Valve switching system for selectively interconnecting components of bioprocess device

Abstract

The invention relates to a valve switching system for selectively interconnecting components of a biological process device (2), comprising a valve switching cartridge (15) and an actuator block (16). According to the invention, the valve switching cartridge (1) comprises a perforated backing plate (22) which secures the valve membrane structure (20) to the cartridge manifold (17), the actuator block (16) comprises a drive membrane structure (23) with at least one drive membrane (dx, y), and a perforated backing plate (24) which secures the drive membrane structure (23) to the actuator block body (21), an actuator of the actuator block (16) can urge the drive membrane structure (23) into engagement with the valve membrane structure (20) through aligned through-holes (25, 26) of the two backing plates (22, 24).

Description

[0001] This application was filed as a PCT international patent application on August 17, 2023 in the name of all national designated applicants (U.S. national company, Sartorius Stedim North America, Inc.) and all national designated inventors (U.S. citizen, Dinesh Shukla), and claims priority to U.S. application No. 17 / 896,645 filed on August 26, 2022, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0002] The present invention relates to the design of a valve switching system for selectively interconnecting components of a bioprocess plant according to the general part of claim 1, a method for producing such a valve switching system according to claim 11, a bioprocess plant with such a valve switching system according to claim 12, a method for operating such a valve switching system according to claim 14, and the use of such a valve switching system according to claim 15. Background Art

[0003] The term "bioprocess" currently stands for any kind of biotechnological process, in particular biopharmaceutical processes. Operation of a chromatography arrangement with a plurality of chromatography columns connected to a valve switching system for performing simulated moving bed (SMB) chromatography may be part of such a bioprocess.

[0004] The proposed valve switching system can be applied in various fields of biotechnology and in different kinds of bioprocesses. For biopharmaceutical processes, cost efficiency and process reliability are particularly relevant. Cost efficiency not only relates to material costs, but also to manufacturing costs. In addition, cost efficiency is also important considering, for example, the man-hours required for equipment installation and the costs of maintenance and operation of the bioprocess itself. Process reliability is important in view of the materials utilized, the installation procedures, and the correct operation of the bioprocess. Especially in an environment that is strictly regulated by authorities, such as the Food and Drug Administration (FDA), process reliability is crucial to ensure product safety.

[0005] For the valve switching system as part of the SMB process related to biopharmaceutical production, it is also critical to ensure the simple installation of the valve switching system. Therefore, the disposable and compact design of the separate valve and connector is indispensable. In EP1775001A1, a valve switching box as part of the valve switching system is disclosed, which is designed as a disposable item and has a compact design of the valve switching box. In the known valve switching system mentioned above (which is the starting point of the present invention), the port and fluid pipeline of the valve switching box are organized in a compact box manifold. The fluid pipeline in the box manifold is selectively connected by an array of switchable valve units designed as film valve units to control the fluid flow in the box manifold. The valve units all include valve seats, wherein the corresponding valve membranes selectively engage the valve seats or disengage from the valve seats to switch the valve units. The valve membrane can be actuated by an actuator. The actuator acts on the valve membrane to switch the valve unit. The actuator is part of an actuator block, which is part of the valve switching system. Several actuators can be arranged on the actuator block body.

[0006] For the actuation of the valve membrane, liquid or gas pressure can be used. To achieve this, the actuator comprises an actuation outlet which opens into a recess in the actuator block. The actuator block recess refers to the part of the actuator block body into which the actuation outlet opens and which has contact points with respect to the valve membrane. When the gas or liquid is guided through the actuation outlet towards the valve membrane, these contact points need to be sealed gas-tight or liquid-tight. In order to ensure reliable actuation of the valve membrane and thus correct operation of the valve unit, the contact points between the actuator block and the valve membrane need to be sealed gas-tight or liquid-tight.

[0007] In known systems, high forces are required to establish a leak-free connection at the contact point between the actuator block pocket and the valve membrane, which often presents challenges in terms of ease of installation. In addition, it is expensive to maintain the required high pressure during installation and subsequent operation of the valve switching system. In addition, applying high pressure to plastic materials (e.g., cartridge manifolds) increases the likelihood of stress cracking, and therefore damage to the valve switching system. The increased likelihood of stress cracking also reduces reliability during operation. In addition, the valve membrane may require a certain thickness to withstand the applied force, which in turn may increase the fluid pressure required to actuate the valve unit. Summary of the invention

[0008] It is therefore an object of the present invention to provide means for simplifying the installation and assembly of a valve switching system while improving its reliable operation and cost-efficiency.

[0009] The above-mentioned problem is solved by a valve switching system according to the general part of claim 1 having the features of the characterizing part of claim 1 .

[0010] The premise for the present invention is a valve switching system, which includes a valve switching box having: a box manifold with ports and fluid lines, and an array of switchable valve units for selectively interconnecting the fluid lines. The switching of the valve units is achieved by an actuator block as part of the valve switching system.

[0011] Now, the basic general idea of ​​the present invention is based on a valve switching system using two backing plates with perforations and a drive membrane structure. According to the present invention, it is found that the installation of the valve switching system is simplified and that by using two backing plates and a drive membrane structure, the pressure required for airtight and / or liquid-tight operation on the side of the valve switching box can be significantly reduced.

[0012] The general idea is to realize the valve switching box and the actuator block as a separate unit, which can be preassembled separately, wherein the two units achieve the proposed valve switching system by joining their backing plates face to face.

[0013] In detail, it is proposed that the valve switching box comprises a perforated backing plate that fixes the valve membrane structure to the box manifold. In addition, the actuator block comprises a drive membrane structure and a perforated backing plate, whereby the perforated backing plate fixes the drive membrane structure to the actuator block body. Both backing plates comprise a pattern of through holes. The through holes of the two backing plates are at least partially aligned with each other, so that in order to selectively switch the valve unit, the drive membrane structure can be pushed through any of the through holes of the backing plate by an actuator of the actuator block. In this way, the drive membrane structure engages with the valve membrane structure to selectively close the corresponding valve unit.

[0014] Here, the advantage is that the valve switching box and the actuator block can be preassembled, which simplifies the installation of the valve switching system. In addition, by including the drive membrane structure, the thickness of the valve membrane structure can be reduced considerably. In this way, reliable actuation of the valve membrane structure switching valve unit is ensured, while the cost for the valve membrane structure is reduced. In addition, the sensitivity of the actuation can also be increased, and the fluid pressure required to actuate the valve membrane can be reduced, which further contributes to improving the reliability and sensitivity of the process.

[0015] In addition, due to the separation from the actuator block, less pressure will be applied to the cassette manifold. Therefore, less material can be used for the cassette manifold. In addition, by improving the durability of the material, the material cost is reduced. This also enhances process reliability. In addition, by ensuring a compact design and enabling pre-assembly of the valve switching cassette and the actuator block, it is now possible to reduce the time required for equipment installation.

[0016] According to claim 2, the drive membrane protrudes through the aligned through-holes in the two backing plates in order to switch the corresponding valve unit(s). Here, the advantage is that a gap between the actuator block and the valve switching box can be achieved. This increases the flexibility of the design. In addition, the protrusion of the drive membrane is directed in a defined manner toward the valve membrane.

[0017] According to claim 3, the valve switching box and the actuator block are joined together via respective backing plates, in particular via respective flat surfaces of the backing plates. This facilitates easy installation and setting of the valve switching system and protects the membrane during installation.

[0018] According to claim 4, the through-hole of the backing plate can be aligned with the valve seat of the valve unit. This enables an easy solution of a predetermined protrusion of the membrane structure. In this way, mechanical wear of the membrane structure is reduced and reliable switching of the valve unit is ensured.

[0019] Claims 5 and 6 relate to materials for the valve membrane structure and / or the drive membrane structure. Here, the advantage is that different materials with different properties can be used for the membrane structure, which increases the flexibility of operation. In addition, the two membrane structures can be selected to adapt their respective functions in an optimal manner.

[0020] Claim 7 relates to the structure of the valve membrane and / or the drive membrane. Each of the membrane structures may include strips. The use of strips enhances the proper positioning of the membrane. In this way, process reliability is increased, since incorrect placement of the membrane structure is avoided. In addition, the amount of membrane material required is reduced, which also reduces the overall costs.

[0021] Claims 8 and 9 relate to the fastening of the membrane structure. By using backing plates to fasten the membrane structure, the backing plates play a dual role, as they enable preassembly of the different parts and establish the required leak-free connection. This dual function simplifies the overall design of the valve switching system.

[0022] According to claim 10, the actuator of the actuator block comprises an actuation outlet. In this way, a uniform actuation of the drive membrane structure is achieved. Furthermore, since the actuator block is not in contact with any process fluid distributed in the cassette manifold, the actuator block can have a simple construction and is reusable.

[0023] Claim 11 relates to a method for producing a valve switching system. By connecting the valve switching box and the actuator block via a corresponding backing plate, the production of the valve switching system is simplified because the two parts can be preassembled. This simplifies installation because the membrane is already assembled and protected from damage.

[0024] The independent teaching according to claim 12 relates to such a bioprocess device. Reference is made to all the explanations given with regard to the proposed valve switching system.

[0025] According to claim 13, the valve switching system is used as part of a bioprocess device for performing simulated moving bed (SMB) chromatography. Here, a compact arrangement of the liquid path network controlling the fluid flow is advantageous.

[0026] In a further independent teaching, a method for operating a valve switching system is thus claimed according to claim 14. Reference is again made to all the explanations given with regard to the proposed valve switching system.

[0027] In a further independent teaching, the use of the proposed valve switching system for switching columns of a bioprocess plant is claimed according to claim 15. All the explanations given with regard to the proposed valve switching system and the proposed bioprocess plant apply in their entirety. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In the following, embodiments of the invention are explained with reference to the accompanying drawings. The accompanying drawings show:

[0029] Figure 1 is a schematic overview of the proposed valve switching system as part of the proposed bioprocess device,

[0030] Figure 2 is an exploded view of the proposed valve switching system,

[0031] Figure 3 The working principle of the valve unit of the valve switching box as part of the valve switching system,

[0032] Figure 4 For an exemplary mode of operation according to Figure 1 Parts of bioprocess equipment. DETAILED DESCRIPTION

[0033] like Figure 1 As shown in , the proposed valve switching system 1 is used here and preferably for selectively interconnecting components of a bioprocess system 2. The expression "interconnect" is to be understood in the sense of a fluid connection.

[0034] In particular, Figure 1 Depicts the sequential steps performed to recover and purify a desired product (such as a monoclonal antibody) as part of a downstream process within a bioprocess. In the first step of the downstream process, the product is isolated in an isolation unit 3. Assuming the product is in the supernatant of the fermentation broth, centrifugation can be performed to separate the product from cells and cell debris. In order to increase the product concentration and reduce the amount of material to be processed in the sequential downstream processing steps, concentration (e.g., by ultrafiltration) can also be performed as part of the product isolation.

[0035] After the isolation of the product in isolation unit 3, product purification is performed in purification unit 4. Product purification can be performed by including multiple column chromatography (e.g. Figure 1 This is done by different means (as depicted in the chromatographic arrangement 5). Figure 1As shown in , the chromatography arrangement 5 may comprise a plurality of chromatography columns 6 - 13. In a preferred embodiment, the number of chromatography columns 6 - 13 connected to the valve switching system 1 is between one and eight.

[0036] Compared to conventional single column chromatography, multi-column chromatography significantly improves the efficiency of the purification step. However, multi-column chromatography is more complicated than single column chromatography, especially with respect to fluid flow. Therefore, advanced control of the fluid flow path is necessary, which is currently achieved by using, for example, Figure 1 This is accomplished by the proposed valve switching system shown in FIG.

[0037] After purification, the refining of the product is preferably performed in the refining unit 14. At the end of the product refining, the product is typically packaged for further distribution. Depending on the bioprocess, the product refining may, for example, include a virus inactivation step to meet regulatory requirements. Another example for product refining is a crystallization step, to convert the fluid product into a solid form, and thus, a form that can be easily transported. Another example for refining is the use of chromatography (such as, ion exchange chromatography or hydrophobic interaction chromatography).

[0038] The valve switching system 1 comprises a valve switching box 15 and an actuator block 16, wherein the valve switching box 1 comprises a box manifold 17 having ports and at least one fluid flow system 18, 19 of fluid lines. The first fluid flow system 18 comprises a main fluid line L p Connected main port P p , and the secondary fluid line L s Connected secondary port P s The second fluid flow system 19 includes a main fluid pipeline l p Connected primary port p p , and a secondary port p communicating with the secondary fluid line ls s .

[0039] The general functionality of the two fluid flow systems 18, 19 of ports and fluid lines is identical, so that explanations given for one fluid flow system 18, 19 apply equally to the respective other fluid flow system 18, 19. In the following, reference is mainly made to the second fluid flow system 19 in order to reduce complexity.

[0040] The valve switching box 15 also includes a switchable valve unit n x,y array, for transferring the main fluid line L via the transmission fluid line T p ,l p With secondary fluid line L s ,l s Selectively interconnect.

[0041] The expression "port" represents an interface for interconnecting components of the bioprocess device 2 to corresponding fluid lines. It may include a fluid connector leading to the corresponding fluid lines.

[0042] The expression "line" refers to any longitudinal volume that can contain and conduct a fluid between two locations. Fluid Line L p ,l p ,L s ,l s ,T is drilled or otherwise machined into the box manifold 17, preferably by deep hole drilling or similar method.

[0043] The terms "primary" and "secondary" are used to indicate the x,y In the embodiment shown and so far preferred, these expressions also indicate the direction of the fluid flow F, which is then directed from the primary fluid port to the secondary fluid port. However, this can also be achieved in reverse. Therefore, the expressions "primary" and "secondary" neither imply nor exclude construction and / or functional differences between the corresponding ports and fluid lines.

[0044] The expression "selectively interconnected" means that the main fluid pipeline l p One or more of the following may be selected to be connected to the secondary fluid line l s One or more interconnects in.

[0045] The expression "switchable" means that it is possible to switch the valve unit x,y Change from the "valve open" state to the "valve closed" state, or change from the "valve closed" state to the "valve open" state. If the valve unit n x,y In the "valve open" state, such as Figure 1 As exemplarily depicted in the illustration in FIG. 1 , the fluid may be drawn from the main fluid line l p Flows through the transmission fluid pipeline T to the secondary fluid pipeline l s Preferably, each of the transmission pipelines T is connected to the main fluid pipeline l p Or secondary fluid pipeline s Connected. Open valve unit n x,y exist Figure 1 and Figure 4 Indicated by a solid ellipse. If the valve unit n x,y In the "valve closed" state, it prevents the main fluid line from p Via the transmission fluid pipeline T to the secondary fluid pipeline l s The fluid flow in Figure 1 and Figure 4 In the diagram, a closed valve unit is indicated as an outlined ellipse.

[0046] Main fluid pipeline p and secondary fluid liness Preferably, the valve units n are arranged in rows and columns in the valve switching box 15, wherein the valve units n x,y Located in the main fluid line p With secondary fluid pipeline s At each junction between the corresponding fluid lines l p ,l s Through the corresponding valve unit n x,y and interconnected with the corresponding transmission fluid pipeline T. Therefore, the valve unit n x,y The array is aligned with these rows and columns and numbered accordingly. Figure 1 The illustration in FIG. 1 shows the valve unit n in detail. 11,3 .

[0047] Valve unit n x,y All including valve seats x,y .like Figure 3 As shown in x,y , and the main fluid line l p One of the transmission fluid pipelines T and the secondary fluid pipeline l s One of the communicating transfer fluid lines T preferably opens into the valve seat s x,y middle.

[0048] In another preferred embodiment, the main fluid pipeline 1 p Direct access to valve seats x,y In the secondary fluid pipeline l s Connected to valve seat s through transmission fluid pipeline T x,y .

[0049] In order to control the fluid flow, the valve switching box 15 of the valve switching system 1 includes a valve membrane structure 20. The valve membrane structure 20 can sealably engage the valve unit n x,y Valve Seats x,y , in order to switch valve unit n x,y The valve membrane structure 20 can selectively engage the valve seat s x,y (“valve closed” state) or with the valve seat x,y Disengaged ("valve open" state).

[0050] The actuator block 16 further includes an actuator block body 21 having a plurality of valve units n for each valve switching box 15. x,y The actuator block 16 can be driven by actuating the drive membrane d x,y To act on the valve membrane structure 20, especially the valve membrane m x,y Preferably, this results in the valve membrane structure 20 engaging the valve seat s x,y As will also be explained in detail below, when the actuator block 16 does not actuate the drive membrane d x,yWhen the valve membrane structure 20 is preferably connected to the valve seat s x,y Disengage.

[0051] Preferably, the proposed valve switching system 1 is used to control the fluid flow of components to be selectively interconnected, such as the chromatographic arrangement 5 shown. The fluid whose flow is controlled by the valve switching system 1 is called a process fluid. The process fluid to be treated within the present invention may include a variety of liquid media, such as buffers, washing solutions, acids, bases, culture media, liquids containing untreated products, liquids containing partially treated products, liquids containing purified products, sanitary solutions, etc. The fluid to be treated within the present invention may also be a medium in the gas phase.

[0052] Essential to the present invention is that the valve switching cassette 1 comprises a perforated backing plate 22 securing the valve membrane structure 20 to the cassette manifold 17 , wherein the actuator block 16 comprises a drive membrane structure 23 and a perforated backing plate 24 securing the drive membrane structure 23 to the actuator block body 21 .

[0053] The perforations of the two backing plates 22, 24 each comprise a pattern of through-holes 25, 26, wherein the perforations of the two backing plates 22, 24 are at least partially aligned with one another so that for the selective switching of the valve unit n x,y , the actuator of the actuator block 16 can push the drive membrane structure 23 through the aligned through holes 25, 26 of the two backing plates 22, 24 to engage with the valve membrane structure 20. Figure 3 is shown on the right side of .

[0054] The expression “perforated” is to be understood as a pattern of through holes 25 , 26 in the respective backing plate 22 , 24 , which extend through the entire thickness of the respective backing plate 22 , 24 .

[0055] It has now been found that the use of the actuated membrane structure 23 significantly improves the operating reliability of the valve switching system 1 , as will now be explained.

[0056] If the backing plate 24 is used to firmly fasten the driving membrane structure 23 to the actuator block body 21, the pressure required during installation and operation of the valve switching system 1 can be significantly reduced. By using the backing plate 24 to fasten the driving membrane structure 23, an airtight or liquid-tight connection between the driving membrane structure 23 and the actuator block body 21 is completed with less force. In addition, the use of the backing plate 24 enables pre-assembly of the actuator block 16.

[0057] Furthermore, since an air-tight or liquid-tight connection of the actuator block body 21 is now achieved between the actuator block body 21 and the drive membrane structure 23, the valve membrane structure 20 only needs to be fluid-tightly sealed relative to the box manifold 17, and is not as previously required to be air-tightly or liquid-tightly sealed relative to the actuator block body 21.

[0058] If less pressure is required during installation and operation of the valve switching system 1, the pressure exerted on the valve membrane structure 20 and the cassette manifold 17 is reduced. As a result, the thickness of both the valve membrane structure 20 and the cassette manifold 17 can be reduced, which reduces the overall material costs. In particular, the reduced thickness of the valve membrane structure 20 contributes to an increased sensitivity and precision regarding the actuation of the valve unit. In addition, the lower required pressure also reduces the cost of the actuator block body 21, since it is no longer necessary to handle relatively high pressures and the associated high forces.

[0059] The valve switching cassette 15 can also be preassembled by using the backing plate 22 to fasten the valve membrane structure 20 to the cassette manifold 17. Here, the backing plate 22 also serves to establish a fluid-tight connection between the cassette manifold 17 and the valve membrane structure 20.

[0060] The drive membrane structure 23 can be pushed by an actuator so that it protrudes through any of the aligned through-holes 25, 26 in the backing plates 22, 24, thereby engaging the valve membrane structure 20 to switch the corresponding valve unit n x,y As will be explained later, different principles are envisaged for actuation.

[0061] Since the valve switching box 15 and the actuator block 16 can be checked for fluid tightness and / or gas tightness before installation, the installation process of the valve switching system 1 is further simplified.

[0062] Figure 2 The backing plates 22, 24 depicted in the drawings may be made of different materials. Preferably, the two backing plates 22, 24 are made of the same material, more preferably, the two backing plates 22, 24 are made of acrylic plastic. However, other (e.g. more durable) materials may also be used, like aluminum. In addition, other types of plastic materials may also be used, such as PMMA, PEEK or PVDF. It is further preferred that the backing plates 22, 24 are identical in terms of their geometry. Similar designs of the backing plates 22, 24 with respect to geometry and / or material may be advantageous in terms of manufacturing.

[0063] Alternatively, by using one backing plate 22 for the valve switching box 15 and one backing plate 24 for the actuator block 16, different materials may be used for each backing plate 22, 24. For example, a disposable plastic material may be used for the backing plate 22 of the valve switching box 15, while a reusable material (e.g., aluminum) may be used for the backing plate 24 of the actuator block 16. The geometry of the backing plates 22, 24 may also alternatively differ in their geometry.

[0064] It should be noted that the realization of the backing plates 22, 24 is very simple. The through-holes 25, 26 can be introduced into the backing plates 22, 24 by drilling, punching, injection molding or the like.

[0065] like Figure 3As shown in x,y When the actuator of the actuator block 16 is pushed, the driving membrane d x,y The drive membrane d protrudes through corresponding through-holes 26 in the backing plate 24 of the actuator block 16 and through aligned through-holes 25 in the backing plate 22 of the valve switching box 15. x,y Then act on the valve membrane m x,y Switching valve unit n x,y , as will be explained later. Here, the drive film d x,y Not only provides drive membrane d x,y The air-tight or liquid-tight seal between the actuator block cavity 26 and the drive membrane d x,y To valve diaphragm x,y The deflection provides additional resistance, thus reducing the valve diaphragm m x,y Mechanical wear, which enhances the valve unit x,y proper operation.

[0066] like Figure 2 As shown in , the valve switching box 15 and the actuator block 16 are linked together via respective backing plates 22, 24. As already explained, this enables pre-assembly of the valve switching box 15 and the actuator block 16 and thus enhances proper installation of the valve switching system 1. Further aspects related to the manufacturing process of the valve switching system 1 will be explained below.

[0067] The assembly of the preassembled valve switching box 15 with the backing plates 22, 24 and the preassembled actuator block 16 can be performed in many ways. Figure 2 24 are connected together as indicated by the arrows in . It should be noted that the connection can be permanent, but is preferably achieved non-permanently, which means that the connection can be terminated in a non-destructive manner. For example, the backing plates 22, 24 can be connected using screws or clamps, which can be removed after the process is completed. Alternatively, an adhesive can be used to connect the backing plates 22, 24. However, the options mentioned are only examples and other options that allow the connection of the backing plates 22, 24 can also be envisaged.

[0068] If available from Figure 2 It can be seen that at least part of the through holes 25, 26 of the backing plates 22, 24 are in contact with the valve unit n. x,y Valve Seats x,y alignment.

[0069] In a preferred embodiment, the through holes 25, 26 are arranged in rows and columns. Preferably, the through holes 25, 26 are arranged in such a way that each column comprises an equal number of valve units n in the corresponding column. x,y In yet another preferred embodiment, the number of through holes 25, 26 in each row corresponds to the number of valve units n in the corresponding row. x,yIn the depicted and hitherto preferred embodiment, each row comprises eight through-holes 25 , 26 .

[0070] In a preferred embodiment, the number of through holes 25, 26 in each backing plate 22, 24 is equal to the number of valve units n. x,y It is also preferred that each through-hole 25 , 26 in each backing plate 22 , 24 is assigned to exactly one valve unit n. x,y By aligning the through holes 25, 26 of the backing plates 22, 24 with the valve seat x,y Alignment, drive membrane d x,y The protrusion of the valve element is defined by the shape of the through-holes 25, 26. This ensures that only the corresponding valve unit n x,y is actuated because each membrane structure 20 , 23 is held in its position by the respective backing plate 22 , 24 .

[0071] In yet another preferred embodiment, the shape of each of the through holes 25, 26 corresponds to a given valve seat s x,y Preferably, the through holes 25, 26 have an elliptical geometry. This enhances the film m x,y ,d x,y The definition is prominent, especially if the actuation is performed indirectly (eg by air pressure), because the membrane m x,y ,d x,y The protrusions are then guided by the shape of the through-holes 25, 26. In addition, by choosing an elliptical geometry, it is avoided that the valve membrane m x,y and / or drive membrane d x,y The structural integrity of sharp corners and edges.

[0072] At least one valve membrane m of the valve membrane structure 20 x,y It is preferably composed of a fluorocarbon-based fluoroelastomer (FKM) which is a rubber compound using vinylidene fluoride as its monomer (e.g., ). As mentioned above, FKM is robust even when in contact with fluids like acids and bases that tend to attack the material.

[0073] Diaphragm x,y The hardness (Shore A) of the valve membrane is preferably between 50 and 80, more preferably 75. x,y The material thickness of is preferably less than 3 mm and further preferably between 0.5 mm and 0.75 mm.

[0074] The valve membrane structure 20 and the drive membrane structure 23 can have the same layout in terms of material and / or geometry (particularly thickness), which is logistically advantageous. However, it is preferred that different materials are selected for the membrane structures 20, 23 due to cost optimization and the different functions of the respective membrane structures 20, 23 (which will be explained in detail below).

[0075] Preferably, at least one driving membrane d of the driving membrane structure 23 x,y Made of soft flexible plastic material. It can be noted that the drive membrane d x,y The material of the drive membrane needs to be flexible and wear-resistant. In addition, it needs to be durable. For example, suitable materials can be selected based on their airtightness. In a preferred embodiment, the drive membrane d x,y The driving membrane is preferably composed of a thermoplastic elastomer (TPE). x,y Made of polychloroprene (also known as chloroprene rubber), thermoplastic polyester (e.g. ) or thermoplastic vulcanizates (e.g., Santroprene TM However, the driving film d x,y The material of is not limited to the materials listed above, but may be composed of any other material that meets the requirements described above and below.

[0076] Preferably, the driving film d x,y The hardness (Shore A) of the drive film is between 40 and 70, and more preferably 55. x,y The material thickness of is preferably less than 2 mm and further preferably between 1.25 mm and 1.75 mm.

[0077] Depending on the process performed using the valve switching system 1, different requirements may need to be met by the valve membrane structure 20 and the drive membrane structure 23, respectively. x,y Certain certifications ("USP Class") based on General Chapter 88 of the United States Pharmacopeia National Formulary (USP-NF) may be required. x,y The material meets the requirements set forth in USP Class VI certification. However, this requirement does not necessarily have to be driven by the membrane d x,y Satisfied, because the drive membrane d x,y There is no contact with the process fluid distributed in the cartridge manifold 17. This is achieved for driving the membrane d x,y A wider choice of materials.

[0078] Utilize membrane materials that can vary in thickness, properties and material for valve membranes x,y and drive membrane d x,y The particular advantage is that the membrane d x,y ,m x,yEach of these can be tailored to best suit its respective purpose. This means, for example, that the valve membrane m x,y The thickness can be selected and optimized for the valve unit n x,y The best switching while driving the membrane d x,y Can be selected to provide optimal air sealing capability. This increases operational flexibility and contributes to improved process reliability as the service life of both membranes can be increased.

[0079] Since the backing plates 22 , 24 are firmly pressed against the cassette manifold 17 and the actuator block body 21 , respectively, a fluid-tight seal between the cassette manifold 17 and the valve membrane structure 20 , and an air-tight or liquid-tight seal between the drive membrane structure 23 and the actuator block body 21 is ensured.

[0080] In detail, the valve unit n x,y Designed as a membrane valve unit, each membrane valve unit has a valve membrane m x,y , which can be in the open position ( Figure 3 , valve unit n 11,3 ) and closed position ( Figure 3 , valve unit n 10,3 )

[0081] Valve unit n x,y All including valve seats x,y , wherein the corresponding valve membrane m provided by the valve membrane structure 20 x,y Selectively engageable valve seats x,y (“valve closed” state) or with the valve seat x,y Disengagement ("valve open" state) in order to switch valve unit n x,y .like Figure 3 As shown in x,y , fluid pipeline p ,l s One of them leads to the transmission fluid pipeline T. Preferably, the transmission fluid pipeline T leads to the valve seat s x,y In. Valve Seats x,y The valve membrane m provided by the valve membrane structure 20 can be x,y interact tightly.

[0082] As will be explained in detail later, the valve membrane m x,y The actuation is performed by the driving membrane d of the driving membrane structure 23. x,y accomplish.

[0083] like Figure 2 As depicted in FIG. 2 , the valve membrane structure 20 includes valve membrane strips 27. Preferably, the number of valve membrane strips 27 is equal to the number of columns of through holes 25, 26 on at least one of the backing plates 22, 24. In yet another preferred embodiment, each valve membrane strip 27 covers the valve unit n. x,yA column.

[0084] If you can also Figure 2 As can be seen, the driving membrane structure 23 includes driving membrane strips 28. Preferably, the number of driving membrane strips 28 is equal to the number of columns of through holes 25, 26 on at least one of the backing plates 22, 24. In another preferred embodiment, each driving membrane strip 28 covers the valve unit n x,y A column.

[0085] It is further preferred that the number and shape of the valve membrane strips 27 are the same as the number and shape of the drive membrane strips 28. In addition, it is preferred that the valve membrane strips 27 and the drive membrane strips 28 are aligned. Preferably, the membrane strips 27, 28 have a certain cross-sectional form, preferably an arcuate, polygonal, and particularly rectangular form.

[0086] like Figure 2 As depicted in FIG. 1 , the space between each of the membrane strips 27, 28 is the same. Preferably, a fixing element 29 for connecting the respective backing plates 22, 24 to the cartridge manifold 17 or the actuator block body 21, respectively, is inserted between the membrane strips 27, 28 in such a manner that the membrane strips 27, 28 are not in direct contact with the fixing element 29, but are indirectly fastened by a compressive force.

[0087] The number and arrangement of the membrane strips 27, 28 are merely exemplary and are not limited to the description given above. x,y Different designs can be selected. For example, the valve membrane m x,y and / or drive membrane d x,y Can include covering all valve units n x,y Only one membrane strip of the valve unit n x,y A number of rows and / or columns.

[0088] The valve membrane structure 20 is attached to the cassette manifold 17 ( Figure 2 Preferably, the backing plate 22 is connected to the valve membrane structure 20 in a constant force fit, pressing the valve membrane structure 20 to the cartridge manifold 17. Here, it is also essential that the valve membrane m x,y Sealingly connected to the cartridge manifold 17 so that the valve seat s x,y With valve diaphragm x,y A fluid-tight and leak-free connection is established between the backing plate 22. In a preferred embodiment, the backing plate 22 is connected to the cassette manifold 17 using fixing elements 29 (such as screws). It is further preferred that the fixing elements 29 are arranged in rows and columns. Preferably, the backing plate 22 includes an opening for the insertion of the fixing elements 29.

[0089] In order to correctly position at least one valve membrane strip 27, the backing plate 22 may include corresponding grooves (not depicted) on the flat side of the backing plate 22 facing the cassette manifold 17. These grooves preferably have the same shape as the membrane strips 27, so that each membrane strip 27 can be inserted into one groove. This contributes to simplified pre-assembly of the valve switching cassette 15.

[0090] The driving membrane structure 23 is attached to the actuator block body 21 through the backing plate 24 ( Figure 2 ). Preferably, the backing plate 24 is connected to the drive membrane structure 23 in a constant force fit, pressing the drive membrane structure 23 to the actuator block body 21. Here, it is also essential that the drive membrane structure 23 is sealingly connected to the actuator block body 21 to establish an airtight or liquid-tight connection between the actuator block body 21 and the drive membrane structure 23. In a preferred embodiment, the backing plate 24 is connected to the actuator block body 21 using fixing elements 29 (such as screws). It is further preferred that the fixing elements 29 are arranged in rows and columns. Preferably, the backing plate 24 includes an opening for the insertion of the fixing elements 29.

[0091] In order to correctly position the at least one drive membrane strip 28, the backing plate 24 may include corresponding grooves (not depicted) on the flat side of the backing plate 24 facing the actuator block body 21. These grooves preferably have the same shape as the membrane strips 28, so that each membrane strip 28 can be inserted into one groove. This contributes to simplified pre-assembly of the actuator block 16.

[0092] like Figure 2 As shown in FIG, the backing plate 22 assigned to the valve switching cassette 15 provides a detachable fluid-tight connection between the valve membrane structure 20 and the cassette manifold 17. Therefore, no adhesive is required to connect the valve membrane structure 20 to the backing plate 22 and the cassette manifold 17, which generally makes it possible to replace the valve membrane structure 20 and / or to separately arrange the valve membrane structure 20 from the backing plate 22 and the cassette manifold 17.

[0093] like Figure 2 As shown in , the backing plate 24 assigned to the actuator block 16 also provides a detachable air-tight or liquid-tight connection between the driving membrane structure 23 and the actuator block body 21. Therefore, no adhesive is required to connect the driving membrane structure 23 to the backing plate 24 and the actuator block body 21, which generally makes it possible to replace the driving membrane structure 23 and / or to arrange the driving membrane structure 23 separately from the backing plate 24.

[0094] It should be noted that the use of screws as fixing elements 29 is only one example for connecting the backing plates 22, 24 to the cartridge manifold 17 and / or the actuator block body 21, respectively. The use of other fixing elements, such as clamps, is also conceivable.

[0095] As explained above, the backing plates 22 , 24 respectively enable the preassembly of the valve switching box 15 and the actuator block 16 and guide the projection of the membrane structures 20 , 23 .

[0096] Here, the backing plates 22, 24 are shown to play the additional role of securely fastening the membrane structures 20, 23 and providing the required gas-tight and / or liquid-tight connection for the correct operation of the valve switching system 1. By this multifunctionality of the backing plates 22, 24, the overall design of the valve switching system 1 is simplified.

[0097] like Figure 3 As shown in FIG. 1 , the actuator block 16 includes an actuator (not shown) having an actuation outlet 30. Through the actuation outlet 30, pressure is applied to the drive membrane structure 23. In a preferred embodiment, the actuation outlet 30 is a gas pressure outlet or a liquid pressure outlet. In yet another preferred embodiment, one actuation outlet 30 is assigned to each valve unit n. x,y . Driving membrane structure x,y The actuation is preferably carried out in a contactless manner, in particular pneumatically or hydraulically by applying a gas or a liquid to the drive membrane structure 23 via the actuation outlet 30. Preferably, compressed air is used for actuation. In this case, the construction of the actuator block 16 is simplified, since no mechanical actuator (e.g. a plunger) is required. In addition, since the pressure is applied uniformly to the membrane m x,y ,d x,y So the membrane m x,y ,d x,y Reduced mechanical wear.

[0098] However, the plunger or is suitable for directly actuating the drive membrane d x,y Any other system can also be used to actuate the drive membrane in a direct manner. x,y In this case, the plunger will be actuated, for example, pneumatically, hydraulically, electromagnetically, etc. Although it will not be required that the actuator block body 21 is connected to the drive membrane d x,y airtightness or liquid-tightness between them, but if the drive membrane d x,y Directly actuated by a plunger or the like, the other advantages of the proposed valve switching system 1 (especially the option for pre-assembly) would still apply.

[0099] By actuating the outlet 30 at the driving membrane d x,y The pressure exerted on can be controlled in several ways, as will be explained below.

[0100] By applying liquid or gas pressure to the drive membrane d through the actuation outlet 30 x,y on or by directly actuating the drive membrane d x,y , driving membrane d x,y protrudes through the through holes 25, 26 in the backing plates 22, 24 and flexes against the valve membrane structure 20 ( Figure 3 ). In particular, the valve membrane m x,y is actuated, which causes the valve membrane structure 20 to contact the valve seat s x,y Enter the sealing joint. Figure 3 This applies to valve unit n 10,3 If the pressure is removed, or the plunger is retracted, the pressure of the process fluid distributed inside the cartridge manifold 17 causes the valve diaphragm structure 20 (particularly the valve diaphragm m x,y ) against the driving membrane d x,y Flexure ( Figure 3 ). This deflection causes the valve membrane m x,y Separation from valve seat x,y Sealed joint. Figure 3 This applies to valve unit n 11,3 Describe.

[0101] It may be noted that the expression "entering into sealing engagement" means that the valve membrane structure 20 and the valve seat s x,y A fluid-tight seal is established between the valve membrane structure 20 and the valve seat s, which is generally a force fit engagement, and the expression "disengagement from sealing engagement" may include the valve membrane structure 20 and the valve seat s x,y There is loose contact between the two, however it is not fluid-tight.

[0102] like Figure 3 As depicted in FIG. 1 , the control valve 31 can be used to control the pressure in the actuation outlet 30. As explained above, if the control valve 31 is opened ( Figure 3 In the figure, the pressure introduced into the actuator block cavity 32 through the actuation outlet 30 is greater than the pressure exerted on the valve diaphragm structure 20 by the process fluid flow F, then the drive membrane d x,y is actuated. If the control valve 31 is closed ( Figure 3 The current pressure is maintained in the actuator block cavity 32 (indicated by the letter "c" in the figure). Depending on the pressure difference between the pressure exerted by the process fluid flow F and the pressure in the actuator block cavity 32, the valve membrane m can be controlled in a precise manner. x,y and drive membrane d x,y As mentioned above, the valve membrane m x,y The thickness of the valve membrane can be reduced significantly. This further contributes to the precise controllability, because the valve membrane m x,y will be more sensitive to applied pressure and may be actuated at lower pressures applied by process fluid flow F, for example.

[0103] Depending on the difference in elasticity between the materials of the membrane structures 20, 23, each of the membrane structures 20, 23 can constrain the deformation of the respective other membrane structure 20, 23. This means in particular that when the valve membrane structure 20 is separated from the valve seat s x,yWhen the sealing engagement of the valve membrane structure 20 is achieved, the deflection of the valve membrane structure 20 can be constrained by the drive membrane structure 23. This results in a limited deflection of the valve membrane structure 20. As a result, in particular the design of the backing plate 22 of the valve switching box 15 is simplified, because no recess is required to limit the protrusion of the valve membrane structure 20. In addition, this enables the use of flexible materials for the valve membrane structure 20 for the valve unit n x,y Reliable actuation is achieved while reducing the risk of mechanical exhaustion of the valve membrane structure 20.

[0104] The actuator block 16 may preferably be controlled by an electronic control device (not shown) comprising a microprocessor operating on the basis of control software.Here it becomes apparent that the entire process fluid flow F may be flexibly and accurately controlled electronically simply by corresponding modifications of the control software.

[0105] Since the valve switching box 15 and the actuator block 16 can be preassembled separately, the manufacture of the valve switching system 1 is simplified. This also means that, for example, the valve switching box 15 and the actuator block 16 can be sterilized separately (for example, by gamma ray irradiation), or only the valve switching box 15 can be sterilized. The latter is preferred because sterilization of the actuator block 16 is not required when the actuator block 16 is not in contact with the process fluid. In addition, the liquid tightness and / or gas tightness of the two parts can be checked before installation. This enables corrective measures and, if necessary, readjustment of the membrane structure 20, 23 or the backing plate 22, 24 before assembly. In this way, leakage problems caused by improper installation are reduced. This greatly improves the installation procedure and significantly reduces the potential for operational failure.

[0106] Since the two parts (i.e., the valve switching box 15 and the actuator block 16) are preassembled and can be checked for liquid tightness and / or air tightness before installation, the preassembled parts can be connected together in a more flexible manner via the corresponding flat surfaces of the backing plates 22, 24, because the slightly different positioning of the valve switching box 15 and the actuator block 16 does not affect the liquid tightness and / or air tightness. In addition, the actuator block 16 (or part thereof) can be easily reused, while the valve switching box 15 (or part thereof) is discarded after the process is completed. In addition, the valve switching box 15 can be sterilized after assembly and then distributed in a sterile form. As explained above, the connection of the preassembled valve switching box 15 and the preassembled actuator block 16 can be carried out in many ways. This is the subject of the second independent teaching.

[0107] According to the third independent teaching, the bioprocess plant 2 is thus claimed. Reference is made to all the explanations given with regard to the first teaching.

[0108] According to a fourth independent teaching, a bioprocess device 2 comprises components to be selectively interconnected, which components are here and preferably a chromatography arrangement 5 with its multiple chromatography columns 6-13, which are connected to a valve switching system 1 for performing, for example, a simulated moving bed (SMB) chromatography process. Reference is made to all explanations given in connection with the previous teachings.

[0109] Figure 4 Only another exemplary operation of the proposed valve switching system 1 is shown. Here, it becomes clear that multiple variations of the sequential and parallel utilization of the chromatographic columns 6-13 are possible. When the chromatographic columns 6, 7, 8 are utilized sequentially, the chromatographic column 10 is utilized in parallel therewith. In general, any number of chromatographic columns can be utilized in any desired sequence or in parallel, and the process fluid flow can be from the main port P of the first fluid flow system 18. p Any of the provided inlets leads to a secondary fluid port p provided by the second fluid flow system 19. s As explained above, by reducing the fluid flow pressure within the cassette manifold 17, the fluid flow pressure in the connected chromatography columns 6-13 may also be reduced.

[0110] Further independent teachings relate to a method for operating the valve switching system 1 and to the use of the valve switching system 1. For operating the above-mentioned valve switching system 1, it is essential that the drive membrane structure 23 is selectively pushed by an actuator through one of the through-holes 25, 26 in the backing plates 22, 24. Reference is made to all the explanations given previously.

[0111] Finally, it may be pointed out that the valve switching system 1 according to the various teachings can be subjected to scale-up or scale-down to different levels of process size without having to introduce structural modifications.

[0112] The proposed solution is particularly advantageous in bioprocess devices 2 involving a chromatography arrangement with a plurality of chromatography columns for performing simulated moving bed (SMB) chromatography.

[0113] When the valve switching system 1 includes two backing plates 22, 24 and two membrane structures 20, 23, pre-assembly of the valve switching box 15 and the actuator block 16 including the corresponding membrane structures 20, 23 is possible. This improves the applicability during process assembly and reduces the cost during installation. In addition, since the backing plates 22, 24 are used to seal the corresponding membrane structures 20, 23 to the box manifold 17 and the actuator block body 21, respectively, the valve unit n is ensured. x,y The gas-tight and / or liquid-tight seal, as well as the valve diaphragm m x,y Switching valve unit n x,yReliable actuation. In addition, the pressure required for air-tight or liquid-tight sealing is reduced, and less pressure is applied to the cassette manifold 17. The required less pressure reduces operating costs and improves process reliability by eliminating a high-cost pressurizing mechanism and preventing damage to the cassette manifold 17. In addition, if less pressure is applied, the thickness of the cassette manifold 17 and the valve membrane structure 20 can be reduced. In summary, the proposed design of the valve switching system 1 improves currently known designs in several ways.

Claims

1. A valve switching system for selectively interconnecting components of a bioprocess device (2), comprising a valve switching box (15) and an actuator block (16), wherein the valve switching box (15) comprises a box manifold (17), the box manifold (17) having ports and at least one fluid flow system (18, 19) of fluid lines, the at least one fluid flow system (18, 19) comprising a main fluid line (L p ) connected to the main port (P p ) and the secondary fluid pipeline (L s ) connected to the secondary port (P s ), wherein the valve switching box (1) comprises a switchable valve unit (n x,y ) array, for transferring the main fluid line (L) via a transmission fluid line (T) p ) and the secondary fluid pipeline (L s ) are selectively interconnected, wherein the valve units (n x,y ) include valve seat (s x,y ), wherein the valve switching box (1) comprises at least one valve membrane (m x,y ) of the valve membrane structure (20), wherein at least one valve membrane (m x,y ) can selectively engage the valve seat (s x,y ) in order to switch the valve unit (n x,y ), wherein the actuator block (16) comprises an actuator block body (21) having a plurality of actuators for each valve unit (n x,y ) of the actuator, It is characterized in that The valve switching box (1) includes a perforated backing plate (22) for fixing the valve membrane structure (20) to the box manifold (17), and the actuator block (16) includes at least one driving membrane (d x,y ) and a perforated backing plate (22) fixing the drive membrane structure (23) to the actuator block body (21), wherein the perforations of the two backing plates each include a pattern of through holes, wherein the perforations of the two backing plates are at least partially aligned with each other so that in order to selectively switch the valve unit (n x,y ), the actuator of the actuator block (16) can push the drive membrane structure (23) through the aligned through holes (25, 26) of the two backing plates (22, 24) to engage with the valve membrane structure (20).

2. The valve switching system according to claim 1, characterized in that: The driving film (d x,y ) if pushed by the actuator of the actuator block (16), it protrudes through the corresponding through-hole (26) in the backing plate (24) of the actuator block (16) and through the aligned through-hole (25) in the backing plate (22) of the valve switching box (15).

3. A valve switching system according to any one of the preceding claims, characterized in that The valve switching box (15) and the actuator block (16) are connected together via corresponding backing plates (22, 24).

4. A valve switching system according to any one of the preceding claims, characterized in that At least part of the through hole (25, 26) of the backing plate (22) of the valve switching box (15) and / or at least part of the through hole (25, 26) of the backing plate (24) of the actuator block (16) is aligned with the valve unit (n x,y ) of the valve seat (s x,y )alignment.

5. The valve switching system according to any one of the preceding claims, characterized in that At least one valve membrane (m x,y ) is composed of fluorocarbon-based fluoroelastomer material (FKM).

6. A valve switching system according to any one of the preceding claims, characterised in that At least one driving membrane (d x,y ) is made of soft plastic material.

7. A valve switching system according to any one of the preceding claims, characterized in that The valve membrane structure (20) and / or the drive membrane structure (23) comprises membrane strips (27, 28).

8. A valve switching system according to any one of the preceding claims, characterised in that The valve membrane (m x,y ) is fixed to the cartridge manifold (17) via a corresponding backing plate (22) which provides a seal between the valve membrane (m x,y ) and a detachable air-tight and / or liquid-tight connection between the box manifold (17).

9. A valve switching system according to any one of the preceding claims, characterized in that The driving film (d x,y ) is fixed to the actuator block body (21) through a corresponding backing plate (24), and the backing plate (24) provides the driving membrane (d x,y ) and the actuator block (16) have a detachable gas-tight and / or liquid-tight connection.

10. The valve switching system according to any one of the preceding claims, characterized in that The actuator of the actuator block (16) comprises at least one actuation outlet (30), preferably a gas pressure outlet or a liquid pressure outlet.

11. Method for producing a valve switching system according to any one of the preceding claims, characterized in that The valve switching box (15) and the actuator block (16) are connected together via corresponding backing plates (22, 24).

12. A bioprocess device comprising the valve switching system according to any one of claims 1 to 10.

13. The bioprocess device according to claim 12, characterized in that The bioprocess device (2) comprises a chromatography arrangement (5) having a plurality of chromatography columns (6-13), which are connected to a valve switching system according to any one of claims 1 to 10 for performing a simulated bed (SMB) chromatography process.

14. A method for operating a valve switching system according to any one of claims 1 to 10, wherein the valve unit (n x,y ) is selectively switched by the drive membrane structure (23), which is pushed by the actuator block (16) through the aligned through-holes of the two backing plates (22, 24), thereby engaging the valve membrane structure (20) to switch the corresponding valve unit (n x,y ).

15. Use of the valve switching system for switching the chromatography columns (6-13) of the bioprocess device according to claim 13.

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