the access.

[0047] In optional step S5a, cleaning is then carried out again, for example by rinsing with a cleaning solution, spraying or wiping, and finally, if caps are used, these are reinstalled in step S5b. The caps are optionally sprayed with a disinfectant.

[0048] If the multi-connector port is to be used with further reaction vessels at the same location, then proceed again with optional step S2a, otherwise positioning of the multi-connector port or connection to further reaction vessels is performed again in step S1.

[0049] FIG. 6 shows an embodiment of a system 1000 according to a third aspect of the present invention. In the illustrated embodiment, the system 1000 comprises a multi-connector 500, which comprises an air connection for sterile air, at least one access arranged in a connecting piece, and at least one line arranged in the connecting piece. The access may comprise, for example, a self-closing diaphragm, as described in detail in FIGS. 1 to 4. Furthermore, the system 1000 comprises a handling system 600 having at least one tip 680, which in this case is in the form of a hollow needle. In the illustrated illustration, only a portion of the handling system is shown. In the system 1000, when the multi-connector port 500 is connected to, for example, a bioreactor, withdrawal from or filling of the bioreactor can be performed automatically in a non-sterile environment.

[0050] FIG. 7 shows some details of an embodiment of a system according to the third aspect of the invention. Here, the tip 780 of a handling system 700 (not further shown) is shown in detail as part of the system. The system comprises a nozzle arrangement 790 with a nozzle for flowing sterile air around the tip 780. The nozzle is connected to a sterile air connection 791 and is directed towards the tip. Sterile air flows around the tip, which does not come into contact with ambient air over a length L. In this way, a sterile air curtain 792 around the tip is formed by the nozzle arrangement 790. Sterile air can flow continuously, or until the tip has completely penetrated, and at least while the tip is penetrated. FIG. 8 shows some details of two states of an embodiment of a system according to the third aspect of the invention. The system, part of which is shown here, comprises a sealing device in the form of a self-closing casing 890. The self-closing casing 890 is designed here as a silicone cap with a cross-shaped slot. Here, at the end facing away from the open end of tip 880, the silicone cap has an opening for receiving the tip, and at the opposite end facing the open end of the tip, the silicone cap has a cross-shaped slot. In the top diagram, the tip 880 of the handling system is free and sealed from the ambient air by the self-closing casing. As shown in the bottom diagram, when tip 880 is pressed, for example, into self-closing diaphragm 815, the self-closing casing 890 comes into contact with self-closing diaphragm 815, pushing open the self-closing casing and causing a portion of tip 880 to penetrate the self-closing diaphragm. Meanwhile, the other portion of tip 880 enclosed by casing 890 remains protected by casing 890. In this way, casing 890, together with self-closing diaphragm 815, seals the tip from the ambient air. As soon as tip 880 is withdrawn, casing 890 returns to its original position and wraps around tip 880.

Claims

1. an air connection for sterile air; at least one access arranged on the connection part; at least one line disposed on the connection piece; Equipped with the access has a self-closing diaphragm; Multi-connector port.

2. The air connection With additional self-closing diaphragm, a sterile filter, in particular a sterile filter with a pore size of 0.22 μm or less; Equipped with The multi-connector port of claim 1 .

3. the side of the sterilizing filter facing opposite the self-closing diaphragm is in contact with the outside air; The multi-connector port of claim 2 .

4. the air connection is configured so that sterile air is drawn through the air connection to the tip; A multi-connector port according to any one of claims 1 to 3.

5. At least one of the access, the air connection and the at least one of the lines are fluidly connected to one another via at least one of the connecting pieces.

3. The multi-connector port according to claim 1 or 2.

6. It has exactly two accesses, one of which is configured for loading media and the other is configured for extracting media; A multi-connector port according to any one of claims 1 to 5.

7. having a fixing device, in particular a fixing device for connection to a handling system, in particular a processing robot, A multi-connector port according to any one of claims 1 to 6.

8. Designed to be sterilizable, The sterilization procedure can preferably be carried out using an autoclave, irradiation, or ethylene oxide. A multi-connector port according to any one of claims 1 to 7.

9. a cap for covering at least one of the access and / or air connections; A multi-connector port according to any one of claims 1 to 8.

10. The self-closing diaphragm is configured as a pierceable septum, or the access is configured as a needleless diaphragm valve including a self-closing diaphragm. A multi-connector port according to any one of claims 1 to 9.

11. 11. A method for filling or withdrawing via the multi-connector port of any one of claims 1 to 10, comprising: connecting at least one of the lines of the multi-connector port to a vessel, in particular a bioreactor; cleaning the outer surface of at least one of said accesses and / or the outer surface of said air connection by wiping or rinsing with a cleaning agent, in particular comprising isopropanol; - piercing the self-closing diaphragm of at least one of the accesses with a tip, in particular a tip in the form of a hollow needle, a pipette tip or a male connection part; filling or withdrawing a medium into or from the container via the tip; withdrawing the tip; applying sterile air; Including, method.

12. The step of applying sterile air comprises: piercing the additional self-closing diaphragm of the air connection with a tip; Drawing ambient air through the tip, through the sterile filter, and into a reservoir connected to the tip; withdrawing the tip from the additional self-closing diaphragm; piercing the self-closing diaphragm of at least one of the accesses of the multi-connector port with the tip; applying air from the reservoir to the access; Including, The method of claim 11.

13. After the step of applying sterile air, a final cleaning of at least one outer surface of the access and / or the outer surface of the air connection is performed.

13. The method of claim 11 or 12.

14. the multi-connector port comprises at least one cap; The cap is removed before the cleaning is performed and / or replaced after the final cleaning is performed.

14. The method according to any one of claims 11 to 13.

15. the tip is part of a handling system; the connecting part has a fixing device; the multi-connector port is accurately positioned relative to the handling system by the fixing device before the cleaning is performed; 15. The method according to any one of claims 11 to 14.

16. The multi-connector port according to any one of claims 1 to 10; a handling system having at least one tip, in particular in the form of a hollow needle, a pipette tip or a male connection part; Equipped with system.

17. further comprising a sealing device for sealing the tip against ambient air, in particular a nozzle device for flowing sterile air around the tip, or a self-closing casing, 17. The system of claim 16.

Images