arrangement

Abstract

Instructions for handling biological material, including: a first biological handling element comprising a first volume having a first connection; a second biological handling element comprising a second volume having a second connection; an aseptic connecting element configured to aseptically fluidically connect the first port and the second port to provide aseptic fluid communication between the first volume and the second volume; an aseptic separation element configured to aseptically separate the first and second ports fluidically in order to prevent aseptic fluid communication between the first and second volumes; and one or more robot arms; wherein one or more robot arms are arranged to move the first biological handling element and / or the second biological handling element to align the first port and the second port with each other to enable the aseptic connecting element, when used, to aseptically fluidically connect the first port and the second port, and to enable the aseptic separating element, when used, to aseptically fluidically separate the first port and the second port.

Description

TECHNICAL AREA OF INVENTION

[0001] The invention relates to an arrangement for handling biological material. BACKGROUND

[0002] Biological handling processes, such as cell and / or gene therapy (CGT) manufacturing processes, are often complex and involve manual steps across multiple pieces of equipment. The equipment systems used in the various steps or unit operations of cell-based therapeutic product (CTP) manufacturing may include devices for different unit operations. These unit operations might include, for example, cell collection, cell isolation, selection, cell expansion, cell washing, volume reduction, cell storage, or cell transport. The unit operations can vary considerably depending on the manufacturing model (i.e., autologous versus allogeneic), cell type, intended use, and other factors. Furthermore, cells are living entities that are sensitive to even the simplest manipulations (such as differences in the cell transfer procedure).The role of cell manufacturing equipment in ensuring scalability and reproducibility is an important factor for cell and gene therapy manufacturing.

[0003] Furthermore, cell-based therapeutic products (CTPs) have gained considerable importance, creating a need for improved cell manufacturing equipment for various cell manufacturing processes, for example, but not limited to stem cell enrichment, chimeric antigen receptor (CAR) T cell generation, and various cell manufacturing processes such as extraction, purification, gene modification, incubation / recovery, washing, infusion into patients, and / or freezing.

[0004] The cultivation or processing of cells typically requires the use of a device for storing the cells, for example, in a suitable culture medium. Known devices include shake flasks, rolling flasks, T-flasks, and bags. Such flasks or bottles are widely used but have several disadvantages. Among the main problems is the need to transfer cells, media, or other material during transport or processing without contamination.

[0005] A current problem in the production of cells or gene therapies for medical use is the lack of compact, automated, closed systems for performing unit operations without contamination. For example, there is a risk of contamination during cell culture, upstream or downstream processing of cells, when additives are added to the culture vessel, or when cells or fluid samples are removed. Furthermore, current operating systems are largely manual and therefore expensive to use. Typically, multiple pieces of equipment are required to cover all steps outside of cell culture, which involves numerous transfers, each with the risk of operator error and contamination.

[0006] Furthermore, with increasing manual processes, the risk of manual errors increases, so the current labor-intensive processes may not have the robustness required for the manufacture of clinical-quality therapeutics.WO 2018 / 087558vA1 discloses a device for use in the breeding, cultivation and / or modification of cells, wherein the device comprises a primary container with a base section, an upper section arranged substantially parallel to the base section and a flexible wall element arranged between the upper section and the base section, defining an inner lumen of the primary container, wherein the wall element of the primary container is compressible with respect to the upper section and the base section, and wherein the primary container has at least one optionally closable inlet; and wherein the device further comprises a plurality of auxiliary containers which are detachably connected and are in fluid communication with the primary container.

[0007] Therefore, there is a need for arrangements for handling biological material, such as multi-stage processors of biological material or cells, which enable such processing in an automated or at least semi-automated manner, i.e., with minimal user intervention and / or minimal operation, while maintaining the sterility of the overall system.

[0008] Therefore, an objective of the present invention is to provide improved arrangements for handling biological material, in particular those for use in cell and / or gene therapy processing, and more precisely a device that enables the insertion and removal of material into and from a container in a sterile and automated or semi-automated manner.

[0009] Another objective of the present invention is to provide a device that combines the advantages of cell culture containers, which eliminate the need for pumps and the continuous transfer of cells into fresh culture devices, storage vessels, tubes, etc., with the advantages of individually configurable cell and / or gene therapy processing devices.

[0010] A further objective of the present invention is to provide a device that enables a variety of biological processes, such as one or more unit operations in cell processing, to be carried out within a single device or instrument that requires less space and is less complex than existing devices. Furthermore, the device described here allows for greater compatibility with automated systems. Further advantages will become apparent from the drawings and the description below. SUMMARY OF THE INVENTION

[0011] According to one aspect of the present invention, an arrangement for handling biological material according to claim 1 is provided.

[0012] An arrangement for handling biological material is provided, which includes the following: a first biological handling element comprising a first volume having a first connection; a second biological handling element comprising a second volume having a second connection; an aseptic connecting element configured to aseptically fluidically connect the first port and the second port to provide aseptic fluid communication between the first volume and the second volume; an aseptic separation element configured to aseptically fluidically separate the first port and the second port to prevent aseptic fluid communication between the first volume and the second volume; and one or more robotic arms; wherein one or more robot arms are arranged to move the first biological handling element and / or the second biological handling element to align the first port and the second port with each other to enable the aseptic connecting element, when used, to aseptically fluidically connect the first port and the second port, and to enable the aseptic separating element, when used, to aseptically fluidically separate the first port and the second port.

[0013] This offers the advantage that biological material can be handled in a "just-in-time" process. This means that the transfer of material between volumes occurs precisely when it is needed, instead of involving multiple pre-connected components. This ensures that biological material can be handled efficiently, aseptically, and in an automated or semi-automated manner.

[0014] In some embodiments, the first biological handling element comprises a substantially planar interface, as described herein.

[0015] In some embodiments, the first biological handling element comprises a first retention element that holds a first container having a first volume and a first connection.

[0016] In certain embodiments, the substantially planar interface comprises at least one port that is fluidically coupled to a container, for example, a bioreactor, the container comprising the first volume. The substantially planar interface may comprise multiple ports. Each of the multiple ports may be fluidically coupled to the container. The container may comprise an upper section, a base section, and a flexible or compressible wall element between the upper section and the base section. The wall element may comprise a plurality of grooves or coils, or a bellows wall element.

[0017] In some embodiments, the second biological handling element comprises a component retention element as described herein. The component retention element described herein can hold a container with the second volume and the second connection.

[0018] In some embodiments, the second biological handling element comprises a second retention element that holds a second container with a second volume and a second port.

[0019] In certain embodiments, the component retention element holds a component or is configured to hold it. The component may comprise a container with the second volume and the second connection. The container may include an upper section, a base section, and a flexible or compressible wall element between the upper section and the base section. The wall element may have a plurality of grooves or a bellows wall element. The container may be a bag, a flexible bag, or a container with a piston.

[0020] The first and / or second connection may comprise an open-end tube, a closed-end tube, or a tube with a removable aseptic membrane positioned over one end. The tube may be flexible. Alternatively or in combination, the first and / or second connection may comprise a hermetic seal, a septum gasket, a Luer-lock fitting, or the like.

[0021] The aseptic connecting element and the aseptic separating element can be a single unit. That is, a single aseptic connecting and separating element can be provided. The single aseptic connecting and separating element can include a connector, such as a sterile or aseptic connector, as described herein. In particular, the connector can include a needle. The needle can be actuated to engage or pierce the first and second ports, such as a first septum seal and a second septum seal, during use.

[0022] The aseptic connecting element can be a separate component in relation to the aseptic separating element.

[0023] The aseptic connection element may include an aseptic welding element. In particular, the aseptic connection element may include an aseptic pipe welding device configured and / or arranged to aseptically weld a first pipe, for example, the first connection, to a second pipe, for example, the second connection. The aseptic connection element may include a robot arm that terminates in an aseptic welding element. The aseptic welding element may be configured to apply heat and, optionally, pressure to the respective connections to weld them by heat. The aseptic welding element may also be configured to apply heat such that the closed end of a pipe or the aseptic membrane covering the end of a pipe is melted, thereby allowing fluid passage through the respective pipe.

[0024] The aseptic separation element may include an aseptic sealing element. In particular, the aseptic separation element may include an aseptic pipe sealing device configured and / or arranged to aseptically seal a first section of a pipe, for example, the first pipe or the first connection, with respect to a second connection of a pipe, for example, the second pipe or the second connection. The aseptic separation element may include a robotic arm terminating in an aseptic sealing element. The aseptic sealing element may be configured to apply heat and, optionally, pressure to a section of the connected connections to hot-seal it, thereby providing a first section of the connected connections that is hot-sealed against a second section of the connected connections.The aseptic sealing element can further be configured to cut or otherwise separate the sealed area between the first section and the second section of the connected terminals, thereby releasing the respective components.

[0025] The device may include a component retention element as described herein. The component retention element may be configured to hold the first biological handling element and / or the second biological handling element.

[0026] The device comprises one or more robotic arms. The one or more robotic arms are arranged to move the first biological handling element and / or the second biological handling element to align the first and second ports. The one or more robotic arms may include a retaining section arranged to hold the first and / or the second biological handling element. The one or more robotic arms may include an actuator section arranged to actuate a section of the first and / or the second biological handling element to cause the release of biological material from the first and / or second volume. The one or more robotic arms, the retaining section, and / or the actuator section may be controlled by a controller.The controller may include a user interface. The controller may be configured to control one or more robot arms, the restraint section, and / or the actuator section in response to user input into the user interface.

[0027] The device can be fully automated. This means that the device requires no manual intervention or user input. Alternatively, the device can be semi-automated. This means that the device may require minimal manual intervention or user input, such as inserting biological handling elements into the device.

[0028] The device may include an incubator or a housing that encloses the respective components of the device.

[0029] According to yet another aspect, a procedure for handling biological material is provided, which includes the following: Moving at least one of a first biological handling element comprising a first volume having a first port and a second biological handling element comprising a second volume having a second port, using one or more robotic arms to align the first port and the second port with each other; aseptic fluidic connection of the first port and the second port, thereby providing fluid communication between the first volume and the second volume; Transfer of biological material from the first volume to the second volume or from the second volume to the first volume; and Aseptic fluidic separation of the aseptically fluidically connected first and second ports, thereby preventing fluid communication between the first volume and the second volume.

[0030] This offers the advantage that biological material can be handled in a just-in-time process. This means that the transfer of material between volumes occurs precisely when required, instead of involving multiple pre-connected components. This ensures that biological material can be handled efficiently, aseptically, and in an automated or semi-automated manner.

[0031] In certain embodiments, the step of aseptically joining the first and second ports comprises aseptically welding the first port to the second port. In particular embodiments, the aseptic welding step can be performed by an aseptic pipe welding device.

[0032] In certain embodiments, the step of aseptically separating the first and second ports includes aseptically sealing the connected first and second ports to provide an aseptically sealed first port and an aseptically sealed second port. In particular embodiments, the aseptic sealing step can be performed by an aseptic tube sealing device.

[0033] Experts will recognize that the method may include one or more components of the apparatus described above or elsewhere, such as the substantially planar interface, the component retention element, the aseptic pipe welding device, the aseptic pipe sealing device, or the like. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Exemplary embodiments of the invention are described in the Fig. 24(a) to 24(d) are shown. Fig. Examples 1 to 23 are reference examples. Fig. Figure 1 illustrates a perspective overview of a system comprising an arrangement according to the invention, a housing and a component; Fig. Figure 2 illustrates a perspective view of the arrangement, the housing, and the component made of Fig. 1 during use; Fig. Figure 3 illustrates a perspective view of a planar interface, including a container attached to it; Fig. Figure 4 illustrates a cross-sectional side view of the arrangement. Fig. 3, including an expandable container and a cover attached to the planar interface; Fig. Figure 5 illustrates a perspective view of another planar interface with a container attached to it; Fig. Figure 6 illustrates (a) a perspective view of another planar interface, including a container attached to it, (b) a cross-sectional view of the planar interface from (a), (c) an enlarged cross-sectional view of the planar interface from (a), and (d) another cross-sectional view of the planar interface from (a); Fig. Figure 7 illustrates a perspective view of the arrangement. Fig. 5, which additionally includes a component retention element of an arrangement; Fig. Figure 8 illustrates (a) a perspective view of the insertion of the planar interface from Fig. 5 into a drawer of a housing, (b) a perspective view of the planar interface placed in the drawer in the open position and (c) a perspective view of the housing with the drawer in the closed position; Fig. Figure 9 illustrates (a) an enlarged perspective view of Fig. 8(b), (b) a partially cutaway perspective view of Fig. 8(c), and (c) an enlarged perspective view of (b) showing a drive mechanism. Fig. Figure 10 illustrates (a) a perspective view of another enclosure, illustrating positioning features of another planar interface and the drawer of the enclosure, and (b) a perspective view of (a) illustrating the planar interface inserted into the drawer; Fig. Figure 11 illustrates a partially cut-away front view of the casing made of Fig. 8(c) with a component retention element formed as part of the housing. Fig. Figure 12 illustrates (a) a cross-sectional side view of a component and (b) a cross-sectional perspective view of a connector of the component from (a); Fig. Figure 13 illustrates (a) a partially cutaway perspective view of Fig. 8(c) omitting the component retention element, (b) a perspective cross-sectional view of (a), (c) another perspective view of (a) showing a stirring mechanism and a stirring mode thereof, and (d) a side view of (a) showing another stirring mode of the stirring mechanism shown in (c); Fig. Figure 14 illustrates (a) a perspective view of another housing, (b) a perspective view of the insertion of the planar interface from Fig. 5 into the housing from (a), and (c) an enlarged view of (b); Fig. Figure 15 illustrates a perspective view of the casing. Fig. 14(a) with (a) an upper access door in the closed position and (b) an access door in the open position; Fig. Figure 16 illustrates (a) a perspective view of a component and the housing made of Fig. 14(a) before insertion, (b) an enlarged perspective view of Fig. 15(b), which shows the insertion of the component into a component retention element of the arrangement, and (c) an enlarged perspective view of Fig. 15(b), which shows a component that is inserted into a component retention element of the arrangement; Fig. Figure 17 illustrates a perspective view of (a) the component held in place by the component restraint element as shown in Fig. 16(c) shown, (b) the initial actuation of the component by the component retention element and (c) the further actuation of the component by the component retention element to bring the component into engagement with the planar interface; Fig. Figure 18 illustrates a schematic side view (a) of the component, which is held in place by the component retention element as shown in Fig. 16(c) shown, (b) the engagement of the component with the planar interface such that they are in alignment with each other, and (c) the removal of aseptic barriers of the component and the planar interface in order to bring the respective connections into engagement with each other; Fig. Figure 19 illustrates a perspective view of a system for removing aseptic barriers and in particular (a) a first step, (b) a second step and (c) a third step for actuating the system for removing aseptic barriers; Fig. Figure 20 illustrates a perspective view of the component, including a connector that passes through the component retention element as shown in Fig. 17(c) shown, (a) before actuation of the connector and (b) after actuation of the connector; Fig. Figure 21 illustrates a cross-sectional side of the connector made of Fig. 20 during various stages of its operation, including (a) before the connector is actuated, (b) after the first actuating of the connector, (c) after further actuating of the connector and (d) after the connector has been actuated; Fig. Figure 22 illustrates a perspective view of the component, which is held in place by the component retention element as shown in Fig. 17(c) shown, and furthermore comprising a dispensing device, (a) before dispensing and (b) after dispensing; Fig. Figure 23 illustrates a schematic side view of the component, which is held in place by the component retention element as shown in Fig. 17(c) shown is held after it has been removed from the planar interface; and Fig. Figures 24(a) to 24(d) illustrate a method for aseptically joining and separating biological handling components according to an example. DETAILED DESCRIPTION

[0035] The described embodiments relate to an arrangement for handling biological material. In particular, some embodiments relate to an arrangement that is aseptic or sterile. It should be noted that the terms "aseptic" and "sterile" may be used interchangeably throughout this disclosure. References to fluids in the detailed description are not intended to limit the scope of protection to such materials. As is known to those skilled in the art, the fluids described herein are merely an example of a suitable material for use with the described device. Likewise, reference may be made to a container, a receiving device, or the like; however, such references are not intended to limit the scope of protection to such containers or receiving devices. As is known to those skilled in the art, containers, receiving devices, or the like are described here merely as examples.

[0036] Certain terms are used in the following description for simplicity only and are not restrictive. The terms "top" and "bottom" denote directions in the referenced drawings and refer to the described component in its assembled and mounted state. The terms "inside," "inward," and "outside," as well as "outward," refer to directions toward and away from a particular centerline or geometric center of a described element (e.g., a central axis), the respective meaning being readily apparent from the context of the description. Furthermore, the terms "proximal" (i.e., closer to) and "distal" (i.e., farther from) denote positions relative to an axis or attachment point.

[0037] Furthermore, the terms "connected," "fastened," "coupled," and the like, as used here, are intended to encompass both direct connections between two elements without any intervening elements and indirect connections between elements where one or more other elements are involved. The terminology includes the terms explicitly mentioned above, derivatives thereof, and terms with similar meanings.

[0038] Unless otherwise stated, the use of ordinal adjectives such as "first," "second," "third," etc., merely indicates that different instances of the same objects are meant and does not imply that the objects so described must be arranged in a particular order, whether temporally, spatially, rank-wise, or otherwise. Identical reference numbers are used to consistently represent identical features.

[0039] As in the reference example in Fig. Figure 1 shows a system 1 for handling biological material, which includes an arrangement 10 for handling biological material.

[0040] In particular, the system 1 comprises a housing 12, a component retention element 14, a planar interface 16, a container 18, and a component 20. In this specific example, the component 20 is a connector 22 with a fluidically attached receiving device 24. The component 20 can be another component, such as an add-on, for example, a cell insert component 20a for inserting cells into the container 18; a bead insert component 20b for inserting beads, such as magnetic beads, into the container 18; a virus insert component 20c for inserting viruses into the container 18; or a media insert component 20d for inserting media, such as biological media suitable for cell storage, into the container 18.Furthermore, component 20 can be a withdrawal component, for example a cell withdrawal component 20e for removing cells from container 18 into a suitable container; a sampling component 20f for taking a sample of the contents of container 18; or a media removal component 20g for removing part, most, or all of the medium or contents of container 18. In general, in the described embodiments, component 20 comprises a connector 22 and a receiving device 24, wherein the receiving device 24 is arranged for suitable use as an addition or removal component 20a-20g.

[0041] With further reference to Fig. 2. The housing 12 forms an internal volume for receiving the component retention element 14, the planar interface 16, the container 18, and the component 20 located therein. The housing 12 generally has the form of an incubator unit. The component retention element 14 is integrally formed with the housing 12; that is, the component retention element 14 is formed as part of the housing 12 in an internal region thereof and is configured to hold, receive, or otherwise retain the component 20 during use. Furthermore, as shown in Fig. Figure 1 shows the planar interface 16 coupled to a container 18, for example a bioreactor, which may have flexible walls or be otherwise collapsible, to be fluidically and aseptically connected to it. When in use, the planar interface 16 and the container 18 are housed in the casing 12, as shown in the Fig. 1 and Fig. 2 shown.

[0042] Fig. Figure 3 shows part of a reference setup. In particular, it shows Fig. 3 a planar interface 116 with a container 118 attached thereto, for example a bioreactor. In particular, the planar interface 116 comprises a screw thread, as shown below. Fig. As explained in section 4, the planar interface 116 is connected to a complementary screw thread of the container 118. This creates an aseptic and fluid-tight or hermetic seal between the planar interface 116 and the container 118. The planar interface 116 comprises a plurality of ports 150, which in this example are configured as twenty-two septum seals through which a needle can pierce to allow the handling of biological material or fluid. Any number of septum seals can be used. Such uses may include, for example, taking samples from the contents of the container 118, adding substances to the container 118 in use, and / or removing contents, i.e., emptying, from the container 118 in use.In general, each connection 150 is configured to allow fluid passage through the planar interface 116 to the container 118 when in use and as described below. A person skilled in the art would recognize that other connections can also be used, which may have openings, doors, valves, or the like, to allow selected fluid communication through them.

[0043] As shown in this example, an aseptic barrier 152 is placed over each individual port 150. The aseptic barrier 152 is generally removable and attached to a surface of each port 150. The aseptic barrier 152 ensures the sterility of each port 150 before use and is generally removed before a connection is made to each port 150. In this example, the aseptic barrier 152 generally has the form of an aseptic skin made of paper or a polymer material. Each aseptic barrier 152 is designed to be removed by a section, for example, a barrier removal system, of the housing 12 (see housing in Fig. 1) or can be removed by the user, as described in more detail below.

[0044] The planar interface 116 of the present example further comprises a central hub 154 projecting from an upper surface of the planar interface 116 and comprising a plurality of coupling elements 156, which in the present embodiment are designed as clamps and configured to receive and be coupled to an extendable receiving device, as described in relation to Fig. 4 described.

[0045] Furthermore, the container 118 in the present example, which is designed as a bioreactor with an inner chamber, a base wall, and a compressible side wall, has a maximum volume of 1.5 l. In general, the base of the container 118, i.e., the cell growth area, can be 150 cm². 2Additionally, in some embodiments not shown, the container 118 can accommodate a 0.2-micrometer filter, which is formed as part of the base or side walls of the container 118 or, alternatively, as part of the planar interface 116. The filter can allow gas exchange between the environment, such as the housing, and the inner chamber of the container 118. The container 118 can generally be manufactured using a blow molding process, such as extrusion or injection blow molding, which simplifies the production of a container 118 as a one-piece unit, i.e., without joints, thus providing no leakage paths, a flatter base, and also less plastic entering the clinical waste stream.Container 118 can be made of any suitable material, such as low-density polyethylene (LDPE), high-density polyethylene (HDPE), a thermoplastic elastomer (TPE), or silicone.

[0046] Fig. 4 shows the part of the arrangement made up of Fig. 3, including the planar interface 116 and the container 118. As shown, the planar interface 116 is coupled to the container 118 via a threaded section 160 of the planar interface 116, which is complementary to a threaded section 162 of the container 118. In addition, a cover 164 is provided in this example, which is arranged over and coupled to a top surface of the planar interface 116, for example by clamping, and can be removed before use or retained during use. The central hub 154 of the planar interface 116 is shown coupled to an expandable receiving device 166, which is located in Fig. Figure 4 is shown in the compressed configuration. The expandable receiving device 166 comprises coupling elements, such as clamps, which are complementary to and coupled with the coupling sections 156 of the central hub 154. In one particular example, the expandable receiving device 166 comprises a screw thread that is complementary to a screw thread formed in the central hub 154. The expandable receiving device 166 is fluidically coupled to the container 118 via a fluid passage 168, shown by dashed lines. The fluid passage 168 can be formed by a port (not shown) in the planar interface 116 or an opening (not shown) in the planar interface 116, which is connected to a corresponding port or opening (not shown) of the expandable receiving device 166.In this way, a breathing mechanism is provided whereby fluid, for example air, can enter the expandable receiving device 166 from the container 118 when the container 118 is compressed, thereby expanding the expandable receiving device 166 into an expanded configuration. Likewise, during use, fluid such as air can be drawn from the expandable receiving device 166 into the container 118 as it expands, thereby compressing the expandable receiving device 166 into a compressed configuration. Thus, the pressure inside the container 118 is maintained at a substantially constant level during its compression and decompression.In other embodiments not shown, the expandable receiving device 166 can be replaced by a filter that provides the breathing mechanism by allowing a fluid, such as air, to escape from the container 118 or, if necessary, to enter the container 118. Such a filter can be gas-permeable or oxygen-permeable and / or carbon dioxide-permeable and liquid-impermeable.

[0047] Fig. Figure 5 shows another planar interface 216, as described below. Planar interface 216 is essentially identical to planar interface 116 from the Fig. 3 and Fig. 4, since it comprises a number of connections (not shown) to which, or above which, aseptic barriers 152 are detachably attached. The planar interface 216 further comprises a circumferential rim 250 with a number of drive elements 252, which in the present example are configured as a series of groove sections designed to interact with a drive mechanism of the housing, as described in more detail below. The planar interface 216 also comprises a central hub 254 projecting from the top of the planar interface 216, which, as shown, is not coupled to an expandable receiving device, but may have features that allow connection to an expandable receiving device or filters, such as those described in relation to the Fig. 3 and Fig. 4 are described.

[0048] The Fig. Figures 6(a) to 6(c) show another planar interface 216a, as described below. The planar interface 216a is essentially identical to the planar interfaces 116 and 216 from the Fig. 4 and Fig. 5, so that similar features, such as the circumferential rim 250 and the container 118, are not described further.

[0049] The planar interface 216a comprises a central hub 254a with an inner circular wall 254b and an outer, concentrically arranged circular wall 254c. The outer circular wall 254c is designed to couple, during use, an expandable receiving device 166, as shown in Fig. 6(b) shown, enables. For example, the outermost surface of the outer circular wall 254c may have a screw thread, a clip section or the like to enable the coupling of the expandable receiving device 166.

[0050] The inner circular wall 254b includes a radially extending flange 255, which extends radially outward from the inner circular wall 254b to the outer circular wall 254c. The flange 255 is shown as C-shaped, although it can extend around the entire circumference of the inner circular wall 254b. In this example, the central hub 254a is further provided with a partition 257, which extends from a section of the outer circular wall 254c to a section of the inner circular wall 254b, connecting them, for example, the section of the inner and outer circular walls 254b, 254c that does not include the C-shaped flange 255. Thus, the partition 257 can connect opposite ends of the C-shaped flange 255.

[0051] The outer circular wall 254c comprises a rib 259 extending radially inward from a base 259a of the same toward the inner circular wall 254b. In general, the rib 259 and the flange 255 define a fluid passage 168 between them, in particular a fluid passage 168 between the underside of the planar interface 216a, to which a container 118 is attached, and the top side of the planar interface 216a, in particular the central hub 254a, to which an expandable receiving device 166 is attached, as best described in the Fig. 6(b) and Fig. Figure 6(c) illustrates this. In this way, the central hub 254a defines a fluid passage 168 from a fixed container 118 to a fixed expandable receiving device 166 to allow breathing or equalization of air pressure between the respective containers 118 and 166. More precisely, the bar 259 and the flange 255 define a convoluted or non-linear fluid passage 168, such that air or gases can flow through the passage 168, while a fluid, such as a medium containing biological material, is prevented from entering the expandable receiving device 166 through this passage 168.

[0052] Furthermore, a series of radially extending ribs 261 are provided, which connect the flange 255 to the inner surface of the outer circular wall 254c, the ribs 261 being spaced apart from one another. Each adjacent pair of ribs 261 defines an individual fluid passage 168 between them. In addition, the flange 255 forms, as is best described in Fig. As shown in Figure 6(c), the flange 255 is angled to the horizontal, namely the horizontal plane in which it is located, so that it is directed downwards or angled towards the rib 259 of the outer circular wall 254c. In this way, any liquid or condensate that escapes from the container 118 is directed back to the container 118, so that no material is lost from the container 118 into the expandable receiving device 166 during use.

[0053] Furthermore, the planar interface 216a includes a number of connections 150 (see Fig. 6(b)) with removable aseptic barriers 152 which are removablely attached to and above them to seal them aseptically. In particular, the removable aseptic barriers 152 comprise a fastening section 152a which is coupled to an aseptic skin 152b, the aseptic skin 152b being aseptically coupled to each connection 150 (see Fig. 6(b)). The fastening section 152a is arranged in a space 263 formed between the respective guide walls 265 and is held in place by means of a clamp 267 attached to adjacent guide walls 265. Thus, the fastening section 152a is movable within the space 263, so that the aseptic skin 152b can be removed from the connection 150 during use and as described in more detail below.

[0054] With particular reference to Fig. 6(d) The planar interface 216a further comprises a low-volume sampling element 150a extending from a lower surface of the planar interface 216a. More precisely, the low-volume sampling element 150a is integrally formed with one or more of the ports of the planar interface 216a. The low-volume sampling element 150a is configured as a hollow, tubular element 150b, having a through-bore extending from its distal end to its proximal end and communicating with the respective port 150, and is made of an elastic material, such as a thermoplastic elastomer or silicone.In particular, the hollow tubular element 150b is coupled to the underside of the planar interface 216a next to the connection 150 by means of a screw cap 150c, which has a screw thread that engages in a corresponding screw thread of the hollow tubular element 150b. The screw cap 150c can be coupled to the underside of the planar interface 216a by any suitable means, such as an adhesive, a clamp, or the like.

[0055] During use, the container 118 and / or the planar interface 216a can be moved such that the hollow tubular element 150b extends into any liquid contained in the container 118, allowing for sampling. Furthermore, due to its elastic nature, the hollow tubular element 150b can be configured to contact the base of the container 118 without damaging it. In particular, the hollow tubular element 150b, which is made of elastic material, is configured to bend towards a corner of the container 118, especially a corner connecting the base of the container 118 to a side wall of the container 118. In this way, samples can be taken from the container 118, even small volumes, without the risk of damaging the container 118.In this particular example, a needle of a connector, as explained below, is inserted through the port 150 so that its through-bore is in fluid communication with the through-bore of the hollow tubular element 150b. A component coupled to the other end of the connector's needle can then be actuated to draw fluid from the container 118 through the hollow tubular element 150b and through the connector's needle into or to the component. In this way, a sample can be taken from the container 118.

[0056] Furthermore, as in the Fig. 6(b) and Fig. As shown in Figure 6(d), the container 118 in this example is coupled to the planar interface 216a by means of a clamping ring 269. The clamping ring 269 comprises a projection 269a that engages frictionally with the outer surface of the container 118 and clamps the container 118 between the projection 269a of the clamping ring 269 and a coupling wall 271 that extends distally from the underside of the planar interface 216a. The clamping ring 269 is coupled to the planar interface 216a by means of a variety of fastening elements 269b, such as screws or bolts. Alternatively, the container 118 can have a screw thread that engages with a screw thread of the planar interface 216a, thus eliminating the need for a clamping ring 269.

[0057] Furthermore, as in the Fig. 6(b) and Fig. Figure 6(d) shows an expandable receiving device 166 coupled to the central hub 254a. The expandable receiving device 166 comprises an upper section 166a, a base section 166b, and a wall section 166c extending between the base section and the upper sections 166a, 166b. The wall section 166c is configured as a bellows with a plurality of foldable coils, enabling expansion and compression of the receiving device 166. The upper section 166a of the expandable receiving device 166 includes an air filter 273, which is connected to the internal volume of the expandable receiving device 166 and the external environment. The air filter 273 is configured to allow air to flow into or out of the expandable receiving device 166 without allowing liquids to enter or escape from it.The air filter 273 can be gas-permeable, such as permeable to oxygen or carbon dioxide, but impermeable to liquids. In general, the air filter 273 is an aseptic air filter and, as such, can filter bacteria, viruses, or other substances that would otherwise create an aseptic environment within the container 118 and / or the expandable receiving device 166. The base section 166b of the expandable receiving device has an open end and comprises a circular base wall 166d arranged to couple with the central hub 254a of the planar interface 216a. In particular, the circular base wall 166d is coupled to the outer circular wall 254c of the central hub 254a by means of a spring clamp or spring clip (not shown).Alternatively, the circular base wall 166d can have an external thread configured to engage with a thread on the outer circular wall 254c of the central hub 254a.

[0058] Fig. Figure 7 shows an arrangement 100 with the planar interface 216 made of Fig. 5 and a container 118. Alternatively, the planar interface 116 can be made of Fig. 3, Fig. 4 or Fig. 6(a) are used. The arrangement comprises a component receiving element 114, for example the component receiving element 14, which is part of the housing 12 made from the Fig. 1 and Fig. 2 is designed to hold a component 120, for example component 20 from the Fig. 1 and Fig. 2. In particular, the component receiving element 114 is formed by an arm 114a extending from an inner volume of the housing (not shown) and terminating in a component retention head 114b. The component retention head 114b includes a retention element for holding, receiving, or otherwise securing the component 120 during use. For example, the component retention head 114b may include a rail for receiving a portion of the component 120 to allow the component 120 to slide within the component retention head 114b when required. In other examples, the component retention head 114b holds the component 120 by friction. In further examples, the component retention head 114b includes a base and one or more side walls, forming a volume into which the component 120 is received, wherein, in particular, during use, the component 120 rests on or is supported against the base.As is known to those skilled in the art, any suitable mechanism for holding component 120 on component retention element 114 is conceivable.

[0059] In general, the component retention element 114 and / or the planar interface 216 are movable to align or match a connection of the component 120 with one of the connections of the planar interface 216. In this particular example, the planar interface 216 is rotatable about a central longitudinal axis L of the planar interface 216, as indicated by arrow A. Additionally, the component retention element 114 is essentially immobile laterally, i.e., within the plane formed by the component retention element 114, but movable longitudinally along a longitudinal axis L1 of the component retention element 114, in particular of the component retention head 114b, for example, in the direction indicated by arrow B.Thus, during use and as described below, the planar interface 216 is caused to rotate about the central longitudinal axis L so that a connection of component 120, which is held by the component retention head 114b of the component retention element 114, is aligned with a connection of the planar interface 216. Then, the component retention head 114b, or alternatively the entire component retention element 114, is caused to move along axis L1 in the direction of B to engage the connection of component 120 with the connection of the planar interface 216, in particular initially with the aseptic barriers 152. Afterward, the component retention head 114b, or the component retention element 114 as a whole, is moved along axis L1 in a direction opposite to direction B to disengage the engagement between the respective connections.The planar interface 216 is then rotated about the central longitudinal axis L to sequentially align the next connection of the planar interface 216 with a connection of component 120. This process can then be repeated as often as desired. The detailed operation of the arrangement 100 is described below.

[0060] In general, the described arrangement 100 offers an arrangement that is better suited for automation and requires less manual intervention or operation.

[0061] In other examples, the arm may be rotatable and movable to align the respective ports, and the planar interface may be essentially fixed. Further examples may also include both a movable arm and a movable planar interface.

[0062] The Fig. Figures 8(a) to 8(c) illustrate a method for inserting the planar interface 216 and the container 118 from Fig. 7 into a housing 112. As in Fig. As shown in 8(a), the housing 112 comprises a sliding drawer 180 with a loading plate 182, which is mounted on telescopic rails between an open configuration (see Fig. 8(a) and (b)), in which the planar interface 216 can be inserted into the drawer 180, and is movable in a closed configuration (see Fig. 8(c)), in which the drawer 180 is located and housed within the housing 112. Generally, when using the drawer 180, a user slides it into an open configuration in a direction perpendicular to the central longitudinal axis of the planar interface 216 and places the planar interface 216 onto the loading plate 182 and thus into the drawer 180 ( Fig. 8(a)). After insertion, the user slides the drawer 180, and thus the planar interface 216, closed, in the specified direction C into the closed configuration ( Fig. 8(b)). In the closed configuration, the planar interface 216 and the receiving device 118 are inserted into and housed in the casing 112, in particular in its internal volume ( Fig. 8(c)), and the use of the system can begin.

[0063] The Fig. Figures 9(a) to 9(c) show a more detailed view of the housing 112, the planar interface 216, and a drive mechanism 184 of the housing 112. As shown in the Fig. 9(a) and Fig. As shown in Figure 9(b), the planar interface 216 is inserted into the drawer 180 of the housing 112 as described above. After insertion and as shown in Fig. As shown in Figure 9(c), a drive mechanism 184, in particular a grooved drive wheel 186, engages with the circumferential rim 250 and the plurality of drive elements 252. During use, the grooved drive wheel 186 and the drive elements 252 of the circumferential rim 250 mesh, acting as a gear arrangement and thereby causing the planar interface 216 to rotate about its central longitudinal axis. In particular, the drive wheel 186 can be driven clockwise, as shown by arrow D, by a motor, which drives the planar interface 216 counterclockwise about its central longitudinal axis.

[0064] The drive mechanism 184, in particular the drive wheel 186, can be driven by a controller (not shown) of the housing 112, which can be coupled with a number of sensors (not shown) to detect the positioning of the planar interface 216 inside the housing 112.

[0065] For this purpose, the planar interface 216 can include a number of magnets, and the housing 112 can include a Hall-effect sensor, or vice versa. The controller can control the positioning of the planar interface 216, particularly with respect to the component retention element during use, to position the respective terminals of the planar interface 216 and the component. This provides a controlled or automated homing and / or rotation of the planar interface 216 within the housing 112 without manual intervention or actuation. In this way, the planar interface 216 can be inserted into the housing 112 without the user having to align it correctly; that is, the planar interface 216 can be inserted into the housing without aligning it with a terminal of the component held by the component retention element.The planar interface 216 is then located and rotated by the controller according to a user input, such as the selection of a specific port of the planar interface 216 on a user interface of the housing 112, whereby the drive wheel 186 is controlled so that the respective ports of the planar interface 216 and the component are aligned. The drive wheel 186 can then control the subsequent movement of the planar interface 216 to align another port of the planar interface 216 with a port of the component in a sequential manner, as described below, thus providing an automated system.

[0066] The Fig. 10(a) and Fig. Figure 10(b) shows another planar interface 316 and another housing 212. The planar interface 316 is essentially identical to the planar interface 216 of Fig. 5, Fig. 6 and Fig. 7, except that the planar interface 316 has a number of positioning features 352 formed on a lower surface, i.e., a bottom surface, of the planar interface 316. In this particular example, the positioning features 352 are formed as a sinusoidal section, for example, as a cut-out section, of the lower surface. Furthermore, the planar interface 316 does not have a circumferential edge with a grooved outer surface, as in the planar interface 216 of the Fig. 5, Fig. 6 and Fig. 7 shown, but instead comprises a smooth circumferential edge 350. In other embodiments, the planar interface 316 can comprise both the positioning features 352 on a bottom surface of the planar interface 316 and a circumferential edge with a groove.

[0067] The housing 212 similarly includes a drawer 280, as described in relation to the Fig. 8(a) to 8(c) described. In the present example, however, the drawer 280 includes a loading plate 282 with corresponding positioning features 284 on its upper surface. In this particular example, the positioning features 284 are designed as a sinusoidal section, for example, as a cutout, on the upper surface. Thus, the positioning features 284 are complementary to the positioning features 352 of the planar interface 316. In this way, the user receives tactile feedback that the planar interface 316 is located in the drawer 280. When in use, the arrangement 212 can cause a rotation of the planar interface 316 in a manner that is relative to the Fig. as described in 9(a) to 9(c), or alternatively, the drawer 280, in particular the loading plate 282, can be set in rotation by a drive mechanism, as indicated by the arrow in Fig. 10(a) is displayed. Thus, the positioning features 284, 352 can assure a user that the planar interface 316 is in the drawer 280, while at the same time eliminating the need for a user to insert the planar interface 316 in a specific orientation.

[0068] Fig. Figure 11 shows the arrangement of 100 from Fig. 6, which is housed in a casing 312, which may be one of the casings described above. In particular, the arrangement comprises 100, as shown in Fig. Figure 11 shows the component retention element 114, which in the present example is designed as part of an interior area of ​​the housing 312 and holds a component 120.

[0069] With further reference to Fig. 11 the component retention element 114 is further shown comprising an actuator 170 which is configured to hold the component 120, in particular its connector 124 (see Fig. 12(a) and Fig. 12(b)). For example, actuator 170 can be operated with reference to the Fig. 11, Fig. 12(a) and Fig. 12(b) effect a fluid coupling between the second septum seal 128b of the connector 122 and a connection of the planar interface 116, as described in more detail below. The planar interface 116 is housed within the housing 312, in particular between a stirring plate 350, which can engage with a base surface of the vessel 118 attached to the planar interface 116, and a plate 352, which can receive or house the planar interface 116 and / or include a drive mechanism (not shown) for driving the planar interface 116. The planar interface 116 can be housed within the housing 312 according to any of the examples described above, for example by means of a drawer.

[0070] With further reference to the Fig. 12(a) and Fig. 12(b) In this example, component 120 comprises a connector 122 with a receiving device 124 attached to it, for example a Vacutainer. Thus, in this specific example, component 120 is a sampling component 20e (see Fig. 1) provided. As will be clear to the person skilled in the art, this is only one example of a component that can be used with the present arrangement.

[0071] With reference to the Fig. 12(a) and Fig. In section 12(b), the connector 122 of component 120 is described. The connector 122 is generally configured to connect two fluid volumes. The connector 122 comprises a housing with an upper housing section 123a and a lower housing section 123b. The housing extends along a longitudinal axis between a distal end 125a and a proximal end 125b. The upper housing section 123a is axially movable or displaceable with respect to the lower housing section 123b, as described in more detail below.

[0072] The housing includes at its distal end 125a a threaded section 126 for connection to a corresponding threaded section of a receiving device, for example a threaded screw cap 127 of which in Fig. Figure 12(a) shows a receiving device 124, wherein the receiving device comprises a first volume of a fluid. As will be clear to those skilled in the art, the housing may be provided without the threaded section 126 and instead be provided with another suitable connection mechanism for connecting to a section of the receiving device. Furthermore, a receiving device may be attached directly to the distal end 125a by any suitable mechanism; for example, the receiving device may be pre-connected or sealed, for instance by an adhesive or the like. In some embodiments, the receiving device is manufactured to have a connector 122.

[0073] In this embodiment, the connector 122 comprises a first connection, configured as a first septum seal 128a and located at the distal end 125a of the housing, and a second connection, configured as a second septum seal 128b and located at the proximal end 125b of the housing. The housing further comprises a hollow needle 129, which in this particular example is pre-tensioned within the housing. The hollow needle 129 is generally aligned coaxially with the longitudinal axis of the connector 122. The hollow needle 129 comprises a first end 130a facing the first septum seal 128a and a second end 130b facing the second septum seal 128b. The first end 130a is configured so that it can pierce the first septum seal 128a when in use, and the second end 130b is configured so that it can pierce the second septum seal 128b when in use.The first septum seal 128a, the second septum seal 128b, or both the first and the second septum seals 128a, 128b can optionally be provided with an aseptic barrier 131 arranged above it. The aseptic barrier 131 is generally configured to connect with a corresponding aseptic barrier 152 (see . Fig. 3) a planar interface 116, 216, 216a, 316 (see Fig. 3 to 7 and 8) fit together. The aseptic barrier 131 can be configured to adhere to or otherwise couple with the corresponding aseptic barrier 152, so that both barriers 131, 152 can be removed simultaneously, as described in more detail below.

[0074] The hollow needle 129 is secured within the housing by a collar 132, which in this particular example is spring-loaded by a first helical spring 133a and a second helical spring 133b. In other embodiments, the hollow needle 129 can be secured in another suitable manner; for example, the hollow needle 129 can be statically fixed, i.e., so that it does not move, and the housing can be movable around the hollow needle 129. Alternatively, the hollow needle 129 can be axially movable via the collar 132, and the upper housing section 123a can also be axially movable, while the lower housing section 123b remains static, i.e., does not move.For this purpose, the upper housing section 123a can be provided with actuating tabs, and the collar 132 can be provided with actuating tabs, each set of actuating tabs being operable by an actuating mechanism configured to move the hollow needle 129 and the upper housing section 123a to cause the respective septum seals 128a, 128b to be pierced. In the present example, the sequence of piercing the septum seals 128a, 128b is controlled by the respective spring forces of the springs 133a, 133b. In particular, the first spring 133a exerts a first preload force on the hollow needle 129 via the collar 132 in the direction of the proximal end 125b of the housing, and the second spring 133 exerts a second preload force on the hollow needle 129 via the collar 132 in the direction of the distal end 125a of the housing.The first preload force can be greater than, equal to, or less than the second preload force to control the sequential piercing of the septum seals 128a, 128b. In this example, the first preload force is greater than the second preload force because the wire diameter of the first spring 128a is larger than that of the second spring 128b.

[0075] When used, as is known to a person skilled in the art, the hollow needle 129 engages in and pierces the respective connections 128a, 128b in order to access a receiving device 124 (see Fig. 12(a)) with a second fluid volume, for example a container 118, which is coupled to a planar interface 116, 216, 216a (see for example Fig. 3, Fig. 5 and Fig. 6) to connect fluidically. To achieve such a piercing, the connector 122 is provided with an actuating mechanism designed as an outer cover 133, which in this example encloses the upper and lower housing sections. The outer cover 133 is rotatable about the central longitudinal axis of the connector 122. The outer cover 133 has a projection (not shown) on its inner surface that engages in a slot (not shown) on the outer surface of the upper housing section 123a. The projection and the slot form a cam mechanism such that a rotation of the outer cover 133 causes an axial displacement of the upper housing section 123a relative to the lower housing section 123b. In general, the second septum seal 128b is configured in use to interact with a connection, for example, a septum seal, a planar interface, as described below.For this purpose, the hollow needle 129 can, during piercing, pierce both the second septum seal 128b and the septum seal of the planar interface to provide a fluid communication channel through these septum seals. The fluid connection procedure is described below. Fig. 21(a) to 21(d) are explained in more detail.

[0076] The Fig. Figures 13(a) to 13(d) show another view of the arrangement 100 and the housing 312. Fig. 11. In particular, several linear actuators 354 are provided as part of the housing 312, which are designed to move the agitator plate 350 during operation. As shown in the Fig. 13(b) and Fig. As shown in Figure 13(c), the linear actuators 352 are configured to move the agitator plate 350 along a longitudinal axis L2 in the direction of arrow E. There can be four linear actuators 354, in particular a pair of linear actuators 354a, 354b, arranged on opposite sides of the arrangement 100, specifically on opposite sides of the planar interface 116 and the container 118. The linear actuators 354a, 354b are set up and configured to operate synchronously. For example, one pair of linear actuators 354a acts in one direction and the other pair of linear actuators 354b acts in the same direction. In this way, the linear actuators 354a, 354b are configured to cause a linear compression, i.e., an axial displacement, of the container 118 during use. Such a movement can be useful, among other things, for removing material from container 118 and / or for mixing material inside container 118.Furthermore, how best to do this in . Fig. Figure 13(d) shows the opposite pair of linear actuators 354a, 354b set up and configured to operate asynchronously, for example, one pair of linear actuators 354a in one direction and the other pair of linear actuators 354b in the opposite direction, thereby giving the container 118 a rocking or wave-like motion, as indicated by arrows E and F in Fig. 13(d) is shown. Such a movement can be useful, among other things, for mixing material within the container 118, for example for resuspending biological material, such as cells, within a medium contained therein.

[0077] The Fig. Figures 14(a) to 14(c) show another housing 412 for use with the arrangement described here. In particular, as shown in the Fig. 14(a) and Fig. As shown in Figure 14(b), the housing 412 includes a pivoting door 450 which is configured to pivot in a direction G about an axis between a closed configuration ( Fig. 14(a)), which encloses the contents of the housing 412, and an open position ( Fig. 14(b)), which allows access to the contents of the housing 412, can rotate. In this particular example, the planar interface 116 and the container 118 are located in the housing 412 ( Fig. 14(b) and Fig. 14(c)) insertable, as shown by the arrow H, wherein the circumferential edge of the planar interface 116 is inserted into a slot 452 of a plate (see, for example, plate 352 in Fig. 13(a)) of the housing 412 is slidably mounted. In addition, positioning features 454 may be provided in a stirring plate of the housing 412 to facilitate the insertion of the planar interface 116, in particular the container 118 attached thereto, into the housing 412.

[0078] The Fig. 15(a) and Fig. Figure 15(b) shows another enclosure 512 for use with the arrangement described here. In particular, the enclosure 512 comprises a pair of sliding doors 550 which are movable away from each other within a plane of the doors 550. Thus, the sliding doors 550 can be moved between a closed position ( Fig. 15(a)), in which the contents of the housing are enclosed, and an open position ( Fig. 15(b)), in which the contents of the enclosure 512 can be accessed, be movable. In this particular example, the doors 550 are to be opened in a direction I to allow access to the component retention element 114, the component 120, and / or the top of the planar interface 116. In this way, the upper components of the enclosure 512, i.e., the component retention element 114, the top of the planar interface 116, and the component 120, are accessible via the doors 550, while the lower components of the enclosure 512, i.e., the container (not shown) and the lower part of the planar interface 116, are accessible via a drawer or a hinged door 554, as described in the examples above. In this way, different accessible parts are housed in compartments, so that the user's access to specific parts of the system can be restricted during use.

[0079] The use of the arrangement and its components, as well as the exemplary enclosures, will now be explained using a non-restrictive example and with reference to the Fig. described in paragraphs 16(a) to 23.

[0080] Referring first to Fig. 16(a) The component 120, which is to be held by the component retention element, and a housing 512 are provided, as described in relation to the Fig. 15(a) and Fig. 15(b) described, wherein such an enclosure can be any of the enclosures described herein. The enclosure 512, in particular its upper sliding doors 550, are opened ( Fig. 16(b)), whereby the component retention element 114 of the arrangement 100 becomes visible within the housing 512. The component 120, shown as a connector 122 with a receiving device 124 having a compressible piston 124a, is inserted into the component retention element 114, in particular into the component retention head, as indicated by arrows J and K, and held by it ( Fig. 16(c)). The component retention element 114 can hold the component 120 by any suitable means as described above, but in this example, the component retention element 114 holds the component 120 by virtue of a rail formed in the component retention head, which interacts with a section, for example, a projection, of the component 120. In this particular example, the planar interface 116 and the container (not shown) are pre-installed inside the housing 512. As is known to those skilled in the art, the planar interface 116 and the container (not shown) can be inserted according to any of the examples described above. The user can close the sliding doors 550 to seal the contents of the housing 512 after insertion.

[0081] With reference to the Fig. Figures 17(a) to 17(c) illustrate a method for engaging a component held by a component retention element with a planar interface. As shown in Fig. As shown in Figure 17(a), a controller activates the actuator 170 as soon as the component 120 has been inserted into the component retention element 114. For this purpose, the user can input a command into a user interface of the controller. In particular, the actuator 170, which is formed as part of the component retention element 114, comprises a rotatable disk 171 with a cutout located therein, which is housed in an actuator housing 173. The housing 173 also has a cutout. The respective cutouts are arcuate, so that they form a crescent-shaped cutout. Thus, as shown in Fig. As shown in Figure 17(a), with aligned cutout sections, component 120 is inserted into the component retaining head 114b before use. With further reference to Fig. 17(b) Upon activation, the rotatable disk 171 rotates about a central longitudinal axis of the component retention head 114b in the specified direction L to expose an engagement surface of the disk 171, which is configured to engage with the component 120. In this example, the engagement surface is provided as a segment of the rotatable disk 171. The rotatable disk 171 is also axially movable, as shown in Fig. 17(c) shows that the engagement surface engages with a top surface of component 120, and that, due to the configuration of interacting rails of the component retention head 114b and component 120, component 120 is axially displaced within the component retention head 114b. For this purpose, component 120 is slidably received and can thus slide or be axially displaced within the component retention head 114b. Component 120 is axially displaced in the specified direction M until an aseptic barrier 131 of the connector 122 of component 120 (see Fig. 12(b)) attacks a corresponding aseptic barrier 152 of the planar interface 116. In particular, the aseptic barriers 131, 152 are brought into direct, planar contact with each other.

[0082] With reference to the Fig. Figures 18(a) to 18(c) show a schematic representation of an example of the component retention element 114, the component 120, and the planar interface 116 housed in the casing 512. In this example, a further example of an aseptic barrier 650 is provided over the port 150 of the planar interface 116. The aseptic barrier 650 comprises an aseptic skin 652 positioned over the port 150 and terminating in a mounting section 654a. The mounting section 654a is generally accommodated in a slot (not shown) of the planar interface 116, allowing the mounting section 654a to be moved within the slot between a first configuration in which the aseptic skin 652 is positioned over the port 150 and a second configuration in which the aseptic skin 652 is located away from the port 150.The attachment section 654a is generally made of rigid plastic material, while the aseptic skin 652 is made of paper or polymer material. The attachment section 654a is suitably coupled to the aseptic skin 652, for example by mechanical coupling of a projection to an opening (see ). Fig. 19(a) to 19(c)) of aseptic skin 652, by adhesion to aseptic skin 652 or the like.

[0083] Furthermore, in this specific example, an aseptic barrier 131 of the connector 122 is included (see also Fig. 12(b)), which is arranged above the connection 128b of the connector 122, and furthermore an aseptic skin which is coupled to a fastening section 654b. In other examples, and as is known to those skilled in the art, the fastening sections 654a, 654b may also be provided only on component 120 or only on the interface plate 116. In this example, the fastening sections 654a, 654b have corresponding features, such as an arrangement of projections and openings, so that the fastening sections 654a, 654b are configured to be coupled to each other in use. With further reference to the Fig. 18(b) and Fig. 18(c) and as described below, the fastening sections 654a, 654b are coupled together, and their respective aseptic skins are also coupled together, when the connector 122 is brought into direct planar engagement with the interface 116 (see Fig. 18(b)). Subsequently, the aseptic barriers 131, 650 are removed, mainly by removing the coupled fastening sections 654a, 654b from component 120 and planar interface 116 respectively (see Fig. 18(c)). In this way, the lateral movement of the fastening sections 654a, 654b, which are coupled with their respective aseptic membranes, causes the aseptic membranes to be removed from their respective connections 150, 128b, allowing the connections 150, 128b to come into direct planar engagement with each other.

[0084] With reference to the Fig. Figures 19(a) to 19(c) describe a system 600 for removing aseptic barriers and a method for its operation. The system 600 for removing aseptic barriers comprises a laterally extending support 602, which includes a rail 604 in one of its side walls. A movable arm element 606 is also provided, which is slidably received in the rail 604 and is slidable along and within the rail 604, terminating in a longitudinally extending actuating projection.

[0085] In the present example, the aseptic barriers 131, 650 are from the Fig. 18(a) to 18(c) are intended for use with the System 600 for removing aseptic barriers. When used, the System 600 for removing aseptic barriers is configured to remove the aseptic barriers 131, 650 of the connector 120 and the planar interface 116 (see Fig. 18(a)) removed, which are cooperatively coupled to each other as described above. In particular, in the present example, the actuating projection 608 is moved in the direction N along the rail 604 so that it engages the coupled fastening sections 654a, 654b, as shown in Fig. 19(a) shown. More precisely, the fastening sections 654a, 654b can form an insertion edge 655 (see Fig. 19(a)) to extend the projection 608 into an opening 657 (see Fig. 19(b)) of the fastening sections 654a, 654b. Upon engagement between the actuating projection 608 and the fastening sections 654a, 654b, the actuating projection 608 is retracted, i.e., it moves in the direction O along the rail 604 away from component 120, thus exerting a removal force on the fastening sections 654a, 654b. In this way, the fastening sections 654a, 654b are pulled outwards, away from component 120 and the planar interface 116, respectively, thereby also pulling the respective aseptic skins outwards and away from their respective connections 128b, 150 (see Fig. 18(a)). In this way, a connection 150 of the planar interface 116 and a connection, i.e. the second septum seal 128b, of the connector 122 can directly engage with each other in a planar manner (see Fig. 18(c)). Furthermore, if the aseptic barriers 131, 650 are removed, they fall into a waste chute 660, as indicated by arrow P in Fig. 19(c) shown. The waste chute 660 can provide a passage, for example to a container, to direct remote aseptic barriers directly or indirectly into a clinical waste stream.

[0086] With reference to the Fig. 20(a) and Fig. 20(b) and further to the Fig. 21(a) to 21(d) describes a method for actuating the component to establish fluid communication through the planar interface.

[0087] As in Fig. As shown in Figure 20(a), prior to establishing the fluid communication, component 120, in particular a connection thereof, was aligned with the planar interface 116, in particular a connection thereof. As shown in Fig. As shown in Figure 20(b), the actuator 170 is configured to actuate the component 120, in particular the connector 122, in order to establish fluid communication through the respective ports of the component 120 and the planar interface 116. More precisely, the actuator 170 is configured to rotate in the direction Q about a longitudinal axis of the component 120, in particular the connector 122, as described below. For this purpose, the actuator 170 can include a pair of gripping fingers (not shown) to enable rotation of the connector 122. In this way, fluid communication is established between the component 120, in particular its receiving device 124, and the receiving device (not shown) attached to the planar interface 116.

[0088] With reference to the Fig. Sections 21(a) to 21(d) describe the different steps of operating the component. Fig. Figure 21(a) shows a connection, i.e., the second septum seal 128b of the connector 122 of component 120, which is aligned with the connection 150 of the planar interface 116. That is, the connections 128b and 150 are coaxially or otherwise aligned. Fig. Figure 21(b) shows a first step in the actuation of the connector 122, in particular an initial rotation of the outer cover 133 by the actuator of the component retention element (not shown). Following this first step of actuation of the connector 122, the second end 130b of the hollow needle 129 is caused to pierce the second septum seal 128b of the connector 122 and the septum seal 150 of the planar interface 116. This is achieved by the rotation of the outer cover 133, causing the upper housing 123a to collapse relative to the lower housing 123b, thereby causing the hollow needle 129 to pierce the second septum seal 128b and the connector 150 at its second end 130b. As shown, the opposite first septum seal 128a of the connector 129 remains closed due to the change in position relative to the Fig. 12(b) discussed spring preload without puncture.

[0089] Fig. Figure 21(c) illustrates a second step in the actuation of the connector 122, in particular a further rotation of the outer cover 133 by the actuator of the component retention element (not shown). Following this second step of actuation of the connector 122, i.e., by the further rotation of the outer cover 133, the first end 130a of the hollow needle 129 is caused to pierce the first septum seal 128a of the connector 122 and penetrate the receiving device 124. In this particular example, the receiving device 124 also includes a septum seal with a trapezoidal cutout through which the first end 130a of the hollow needle 129 is also pierced. As shown in Figure 21(c), the first end 130a of the hollow needle 129 is also pierced. Fig. As shown in Figure 21(c), fluid communication is established through the bore of the hollow needle 129 between the receiving device 124 and the internal volume, for example, of an attached receiving device, of the planar interface 116. At this point, fluid, such as media, biological material, or the like, can be passaged in both directions between the receiving device 124 and a container attached to the planar interface 116. To interrupt the fluid communication, the outer cover 133 is rotated by the actuator of the component retention element (not shown) in a direction opposite to the direction of rotation, causing the hollow needle 129 to pierce through the respective septum seals. Thus, as shown in Figure 21(c), Fig. As shown in Figure 21(d), the piercing of each septum seal 128a, 128b is completed when the hollow needle 129 returns to its original configuration. In particular, the order in which the piercing of each septum seal 128a, 128b is completed is the opposite of the piercing sequence. In other words, in this particular example, the first end 130a of the hollow needle 129 is caused to complete the piercing of the first septum seal 128a first, and then the second end 130b of the hollow needle is caused to complete the piercing of the second septum seal 128b. As is known to those skilled in the art, the piercing sequence and the completion of the piercing can be modified by controlling the spring preload forces and / or by providing an alternative actuating mechanism for the connector 122.

[0090] The Fig. 22(a) and Fig. 22(b) illustrates a method for providing a fluid output from the receiving device 124 of component 120, while fluid communication is established via the respective ports of component 120 and the planar interface 116, as for example in Fig. 21(c) fluid communication shown above. In particular, fluid communication is established between the receiving device 124 of component 120 via the planar interface 116 and a container (not shown) attached to the planar interface 116, as shown in 21(c) and 22(a). Once fluid communication is established, an output actuator 172, formed as part of the component retention element 114, acts on a piston 124a of the receiving device 124, thereby driving a piston 124b axially downwards in direction R, i.e., axially towards the connector 122 and the planar interface 116. In the present example, the output actuator 172 is configured as a motor-driven paddle. In other examples, the output actuator 172 may be configured as part of the actuator 170 described above (see Fig. 17(a) to 17(c)), thereby providing a single actuator for actuating the connector 122 and the receiving device 124. When the piston 124b is pressed downwards, the contents of the receiving device 124 are forced through the hollow needle of the connector 122 (see also Fig. 21(c)) from the receiving device 124 and through the connector 122 and the planar interface 116 into a container (not shown) attached to the planar interface 116. Thus, an addition of fluid from component 120 into a container attached to the planar interface (not shown) is provided. Likewise, as is known to those skilled in the art, the output actuator 172 can be replaced by a withdrawal actuator configured to act on piston 124a in a direction opposite to that described above, i.e., to move piston 124a and piston 124b axially upwards, i.e., axially away from connector 122 and the planar interface 116. In this way, a vacuum arrangement can be provided so that the contents of a receiving device attached to the planar interface 116 (not shown) are removed, i.e., drawn into the receiving device 124.Likewise, as is known to those skilled in the art, the actuator 172 can be configured and arranged in such a way that it both discharges fluid from the receiving device 124 and draws fluid into the receiving device 124.

[0091] Fig. Figure 23 shows a schematic representation of a final step in the use of the arrangement and other coupled components. In particular, once the liquid dispensing is complete and component 120 is separated from the planar interface 116, the component retention element 114, in particular its actuator 170, is removed (see Figure 23). Fig. 17(b)), the component 120 from the planar interface 116 by displacing the component 120 axially away from the planar interface 116 in the direction S. The component 120 can then be removed from the component retention element 114 by the user or by a robot arm of the housing or the like and replaced by another component. The operation of the arrangement and similar features can then be repeated as often as desired by utilizing subsequent ports of the planar interface 116. In particular, the planar interface 116 can be rotated to align a port of the new component and subsequent ports of the planar interface 116, as shown in the Fig. 7 and Fig. 9(c) is shown.

[0092] As in the Fig. Figures 24(a) to 24(d) disclose a further embodiment of an arrangement 1000 for handling biological material. As shown in Fig. As shown in Figure 24(a), the arrangement 1000 comprises a component retention element 1002 that holds a container 1004 with a tube 1006. The tube 1006 may include an aseptic membrane (not shown) coupled to its distal end. The component retention element 1002 is configured as a robot arm 1008 that terminates in a retention section 1010 formed by gripping arms 1012. The gripping arms 1012 are configured to grasp and hold the container 1004 during use. The robot arm 1008 is movable to move the container 1004 during use. The arrangement 1000 also comprises a substantially planar interface 1014, as shown herein, for example, with respect to the Fig. 3 to 7, which is coupled to a bioreactor 1016. In this particular embodiment, however, the substantially planar interface 1014 comprises a plurality of tubes 1018 with aseptic membranes (not shown) connected to its ends.

[0093] As in the Fig. 24(b) and Fig. As shown in Figure 24(c), the arrangement 1000 also includes an aseptic pipe welding device 1022 and an aseptic pipe sealing device 1024. The aseptic pipe welding device 1022 is configured at one end point of a robot arm. Similarly, the aseptic pipe sealing device 1024 is configured at one end point of another robot arm. Thus, the respective robot arms are movable so that the aseptic pipe welding device 1022 and the aseptic pipe sealing device 1024 can be operated during use. The robot arms can also actuate their respective aseptic pipe welding device or pipe sealing device 1022, 1024.

[0094] Order 1000 will now be based on the Fig. 24(a) to 24(d) describe their use. As in the Fig. As shown in Figures 24(a) and (b), the component retention element 1002 is movable to align the tube 1006 of the container 1004 with a tube 1018 of the planar interface 1014. Once the tubes 1006 and 1018 are aligned with each other, as shown in Figure 24(a) and (b), the component retention element 1002 is movable to align the tube 1006 of the container 1004 with a tube 1018 of the planar interface 1014. Fig. As shown in Figure 24(b), the aseptic pipe welding device 1022 is actuated to form an aseptic weld between the respective pipes 1006, 1018, as shown in Figure 24(b). Fig. 24(c). The aseptic membranes, if coupled, can also be removed during this step, either as part of the welding process, i.e., by hot welding, melting, or the like, or in a separate removal actuation process performed by the aseptic tube welding device 1022 or another actuation component. The aseptic tube welding device 1022 thus forms an aseptic weld between the tubes 1006 and 1018, fluidically connecting the lumens of each tube 1006 and 1018. This provides an aseptic fluid passage 1026 through the connected tubes 1006 and 1018 to connect the vessel 1004 and the bioreactor 1016 via the planar interface 1014, as shown in Fig. 24(c) is shown. Biological material is then transferred from container 1004 to bioreactor 1016, for example in the manner described above. As in Fig. As shown in Figure 24(d), after the transfer of the biological material, the aseptic tube sealing device 1024 is actuated to form an aseptic seal between the connected tubes 1006 and 1018. In this way, the aseptic fluid passage 1026 between the container 1004 and the bioreactor 1016 is prevented by a heat seal 1027. The aseptic tube sealing device 1026 can also include a cutting element configured to cut the sealed tubes 1006 and 1018 along the heat seal 1027 to release the respective components, or the user can perform the required cutting manually. Afterward, the container 1004 is removed from the planar interface 1014.Container 1004 can then be disposed of, and the component retention element 1002 can hold the next container 1004 for the next addition to or removal from the bioreactor 1016 via the planar interface 1014, and the process can begin with . Fig. 24(a) will be repeated. Generally, experts are familiar with aseptic pipe welding and sealing devices, which is why these are not described further here. The present example provides an automated or at least semi-automated method for the aseptic fluidic joining and separation of fluid volumes, suitable for the just-in-time addition or removal of media to or from a bioreactor. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] WO 2018 / 087558vA1

[0006]

Claims

[1] Arrangement for handling biological material, comprising: a first biological handling element comprising a first volume having a first connection; a second biological handling element comprising a second volume having a second connection; an aseptic connecting element configured to aseptically fluidically connect the first port and the second port to provide aseptic fluid communication between the first volume and the second volume; an aseptic separation element configured to aseptically separate the first and second ports fluidically in order to prevent aseptic fluid communication between the first and second volumes; and one or more robot arms; wherein one or more robot arms are arranged to move the first biological handling element and / or the second biological handling element to align the first port and the second port with each other to enable the aseptic connecting element, when used, to aseptically fluidically connect the first port and the second port, and to enable the aseptic separating element, when used, to aseptically fluidically separate the first port and the second port. [2] Arrangement according to claim 1, wherein the first biological handling element comprises a substantially planar interface having the first connection, wherein the first connection is fluidically coupled to the first volume or configured to be fluidically coupled to it. [3] Arrangement according to claim 1 or claim 2, wherein the second biological handling element comprises a component retention element that retains a component having the second volume and the second connection. [4] Arrangement according to one of claims 1 to 3, wherein the aseptic connecting element and the aseptic separating element are a single aseptic connecting and separating element. [5] Arrangement according to claim 4, wherein the uniform aseptic connecting and separating element is an aseptic connector. [6] Arrangement according to any one of claims 1 to 4, wherein the first connection comprises a first tube, the second connection comprises a second tube and the aseptic connecting element comprises an aseptic tube welding device. [7] Arrangement according to one of claims 1 to 4 or claim 6, wherein the first connection comprises the first tube, the second connection comprises a second tube and the aseptic separation element comprises an aseptic tube sealing device. [8] Arrangement according to a preceding claim, wherein the one or more robot arms are controlled by a controller. [9] Arrangement according to claim 8, wherein the controller comprises a user interface and wherein the controller is arranged to control the one or more robot arms in response to user input at the user interface. [10] Arrangement according to a preceding claim, wherein the arrangement is an automated arrangement.

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