Modular device for fixedly arranging and interconnecting individual separation and / or functional units

Abstract

The present invention relates to a modular device for fixing and interconnecting various separation units (12) and / or first functional units (74) to each other to perform one or more basic operations in a biotechnology process. The modular device includes a plurality of dispensing caps (14), wherein at least one dispensing cap (14) is designed to be disposed on a separation unit (12) and one or more other dispensing caps (14) are respectively designed to be disposed on another separation unit (12) or first functional element (74). The distribution cover (14) has the following components: a fluid distribution device having a working interface (28) and at least two supply or discharge interfaces (30), wherein the fluid distribution device can occupy at least two defined switching positions; an interface mechanism for establishing a fluid connection between the fluid inlet or outlet (34; 34a, 34b) of the separation unit (12) or the first functional unit (74) and the working interface (28) of the fluid distribution device; a connection mechanism for establishing a rigid mechanical and fluid connection with the adjacent distribution cover (14); and an interface for manually or automatically changing the switching position of the fluid distribution device.

Description

Technical Field

[0001] This invention relates to a modular device for fixing and interconnecting various separate units and / or first functional units to perform one or more basic operations in a biotechnology process. The invention also relates to a process apparatus for performing one or more basic operations in a biotechnology process. Background Technology

[0002] Within the purification (downstream process) scope, separation units are used, such as, for example, filter capsules, chromatography columns, or membrane adsorbers. Currently, these separation units and other functional units (sensors, pumps, mixers, etc.) are interconnected with each other by means of hoses and / or pipes so that specific process steps can be performed.

[0003] Such conventional process equipment requires a large amount of space and is very inconvenient to use, also because many components of the equipment must be fixed in place. Furthermore, such equipment has large dead spaces, which on the one hand introduces the risk of unwanted backmixing, and on the other hand conflicts with the desired maximum product yield. This is particularly important when manufacturing high-quality biopharmaceutical active ingredients. Another disadvantage of conventional process equipment is that the media to be purified must always be cumbersomely stored, for example, in separate tanks or bags, before performing additional separation steps in downstream processes, due to the current lack of compatibility with the interfaces of these intermediate steps (susceptibility to pressure, lack of sterility barriers, lack of compatible interfaces, etc.). Summary of the Invention

[0004] The purpose of this invention is to enable simpler and more flexible design of the execution of one or more basic operations in biotechnology processes, especially in downstream processes.

[0005] The objective is achieved by a modular device according to the invention. Advantageous and suitable designs of the modular device according to the invention are given herein.

[0006] The modular device according to the invention is used to fix and / or interconnect various separation units and / or first functional units to each other to perform one or more basic operations in a biotechnology process. The modular device includes a plurality of dispensing caps, wherein at least one dispensing cap is designed to be disposed on a separation unit and one or more other dispensing caps are respectively designed to be disposed on another separation unit or first functional element. Each dispensing cap has the following components:

[0007] - A fluid distribution device having a working interface and at least two supply or discharge interfaces, wherein the fluid distribution device can occupy at least two defined switching positions;

[0008] - An interface mechanism, used to establish a fluid inlet in the separation unit or the first functional unit or

[0009] Fluid connection between the outlet and the working interface of the fluid distribution device;

[0010] - A connecting mechanism for establishing a rigid mechanical connection and fluid connection with the adjacent dispensing cover.

[0011] Connection; and

[0012] - An interface for manually or automatically changing the switching position of the fluid distribution device.

[0013] Here, the separation unit is understood as a filter capsule, chromatography column, or membrane adsorber, or a similar unit, typically used in downstream processes to separate biopharmaceutical products. In contrast, an additional functional unit, referred to herein as the first functional unit, is used for other purposes during process execution or control. This first functional unit can be, for example, a pump (head), sensor (device), static mixer, reservoir or temporary storage unit, sample extraction device, or venting device, wherein the first functional unit may also possess only the functionally essential parts of these units. The first functional unit can also simply be an empty tube, for example, used as a bypass for transporting the medium.

[0014] The dispensing cap is primarily designed for placement on a separation unit, which in turn is designed to perform corresponding basic operations in a biotechnology process. The interface mechanism of the dispensing cap establishes a fluid connection between the fluid inlet or outlet of the separation unit and the working interface of the fluid dispensing device. However, the interface mechanism of the dispensing cap also allows it to be placed on other (first) functional units. In this case, the interface mechanism of the dispensing cap establishes a fluid connection between the fluid inlet or outlet of the first functional unit and the working interface of the fluid dispensing device.

[0015] This means that, in order to perform at least one of the desired basic operations, it is preferable that multiple separation units are provided with dispensing covers, and if necessary, additional first functional units are also interconnected into process equipment devices by means of such dispensing covers.

[0016] Here, each dispensing cap is connected to at least one other adjacent dispensing cap via its connecting mechanism (which differs from the previously mentioned interface mechanism). This connection represents not only a rigid mechanical connection with the adjacent dispensing cap but also a fluid connection with the adjacent dispensing cap, preferably between the supply or discharge port of the fluid dispensing device of one dispensing cap and the supply or discharge port of the fluid dispensing device of the adjacent dispensing cap.

[0017] The supply or discharge ports of the fluid distribution device of the dispensing cap are, in principle, suitable not only for supplying but also for discharging fluid. In practical applications, the actual function of each individual port is derived from the final interconnection between the dispensing cap and its associated separation unit, or first functional unit.

[0018] Furthermore, the device according to the invention may also include an additional dispensing cap, which is not mounted on the separation unit or the first functional unit via its interface mechanism, but is connected to at least one additional dispensing cap only via its connecting mechanism. In particular, such a dispensing cap may be connected on its free side to a second functional unit, such as, for example, a sensor, a sample extraction device, or a venting device, via an additional connecting mechanism. This second functional unit, which is connected to the supply or discharge interface of the dispensing cap rather than to the working interface, is generally smaller and / or lighter than the first functional unit previously described as designed for connection to the working interface of the dispensing cap. It goes without saying that the dispensing cap may be connected not only to the first functional unit but also additionally to one or more second functional units.

[0019] Particular emphasis is placed on the modular nature of the device according to the invention. The distribution cover allows for different interconnections between the connected separation units and, if necessary, the first functional units, enabling individually configurable process equipment. Parallel or series operation of the separation units or, if necessary, the first functional units can be achieved through correspondingly switched fluid distribution devices.

[0020] Series-connected separation units enable the sequential, uninterrupted execution of different sub-steps, such as pre-filtration and aseptic filtration, chromatography, clarification, ultrafiltration / distillation, dilution and adjustment (pH setting, etc.), virus filtration and inactivation, and deep-bed filtration. Temporary media storage in the container is thus significantly reduced or even redundant, requiring less production space in the laboratory. Parallel connections of multiple separation units of the same type result in increased capacity and / or flow rate. Combinations of series and parallel connections can also be meaningful, allowing for capacity expansion of specific sequential steps. Configurations of other branches with different operating modes within a single unit are also possible, such as the integration of a residence loop to ensure residence time within the module.

[0021] The required switching position of the fluid distribution device for each distribution cap to the corresponding operating position can be set manually or (partially) automatically via the interface.

[0022] Regardless of the selected connections between the dispensing covers and their respective separation units and, if necessary, the first functional units, all dispensing covers together form a compact and stable assembly due to their rigid mechanical connections to each other. This makes the entire device (including the separation units and, if necessary, the first functional units) a pre-assembled unit that can be transported, assembled, and put into operation as a whole. Pre-assembly can be carried out at the manufacturer's location, thus eliminating potential errors at the user's end.

[0023] When a device consists of disposable components and is intended for single use, assembling it into a compact and stable assembly proves particularly advantageous because the device can then be disposed of as a whole after use. This means that the components do not need to be separated before disposal to fit into a designated container; instead, they can be transported away as a compact unit and disposed of together. If necessary, it may also be proposed to (partially) separate the components before disposal, especially at the previously defined disassembly points.

[0024] Another key advantage of the device according to the invention is that no additional hoses or pipes and valves are required to establish the necessary fluid connection between the separation unit and, if necessary, the first functional unit. Besides requiring significant space, such connections to the separation unit and valves are inherently prone to errors and also carry the risk of contamination. In the device according to the invention, the fluid connection is achieved directly via the connection mechanism of the dispensing cap and the fluid dispensing device without requiring additional space. Therefore, a compact arrangement of the dispensing cap is achieved, preferably in a single plane, where dead space and the possibility of leakage are minimized. The latter is particularly important for the stability of constrained hose pressure. The fluid connection established by means of the connection mechanism is short and rigid, and can be designed accordingly for greater stability.

[0025] By distributing pre-defined, protected (i.e., unexposed) connections between the covers and eliminating the temporary storage of the medium, significantly improved safety is guaranteed before, during, and after operation, compared to process units to date, also in terms of product sterilization.

[0026] The dispensing cover of the device according to the invention is preferably fastened to the end (end side) of the housing of the separation unit or the first functional unit, so that the separation unit or the first functional unit and the associated dispensing cover form a fixed combination. Therefore, in addition to the interface mechanism required for establishing the fluid connection between the working interface of the fluid dispensing device for the dispensing cover and the fluid inlet or outlet of the separation unit or the first functional unit, the dispensing cover preferably also includes a mounting mechanism for fixing the dispensing cover to the end of such housing.

[0027] The particular flexibility of the device according to the invention is achieved by the fact that all or at least a number of dispensing covers have substantially the same shape and size, and that the supply or discharge interfaces, if present, are respectively located in the same positions. The mounting mechanisms for securing the dispensing covers are preferably uniformly configured. Therefore, the dispensing cover is a compatibility standard that not only provides a wide range of usage possibilities (easily configurable interconnections of the separation units and, if necessary, the first functional units), but also allows for easy pre-planning of the desired arrangement, as individual, identically configured dispensing covers, along with their associated separation units and, if necessary, first functional units, can be assembled almost arbitrarily without regard to individual interface accessories.

[0028] A particularly preferred configuration of the dispensing cap is that the supply or discharge interface of the fluid dispensing device is located in a plane, preferably perpendicular to the axial direction of the working interface. This design is optimally matched to the separation unit, its fluid inlet or outlet, and is positioned at the end of the end side. The dispensing cap is then fitted onto the end as an (additional) cap. Here, the working interface of the fluid dispensing device of the dispensing cap connects to the fluid inlet or outlet of the separation unit. The supply or discharge interface of the fluid dispensing device of the dispensing cap is then available on the free side of the dispensing cap perpendicular to this. Because the supply or discharge interfaces of the dispensing cap are all in the same plane, the connection of multiple dispensing caps results in a flat (non-stepped) combination that allows for simple operation.

[0029] In a preferred embodiment of the invention, the fluid distribution device of the dispensing cap has four supply or discharge ports arranged at 90° angular intervals. The connection of the dispensing cap thus results in a simple, predictable pattern.

[0030] In terms of the particularly space-saving design and flexible relative arrangement possibilities of the dispensing covers that need to be connected to each other, a straight prism is recommended as the basic shape of the dispensing cover, which, according to the mathematical definition, includes a right prism. Accordingly, the bottom and top surfaces of the dispensing covers are substantially circular or equiangular polygons, preferably octagonal.

[0031] The fluid distribution device of the distribution cap is intended to provide fluid connectivity between a working interface designed for connection to a fluid inlet or outlet of a separation unit or a first functional unit and all existing supply or discharge interfaces, which can be connected to the supply or discharge interface of an adjacent distribution cap or a second functional unit. According to the embodiment, at least two switching positions of the fluid distribution device can be achieved:

[0032] - Selective release or interruption of the fluid connection between the working interface and at least one supply or discharge interface; and / or

[0033] - Selective release or blockage of fluid connections between the working interface and multiple specific or all supply or discharge interfaces.

[0034] Therefore, the fluid distribution device preferably has at least one valve, preferably a ball valve and / or a diaphragm valve.

[0035] The valve can be, in particular, a multi-port valve with multiple valve positions, by means of which different fluid connections can be set between the working port and the supply or discharge port and / or between the supply or discharge ports and each other, wherein the working port is preferably centered in the distribution cover about a plane perpendicular to its axial direction.

[0036] In certain separation units, particularly in certain types of filter capsules or membrane adsors, the fluid inlet and fluid outlet can be located on the same end side (below in the operating position). Typically, with respect to the central axis of the substantially cylindrical separation unit, the fluid outlet is centrally located and the fluid inlet is radially offset from it. For the separation unit of this type, hereinafter referred to for simplicity as the T-type variant, the present invention proposes a dispensing cap, wherein the working interface is configured such that it is radially offset from the centrally located fluid outlet of the separation unit, such that when the dispensing cap is placed on the separation unit, the working interface forms a fluid connection with the correspondingly offset fluid inlet of the separation unit. The centrally located fluid outlet of the separation unit forms a fluid connection with one or more discharge ports of the dispensing cap by means of a fluid dispensing device.

[0037] According to the basic idea of ​​the invention, it is also possible for the T-shaped variant of the dispensing cap described above to be combined not with the separation unit, but with a first functional unit, such as a sensor device. In this case, the working interface of the dispensing cap is connected to the fluid inlet of the first functional unit and the supply or discharge interface of the dispensing cap is connected to the fluid outlet of the first functional unit, or vice versa.

[0038] For the T-type variant of the distribution cover, a ball valve is suitable as a valve in a fluid distribution device, which can be reached in at least two different valve positions via a centrally located actuating element and a bevel gear drive. Alternatively, a diaphragm valve can also be used here.

[0039] Suitable connectors, preferably sterile connectors, hose fittings, or blind plugs, can be placed on the supply or discharge interface of the fluid dispensing device of the dispensing cap. These connectors are preferably secured by fastening elements, which are more preferably locked onto a locking mechanism formed on the housing of the dispensing cap.

[0040] As already mentioned, in at least one dispensing cover, a second functional unit, such as, for example, a sensor, a sample extraction device, or a venting device, is connected to at least one of the supply or discharge ports. (This connection of the "second" functional unit does not presuppose that the first functional unit must also be forcibly connected to the working port of the dispensing cover.) If a second functional unit is provided, the corresponding connection mechanism of the dispensing cover is used to establish a rigid mechanical and fluid connection with the second functional unit. Therefore, the second functional unit is also part of the overall rigidity of the dispensing cover.

[0041] As a protective measure, an overpressure protection mechanism, especially an overpressure valve or rupture diaphragm, can be installed on at least one working interface or supply or discharge interface.

[0042] The present invention also relates to a process apparatus for performing one or more basic operations in a biotechnology process, having at least one separation unit and at least one additional separation unit and / or first functional unit. The process apparatus according to the invention also includes modular equipment, as defined above, by means of which the separation unit and the additional separation unit and / or first functional unit are fixedly arranged relative to each other and interconnected. The modular nature of the dispensing cap and its configurable fluid dispensing device makes it possible for the separation units to be connected in parallel or in series. More complex apparatuses with branches connected in parallel and / or in series are also feasible.

[0043] The process apparatus according to the invention can be advantageously used to divide a large volume of medium into multiple smaller containers (sub-volumes). In particular, it is proposed that multiple supply or discharge ports of different dispensing caps be connected to the respective containers.

[0044] In particular, for online analysis during ongoing processes, it can be proposed that the supply or discharge interface of the dispensing cap or the first functional unit be connected to the analytical measuring device.

[0045] To reduce the space occupied by the process equipment according to the invention, multiple sub-units can be assembled into modular components with a separation unit or a first functional unit and at least one dispensing cover, respectively. The modular components can then be stacked on top of each other.

[0046] Fluid connections between modular components can be easily established via connecting lines that are connected to the supply or discharge port on the free side of the dispensing cap.

[0047] In particular, in order to connect the separated units in parallel, the fluid connection between the stacked modular components can also be established through the vertically oriented connection interface of the fluid distribution device of the distribution cover, which is opposite to the working interface.

[0048] The current trend in the biopharmaceutical industry is increasingly towards the use of single-use components. These single-use components are no longer limited to product and process development, but are also used in the clinical trial manufacturing (CTM) phase of the approval process, and even in commercial Good Manufacturing Practice (GMP) for drug production. Therefore, an embodiment of the process equipment according to the invention is preferred, wherein the dispensing cap and all units of the process equipment disposed on the dispensing cap are configured as single-use components, and preferably the entire process equipment is pre-sterilized before being put into operation, so that it can be put into immediate use. Attached Figure Description

[0049] Other features and advantages of the invention will become apparent from the following description and from the accompanying drawings. The drawings illustrate:

[0050] - Figure 1 A process apparatus according to the invention is shown, which is used to perform one or more basic operations in a biotechnology process and has modular equipment according to the invention for fixing and interconnecting various separate units and / or first functional units to each other.

[0051] - Figure 2 Show Figure 1 Another view of the process equipment and apparatus in the middle;

[0052] - Figure 3 Show Figure 1 Sub-units (modules) of process equipment and devices in the process;

[0053] - Figure 4 An exploded view of the dispensing cover according to the first embodiment is shown;

[0054] - Figure 5 Show Figure 4 A partial cross-sectional view of the dispensing cover with an inserted connector and a blind plug;

[0055] - Figure 6 The various components of the fluid distribution device are shown;

[0056] - Figure 7 Different connectors and blind plugs are shown;

[0057] - Figure 8 The assembly of the dispensing caps is shown;

[0058] - Figure 9 A bracket is shown for accommodating a process equipment device according to the invention;

[0059] - Figure 10A cross-sectional view of the dispensing cover according to the second embodiment is shown;

[0060] - Figure 11 The second functional unit, in the form of a sensor, is shown.

[0061] - Figure 12 The second functional unit, in the form of an exhaust unit, is shown;

[0062] - Figure 13 The invention illustrates a working unit with an exhaust unit connected via a flexible conduit.

[0063] Artificial equipment and devices;

[0064] - Figure 14 A subunit (module) of the process equipment apparatus according to the invention is shown, having a first functional unit in the form of a sensor device rather than a separate unit;

[0065] - Figure 15 Showing has Figure 14 The sub-units (modules) in the present invention are based on the process design of the present invention.

[0066] Equipment;

[0067] - Figure 16 A schematic diagram of a process apparatus according to the present invention for dividing large media volumes is shown;

[0068] - Figure 17 Variations of the process apparatus according to the invention for dividing large media volumes are shown; and

[0069] - Figure 18 A schematic diagram of a space-saving process equipment apparatus according to the present invention is shown. Detailed Implementation

[0070] exist Figure 1 and 2 The illustration exemplifies a process apparatus 10 for performing one or more basic operations in a biotechnology process. The process apparatus 10 includes a plurality of separation units 12, which may differ in separation technology (e.g., filter capsules, chromatography columns, membrane adsorbers) and / or filter materials and / or construction methods and / or construction dimensions and / or other parameters. The separation units 12 are interconnected with each other by means of a modular device. The modular device is formed by a plurality of individual dispensing caps 14, each dispensing cap being connected to at least one adjacent dispensing cap. In the illustrated embodiment, all dispensing caps 14 have the same basic construction, and each dispensing cap 14 is associated with and fixedly mounted on a separation unit 12, thereby obtaining a compact and stable process apparatus 10 with separation units 12 arranged in a defined (grid-like) manner.

[0071] Figure 3 —Similarly, by example—a sub-unit (module) 16 of process equipment device 10 is shown, having a separation unit 12 and two dispensing covers 14, the separation unit having a generally cylindrical basic shape, the two dispensing covers being disposed on two end sides of the separation unit 12.

[0072] from Figure 4 and 5 The basic structure of the first variant of the dispensing cover 14 is obtained. The dispensing cover 14 has a housing 18, which is essentially in the shape of a right prism, and whose bottom and top surfaces are essentially in the shape of an isoangular polygon, in this case, an octagon. Four main sidewalls 20, oriented at right angles to each other, are connected to each other by secondary sidewalls 22 located between them. On one end side, the housing 18 is closed by a top cover 24, and on the other end side, the housing 18 is open and covered by the bottom section or top cover section 26 of the associated separation unit 12 (which is fitted onto the separation unit 12, depending on whether the dispensing cover 14 is below or above the separation unit 12 in terms of its operating position). Figure 4 and 5 It is not fully shown in the text.

[0073] A fluid distribution device is located inside the housing 18, having a centrally located working interface 28 accessible through the open housing side and multiple side supply or discharge interfaces 30. The supply or discharge interfaces 30 of the fluid distribution device are located in a plane oriented perpendicular to the axial direction of the working interface 28. The fluid distribution device shown here has four supply or discharge interfaces 30, which are arranged at 90° angles and are accessible through corresponding openings 32 in the main sidewall 20 of the housing 18.

[0074] The dispensing cover 14 also includes an interface mechanism, by means of which a fluid connection is established between the fluid inlet or outlet 34 of the separation unit 12 and the working interface 28 of the fluid dispensing device when the dispensing cover 14 is fitted onto the bottom section or top cover section 26 of the separation unit 12. The dispensing cover 14 is secured to the bottom section or top cover section 26 of the separation unit 12 by means of a mounting mechanism 36 (locking element, etc.). All bottom sections or top cover sections 26 of the separation unit 12 have standardized interface mechanisms and mounting mechanisms 36 that mate with the dispensing cover 14.

[0075] In this variant, the fluid distribution device is essentially formed by a multi-way valve, which provides the interface and can occupy different switching positions. The main components of this valve, configured here as a ball valve 38, are... Figure 6The ball 44, which is sealed by a sealing ring 40 on each supply or discharge port side and held in position by a support element 42, can be rotated to different switching positions via a spindle 50. The ball has boreholes 46, 48.

[0076] In the illustrated embodiment, the sphere 44 has a first borehole 46 aligned with the fluid inlet or outlet 34 of the separation unit 12 and a second borehole 48 connected to its vertical side. By rotating the sphere 44 about the axis of the first borehole 46, the second borehole 48 can selectively form a fluid connection with the supply or discharge interface 30, i.e., the second borehole 48 is aligned with the corresponding supply or discharge interface 30 in the corresponding switching position.

[0077] Therefore, in this embodiment, four switching positions are possible, wherein the working interface 28 connected to the fluid inlet or outlet 34 of the separation unit 12 is in fluid connection with exactly one of the four supply or discharge interfaces 30. That is, depending on the operating mode, fluid can be supplied to the separation unit 12 through the selected supply or discharge interface 30, or fluid can be discharged from the separation unit 12 through the selected supply or discharge interface 30.

[0078] It goes without saying that the fluid distribution device is not limited to this embodiment. Embodiments with switching positions are also feasible, in which multiple supply or discharge ports 30 can simultaneously form fluid connections with the working port 28, or can alternately form fluid connections with one or more of the other supply or discharge ports 30. Selectively blocking the working port 28 in combination with one of other functionalities is also feasible in principle. However, the fluid distribution device can switch between at least two defined switching positions.

[0079] The spindle 50 of the fluid distribution device, extending from the housing 18 of the distribution cover 14 along the central axis of the separation unit 12, serves as an interface for changing the switching position. A manual operating element 52 may be coupled to the spindle 50, or the spindle 50 may be coupled to an electrically or otherwise operated operating device connected to a control unit.

[0080] To connect two adjacent dispensing caps 14, a connecting mechanism is provided, which establishes both a rigid mechanical connection between the adjacent dispensing caps 14 and a fluid connection between them. Specifically, a connector 54, here a double connector (double male connector), is used as the connecting mechanism. Its first end connects to the supply or discharge port 30 of the fluid dispensing device of the first dispensing cap 14. The connector 54 extends from an opening 32 in the associated main sidewall 20 of the housing 18 and extends through an opening 32 in the opposite main sidewall 20 of the housing 18 of the adjacent second dispensing cap 14. The second end of the connector 54 connects to the associated supply or discharge port 30 of the fluid dispensing device of the second dispensing cap 14. Within the housing 18, the connector 54 is sealed by two O-rings 56 and secured to the housing 18 by means of fastening elements 58.

[0081] A flow channel 60 is formed inside the connector 54, establishing a fluid connection between the two supply or discharge ports 30. The walls surrounding the flow channel 60 are thick and stable, allowing them to withstand high pressures (4 bar and more if necessary). The length of the connector 54 is determined such that the dispensing caps 14, which are connected to each other, fit together or contact each other in a very tight seal.

[0082] The geometry of the distribution cover 14 and the connector 54 is pre-defined with a logical grid of defined locations where distribution covers 14 can be positioned for connection with adjacent distribution covers 14. The rigid connector 54, as a connecting mechanism, ensures a stable assembly of the distribution covers 14.

[0083] exist Figure 7 Other types of connectors 54, including a hose barb 62, are exemplarily shown, which can replace the... Figure 5 The connector 54 shown is used. Unused supply or discharge ports 30 can be closed by means of blind plug 64 (see also...). Figure 5 Each connector 54, each hose fitting 62, and each blind plug 64 is sealed with respect to the housing 18 by two O-rings 56 and secured by fastening elements 58, wherein each connector, each hose fitting, and each blind plug is disposed within the housing.

[0084] exist Figure 8 The example shows an assembly of dispensing caps 14 arranged in a 3×2 grid. Due to the sloping secondary sidewalls 22, a defined free space 66 is achieved in this example despite the sealed arrangement. A retaining mechanism 68 can be provided in this free space 66 to secure the assembly to a bracket 70, as illustrated in the example. Figure 9 As shown in the diagram. Additional hoses and conduits can also be threaded through the free space 66.

[0085] With the aid of the dispensing cover 14 and its configurable fluid dispensing device, the separation unit 12 can be connected in series and / or in parallel. According to Figure 1 and 2 The process apparatus 10 shown in the figure will be briefly described. In the example setup, five different separation units 12 are connected in series, which differ in, for example, in filter material, pore size, etc. For easier orientation, the five separation units are provided with additional markings (1) to (5). The fluid distribution device, with the distribution caps 14 respectively placed above and below the separation units 12, is switched such that the following flow path is obtained in sequence: from the lower outer distribution cap 14 upward through the corresponding first separation unit 12 (1) to its upper distribution cap 14, from there to the adjacent upper distribution cap 14 and downward through the corresponding second separation unit 12 (2) to its lower distribution cap 14, etc., until the upper distribution cap 14 of the last separation unit 12 (5). In this way, different separation steps can be performed sequentially with only one process apparatus 10, without the need for temporary storage of the medium.

[0086] The filtration area of ​​each separation step can be increased by connecting another separation unit 12 in parallel. Figure 1 and 2 In the process equipment apparatus 10 shown, for example, a separation unit 12(6) of the same type as the first separation unit 12(1) is connected in parallel to the first separation unit 12(1). The fluid distribution device of the lower distribution cover 14 of the first separation unit 12(1) is switched so that the medium being transported is not only guided through the first separation unit 12(1), but also guided toward the lower distribution cover 14 adjacent to the side of the parallel separation unit 12(6). The portion of the medium flowing through the parallel separation unit 12(6) reaches the adjacent upper distribution cover 14 of the first separation unit 12(1) via the upper distribution cover 14 and from there is guided together with the other portion of the medium to the upper distribution cover 14 of the second separation unit 12(2).

[0087] It goes without saying that, in principle, other configurations with other objectives are also possible, such as redundant settings for improving process safety.

[0088] The flow path through the process equipment 10 can be configured before and during operation by means of the configurable fluid distribution device of the distribution cover 14.

[0089] exist Figure 10Other dispenser types, referred to herein as T-type variants, are shown. The dispenser cover type matches the separation unit 12, with its fluid inlet 34a and fluid outlet 34b located on the same end side. In the operating position of the separation unit 12, this is typically the lower end side. With respect to the central axis of the separation unit 12, the fluid outlet 34b is centrally located, while the fluid inlet 34a is radially offset from it.

[0090] Correspondingly, the working interface 28 of the T-shaped dispensing cover 14 is configured such that, in the installed state, the working interface is radially offset from the central axis of the separation unit 12 and establishes a fluid connection with its fluid inlet 34a. The supply or discharge interface 30 of the dispensing cover 14 is aligned with the centrally located fluid outlet 34b of the separation unit 12, thereby establishing a fluid connection thereas as well; in this case, the supply or discharge interface serves as the discharge interface.

[0091] The switchable fluid distribution device of the T-shaped distribution cover 14, which provides a working interface 28 and a discharge interface 30, is configured in this case as a ball valve 38, which can be reached in at least two different valve positions via a centrally located spindle 50 and a bevel gear transmission 72.

[0092] The ball 44 of the ball valve 38 is sealed by a sealing ring 40 and held in position by a support element 42. In the illustrated embodiment, the ball 44 has a first bore 46 aligned with the fluid inlet 34a of the separation unit 12 and a second bore 48 connected to its vertical side, the second bore aligning with the working interface 28 of the fluid distribution device. Rotation of the spindle 50 causes the ball 44 to rotate about the axis of the second bore 48 via a bevel gear transmission 72. Therefore, the working interface 28 moves away from the fluid inlet 34a of the separation unit 12 until a fluid connection is no longer established.

[0093] Therefore, in this embodiment, two switching positions are feasible. In the first switching position, a fluid connection exists between the working interface 28 of the fluid dispensing device of the dispensing cover 14 and the fluid inlet 34a of the separation unit 12. In the second switching position, the fluid connection is blocked.

[0094] The spindle 50 of the fluid distribution device, extending from the housing 18 of the distribution cover 14 along the central axis of the separation unit 12, serves as an interface for changing the switching position. A manual operating element 52 may be coupled to the spindle 50, or the spindle 50 may be coupled to an electrically or otherwise operated operating device connected to a control unit.

[0095] The possibility of selectively distributing the fluid flowing from the fluid outlet 34b of the separation unit 12 to specific or multiple discharge ports 30 is not presented here, however, it is feasible in principle. For example, the fluid distribution device could be equipped with a switchable diaphragm valve on each discharge port 30.

[0096] The modular nature of the device—besides the different interconnection possibilities between the dispensing cover 14 and its associated separation unit 12—indicates that, on the one hand, the working interface 28 of the dispensing cover 14—rather than the separation unit 12—can also be connected to the first functional unit 74, which will be discussed more precisely later, and on the other hand, the supply or discharge interface 30 of the fluid dispensing device of the dispensing cover 14 can also be used to connect the second functional unit 76 to the free side of the dispensing cover 14. In this regard, this second functional unit 76 is not to be understood as the other dispensing cover 14 nor as the separation unit 12, but rather as a special component that provides or enables additional functionality.

[0097] exist Figure 11 An example of this second functional unit 76 is shown. The sensor 78 can be connected to one of the supply or discharge ports 30 of the fluid dispensing device of the dispensing cover 14 via a connection mechanism, here a suitable connector 54 and fastening element 58. This means that not only a rigid mechanical connection is established between the dispensing cover 14 and the sensor 78, but also a fluid connection is established between the inlet and outlet ports 30 and the sensor 78.

[0098] As sensor 78, devices that measure pressure, flow rate, viscosity, pH value, or conductivity can be considered, for example. Spectroscopic measurement devices (UV-VIS, NIR, Raman, etc.) are also possible. The measurements from sensor 78 can, for example, be used to control downstream process equipment 10.

[0099] Figure 12 An additional second functional unit 76, in the form of an exhaust device 80, is shown. This exhaust device can also be connected via a suitable connector 54 to the supply or discharge port 30 of the fluid distribution device on the distribution cover 14 (see also...). Figures 1 to 3 ).

[0100] The second functional unit 76 can also be connected to the supply or discharge port 30 of the fluid distribution device of the distribution cover 14 via a flexible hose, for example by means of a hose connector 62 fixed to the housing 18 of the distribution cover 14.

[0101] exist Figure 13 The following practical examples are shown, which are briefly described below. Figure 13The process apparatus 10 shown includes six separation units 12 in the form of filter capsules of the same structural type. The separation units are arranged in a compact 3×2 grid and each has a dispensing cover 14 on both ends (the non-filtrate side or the filtrate side). The separation units 12 are connected in parallel by means of the dispensing covers 14 to provide a large overall filtration area.

[0102] The supply or discharge port 30 of the upper distribution cover 14 serves as a common inlet for all separation units 12, and the supply hose line 82 is connected to the supply or discharge port. The fluid distribution device of the upper distribution cover 14 is switched so that the fluid delivered via the supply hose line 82 is distributed to all separation units 12.

[0103] The fluid distribution device of the lower distribution cover 14 is switched so that the fluid flowing out of all separation units 12 is guided to a specific supply or discharge port 30 of the lower distribution cover 14, which serves as a common outlet. A discharge hose 84 is connected to the inlet and outlet ports 30.

[0104] The fluid distribution device of the upper distribution cover 14 can also be configured such that its working interfaces 28 are all connected to other supply or discharge interfaces 30 of the upper distribution cover 14. These supply or discharge interfaces 30 serve as common venting interfaces, and a venting device 80 is connected to these venting interfaces via a venting hose 86. The venting device 80 is positioned above the upper distribution cover 14 in the operating position of the process equipment 10 so that fluid not being supplied under normal operating conditions reaches the venting device 80. For this purpose, the venting device 80 is fixed to a rod-shaped retaining mechanism 68, the rod extending upward from one of the free spaces 66 between the upper distribution covers 14. All separation units 12 can be vented jointly via the venting device 80. Due to the configuration possibilities of the fluid distribution device, the supply or discharge interfaces 30 used as venting interfaces can also be used to perform a common integrity test for all separation units 12.

[0105] Another possibility for the use of the dispensing cover 14 in the process equipment 10 is that the working interface 28 of the dispensing cover 14 is not connected to the fluid inlet or outlet 34 of the separation unit 12, but is connected to the fluid inlet or outlet 34 of the first functional unit 74, as exemplified in... Figure 14 As shown in the diagram. This means that, at one or more locations of the process equipment 10, rather than the separation unit 12, the first functional unit 74 is integrated into the flow path or located at the beginning or end of the flow path, as exemplarily in... Figure 15 As shown in the image.

[0106] In order to connect the first functional unit 74 to the dispensing cover 14 in the same manner as the separating unit 12, the first functional unit has a fluid inlet or outlet 34, which corresponds to the fluid inlet or outlet of the separating unit 12. Therefore, the first functional unit 74 is compatible with the dispensing cover 14. Similar to the case of the separating unit 12, it is theoretically possible for the first functional unit 74 to also have a fluid inlet or outlet 34 on the other end side, allowing for flow through the first functional unit 74 and connection to the additional dispensing cover 14 on that other end side (see especially...). Figure 15 ).

[0107] exist Figure 14 and 15 In the embodiment shown, the first functional unit 74 is a combination of a UV sensor 88 and a conductivity and pH sensor 90. Furthermore, in Figure 15 The process equipment device 10 shown in the figure has two first functional units 74 in the form of pumps 92, which are respectively disposed between two distribution covers 14, and fluid is sent from the working interface 28 of the upper distribution cover 14 to the working interface 28 of the lower distribution cover 14, or vice versa as needed.

[0108] Other examples of the first functional unit 74, which can be connected individually or in combination to one or both working interfaces 28 of the dispensing cap 14, are sensors (devices), static mixers, storage containers or temporary storage devices, sample extraction devices, and venting devices, and the enumeration described herein is not exhaustive. The first functional unit 74 in this sense may also include only the functionally important parts of such a unit. A simple form of such a first functional unit 74 is an empty tube.

[0109] Regardless of the final configuration of the process equipment 10, all dispensing covers 14 and at least all separation units 12 directly mounted on the dispensing covers 14, and, if necessary, all first and second functional units 74, 76 and other components (e.g., hoses and tubing) are configured as single-use components, meaning they are designed for single-use and are accordingly formed from suitable plastic materials. The entire process equipment 10 is pre-sterilized before it begins operation, making it readily available for use.

[0110] On the other hand, the modular construction of the equipment allows it to be disassembled and cleaned after use, for example by backwashing, making the reuse of the entire equipment or parts thereof in principle feasible. However, reuse is particularly relevant to the separation unit 12 used and environmental regulatory conditions.

[0111] To prevent damage to the modular equipment due to overpressure, valves, rupture membranes, or similar mechanisms may be installed on one or more of the unused supply or discharge ports 30 and / or working ports 28 of the distribution cover 14, which open under overpressure and release pressure to the surrounding environment or into the connected container.

[0112] Modular devices, as described above with reference to several examples, can be used in the biopharmaceutical industry, particularly for performing one or more process steps in downstream processes. However, the invention is not limited to this application. Furthermore, applications in binding / elution and flow-through processes are feasible within the scope of membrane chromatography and column chromatography applications. Some specific applications are also described below.

[0113] Modular devices can be used in process equipment 10 to divide a large volume of media into multiple smaller units, for example, to dispense the contents of a large bioreactor into multiple bags. With modular devices, multiple dispensing caps 14 can be switched with an integrated fluid dispensing device such that the media to be dispensed is first guided into a first dispensing cap 14 and then guided from the first dispensing cap through one or more separation units 12. This can involve parallel connections of separation units 12 of the same type or series connections of different separation units 12.

[0114] Subsequently, different variations for additional fluid guidance are feasible. In general, the dispensing cap 14 is connected to one or more sub-volumes (containers, such as bags) via one or more of its supply or discharge ports 30.

[0115] When the one or more sub-volumes connected to the dispensing cap 14 are filled, the fluid dispensing device in the dispensing cap 14 switches to a configuration such that the one or more supply or discharge ports 30 are closed while simultaneously opening the flow path to the adjacent dispensing cap 14 via another supply or discharge port 30. Alternatively, a connection can be made via a continuously open working port 28 to the first functional unit 74 (in its simplest form, only one fluid line, possibly with a flow or foam sensor, or the separation unit 12). Thus, a connection can be established to another dispensing cap 14 at the other end of the first functional unit 74, or the separation unit 12, which in turn is connected to one or more sub-volumes via one or more of its supply or discharge ports 30. The same principle can be applied to any number of dispensing caps 14 and sub-volumes.

[0116] Figure 16 The schematic and illustrative examples show how such a process apparatus 10 can be constructed. Figure 16In the diagram, the flow path is indicated by arrows. The supply or discharge port 30 and the sub-volumes connected thereto are not shown. In the linear process equipment 10 shown in the example, the lower distribution cover 14 has up to two supply or discharge ports 30 for connection to the sub-volumes, while the upper distribution cover has up to three supply or discharge ports for connection to the sub-volumes.

[0117] exist Figure 17 The diagram shows a non-linear process apparatus 10 with branches having dispensing caps 14. The two lower dispensing caps 14 of the centrally located separating unit 12, or first functional unit 74, are connected to each other via an invisible dispensing cap 14 disposed between them. The medium to be dispensed is delivered here via an inlet conduit 82 equipped with a sterile connector 94. A filling conduit 96, connected to a supply or discharge port 30, leads to a sub-volume (not shown).

[0118] Online analysis can also be achieved using modular equipment. This requires a discontinuous branching of a portion of the medium to be processed during the process. The branched medium can then be studied using different analytical methods, such as spectroscopic or chemical reaction methods.

[0119] The isolation of a portion of the medium can be achieved via a switchable supply or discharge port 30 of the dispensing cover 14. An analytical measuring device can be directly connected to another supply or discharge port 30 of the dispensing cover 14. Alternatively, the medium isolation function can be integrated into a first functional unit 74, which is connected to the working interface 28 of the dispensing cover 14. Furthermore, the first functional unit 74 may also include a corresponding interface for connecting an analytical measuring device, or the first functional unit may be connected via the dispensing cover 14 disposed at the other end of the first functional unit 74 in the manner described above.

[0120] In specific applications, thorough mixing of the media is desirable. This mixing can be achieved or facilitated by targeted circulation of the media in the separation unit 12 or the first functional unit 74. For this purpose, each supply or discharge port 30 is connected on its respective upper distribution cover 14 to the supply or discharge port 30 of its respective lower distribution cover 14 in the separation unit 12 or the first functional unit 74, such that a closed circulation is achieved, at least for a short period, for mixing purposes. This connection can also be made indirectly, meaning the connection between the upper and lower supply or discharge ports 30 does not necessarily have to be on the distribution cover 14 directly mounted on the separation unit 12 or the first functional unit 74. However, a pump should be included in this connection, and flow must be initiated in other ways.

[0121] Generally, the separation unit 12 and, if necessary, the first functional unit 74 can be mechanically and fluidly connected to each other by means of a dispensing cover 14, more precisely—wherever it is present—via a dispensing cover 14 disposed below and / or above the separation unit 12 or the first functional unit 74. Separation units 12 or first functional units 74 of different heights can also be connected to each other, in which case adjacent separation units 12 or first functional units 74 may be connected only via the upper dispensing cover 14 or only via the lower dispensing cover 14.

[0122] The space-saving structure of the process equipment 10 with reduced footprint can be achieved by stacking sub-units 16, as exemplified in... Figure 18 As shown in the diagram, a plurality of such sub-units 16, each having a separation unit 12 or a first functional unit 74 and at least one dispensing cover 14, are assembled into a modular assembly 98. For example, the modular assembly 98 can be configured separately for multiple process steps. The modular assemblies 98 can preferably be stacked directly, but can also be stacked indirectly.

[0123] If a fluid connection between module components 98 is desired, for example, to interconnect two process steps with each other, the fluid connection can be established via a connecting line 100 connected to a supply or discharge port 30 on the free side of the dispensing cap 14.

[0124] Fluid connection can also be achieved via a vertically oriented connection interface 102 of the fluid distribution device of the distribution cover 14, which is opposite to the working interface 28, especially for connecting the linked separation units 12 in parallel.

[0125] List of reference numerals

[0126] 10. Process equipment and devices

[0127] 12 Separation Units

[0128] 14 Dispensing cover

[0129] 16 Sub-units (Modules)

[0130] 18. Shell

[0131] 20 Main sidewalls

[0132] 22 Secondary sidewalls

[0133] 24 Top Cover

[0134] 26 Bottom or top section

[0135] 28 Working Interface

[0136] 30 Supply or discharge interface

[0137] 32 Opening

[0138] 34. Fluid inlet or outlet

[0139] 34a Fluid Inlet

[0140] 34b Fluid outlet

[0141] 36 Installation Mechanism

[0142] 38 ball valve

[0143] 40 Sealing ring

[0144] 42 Supporting elements

[0145] 44 sphere

[0146] 46 First Drill Hole

[0147] 48 Second Drill Hole

[0148] 50 spindles

[0149] 52 Control elements

[0150] 54 connectors

[0151] 56 O-ring

[0152] 58 Fastening components

[0153] 60 flow channels

[0154] 62 Hose Connector

[0155] 64. Blind Blockage

[0156] 66 Free Space

[0157] 68. Maintenance mechanism

[0158] 70 stents

[0159] 72. Bevel gear transmission device

[0160] 74 First Functional Unit

[0161] 76 Second Functional Unit

[0162] 78 sensors

[0163] 80 Exhaust System

[0164] 82 Supply hose piping

[0165] 84 Discharge hose line

[0166] 86 Exhaust hose piping

[0167] 88UV sensor

[0168] 90 Conductivity and pH sensor

[0169] 92 pumps

[0170] 94 Sterile Connectors

[0171] 96 Filler Piping

[0172] 98 Module Components

[0173] 100 Connecting pipes

[0174] 102 Connection Interface

Claims

1. A modular device for fixing and interconnecting various separate units (12) and / or first functional units (74) to perform one or more basic operations in a biotechnology process, The modular device includes a plurality of dispensing covers (14), wherein at least one dispensing cover (14) is designed to be mounted on a separation unit (12) and one or more additional dispensing covers (14) are respectively designed to be mounted on another separation unit (12) or a first functional unit (74). The dispensing cover (14) has the following components: - A fluid distribution device having a working interface (28) and at least two supply or discharge interfaces (30), wherein the fluid distribution device is capable of occupying at least two defined switching positions, wherein the at least two switching positions of the fluid distribution device are capable of selectively releasing or blocking the fluid connection between the working interface (28) and at least one supply or discharge interface (30); - An interface mechanism for establishing a fluid connection between the fluid inlet or outlet (34; 34a, 34b) of the separation unit (12) or the first functional unit (74) and the working interface (28) of the fluid distribution device; - A connecting mechanism for establishing a rigid mechanical and fluid connection with an adjacent dispensing cover (14), wherein a rigid connector (54) serves as a connecting mechanism between the first dispensing cover (14) and an adjacent second dispensing cover (14), establishing a rigid mechanical connection and simultaneously establishing a fluid connection between the supply or discharge port (30) of the fluid dispensing device of the first dispensing cover (14) and the supply or discharge port (30) of the fluid dispensing device of the second dispensing cover (14); and - An interface for manually or automatically changing the switching position of the fluid distribution device.

2. The modular device according to claim 1, Its features are, The dispensing cover (14) includes a mounting mechanism (36) for fixing the dispensing cover (14) to the end of the housing (18) of the separation unit (12) or the first functional unit (74).

3. The modular device according to claim 1 or 2, Its features are, At least a plurality of dispensing caps (14) have substantially the same shape and the same size and the supply or discharge ports (30) are respectively located in the same position.

4. The modular device according to claim 1 or 2, Its features are, The supply or discharge port (30) of the fluid distribution device is located in a plane oriented in a direction perpendicular to the axial direction of the working port (28).

5. The modular device according to claim 1 or 2, Its features are, The fluid distribution device has four supply or discharge ports (30) set at 90° angular intervals.

6. The modular device according to claim 1 or 2, Its features are, The dispensing cover (14) is essentially cylindrical in shape, with the bottom and top surfaces of the cylindrical body being essentially circular or equiangular polygons.

7. The modular device according to claim 6, Its features are, The isogonal polygon is an octagon.

8. The modular device according to claim 1 or 2, Its features are, In at least one dispensing cover (14), the fluid dispensing device has at least one valve.

9. The modular device according to claim 8, Its features are, The valve is a ball valve (38) and / or a diaphragm valve.

10. The modular device according to claim 8, Its features are, The valve is a multi-way valve with multiple valve positions, by means of which different fluid connections can be set between the working port (28) and the supply or discharge port (30) and / or between the supply or discharge ports (30) and each other.

11. The modular device according to claim 10, Its features are, The working interface (28) is centrally located in the distribution cover (14) about a plane perpendicular to its axial direction.

12. The modular device according to claim 1 or 2, Its features are, In at least one dispensing cover (14) designed for placement on a separation unit (12), the working interface (28) is configured such that it is radially offset from the centrally located fluid outlet (34b) of the separation unit (12), such that when the dispensing cover (14) is placed on the separation unit (12), the working interface (28) forms a fluid connection with the correspondingly offset fluid inlet (34a) of the separation unit (12).

13. The modular device according to claim 8, Its features are, The valve is a ball valve (38) that can be positioned in at least two different positions via a centrally located spindle (50) and a bevel gear transmission (72).

14. The modular device according to claim 1 or 2, Its features are, A hose connector (62) or blind plug (64) is also provided on the supply or discharge port (30), wherein the connector (54) or the hose connector (62) or the blind plug (64) is secured by means of a fastening element (58).

15. The modular device according to claim 14, Its features are, The connector (54) is a sterile connector.

16. The modular device according to claim 14, Its features are, The fastening element is locked onto a locking mechanism formed on the housing (18) of the distribution cover (14).

17. The modular device according to claim 1 or 2, Its features are, In at least one of the dispensing covers (14), a second functional unit (76) is connected to at least one of the supply or discharge ports (30).

18. The modular device according to claim 1 or 2, Its features are, An overpressure protection mechanism is provided on at least one working interface (28) or supply or discharge interface (30), which releases the corresponding interface when the pressure exceeds the limit.

19. The modular device according to claim 18, Its features are, The overpressure protection mechanism is a rupture membrane.

20. The modular device according to claim 1 or 2, Its features are, The supply or discharge port (30) of the fluid distribution device of the distribution cover (14) is configured for supplying and discharging fluid.

21. The modular device according to claim 1 or 2, Its features are, With the aid of corresponding fluid distribution devices, the modular device can be selectively operated in series, parallel, series-parallel combination, or other branch configurations.

22. A process apparatus (10) for performing one or more basic operations in a biotechnology process, the process apparatus having at least one separation unit (12) and at least one additional separation unit (12) and / or a first functional unit (74). Its features are, A modular device is provided according to any one of the preceding claims, wherein the separation unit (12) and the other separation unit (12) and / or the first functional unit (74) are fixedly arranged relative to each other and interconnected with each other.

23. The process equipment (10) according to claim 22. Its features are, To divide the large media volume, multiple supply or discharge ports (30) of different distribution covers (14) are connected to the container.

24. The process equipment (10) according to claim 22 or 23. Its features are, The supply or discharge interface (30) or the first functional unit (74) is connected to the analytical measurement device.

25. The process equipment (10) according to claim 22 or 23. Its features are, Multiple sub-units (16) having a separation unit (12) or a first functional unit (74) and at least one distribution cover (14) are assembled into a module assembly (98), wherein the module assembly (98) is stacked on top of each other.

26. The process equipment (10) according to claim 25. Its features are, A fluid connection is established between the stacked module components (98) via a vertically oriented connection interface (102) of the fluid distribution device of the distribution cover (14) opposite to the working interface (28).

27. The process equipment (10) according to claim 22 or 23. Its features are, The distribution cover (14) of the process equipment device (10) and all units directly mounted on the distribution cover (14) are configured as disposable parts.

28. The process equipment (10) according to claim 27. Its features are, The entire process equipment (10) is sterilized before it is put into operation.

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