Valve switching system for selectively interconnecting components of a bioprocessing facility

Abstract

The present invention is directed to a valve switching system for selectively interconnecting components of a bioprocessing facility (2), comprising a valve switching cassette (15) and an actuator block (16). The valve switching cassette (15) comprises a perforated backer plate (22) that secures a valve membrane structure (20) to a cassette manifold (17), and the actuator block (16) comprises a drive membrane structure (23) having at least one drive membrane (dx, y) and a perforated backer plate (24) that secures the drive membrane structure (23) to an actuator block body (21), wherein the valve units (n x,y For selective switching of the valve membrane structure (20), the actuator of the actuator block (16) can press the drive membrane structure (23) through aligned drilled holes (25, 26) in both backer plates (22, 24) to engage the valve membrane structure (20).

Description

[Technical Field]

[0001] This application is a PCT international patent application filed on August 17, 2023, in the name of Sartorius Stedim North America Inc., a U.S. corporation, as applicant in all designated jurisdictions, and in the name of Dinesh Shukla, a U.S. citizen, as inventor in all designated jurisdictions, 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.

[0002] The present invention relates to the design of a valve switching system for selectively interconnecting components of a bioprocessing installation according to the preamble of claim 1, a method for manufacturing such a valve switching system according to claim 11, a bioprocessing installation equipped 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.

[0003] The term "bioprocess" currently refers to any kind of biotechnological process, especially biopharmaceutical processes. The operation of a chromatography arrangement comprising multiple 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 may be applied in various fields of biotechnology and different types of bioprocesses. For biopharmaceutical processes, cost-efficiency and process reliability are particularly relevant. Cost-efficiency relates not only to material costs but also to production costs. Furthermore, it is important to consider, for example, the labor time required for equipment installation and the costs of maintaining and operating the bioprocess itself. Process reliability is important in terms of the materials used, the installation procedures, and the proper operation of the bioprocess. Particularly in environments that are heavily regulated by authorities (such as the Food and Drug Administration (FDA)), process reliability is essential to ensure product safety.

[0005] For valve switching systems that are part of SMB processes related to biopharmaceutical manufacturing, ensuring simple installation is also key. Therefore, disposable and compact designs of individual valves and connectors are important. A valve switching cassette designed as a disposable item, featuring a compact design, and part of a valve switching system is disclosed in EP 1 775 001 A1. In the known valve switching system, which is the starting point of the present invention, the ports and fluid lines of the valve switching cassette are organized into a compact cassette manifold. The fluid lines in the cassette manifold are selectively connected by an array of switchable valve units designed as membrane valve units to control fluid flow within the cassette manifold. Each valve unit includes a valve seat, where each valve membrane selectively engages or disengages from the valve seat depending on the switching of the valve unit. The valve membranes may 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. A plurality of actuators may be disposed in the actuator block body.

[0006] The valve membrane may be actuated using hydraulic or gas pressure. To achieve this, the actuator includes an actuation outlet that connects to an actuator block pocket. This actuator block pocket refers to the portion of the actuator block body through which the actuation outlet flows and which has contact points with the valve membrane. These contact points must be sealed gas-tight or liquid-tight to allow the gas or liquid to be guided through the actuation outlet toward the valve membrane. To ensure reliable valve membrane actuation and, consequently, proper functionality of the valve unit, the contact points between the actuator block and the valve membrane must be sealed gas-tight or liquid-tight.

[0007] In known systems, a large force is required to establish a leak-tight connection at the contact point between the actuator block pocket and the valve membrane, which often leads to challenges in terms of easy installation. Additionally, maintaining the necessary high pressure during installation and subsequent operation of the valve switching system is costly. Furthermore, applying high pressure to plastic materials such as cassette manifolds can increase the likelihood of stress cracking, thus potentially leading to damage to the valve switching system. The increased likelihood of stress cracking also reduces reliability during operation. Additionally, the valve membrane may require a certain thickness to withstand the applied force, which can result in increased fluid pressure required to operate the valve unit.

[0008] It is therefore an object of the present invention to provide a means for simplifying the installation and assembly of a valve switching system while making it more reliable in operation and cost-effective.

[0009] The above problem is solved by a valve switching system according to the preamble of claim 1, which comprises the features of the characterizing part of claim 1.

[0010] The present invention is based on a valve switching system including a valve switching cassette having a cassette manifold with ports and fluid lines and an array of switchable valve units for selectively interconnecting the fluid lines, wherein switching of the valve units is achieved by an actuator block as part of the valve switching system.

[0011] The general concept underlying the present invention is based on a valve switching system that uses two backer plates with perforations and an actuated membrane structure. It has been found that the use of two backer plates and an actuated membrane structure will simplify the installation of the valve switching system and significantly reduce the applied pressure required for gas-tight and / or liquid-tight operation at the valve switching cassette side.

[0012] The general consideration is to realize the valve switching cassette and the actuator block as separate pre-assembled units, where these two units are added to the proposed valve switching system by mating their backer plates face-to-face.

[0013] Specifically, the valve switching cassette is proposed to include a perforated backer plate that secures the valve membrane structure to the cassette manifold. Furthermore, the actuator block includes a drive membrane structure and a perforated backer plate, whereby the perforated backer plate secures the drive membrane structure to the actuator block body. Both backer plates include a pattern of perforated holes. The perforated holes in both backer plates are at least partially aligned with each other, such that the drive membrane structure may be pressed by an actuator of the actuator block through any one of the perforated holes in the backer plate to selectively switch the valve units. In this manner, the drive membrane structure engages with the valve membrane structure to selectively close the respective valve units.

[0014] The advantage here is that the valve switching cassette and actuator block can be pre-assembled, which simplifies the installation of the valve switching system. Furthermore, by including the actuation membrane structure, the thickness of the valve membrane structure can be significantly reduced. In this way, reliable actuation of the valve membrane structure for switching the valve unit is ensured, while the cost of the valve membrane structure is reduced. Furthermore, the actuation sensitivity is improved, and the fluid pressure required to actuate the valve membrane is also reduced, which further contributes to improving the reliability and sensitivity of the process.

[0015] Additionally, because it is separated from the actuator block, less pressure must be applied to the cassette manifold. As a result, less material can be used for the cassette manifold. Additionally, the increased durability of the material reduces material costs, which also improves process reliability. Furthermore, this ensures a compact design and allows for pre-assembly of the valve switching cassette and actuator block, thereby reducing the time required for equipment installation.

[0016] According to claim 2, the actuating membranes protrude through aligned drilled holes in both backer plates to switch the respective valve units. The advantage here is that a gap can be realized between the actuator block and the valve switching cassette, which increases design flexibility. Furthermore, the protrusions of the actuating membranes are directed towards the valve membranes in a defined manner.

[0017] According to claim 3, the valve switching cassette and the actuator block are coupled together via their respective backer plates, in particular via their respective flat surfaces, which facilitates easy installation and setup of the valve switching system and protects the membrane during installation.

[0018] According to claim 4, the drilled holes in the backer plate may be aligned with the valve seats of the valve unit. This allows for an easy solution to the pre-set protrusion of the membrane structure. In this way, the mechanical wear of the membrane structure is reduced and reliable switching of the valve unit is ensured.

[0019] Claims 5 and 6 are directed to the materials used for the valve membrane structure and / or the drive membrane structure. The advantage here is that different materials with different properties can be used for the membrane structure parts, which increases the flexibility in operation. Furthermore, both membrane structure parts can be selected to suit their respective functions in an optimal way.

[0020] Claim 7 is directed to structures for the valve membrane and / or the drive membrane. Each membrane structure could include stripes. The use of stripes enhances proper positioning of the membrane. In this way, misplacement of the membrane structure is avoided, improving process reliability. Furthermore, the amount of membrane material required is reduced, thereby reducing overall costs.

[0021] Claims 8 and 9 are directed to fixing the membrane structure. By using backer plates to fix the membrane structure, the backer plates perform a dual function: they allow pre-assembly of the different components and establish the required leak-tight connections. This dual function simplifies the overall design of the valve switching system.

[0022] According to claim 10, the actuators of the actuator block include actuation outlets. In this way, uniform actuation of the drive membrane structure is achieved. Furthermore, the actuator block is out of contact with any process fluid distributed in the cassette manifold, so it can be of simple structure and reusable.

[0023] Claim 11 is directed to a method for manufacturing a valve switching system. The coupling of the valve switching cassette and the actuator block via their respective backer plates simplifies the manufacture of the valve switching system because both components can be pre-assembled. This simplifies installation because the membrane is already assembled and protected from damage.

[0024] The independent teaching according to claim 12 is directed to the bioprocessing installation itself. Reference may be made to all the explanations given in connection with the proposed valve switching system.

[0025] According to claim 13, the valve switching system is used as part of a bioprocessing installation for carrying out simulated moving bed (SMB) chromatography, the advantage here being the compact arrangement of a liquid pathway network for controlling fluid flow.

[0026] A method for operating a valve switching system is so claimed in another independent teaching according to claim 14. Again, reference may be made to all the explanations given in connection with the proposed valve switching system.

[0027] In another independent teaching according to claim 15, the use of the proposed valve switching system is claimed for switching columns in a bioprocessing facility. All statements given in relation to the proposed valve switching system and the proposed bioprocessing facility are fully applicable.

[0028] In the following, embodiments of the invention will be described with reference to the drawings. [Brief explanation of the drawings]

[0029] [Figure 1] FIG. 1 is a schematic plan view showing a proposed valve switching system as part of a proposed bioprocessing facility. [Figure 2]FIG. 1 is an exploded view showing the proposed valve switching system. [Figure 3] FIG. 1 is a diagram illustrating the operation principle of a valve unit of a valve switching cassette as part of a valve switching system. [Figure 4] FIG. 2 shows a portion of the bioprocessing facility according to FIG. 1 in an exemplary mode of operation.

[0030] As shown in Figure 1, the proposed valve switching system 1 is preferably used here for selectively interconnecting components of a bioprocessing installation 2. The expression "interconnection" should be understood in the sense of fluid communication.

[0031] In particular, Figure 1 shows the sequential steps performed for the recovery and purification of 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 separated in separation unit 3. Assuming the product is in the supernatant of the fermentation broth, centrifugation may be performed to separate the product from cells and cell debris. Concentration, for example by ultrafiltration, may be performed as part of the product separation to increase the concentration of the product and reduce the amount of material processed in subsequent downstream processing steps.

[0032] After product separation in separation unit 3, product purification is performed in purification unit 4. Product purification may be performed by different means, including multi-column chromatography, as shown by chromatography arrangement 5 in Figure 1. Chromatography arrangement 5 may include multiple chromatography columns 6-13, as shown in Figure 1. In a preferred embodiment, the number of chromatography columns 6-13 connected to valve switching system 1 is between 1 and 8.

[0033] Compared with conventional single-column chromatography, multi-column chromatography significantly improves the efficiency of the purification step. However, multi-column chromatography is more complex than single-column chromatography, especially in terms of fluid flow. Therefore, advanced control of the fluid flow path is required, which is currently achieved by using the proposed valve switching system shown in Figure 1.

[0034] After purification, product polishing is preferably performed in polishing unit 14. At the end of product polishing, the product is typically packaged for further distribution. Depending on the bioprocess, product polishing may include a viral inactivation step, for example to comply with regulatory requirements. Another example of product polishing is a crystallization step to convert a liquid product into a solid, and thereby easily transportable, form. Yet another example of polishing is the use of chromatography, such as ion exchange chromatography or hydrophobic interaction chromatography.

[0035] The valve switching system 1 includes a valve switching cassette 15 and an actuator block 16, where the valve switching cassette 1 includes a cassette manifold 17 having at least one fluid communication system 18, 19 of ports and fluid lines. The first fluid communication system 18 is connected to a main fluid line L p Main port P p and secondary fluid line L s Secondary port P communicating with s The second fluid flow system 19 includes a main fluid line I p Main port p communicating with p and secondary fluid line I s Secondary port p communicating with s Includes:

[0036] The general functionality of the two fluid flow systems 18, 19 of ports and fluid lines is identical, so that a description given for one fluid flow system 18, 19 is equally applicable to the respective other fluid flow system 18, 19. In the following, reference will be made primarily to the second fluid flow system 19 to maintain simplicity.

[0037] The valve switching cassette 15 also p ,I p Transfer fluid line T through secondary fluid line L s ,I s Switchable valve units for selective interconnection to x,y Contains an array of

[0038] The term "port" refers to an interface for interconnecting components of the bioprocessing equipment 2 to respective fluid lines, which may include fluid connectors to the respective fluid lines.

[0039] The term "conduit" refers to any longitudinal volume capable of holding and conducting a fluid between two locations. p ,I p ,L s ,I s , T are preferably drilled or machined into cassette manifold 17 such as by deep drilling.

[0040] The terms "primary" and "secondary" refer to the valve unit n x,y The terms "primary" and "secondary" are used to distinguish between two groups of fluid ports interconnected by a "primary" and a "secondary" fluid line. In the illustrated, and thus preferred, embodiment, these terms also indicate the fluid flow direction F, which is therefore directed from the primary to the secondary fluid ports, although the reverse is also possible. Thus, the terms "primary" and "secondary" do not imply or exclude any structural and / or functional differences between the respective ports and fluid lines.

[0041] The expression "selectively interconnect" means to interconnect one or more main fluid lines I p However, one or more secondary fluid lines I s This means that the 1000 MHz to 1000 MHz signals may be selected to be interconnected with the 1000 MHz to 1000 MHz signals.

[0042] The term "switchable" refers to the valve unit n x,y This refers to the possibility of changing the valve unit n from a "valve open" state to a "valve closed" state or from a "valve closed" state to a "valve open" state. x,y When the valve is in the "valve open" state, as illustrated in the inlay of Figure 1, the fluid flows through the main fluid line I p From the transfer fluid line T through the secondary fluid line I s Preferably, each of the transfer lines T is connected to a main fluid line I p or secondary fluid line I s The valve unit n is in an open state. x,y is shown as a solid oval in Figures 1 and 4. Valve unit n x,y When is in the "valve closed" state, the main fluid line I p From the transfer fluid line T through the secondary fluid line I s A closed valve unit is shown in Figures 1 and 4 as a hollow oval.

[0043] Main fluid pipe I p and secondary fluid line I s are preferably arranged in rows and columns in a valve switching cassette 15, where valve units n x,y is the main fluid line I p and secondary fluid line I s and each fluid line I is disposed at each junction between p ,I s is the valve unit n x,y and may be interconnected by respective transfer fluid lines T. Thus, the valve units n x,y The arrays of are aligned in their rows and columns and numbered accordingly. For example, valve unit n 11,3is shown in detail in the inlay in Figure 1.

[0044] Valve Unit n x,y Each of the valve seats x,y As shown in Figure 3, each valve unit n x,y Preferably, one of the transfer fluid lines T is connected to the main fluid line I p One of the transfer fluid lines T communicates with the secondary fluid line Is, and the valve seat s x,y You will be guided to.

[0045] In another preferred embodiment, the main fluid line I p Direct valve seat x,y , while the secondary fluid line I s The fluid is transferred through the valve seat x,y is connected to.

[0046] To control the fluid flow, the valve switching cassette 15 of the valve switching system 1 includes a valve membrane structure 20. The valve membrane structure 20 includes valve units n x,y Depending on the switching of valve unit n x,y Valve seats x,y The valve membrane structure 20 can be sealingly engaged with the valve seat s. x,y ("valve closed"), or the valve seats x,y can be selectively disengaged ("valve open" state).

[0047] The actuator block 16 further includes a valve unit n x,y The actuator block 16 includes an actuator block body 21 having an actuator for the drive membrane d, as will be described in detail below. x,y By actuating the valve membrane structure 20, in particular the valve membrane m x,y Preferably, this results in the valve membrane structure 20 being in contact with the valve seat s x,yThe actuator block 16 engages with the drive membrane d x,y When not actuated, the valve membrane structure 20 preferably contacts the valve seat s, as will also be described in more detail below. x,y and disengage.

[0048] Preferably, the proposed valve switching system 1 serves to control the fluid flow of selectively interconnected components, such as the illustrated chromatography arrangement 5. The fluids whose flow is controlled by the valve switching system 1 are referred to as process fluids. Process fluids handled within the present invention can include a wide variety of liquid media, such as buffers, cleaning solutions, acids, bases, culture media, liquids containing unprocessed products, liquids containing partially processed products, liquids containing purified products, sanitary solutions, etc. Fluids handled within the present invention can also be gas phase media.

[0049] Important to the present invention is that the valve switching cassette 1 includes a perforated backer plate 22 that secures the valve membrane structure 20 to the cassette manifold 17, where the actuator block 16 includes a drive membrane structure 23 and a perforated backer plate 24 that secures the drive membrane structure 23 to the actuator block body 21.

[0050] Each of the perforations in both backer plates 22, 24 includes a pattern of perforated holes 25, 26, and the perforations in both backer plates 22, 24 are at least partially aligned with one another, thereby providing a valve unit n x,y To selectively switch between valve and drive, an actuator in the actuator block 16 can push the drive membrane structure 23 into engagement with the valve membrane structure 20 through aligned drilled holes 25, 26 in both backer plates 22, 24. This is shown on the right side of Figure 3.

[0051] The term "perforated" should be understood as a pattern of perforated holes 25,26 in each backer plate 22,24 extending through the entire thickness of the respective backer plate 22,24.

[0052] As will be explained below, it has been found that the use of the driving membrane structure 23 significantly improves the operational reliability of the valve switching system 1.

[0053] The pressure required during installation and operation of the valve switching system 1 can be significantly reduced if a backer plate 24 is used to securely fasten the actuation membrane structure 23 to the actuator block body 21. By using the backer plate 24 to secure the actuation membrane structure 23, a gas-tight or liquid-tight connection between the actuation membrane structure 23 and the actuator block body 21 is achieved with less required force. Additionally, the use of the backer plate 24 allows for pre-assembly of the actuator block 16.

[0054] Furthermore, since a gas-tight or liquid-tight connection of the actuator block body 21 is now realized between the actuator block body 21 and the drive membrane structure 23, the valve membrane structure 20 only needs to be fluid-tight sealed to the cassette manifold 17 and does not need to be gas-tight or liquid-tight to the actuator block body 21 as before.

[0055] Lower pressure requirements during installation and operation of the valve switching system 1 reduce the pressure exerted on the valve membrane structure 20 and the cassette manifold 17. Therefore, the thickness of both the valve membrane structure 20 and the cassette manifold 17 can be reduced, which reduces overall material costs. The reduced thickness of the valve membrane structure 20, in particular, contributes to improved sensitivity and accuracy of valve unit actuation. Furthermore, lower pressure requirements also reduce the cost of the actuator block body 21, since it no longer needs to handle the relatively high pressures and associated large forces.

[0056] Valve switching cassette 15 can also be pre-assembled using backer plate 22 to secure valve membrane structure 20 to cassette manifold 17. Here, backer plate 22 is also used to establish a fluid-tight connection between cassette manifold 17 and valve membrane structure 20.

[0057] The actuated membrane structure 23 may be pressed by an actuator, causing it to protrude through any one of the aligned drilled holes 25, 26 in the backer plates 22, 24, thereby causing the valve membrane structure 20 to engage with the respective valve unit n x,y As will be explained below, a different principle of operation is envisaged.

[0058] The installation process of the valve switching system 1 is further simplified as the valve switching cassette 15 and actuator block 16 can be tested for liquid and / or gas tightness prior to installation.

[0059] The backer plates 22, 24 shown in FIG. 2 could be constructed of different materials. Preferably, both backer plates 22, 24 are constructed of the same material, and more preferably, both backer plates 22, 24 are constructed of acrylic plastic. However, other, more durable materials, such as aluminum, could also be used. Additionally, other types of plastic materials, such as PMMA, PEEK, or PVDF, could be used. It is further preferred that the backer plates 22, 24 be identical in terms of their geometry. Similar design of the backer plates 22, 24 with respect to geometry and / or material may be advantageous in manufacturing.

[0060] Alternatively, different materials can be used for each backer plate 22, 24, by using one backer plate 22 for the valve switching cassette 15 and one backer plate 24 for the actuator block 16. For example, a disposable plastic material can be used for the backer plate 22 of the valve switching cassette 15, while a reusable material (e.g., aluminum) can be used for the backer plate 24 of the actuator block 16. The geometries of the backer plates 22, 24 can alternatively differ.

[0061] It should be pointed out that the realization of the backer plates 22, 24 is very simple: the drilled holes 25, 26 could be introduced into the backer plates 22, 24 by drilling, punching, injection molding, etc.

[0062] As shown in Figure 3, the driving membrane d x,y is pressed by the actuator of the actuator block 16, the driving membrane d x,y protrude through respective drilled holes 26 in the backer plate 24 of the actuator block 16 and aligned drilled holes 25 in the backer plate 22 of the valve switching cassette 15. The drive membrane d x,y As will be described later, the valve unit n x,y To switch the valve membrane x,y Here, the driving membrane d x,y is the driving membrane d x,y and the actuator block pocket 26 as well as providing a gas-tight or liquid-tight seal between the drive membrane d x,y is the valve membrane m x,y To provide additional resistance to bending of the valve membrane m x,y This reduces the mechanical wear of the valve unit x,y Improve the proper functioning of

[0063] 2, the valve switching cassette 15 and the actuator block 16 are coupled together via respective backer plates 22, 24. As previously discussed, this allows for pre-assembly of the valve switching cassette 15 and the actuator block 16, thereby enhancing proper installation of the valve switching system 1. Further aspects related to the manufacturing process for the valve switching system 1 are described below.

[0064] The coupling of the backer plates 22, 24 of the pre-assembled valve switching cassette 15 and the pre-assembled actuator block 16 together could be accomplished in several ways, as indicated by the arrows in FIG. 2 . It should be noted that the connection may be permanent, but is preferably realized non-permanently, i.e., the connection can be terminated in a non-destructive manner. For example, the backer plates 22, 24 could be connected using screws or clamps, which can be removed after the process is completed. Alternatively, adhesive could be used to connect the backer plates 22, 24. However, the above options are merely exemplary, and other options for connecting the backer plates 22, 24 could be envisioned.

[0065] As can be seen in FIG. 2, at least some of the drilled holes 25, 26 in the backer plates 22, 24 are x,y Valve seats x,y is aligned to.

[0066] In a preferred embodiment, the drilled holes 25, 26 are arranged in rows and columns. Preferably, the drilled holes 25, 26 are arranged in rows and columns such that each row is associated with one valve unit n in the respective row. x,y In a further preferred embodiment, the number of drilled holes 25, 26 in each row is equal to the number of valve units n in the respective row. x,y In the illustrated and to the extent preferred embodiment, each row contains eight drilled holes 25, 26.

[0067] In a preferred embodiment, the number of drilled holes 25, 26 in each backer plate 22, 24 is equal to the number of valve units n x,y Preferably, each drilled hole 25, 26 in each backer plate 22, 24 is also connected to exactly one valve unit n x,y The drilled holes 25 and 26 in the backer plates 22 and 24 are allocated to the valve seats s x,y By aligning the driving membrane with x,y The protrusion of each valve unit n is defined by the shape of the drilled holes 25, 26. x,y This ensures that only the membrane structures 20, 23 operate because each membrane structure 20, 23 is held in place by its respective backer plate 22, 24.

[0068] In a further preferred embodiment, the shape of each of the drilled holes 25, 26 is such that the assigned valve seat s x,y Preferably, the perforations 25, 26 have an elliptical geometry. This corresponds to the geometry of the membrane m x,y, d x,y and enhance the defined projection of the membrane m, especially if actuation is performed indirectly, for example by air pressure. x,y, d x,y The protrusion of the valve membrane m is guided by the shape of the drilled holes 25, 26. Additionally, by choosing an elliptical geometry, the valve membrane m x,y and / or driving membrane d x,y Sharp corners and edges that could compromise the structural integrity of the device are avoided.

[0069] At least one valve membrane m of the valve membrane structure 20 x,y is preferably constructed of a fluorocarbon-based fluoroelastomer (FKM), a rubber compound that uses vinylidene fluoride as a monomer (e.g., Viton™). As noted above, FKM is robust even when in contact with fluids that tend to attack materials, such as acids and bases.

[0070] Valve membrane mx,y The hardness (Shore A) of the valve membrane m is preferably between 50 and 80, and more preferably 75. x,y The material thickness is preferably less than 1 mm, more preferably between 0.5 mm and 0.75 mm.

[0071] The valve membrane structure 20 and the drive membrane structure 23 may have the same layout in terms of material and / or geometry, especially thickness, which is logically advantageous, but for cost optimization and the different functions of the respective membrane structures 20, 23, which will be explained in more detail below, it is preferable to choose different materials for these membrane structures 20, 23.

[0072] Preferably, at least one driving membrane d of the driving membrane structure 23 x,y The drive membrane d is made of a flexible soft plastic material. x,y The material may need to be flexible and resistant to abrasion. Furthermore, it must be durable. Suitable materials can be selected, for example, according to their airtightness. In a preferred embodiment, the driving membrane d x,y is made of thermoplastic elastomer (TPE). x,y is constructed of either polychloroprene (also known as neoprene), thermoplastic polyester (e.g., Hytrel™), or thermoplastic vulcanizate (e.g., Santoprene®), except that the driving membrane d x,y The material is not limited to the above materials, but could also be composed of any other material that meets the above and below requirements.

[0073] Preferably, the driving membrane d x,y The hardness (Shore A) of the driving film d is between 40 and 70, and more preferably 55. x,y The material thickness is preferably less than 2 mm, more preferably between 1.25 and 1.75 mm.

[0074] Depending on the process carried out in the valve switching system 1, different requirements may need to be met by the valve membrane structure 20 and the driving membrane structure 23, respectively. For example, the valve membrane m of the valve membrane structure 20 x,y may also be required to comply with specific certifications ("USP Class") under General Chapter 88 of the United States Pharmacopeia and National Formulary (USP-NF). In one embodiment, the valve membrane x,y The materials comply with the regulations set forth for USP Class VI certification. However, this requirement does not apply to drive membranes. x,y is not necessarily satisfied by the driving membrane d x,y does not come into contact with the process fluid distributed within the cassette manifold 17. This means that the drive membrane d x,y This allows for a wider range of materials to be selected.

[0075] Valve membrane m x,y and driving membrane d x,y A particular advantage of using membrane materials, which may vary in thickness, properties, and materials, is that membrane d x,y ,m x,y The advantage of this is that each of the valve membranes can be adjusted to suit the individual purpose. x,y The thickness of the valve unit n x,y can be selected and optimized for optimal switching of the driving membrane d x,y can be selected to provide optimum hermetic sealing capability, which provides greater flexibility in operation and contributes to increased process reliability due to the longer operational life of both membranes.

[0076] Fluid-tight seals between the cassette manifold 17 and the valve membrane structure 20, and gas-tight or liquid-tight seals between the drive membrane structure 23 and the actuator block body 21 are ensured because the backer plates 22, 24 are firmly pressed against the cassette manifold 17 and the actuator block body 21, respectively.

[0077] In detail, valve unit nx,y is designed as a membrane valve unit, each of which is a valve membrane m x,y The valve membrane m x,y is in the open position (Fig. 3, valve unit n 11,3 ) and closed position (Fig. 3, valve unit n 10,3 ) can be moved between them.

[0078] Valve Unit n x,y Each of the valve seats x,y wherein each valve membrane m provided by the valve membrane structure 20 x,y is valve unit n x,y For switching between valve seats, selectively x,y ("valve closed") or valve seats x,y As shown in FIG. 3, each valve unit n x,y Regarding fluid pipeline I p ,I s One of the fluid transfer lines T is preferably connected to the valve seat s x,y Valve seats x,y is the valve membrane m provided by the valve membrane structure part 20 x,y can interact hermetically with

[0079] As will be explained in detail later, the valve membrane m x,y The operation of the driving membrane d of the driving membrane structure 23 x,y This is achieved by:

[0080] As shown in Figure 2, the valve membrane structure 20 includes valve membrane stripes 27. Preferably, the number of valve membrane stripes 27 is equal to the number of columns of drilled holes 25, 26 on at least one of the backer plates 22, 24. In a more preferred embodiment, each valve membrane stripe 27 is arranged to define a valve unit n x,y Covers one column of

[0081] As can be seen in Figure 2, the actuated membrane structure 23 includes actuated membrane stripes 28. Preferably, the number of actuated membrane stripes 28 is equal to the number of columns of perforated holes 25, 26 on at least one of the backer plates 22, 24. In a more preferred embodiment, each actuated membrane stripe 28 is connected to valve unit n. x,y Covers one column of

[0082] More preferably, the number and shape of the valve membrane stripes 27 are the same as the number and shape of the drive membrane stripes 28. Additionally, the valve membrane stripes 27 and the drive membrane stripes 28 are preferably aligned. Preferably, these membrane stripes 27, 28 have a predetermined cross-sectional shape, preferably arcuate, polygonal, and especially rectangular.

[0083] 2, the spacing between each of the membrane stripes 27, 28 is the same. Preferably, the fixing elements 29 for connecting the backer plates 22, 24 to the cassette manifold 17 or the actuator block body 21, respectively, are inserted between the membrane stripes 27, 28 so that the membrane stripes 27, 28 are not in direct contact with the fixing elements 29 but are indirectly fixed by a compressive force.

[0084] The number and arrangement of the membrane stripes 27, 28 are merely exemplary and are not limited to the description given above. x,y Depending on the design of the valve membrane m, different configurations may be selected. x,y and / or driving membrane d x,y All valve units x,y It may contain only one membrane stripe covering the valve unit n x,y It may cover multiple rows and / or columns of

[0085] The valve membrane structure 20 is attached to the cassette manifold 17 by a backer plate 22 (FIG. 2). Preferably, the backer plate 22 is matingly connected to the valve membrane structure 20 with a certain force, and presses the valve membrane structure 20 against the cassette manifold 17. Here, the valve seat s x,y and valve membrane m x,y To establish a fluid-tight and leak-free connection between the valve membrane m x,y It is also important that the backer plate 22 is sealingly connected to the cassette manifold 17. In a preferred embodiment, the backer plate 22 is connected to the cassette manifold 17 using fastening elements 29, such as screws. More preferably, the fastening elements 29 are arranged in rows and columns. Preferably, the backer plate 22 includes openings for insertion of the fastening elements 29.

[0086] To properly position the at least one valve membrane stripe 27, the backer plate 22 may include corresponding grooves (not shown) in the flat surface of the backer plate 22 facing the cassette manifold 17. These grooves preferably have the same shape as the membrane stripes 27, so that each membrane stripe 27 may be inserted into one groove. This contributes to simplified pre-assembly of the valve switching cassette 15.

[0087] The driving membrane structure 23 is attached to the actuator block body 21 by a backer plate 24 (FIG. 2). Preferably, the backer plate 24 is matingly connected to the driving membrane structure 23 with a certain force, pressing the driving membrane structure 23 against the actuator block body 21. It is also important here that the driving membrane structure 23 is hermetically connected to the actuator block body 21 to establish a gas-tight or liquid-tight connection between the actuator block body 21 and the driving membrane structure 23. In a preferred embodiment, the backer plate 24 is connected to the actuator block body 21 using fixing elements 29, such as screws. More preferably, the fixing elements 29 are arranged in rows and columns. Preferably, the backer plate 24 includes openings for insertion of the fixing elements 29.

[0088] To properly position the at least one actuation membrane stripe 28, the backer plate 24 may include corresponding grooves (not shown) in the flat surface of the backer plate 24 facing the actuator block body 21. These grooves preferably have the same shape as the membrane stripes 28, so that each membrane stripe 28 may be inserted into one groove. This contributes to simplified pre-assembly of the actuator block 16.

[0089] The backer plate 22 assigned to the valve switching cassette 15 provides a removable fluid-tight connection between the valve membrane structure 20 and the cassette manifold 17, as shown in Figure 2. Therefore, no adhesive is required to connect the valve membrane structure 20 to the backer plate 22 and the cassette manifold 17, which generally allows the valve membrane structure 20 to be replaced and / or positioned separately from the backer plate 22 and the cassette manifold 17.

[0090] The backer plate 24 assigned to the actuator block 16 also provides a removable gas-tight or liquid-tight connection between the drive membrane structure 23 and the actuator block body 21, as shown in Figure 2. Therefore, no adhesive is required to connect the drive membrane structure 23 to the backer plate 24 and the actuator block body 21, which generally makes it possible to replace the drive membrane structure 23 and / or to position the drive membrane structure 23 separately from the backer plate 24.

[0091] It should be noted that the use of screws as fastening elements 29 is just one example for connecting backer plates 22, 24 to cassette manifold 17 and / or actuator block body 21, respectively. Other fastening elements, such as clamps, are also contemplated.

[0092] As explained above, the backer plates 22, 24 allow pre-assembly of the valve switching cassette 15 and the actuator block 16, respectively, and guide the protrusion of the membrane structures 20, 23.

[0093] Here, backer plates 22, 24 are shown to perform the additional functions of rigidly securing membrane structures 20, 23 and providing gas-tight and / or liquid-tight connections necessary for proper functioning of valve switching system 1. This multi-functionality of backer plates 22, 24 simplifies the overall design of valve switching system 1.

[0094] As shown in Figure 3, the actuator block 16 includes an actuator (not shown) having an actuation outlet 30 through which pressure is applied to the actuation membrane structure 23. In a preferred embodiment, the actuation outlet 30 is a gas pressure outlet or a hydraulic pressure outlet. In a more preferred embodiment, one actuation outlet 30 is provided for each valve unit n. x,y Drive membrane structure part d x,yThe actuation of the membrane is preferably carried out in a contactless manner, in particular pneumatically or hydraulically by applying gas or liquid to the actuation membrane structure 23 via the actuation outlet 30. Preferably, compressed air is used for actuation. In this case, the structure of the actuator block 16 is simplified since no mechanical actuators (e.g. plungers, etc.) are required. Furthermore, the pressure is uniformly distributed across the membrane m x,y ,d x,y Because it applies to membrane m x,y ,d x,y Mechanical wear on the surface is reduced.

[0095] However, the driving membrane d x,y A plunger or any other system suitable for directly actuating the drive membrane d x,y In this case, the plunger may be actuated, for example, pneumatically, hydraulically, electromagnetically, etc. The actuator block body 21 and the drive membrane d x,y Even though gas-tightness or liquid-tightness between the driving membrane d x,y If the valve is directly actuated by a plunger or the like, other advantages of the proposed valve switching system 1, in particular the pre-assembly option, would still be applicable.

[0096] Drive membrane d through drive outlet 30 x,y The pressure applied to the may be controlled in several ways, as described below.

[0097] Driven membrane d through drive outlet 30 x,y Liquid or gas pressure is applied to the driving membrane d x,y is directly driven, and the driving membrane d x,y The valve membrane m protrudes through the drilled holes 25, 26 in the backer plates 22, 24 and is bent relative to the valve membrane structure 20 (FIG. 3). x,y As a result, the valve membrane structure 20 is pressed against the valve seat s x,y In FIG. 3, this is exemplarily shown as valve unit n 10,3When pressure is released or the plunger is retracted, the pressure of the process fluid distributed within the cassette manifold 17 is transferred to the valve membrane structure 20, particularly the valve membrane m x,y The driving membrane x,y This bending results in the valve membrane m x,y A, valve seats x,y In Figure 3, this is valve unit n 11,3 The following is shown:

[0098] The expression "come into sealing engagement" refers to the contact between the valve membrane structure 20 and the valve seat s x,y While the term "disengage from sealing engagement" refers to establishing a fluid-tight seal, typically a force engagement, between the valve membrane structure 20 and the valve seat s x,y It may include loose contact between the

[0099] As shown in Figure 3, a control valve 31 could be used to control the pressure in the actuation outlet 30. When the control valve 31 is open (indicated by the letter "o" in Figure 3) and the pressure introduced into the actuator block pocket 32 ​​through the actuation outlet 30 is greater than the pressure exerted on the valve membrane structure 20 by the process fluid flow F, the actuation membrane d x,y is operated as explained above. When the control valve 31 is closed (indicated by the letter "c" in FIG. 3), the current pressure is maintained in the actuator block pocket 32. Depending on the pressure difference between the pressure exerted by the process fluid flow F and the pressure in the actuator block pocket 32, the valve membrane m x,y and driving membrane d x,y The bending of the valve membrane m can be controlled in a precise manner. x,y The thickness of the valve membrane m may be significantly reduced, which further contributes to precise control. x,yis more sensitive to applied pressure and may operate at a lower pressure than that applied by the process fluid flow F, for example.

[0100] Depending on the elasticity difference between the materials of the membrane structures 20, 23, each of the membrane structures 20, 23 can limit the deformation of the respective other membrane structures 20, 23. This is especially true when the valve membrane structure 20 is in contact with the valve seat s x,y This means that when the valve membrane structure 20 is released from its sealing engagement with the driving membrane structure 23, the bending of the valve membrane structure 20 may be limited by the driving membrane structure 23. This results in a defined bending of the valve membrane structure 20. This in particular simplifies the design of the backer plate 22 of the valve switching cassette 15, since no recess is required to limit the protrusion of the valve membrane structure 20. Additionally, this allows the valve unit n x,y This allows the use of soft materials for the valve membrane structure 20 for reliable operation, whereas the risk of mechanical wear of the valve membrane structure 20 is reduced.

[0101] The actuator block 16 may be controlled by an electronic control unit (not shown), preferably including a microprocessor operating on the basis of control software, whereby it becomes clear that by simply corresponding modifications of the control software, the entire process fluid flow F can be flexibly and precisely electronically controlled.

[0102] Manufacturing of the valve switching system 1 is simplified because the valve switching cassette 15 and the actuator block 16 can be pre-assembled separately. For example, this also means that sterilization (e.g., by gamma irradiation) can be performed separately on the valve switching cassette 15 and the actuator block 16, or on the valve switching cassette 15 alone. The latter is preferable because sterilization of the actuator block 16 may not be necessary because the actuator block 16 does not come into contact with the process fluid. Furthermore, both components can be inspected for liquid and / or gas tightness before installation. This allows for corrective action, such as readjusting the membrane structures 20, 23 or backer plates 22, 24 prior to assembly, if necessary. In this way, leakage issues due to improper installation are reduced. This significantly improves the installation procedure and significantly reduces the potential for operational failure.

[0103] Because both components, specifically the valve switching cassette 15 and the actuator block 16, may be pre-assembled and tested for liquid-tightness and / or gas-tightness prior to installation, the pre-assembled components can be coupled together in a more flexible manner via the respective flat surfaces of the backer plates 22, 24, because slightly different positioning of the valve switching cassette 15 and the actuator block 16 does not affect the liquid-tightness and / or gas-tightness. Furthermore, the actuator block 16 (or a portion thereof) could be easily reused. In contrast, the valve switching cassette 15 (or a portion thereof) is discarded after the process is completed. Additionally, the valve switching cassette 15 could be sterilized after assembly and then distributed in a sterile form. As explained above, coupling of the pre-assembled valve switching cassette 15 and the pre-assembled actuator block 16 could be performed in multiple ways. This is the subject of a second, independent teaching.

[0104] According to the third independent teaching, this is also claimed in Bioprocess Facility 2. See all explanations given in relation to the first teaching.

[0105] According to a fourth independent teaching, the bioprocessing facility 2 comprises components to be selectively interconnected, which components herein are preferably a chromatography arrangement 5 comprising a plurality of chromatography columns 6-13 connected to a valve switching system 1, for example to perform a simulated moving bed (SMB) chromatography process. See all explanations given with respect to the preceding teachings.

[0106] 4 shows merely another exemplary operation of the proposed valve switching system 1. Here, it becomes clear that many variations in the serial and parallel use of chromatography columns 6-13 are possible, whereby chromatography columns 6, 7, and 8 are used sequentially, while chromatography column 10 is used in parallel thereto. Overall, process fluid flow can be performed from any one of the inlets provided by the primary port Pp of the first fluid flow system 18 to the secondary fluid port Pp of the second fluid flow system 19, using any number of chromatography columns in any desired sequential or parallel manner. s As explained above, by reducing the fluid flow pressure in cassette manifold 17, the fluid flow pressure in the connected chromatography columns 6-13 may be reduced.

[0107] Further independent teachings are directed to methods for operating the valve switching system 1 and to uses of the valve switching system 1. For operation of the valve switching system 1 described above, it is important that the actuated membrane structure 23 is selectively pressed by an actuator through any one of the drilled holes 25, 26 in the backer plates 22, 24. See all descriptions given above.

[0108] Finally, it will be pointed out that the valve switching system 1 according to the various teachings may be subject to scaling up or down to different levels of process scale without the need to introduce structural modifications.

[0109] The proposed solution is particularly advantageous in bioprocessing installations 2 associated with chromatography arrangements having multiple chromatography columns for performing simulated moving bed (SMB) chromatography.

[0110] Because the valve switching system 1 includes two backer plates 22, 24 and two membrane structures 20, 23, pre-assembly of the valve switching cassette 15 and actuator block 16, including the respective membrane structures 20, 23, is possible. This improves adaptability during process assembly and reduces costs during installation. Furthermore, because the backer plates 22, 24 are used to hermetically connect the respective membrane structures 20, 23 to the cassette manifold 17 and actuator block body 21, respectively, the valve unit n x,y Gas-tight and / or liquid-tight sealing of valve units x,y Valve membrane for switching m x,y Reliable operation of the cassette manifold 17 is ensured. Additionally, the pressure required for a gas-tight or liquid-tight seal is reduced, resulting in less pressure being applied to the cassette manifold 17. Requiring less pressure reduces operational costs and improves process reliability by eliminating expensive pressurization mechanisms and preventing damage to the cassette manifold 17. Additionally, when less pressure is applied, the thickness of the cassette manifold 17 and valve membrane structure 20 can be reduced. In conclusion, the proposed design of the valve switching system 1 improves upon currently known designs in several ways.

Claims

1. A valve switching system for selectively interconnecting components of a bioprocessing facility (2), comprising: a valve switching cassette (15) and an actuator block (16); The valve switching cassette (1) includes a cassette manifold (17) having at least one fluid communication system (18, 19) of ports and fluid lines; The fluid communication system (18, 19) includes a main fluid line (L ｐ ) and the main port (P ｐ ) and a secondary fluid line (L ｓ ) and a secondary port (P ｓ ) and The valve switching cassette (1) is connected to the main fluid line (L) via a transfer fluid line (T). ｐ ) to the secondary fluid line (L ｓ ) and a switchable valve unit (n ｘ，ｙ ) The valve unit (n ｘ，ｙ ) each of the valve seats (s ｘ，ｙ ), The valve switching cassette (1) has at least one valve membrane (m ｘ，ｙ ) and the valve membrane structure (20) has a valve unit (n ｘ， In order to switch the valve seat (s ｘ，ｙ ) and The actuator block (16) is connected to each valve unit (n ｘ，ｙ 1. A valve switching system comprising an actuator block body (21) having an actuator for The valve switching cassette (1) includes a perforated backer plate (22) that secures the valve membrane structure (20) to the cassette manifold (17); The actuator block (16) includes at least one driving membrane (d ｘ，ｙ a driving membrane structure (23) having a perforated backer plate (22) for fixing the driving membrane structure (23) to the actuator block body (21); each of the perforations in both backer plates includes a pattern of perforation holes; The perforations in both backer plates are at least partially aligned with one another, thereby allowing the valve unit (n ｘ，ｙ ), the actuator of the actuator block (16) can press the drive membrane structure (23) through aligned drilled holes (25, 26) in both backer plates (22, 24) to engage with the valve membrane structure (20).

2. The driving film (d ｘ，ｙ 2. The valve switching system of claim 1, wherein when pressed by the actuators of the actuator block (16), the respective drilled holes (26) in the backer plate (24) of the actuator block (16) protrude through aligned drilled holes (25) in the backer plate (22) of the valve switching cassette (15).

3. 3. The valve switching system according to claim 1 or 2, wherein the valve switching cassette (15) and the actuator block (16) are coupled together via respective backer plates (22, 24).

4. At least some of the drilled holes (25, 26) in the backer plate (22) of the valve switching cassette (15) and / or at least some of the drilled holes (25, 26) in the backer plate (24) of the actuator block (16) are connected to the valve units (n ｘ，ｙ ) the valve seat (s ｘ，ｙ 4. The valve switching system according to claim 1, wherein the valve is aligned with the first and second electrodes.

5. At least one of the valve membranes (m ｘ，ｙ 5. The valve switching system according to claim 1, wherein the valve member is made of a fluorocarbon-based fluoroelastomer material (FKM).

6. At least one of the driving membranes (d ｘ，ｙ 6. The valve switching system according to claim 1, wherein the valve member is made of a soft plastic material.

7. 7. The valve switching system according to claim 1, wherein the valve membrane structure (20) and / or the drive membrane structure (23) comprise membrane stripes (27, 28).

8. The valve membrane (m ｘ，ｙ ) are fixed to the cassette manifold (17) by respective backer plates (22), and the backer plates (22) are connected to the valve membranes (m ｘ，ｙ 8. A valve switching system according to claim 1, wherein the valve switching system provides a removable gas-tight and / or liquid-tight connection between the valve and the cassette manifold.

9. The driving film (d ｘ，ｙ ) are fixed to the actuator block body (21) by respective backer plates (24), and the backer plates (24) are connected to the drive membrane (d ｘ，ｙ 9. A valve switching system according to claim 1, wherein the valve switching system provides a removable gas-tight and / or liquid-tight connection between the actuator block (16) and the valve switching system.

10. 10. Valve switching system according to any one of the preceding claims, wherein the actuator of the actuator block (16) comprises at least one actuation outlet (30), preferably a gas pressure outlet or a hydraulic pressure outlet.

11. 11. A method for manufacturing a valve switching system according to any one of claims 1 to 10, comprising:

1. A method according to claim 1, wherein a valve switching cassette (15) and an actuator block (16) are coupled together via respective backer plates (22, 24).

12. 1. A bioprocessing facility comprising: A bioprocessing facility comprising a valve switching system according to any one of claims 1 to 10.

13. 13. The bioprocessing installation (2) according to claim 12, wherein the bioprocessing installation (2) comprises a chromatography arrangement (5) having a plurality of chromatography columns (6-13), the columns being connected to a valve switching system according to any one of claims 1 to 10 for carrying out a simulated bed chromatography (SMB) process.

14. A method for operating a valve switching system according to any one of claims 1 to 10, comprising: Valve unit (n ｘ，ｙ ) are selectively switched by a driving membrane structure (23) pressed by an actuator block (16) through aligned drilled holes in both backer plates (22, 24), thereby engaging a valve membrane structure (20) to switch a respective valve unit (nx, y).

15. Use of a valve switching system for switching chromatography columns (6 to 13) of a bioprocessing installation according to claim 13.

Images