Valve change cassette for selectively interconnecting components of a bioprocessing facility - Patents.com

Abstract

The present invention relates to a valve switching cassette for selectively interconnecting components of a bioprocessing facility (2), the valve switching cassette (1) having at least one fluid flow system (7) comprised of ports and fluid lines, the fluid flow system (7) including a primary fluid line (L p ) connected to the primary port (P p ) and the secondary fluid line (L s ) connected to the secondary port (P s ) and the valve switching cassette (1) includes a primary fluid line (L p ) to the secondary fluid line (L s ) via a transfer fluid line (T), x,y The valve switching cassette (1) has a transfer plate (17) with an opening (18) and a resiliently deformable diaphragm structure (19, 20) on each flat surface (21, 22) of the transfer plate (17), and has a primary fluid line (L p ) and secondary fluid line (L s It is proposed that at least a part of the diaphragm structure (19, 20) extends between the transfer plate (17) and one of the diaphragm structures (19, 20), the transfer fluid line (T) being at least partly provided by an opening (18).

Description

[Technical field]

[0001] This application was filed as a PCT international patent application on February 17, 2023 in the name of applicant Sartorius Stedim North America Inc., a U.S. corporation, in all country designations, and in the name of inventor Dinesh Shukla, a U.S. citizen, in all country designations, and claims priority to U.S. Application No. 17 / 675,318, filed February 18, 2022, the contents of which are incorporated herein by reference in their entirety.

[0002] The present invention relates to a design of a valve switching cassette for selectively interconnecting components of a bioprocessing installation according to the preamble of claim 1, a valve switching system comprising such a valve switching cassette according to claim 16, a bioprocessing apparatus comprising such a valve switching system according to claim 17 and a method for operating the valve switching cassette according to claim 19.

[0003] The expression "bioprocess" in this case denotes any kind of biotechnological process, in particular a biopharmaceutical process, where the operation of a chromatography apparatus with a number of chromatography columns connected to a valve-switching cassette for carrying out simulated moving bed (SMB) chromatography may be part of such a bioprocess.

[0004] The valve switching cassette can be applied in various fields of biotechnology. High cost efficiency and high flexibility in this field have been driven by the increasing demand for biopharmaceuticals. Cost efficiency does not only relate to material costs, but also to manufacturing costs. Flexibility should be understood in a broad sense with respect to the operating scale and operating mode of the bioprocessing equipment itself. With regard to the valve switching cassette as part of an SMB process for biopharmaceutical products, it is particularly important to keep the cleaning effort of the complex network of interconnected fluid lines and valves to a minimum. Therefore, a disposable and compact design of the individual valves and connectors is important. A valve switching cassette designed as a disposable part is disclosed in EP 1 775 001 A1.

[0005] In the above-mentioned known valve switching cassette, which is the starting point of the present invention, the ports and fluid lines are arranged in a compact manifold. The valve switching cassette comprises an array of switchable valve units for selectively interconnecting primary fluid lines with secondary fluid lines via transfer fluid lines. To realize these primary and secondary fluid lines arranged in a number of rows and columns, a number of lines are machined in the manifold. The known valve switching cassette allows the primary and secondary fluid lines to be selectively interconnected in a very flexible manner. However, the production of the valve switching cassette is costly due to the fact that the above-mentioned lines to be machined in the manifold have a very long extension and are usually realized by deep hole drilling. Such cost issues are important in particular in view of the fact that the manifold is often used as a disposable component.

[0006] It is therefore an object of the present invention to provide a means for reducing the manufacturing costs of valve switching cassettes while maintaining flexibility regarding the selective interconnection of fluid lines.

[0007] The above-mentioned object is achieved by a valve changeover cassette of the type set forth in the preamble of claim 1 having the features set forth in the characterizing portion of claim 1.

[0008] The premise of the present invention is that the valve switching cassette has at least one fluid flow system of ports and fluid lines, the fluid flow system including a primary port communicating with a primary fluid line and a secondary port communicating with a secondary fluid line. Furthermore, the valve switching cassette has an array of switchable valve units for selectively interconnecting the primary fluid line with the secondary fluid line via a transfer fluid line. This is the basis for the entire function of the valve switching cassette, i.e., the function of selectively interconnecting the primary and secondary fluid lines.

[0009] In accordance with the present invention, it has now been found that fluid lines can be fully established between a transfer plate with an opening and an elastically deformable diaphragm structure, resulting in new freedom for the design and selective interconnection of the fluid lines.

[0010] In particular, it is proposed that the valve switching cassette has a transfer plate with an opening and a diaphragm structure on each flat surface of the transfer plate, with at least a portion of the primary and secondary fluid lines extending between the transfer plate and one of the diaphragm structures.

[0011] It is now possible to form fluid lines with a considerable longitudinal extension without the need for costly machining such as deep hole drilling. The fluid connection between the primary and secondary fluid lines, which are preferably provided on opposite planar faces of the transfer plate, is realised by transfer fluid lines, which are provided at least in part by simple openings in the transfer plate, making the transfer plate a simple component to manufacture.

[0012] There is now also the flexibility to change the design of the fluid lines, as will be described below. Another new design freedom is the ability to use diaphragm structures as part of the switchable valve, also as will be described below.

[0013] Finally, the proposed solution prevents the occurrence of undesirable so-called "dead legs" in the fluid lines, which have no function in the bioprocess and tend to hold residual fluid. Due mainly to the elasticity of the diaphragm structure, the residual fluid is pushed out and thus expelled from the fluid line. Overall, this leads to a reduction in the hold-up volume. The expression "hold-up volume" describes the volume of residual fluid remaining in the valve switching cassette.

[0014] The proposed solution easily allows complex structures of fluid lines that can be selectively interconnected, in particular two or more of the above mentioned fluid flow systems of ports and fluid lines can be used in combination (claim 2).

[0015] According to claim 3, the primary and secondary fluid lines are located on opposite planar faces of the transfer plate. This makes the selective interconnection of the transfer fluid lines via the valve units particularly simple from a constructional point of view. It also becomes evident that the manufacturing process is simplified, since relatively short transfer fluid lines can be realized by simple drilling.

[0016] The primary and secondary fluid lines of the fluid flow system can be defined in various ways. In one preferred alternative configuration, according to claim 4, in normal operation the fluid flow is directed from the primary fluid line to the secondary fluid line. As a result, the flow direction through each transport fluid line and each valve unit is the same for all transport fluid lines, which makes the valve structure particularly simple.

[0017] According to claim 5, the valve unit is designed as a diaphragm valve unit with a valve diaphragm provided by at least one of the diaphragm structures, whereby each diaphragm structure is used not only for providing the primary and secondary fluid lines but also for providing the valve diaphragm of the valve unit, which results in a compact and at the same time cost-effective solution.

[0018] Claims 6, 7 and 8 relate to a particularly advantageous design of the valve array. In particular, by using the above-mentioned diaphragm structure for providing the valve diaphragms, the construction of the valve unit is simplified with consequent cost advantages.

[0019] According to claim 9, each diaphragm structure has at least one diaphragm extending along one flat surface of the transfer plate. The diaphragm is preferably made of a fluorocarbon-based fluoroelastomer (FKM). FKM can be used with a wide variety of acids and bases, which increases the flexibility of the process.

[0020] The subject of claim 10 is the interaction of a valve switching cassette with an actuator block, the actuator block comprising a plunger system for selectively switching an array of valves, where the actuator block acting on the valve diaphragms is provided with at least one operable plunger, the actuator block being of simple construction, since the plunger is preferably not in contact with the fluid.

[0021] According to claim 11, the fluid line is established by the elastic deformation of the diaphragm structure. Due to the elasticity of the diaphragm structure, the fluid line can be expanded to guide the fluid, and can be collapsed after the fluid guide is finished. This is a simple method for realizing the fluid line and at the same time discharging the residual fluid from the valve switching cassette after use due to the elasticity of the above-mentioned diaphragm structure.

[0022] According to claim 12, the valve switching cassette has at least one retaining frame covering one of the diaphragm structures, which is a simple way to sealingly fix the diaphragm structure to the transfer plate.

[0023] A flexible way of defining the geometry of the fluid lines is proposed in claim 13. According to this measure, the valve changer cassette has at least one passage plate which covers the diaphragm structure, which passage plate defines the deformation of the diaphragm structure. As a result, a wide range of modifications to the structure of the primary fluid line and / or the secondary fluid line are possible by simply replacing the passage plate. Thereby, it is not necessary to replace all parts of the valve changer cassette when a modification of the primary fluid line and / or the secondary fluid line is desired. In this case, the aim is to increase the flexibility of the valve changer cassette by simple measures.

[0024] Claim 14 relates to a preferred solution for the interface between the fluid lines and other components of the bioprocessing installation. The interface lines can be arranged, for example, in the transfer plate, which makes the whole device more compact.

[0025] According to claim 15, the valve switching cassette is sealed by a cassette enclosure. Such a sealed design can improve the above-mentioned evacuation of the fluid lines in the valve switching cassette. The introduction of gas or liquid pressure into the cassette enclosure assists in the contraction of the fluid lines. With the assistance of the contraction of the fluid lines, the fluids in the fluid lines of the valve switching cassette are efficiently evacuated from the valve switching cassette without leaving any residue. Furthermore, such a sealed design further reduces the microbial contamination.

[0026] The second independent teaching according to claim 16 relates to a valve switching system with a valve switching cassette as described above, which has an actuator block assigned to the valve switching cassette, which acts on a diaphragm structure for the actuator block of the valve switching cassette and selectively engages the diaphragm structure with the respective valve seat. Reference is made to all the explanations given regarding the proposed valve switching cassette and its interaction with such an actuator block.

[0027] The third independent teaching according to claim 17 relates to the bioprocessing installation itself. Reference is made to all the explanations given regarding the proposed valve switching system and valve switching cassette.

[0028] According to claim 18, the bioprocessing installation preferably comprises a chromatography device with a plurality of chromatography columns, which is connected to the valve switching cassette. Due to the flexibility in the selective interconnection of the various fluid lines, the combination of the proposed valve switching cassette with such a chromatography device is advantageous.

[0029] In another independent teaching according to claim 19, a method for operating the proposed valve switching system with a valve switching cassette is claimed per se. This method represents the normal operation of the proposed valve switching system with a valve switching cassette, so reference may be made to all the descriptions given regarding the proposed valve switching system and the valve switching cassette.

[0030] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. [Brief description of the drawings]

[0031] [Figure 1] FIG. 1 shows a proposed bioprocessing installation with the proposed valve switching cassette. [Diagram 2] FIG. 2 is an exploded view of the proposed valve-changing cassette according to FIG. 1. [Diagram 3] FIG. 2 is a cross-sectional view showing the valve switching unit according to FIG. [Figure 4] FIG. 2 shows a portion of the bioprocessing installation according to FIG. 1 in an exemplary mode of operation.

[0032] As shown in Figure 1, the proposed valve switching cassette 1 is designed for selectively interconnecting one component of a bioprocessing installation 2 to another component of the bioprocessing installation 2. The expression "interconnect" should be understood in the sense of a fluid connection.

[0033] In particular, FIG. 1 shows the successive steps carried out for the recovery and purification of a desired product, such as a monoclonal antibody, as part of a downstream process in a bioprocess. In a first step of the downstream process, the product is isolated in an isolation unit 3. Assuming that the product is located in the supernatant of the fermentation broth, as is typical for example for secreted monoclonal antibodies, centrifugation can be performed to separate the product from cells and cell debris. Concentration, for example by ultrafiltration, can also be performed as part of the product isolation in order to increase the product concentration and reduce the volume of material to be processed in the successive downstream process steps.

[0034] After product isolation in isolation unit 3, product purification takes place in purification unit 4. Product purification can be performed by various means, including column chromatography, by chromatography device 5, as shown in FIG. 1. 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 regard to fluid flow. Therefore, a high degree of control of the fluid flow path F is required, which is currently achieved by using the proposed valve switching cassette 1 as shown in FIG. 1.

[0035] Typically, product purification is followed by final polishing of the product in polishing unit 6. At the end of product polishing, the product is usually packaged for further distribution. Depending on the bioprocess, product polishing may include, for example, a viral inactivation step to meet regulatory requirements. Another example of product polishing is a crystallization step to convert a fluid product into a solid, and thus easily transportable, form.

[0036] Valve switching cassette 1 is port P p ,P s and fluid line L p ,L s, T, the fluid flow system 7, 8 comprising a primary fluid line L p Primary port P communicating with p and the secondary fluid line L s Secondary port P connected to s The valve switching cassette 1 further includes a primary fluid line L p The secondary fluid line L s a switchable valve unit n for selectively interconnecting the x,y The array has:

[0037] The term "port" refers to an interface for interconnecting components of the bioprocessing equipment 2 to each fluid line. Ports include fluid connectors and conduits such as devices leading to each fluid line, as described below.

[0038] The term "line" refers to any elongated volume capable of holding and directing a fluid between two locations, and may include expandable and contractible conduit structures, as also described below.

[0039] 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 that are to be interconnected by a first fluid port and a second fluid port. In the preferred embodiment shown, these terms also indicate the direction of fluid flow, where the fluid flow is directed from the primary fluid port to the secondary fluid port. However, this can be accomplished vice versa. Thus, the terms "primary" and "secondary" do not imply or exclude any structural and / or functional differences between the respective ports and the fluid lines.

[0040] The term "selectively interconnected" refers to one or more primary fluid lines L p but one or more secondary fluid lines L s This means that the various elements may be selected to be interconnected in a single signal.

[0041] The expression "switchable" refers to the valve unit n x,y This means that the valve unit n can be changed from the "valve open" state to the "valve closed" state, or from the "valve closed" state to the "valve open" state. x,y When the valve is in the "valve open" state, the fluid flows through the primary fluid line L p from the transfer fluid line T through the secondary fluid line L s The valve unit n is opened. x,y is shown by a black circle in Fig. 1 and Fig. 4. Valve unit n x,y If the valve is in the "closed" state, the primary fluid line L p from the transfer fluid line T through the secondary fluid line L s Fluid flow is blocked to the closed valve unit. A closed valve unit is shown as an open circle in Figures 1 and 4.

[0042] Primary fluid line L p and the secondary fluid line L s are preferably arranged in rows and columns on different sides of the valve switching cassette 1, and the valve units n x,y is the primary fluid line L p and the secondary fluid line L s and each of the fluid lines L p ,L s For each valve unit n x,y Therefore, the valve units n x,y The array of valve units n is aligned with these rows and columns and numbered accordingly. 1,1 and 1,2 This is shown in detail in Figure 3.

[0043] Preferably, the proposed valve switching cassette 1 functions to control the fluid flow of components to be selectively interconnected, such as the illustrated chromatography device 5. Fluids to be handled in the present invention can include a wide variety of liquid media, such as buffers, wash solutions, acids, bases, culture media, unprocessed product-containing liquids, partially processed product-containing liquids, purified product-containing liquids, sanitary solutions, etc. Fluids to be handled in the present invention can also be gas-phase media.

[0044] Essential to the invention is that the valve switching cassette 1 comprises a transfer plate 17 with an opening 18 and elastically deformable diaphragm structures 19, 20 on respective flat surfaces 21, 22 of the transfer plate 17. Correspondingly, the diaphragm structures 19, 20 are in contact with the flat surfaces 21, 22 of the transfer plate 17, respectively.

[0045] The expression "aperture" is to be understood as an opening provided in the transfer plate 17 which extends through its entire thickness extending transversely to the xy plane of FIG.

[0046] Primary fluid line L p and secondary fluid line L s At least a portion of the transfer fluid line T extends between the transfer plate 17 and one of the diaphragm structures 19, 20. This means that a fluid line extends along each of the flat faces 21, 22 of the transfer plate 17. This also means that a fluid line is provided at least in part by each of the diaphragm structures 19, 20. The transfer fluid line T is provided at least in part by each of the openings 18 in the transfer plate 17.

[0047] The illustrated preferred embodiment includes not only the fluid flow system described above, hereinafter referred to as a “first” fluid flow system 7 , but also a “second” fluid flow system 8 .

[0048] As mentioned above, the fluid flow system 7 includes the primary fluid line L p Primary port P communicating withp and the secondary fluid line L s Secondary port P connected to s Includes:

[0049] The second fluid flow system 8 includes a primary fluid line l p Primary port p communicating with p and the secondary fluid line l s Secondary port p communicating with s Includes:

[0050] In addition to the interconnection of the primary and secondary fluid lines in the fluid flow systems 7, 8, valve units n x,y The array of fluid lines of the first fluid flow system 7, in this case preferably the secondary fluid lines L s into a fluid line of the second fluid flow system 8, in this case preferably the primary fluid line l p For this purpose, the valve units n x,y The array preferably includes a valve unit c as shown in FIG. x,y The additional lines are:

[0051] The general functionality of the two fluid flow systems 7,8 consisting of ports and fluid lines with respect to the selective interconnection of the respective fluid lines is identical, so that the description given with respect to one fluid flow system 7,8 is equally applicable to the other fluid flow system 8,7, respectively. In the following, to reduce complexity, reference will be made mainly to the first fluid flow system 7.

[0052] In the illustrated preferred embodiment, the primary port P of the first fluid flow system 7 p provides the inlet of the purification unit 4, whereas the secondary port p s provides the outlet of the purification unit 4.

[0053] 1 and as described above, the components to be selectively interconnected are the above-mentioned chromatography apparatus 5 with a plurality of chromatography columns 9-16 for carrying out simulated moving bed (SMB) chromatography, wherein the primary fluid port P p is used as an inlet for the sample, eluent, wash buffer, etc. These fluids are supplied through the primary fluid line L of the first fluid flow system 7. p The secondary fluid line L s The outlets of the chromatography columns 9-16 are selectively directed to the primary ports p of the second fluid flow system 8. p and thus the primary fluid line l p These fluid lines are connected to the secondary fluid lines l of the second fluid flow system 8. s , and hence the secondary port p s are selectively interconnected to

[0054] 4 merely illustrates another exemplary operation of the proposed valve switching cassette 1. In this case, it becomes clear that multiple variations of series and parallel utilization of the chromatography columns 9-16 are possible. The chromatography columns 9, 10, 11 are utilized in series, whereas the chromatography column 13 is utilized in parallel with respect to the chromatography columns 9, 10, 11. Overall, any number of the chromatography columns 9-16 can be used in any desired series or parallel format to couple the fluid flow F to the primary port P of the first fluid flow system 7. p from any one of the inlets provided by the secondary fluid port p of the second fluid flow system 8 s The exit can be directed to one of the exits provided by

[0055] As mentioned above, the primary fluid line L p are preferably arranged in a horizontal row, and the secondary fluid lines L sare preferably positioned in a vertical row. Furthermore, these fluid lines are preferably positioned on opposite flat surfaces 21, 22 of the transfer plate 17. As shown in FIG. 2, the primary fluid lines L p is disposed on one flat surface 21 of the valve switching cassette 1, whereas the secondary fluid line L s is arranged on the other flat surface 22 of the valve switching cassette 1. This is preferably provided for both fluid flow systems 7, 8: the primary fluid line L p ,l p are in this case preferably located on one flat surface 21 of the transfer plate 17, whereas the secondary fluid lines L of each fluid flow system 7, 8 s ,l s are located on the other flat surface 22 of the transfer plate 17.

[0056] Alternatively or additionally, the fluid flow F is always directed through the primary fluid line L p ,l p From the secondary fluid line L s ,l s This is at least defined within each fluid flow system 7, 8.

[0057] For simple manufacture, the transfer fluid lines T preferably extend transversely to the respective flat faces 21, 22 of the transfer plate 17. The transfer plate 17 with the transfer fluid lines T is in this case of particularly simple mechanical construction and can be manufactured at low cost. The transfer plate 17 may be made from any kind of, preferably acrylic, plastic material, such as PMMA, PEEK or PVDF. The transfer fluid lines T can be provided in the transfer plate 17 by drilling, punching, injection molding, etc.

[0058] The transfer plate 17 can be made relatively thin due to its simple structure, which in the first embodiment makes the valve-switching cassette 1 lightweight. The thickness of the transfer plate 17 is preferably less than 40 mm, more preferably less than 30 mm, and even more preferably less than 20 mm, which also does not make the manufacture of the transfer fluid line T difficult in any way.

[0059] Valve unit n x,y The realization of the valve unit n x,y are designed as diaphragm valve units, and are shown in the open position (Fig. 3, valve unit n 1,2 ) and closed position (Fig. 3, valve unit n 1,1 ) the valve diaphragm m x,y It has.

[0060] Each valve diaphragm m x,y is provided by at least one of the diaphragm structures 19, 20, in this case preferably by the diaphragm structure 20. Correspondingly, the diaphragm structures 19, 20 are used in two ways: firstly, as mentioned above, the fluid line L p ,L s Secondly, a valve diaphragm m x,y The use of these two types of diaphragm structures 19, 20 leads to a compact, easy to manufacture and cost-effective realization of the proposed valve switching cassette 1.

[0061] Preferably, each diaphragm structure 19 , 20 includes at least one diaphragm 23 , 24 extending along one planar surface 21 , 22 of the transfer plate 17 .

[0062] In the particularly preferred embodiment shown, at least one of the diaphragm structures 19, 20 has exactly one diaphragm 23, 24 which is a one-piece component. Preferably, both diaphragm structures each have exactly one diaphragm 23, 24 which is a one-piece component.

[0063] Valve unit n x,y are the valve seat s x,y Each valve diaphragm m provided by the diaphragm structure 20 x,y is valve unit n x,y To switch between the valve seats, x,y ("valve closed" state), or the valve seat x,y As shown in FIG. 3, each valve unit n x,y For fluid line L p ,L s and one of the transfer fluid lines T are preferably connected to the valve seat s x,y The valve diaphragm m is provided by a diaphragm structure 20. x,y and can interact with and seal.

[0064] FIG. 3 shows each valve unit n x,y For the valve seat s x,y is disposed in each transfer fluid line T. FIG. 3 further shows that each valve unit n x,y For the valve seat s x,y are the secondary fluid lines L s Preferably, each transfer fluid line T is provided with at least one assigned valve seat s x,y As shown in FIG. 3, this is done by connecting the opening of each transfer fluid line T to a valve seat s x,y This can be easily achieved by using it as

[0065] Various materials may be applied for the diaphragms 23, 24 of the diaphragm structures 19, 20. Preferably, the diaphragms 23, 24 are made of fluorocarbon-based fluoroelastomer (FKM), which is a rubber compound with vinylidene fluoride as a monomer. The material FKM is robust even when in contact with critical fluids such as various acids and bases as mentioned above. The hardness (Shore A) is preferably 50-80, more preferably 75. The material thickness of the diaphragms 23, 24 is preferably less than 3 mm, more preferably 0.75 mm-1.5 mm.

[0066] The diaphragm structures 19,20 may be of identical design, in terms of material and / or geometry, especially thickness, for each flat surface 21,22 of the transfer plate 17, which is logically advantageous. However, in order to optimize costs, it may be preferable to choose a different design for each diaphragm structure 19,20.

[0067] As mentioned above, the valve unit n x,y is the primary fluid line L p The secondary fluid line L s For this purpose, the valve switching cassette 1 preferably interacts with an actuator block 25, which acts on a diaphragm structure 20 for this actuator block to selectively interconnect each valve seat s x,y The valve switching cassette 1 and the actuator block 25 are combined to provide a valve switching system, which will be described below. The interaction between the actuator block 25 and the diaphragm structure 19 may be implemented in a variety of ways and based on a variety of physical principles.

[0068] As shown in Figures 2 and 3, the actuator block 25 has a plunger system 26 with at least one plunger 27 for acting on the diaphragm structure 20. The plunger is connected to the diaphragm structure 20, in particular to the valve diaphragm m. x,yor to engage with the diaphragm structure 20, in particular the valve diaphragm m x,y 2, so that the diaphragm structure 20 is disengaged from the valve seat s. x,y sealingly engages with the valve seat x,y For this purpose, the actuators (not shown) are respectively assigned plungers 27, which can be actuated pneumatically, hydraulically, electromagnetically, etc. The expression "sealingly engages" refers to the contact between the diaphragm structure 20 and the valve seat s. x,y The term "unsealed" refers to the establishment of a fluid-tight seal between the diaphragm structure 20 and the valve seat s, typically a pressure-fit engagement. x,y It may be noted that the contact may include loose, non-fluid-tight contact between the

[0069] Alternatively, the actuator block 25 may include the diaphragm structure 20 and the valve diaphragm m x,y The diaphragm structure 20 can be acted on without contact, in particular pneumatically or hydraulically, by applying a gas or liquid, respectively, to the plunger 27. In this case, the plunger 27 may be omitted, which reduces mechanical friction.

[0070] In this case, preferably, the valve unit n x,y The array of secondary fluid lines L is preferably arranged on only one flat surface 22 of the transfer plate 17. s This simplifies the construction of the actuator block 25, which must again engage the diaphragm structure 20 on the flat surface 22. In general, however, the valve unit n x,y An array of can be formed on both planar surfaces 21, 22 of the transfer plate 17.

[0071] The actuator block 25 may be controlled by an electronic controller (not shown), preferably including a microprocessor, operated on the basis of control software. In this case, it becomes clear that the entire fluid flow can be flexibly modified electronically simply by making a corresponding change to the control software. For example, the configuration of any port can be changed by changing the control software.

[0072] As a particularly simple implementation of the respective fluid line, the primary fluid line L p and / or secondary fluid line L s is the flow rate of each fluid line L p ,L s The diaphragm structures 19, 20 may have a first expanded state configured to form a fluid connection within the primary fluid line L and a second contracted state configured to terminate a fluid connection within each of the fluid lines. The resilience of the diaphragm structures 19, 20 allows the fluid lines to expand against the resilience of the diaphragm structures 19, 20. The expanded state is shown in FIG. 3 as the primary fluid line L p and secondary fluid line L s Regarding valve unit n 1,2 The contracted state is shown in Fig. 3 by the secondary fluid line L s Regarding valve unit n 1,1 is shown in the area.

[0073] The expanded state is preferably p ,L s The contracted state may be formed by the fluid pressure generated by the presence of a fluid inflow into the diaphragm structures 19, 20 and by elastic deformation of the diaphragm structures 19, 20. This deformation is directed primarily in a transverse direction to the respective flat faces 21, 22 of the transfer plate 17. In a preferred design, a fluid pressure of at least 0.08 bar, preferably 0.1 bar, of the fluid inflow is sufficient to expand each fluid line. The contracted state may preferably be formed by the absence of a fluid inflow and by the elastic restoring force of the diaphragm structures 19, 20.

[0074] The expandable fluid lines described above are easy to realize and offer almost unlimited flexibility in terms of their design. Furthermore, the design for the diaphragm structures 19, 20 can be selected such that if each fluid line is opened at its respective end, residual fluid is expelled from the fluid line simply by the elasticity of the diaphragm structure.

[0075] Preferably, the valve switching cassette 1 comprises at least one retaining frame 28, 29 covering one of the diaphragm structures 19, 20 with a flat surface facing the transfer plate 17. The retaining frame 28, 29 provides a fluid-tight and releasable connection between the diaphragm structure 19, 20 and the transfer plate 17 as shown in FIG. 2. Thus, no adhesive is required to connect the diaphragm structure 19, 20 to the transfer plate 17, which allows the diaphragm structure 19, 20 to be replaced and / or discarded upon separation from the transfer plate 17. According to another preferred embodiment, the diaphragm structure 19, 20 may be permanently attached to the transfer plate 17 by alternative manufacturing techniques such as riveting, thermoplastic welding, or encapsulated plastic molding.

[0076] As shown in Fig. 3, the valve switching cassette 1 has at least one passage plate 30, 31, in this case preferably one passage plate 30, 31 for each flat surface 21, 22 of the valve switching cassette 1, which passage plate 30, 31 covers the diaphragm structures 19, 20 with each flat surface facing the transfer plate 17. In this case preferably, each diaphragm structure 19, 20 is sandwiched between each flat surface 21, 22 of the transfer plate and each passage plate 30, 31. The passage plates 30, 31 may be assigned to the above-mentioned holding frames 28, 29 in order to together provide a leak-free connection between the diaphragm structures 19, 20 and the transfer plate 17.

[0077] Each passage plate 30, 31 has a plurality of passages 32-35, where the passages 32, 35 are preferably arranged in horizontal rows and the passages 33, 34 are preferably arranged in vertical columns, preferably forming a horizontal fluid line L. p / l s and preferably a vertical fluid line L s / l p These passages 32 to 35 define the primary fluid line L p and into the secondary fluid line L s The passages 32, 33 define the deformation of the diaphragm structures 19, 20 into the passages such as the primary fluid line L of the first fluid flow system 7. p and secondary fluid line L s whereas the passages 34, 35 define the primary fluid line l of the second fluid flow system 8. p and secondary fluid line l s It defines:

[0078] The passages 32-35 of the passage plates 30,31 are open to the assigned diaphragm structures 19,20 so that the diaphragm structures 19,20 can deform into the passages 32-35 and conform to the passages 32-35. The passages 32-35 thus form grooves in the passage plates 30,31 having a predetermined cross-sectional shape, preferably an arcuate, polygonal, in particular rectangular shape. The cross-sectional shape defines the cross-sectional shape of the resulting fluid line, since the diaphragm structures 19,20 adhere to the walls of the respective passages 32-35 which limit and thus define the deformation of the diaphragm structures 19,20 during the expansion of the respective fluid line. In another embodiment, it is also possible to have non-linear passages, such as loop-back paths defined by paths cut in the passage plates 30,31.

[0079] Preferably, the passage plates 30,31 are connected to the diaphragm structures 19,20 by a certain pressure fit, pressing the diaphragm structures 19,20 onto the respective flat surfaces 21,22 of the transfer plate 17. The passages 32-35 are integrated into the flat surfaces of the diaphragm structures 19,20 facing the respective diaphragm structures 19,20, so that the passage-free areas on the passage plates 30,31 press the diaphragm structures 19,20 onto the respective flat surfaces 21,22 of the transfer plate 17, preventing elastic deformation and the associated expansion of the fluid lines. However, in the areas of the passages 32-35, elastic deformation and the associated expansion of the fluid lines are possible. This therefore shows that the design of the fluid lines can be easily changed by simply designing the passage plates 30,31.

[0080] In this regard, it may be noted that the characteristics of the passages 32-35 only represent exemplary configurations. All aspects of the passages 32-35 may be designed as desired. For example, the passages may be of different sizes and / or geometries.

[0081] The working principle of the passage plates 30, 31 can be understood from Fig. 3. The passages 32-35 define the volume into which the diaphragm structures 19, 20 can deform during expansion of the fluid line, and thus define the resulting design of the expanded fluid line. The expanded fluid line is shown in Fig. 3 as the primary fluid line L p and secondary fluid line L s 3 is shown in the region of the valve unit n1,2.

[0082] It can be pointed out that the passage plate 30, 31 according to the invention is always in no contact with the fluid flowing in the fluid line. That is to say, the contact between the passage plate 30, 31 and the diaphragm structure 19, 20 does not have to be sealed, which further simplifies the manufacturing. This further means that the material of the passage plate does not have to be chemically resistant or inert to the flowing fluid, since the passage plate is not part of the wetted path. Furthermore, the diaphragm structure 19, 20 can be engaged through an opening in the passage plate 30, 31. This is shown in Figures 2 and 3, according to which the passage plate 31 has a hole 43 through which the plunger 27 extends to engage the diaphragm structure 20.

[0083] As described above, each valve unit n x,y For the valve seat s x,y are the secondary fluid lines L s This is because the actuator block 25 is connected to the secondary fluid line L s In the region of the diaphragm structure 20, and the valve diaphragm m x,y In a particularly preferred embodiment, the valve diaphragm m x,y The actuator block 25 acting on the valve diaphragm m x,y In the secondary fluid line L s As a result, each valve unit n x,y Regardless of the state of the secondary fluid line L s Along the valve diaphragm m x,y can pass through.

[0084] Each port P p ,P s ,p p ,p s Preferably, the interface conduit C is provided in the transfer plate 17. p ,C s ,c p ,c sThese interface pipes C p ,C s ,c p ,c s The fluid line L extends from one of the narrow faces 36 of the transfer plate 17. p ,L s ,l p ,l s These interface pipes C p ,C s ,c p ,c s are identical for the two fluid flow systems 7, 8, and will be described only for the first fluid flow system 7. All descriptions will be given with reference to the interface conduit c of the second fluid flow system 8. p ,c s is fully applicable to

[0085] Figure 3 shows interface pipe C. p and each fluid line L p 1 shows that the junction J between provides an interface valve seat K, and that the valve diaphragm provided by the diaphragm structures 19, 20 can engage the valve seat to provide a pressure valve. The pressure valve prevents fluid from passing through the valve until a predetermined threshold pressure is reached within the fluid. This not only results in a check valve function to prevent uncontrolled backflow of incoming fluid, but also allows for precise definition of fluid system characteristics by predefining the pressure threshold.

[0086] Interface Pipe C p ,C s are preferably drilled into the transfer plate 17. However, also if the transfer plate 17 is made of a plastic material, the interface conduits C p ,C s is formed by injection molding. Pipe C p ,C s The reduced length does not diminish the aforementioned advantage of ease of manufacture of the transfer plate 17.

[0087] Most importantly, the fluid lines can be completely emptied after activation or between different operating steps of the valve switcher cassette 1. To achieve this, the valve switcher cassette 1 preferably has at least one cassette enclosure 37, 38 assigned to at least one of the diaphragm structures 19, 20, which defines a sealed internal space 39, 40 between the cassette enclosure 37, 38 and the diaphragm structure 19, 20. This at least one cassette enclosure 37, 38 significantly reduces the hold-up volume at the end of the bioprocess. This allows the transfer of remaining valuable products to the next step of the chromatography process and also aids in the purging of waste buffers from the at least one fluid flow system 7, 8, thereby minimizing the actual disposable waste held in the valve switcher cassette.

[0088] The cassette enclosures 37,38 have cassette enclosure inlets 41,42 for introducing pressure, preferably gas or liquid pressure, into the sealed internal spaces 39,40 and thus assisting in the contraction of the fluid lines. For optimal results, it is preferred to provide two cassette enclosures 37,38, each of which is assigned to one of the flat faces 21,22 of the valve switching cassette 1. Depending on whether gas or liquid pressure is applied, the respective seal between the cassette enclosure 37 and the diaphragm structure 19,20 should be realised.

[0089] As shown in Figures 2 and 3, preferably passage plates 30, 31 are disposed between the diaphragm structures 19, 20 and the cassette enclosures 37, 38 respectively and should be capable of allowing gas or liquid to flow through the passage plates 30, 31 for the above-mentioned evacuation. This can be readily achieved by a number of openings in the passage plates 30, 31.

[0090] 2 shows an overview of the overall structure of the proposed valve switching cassette 1. It turns out that the valve switching cassette 1 is mostly made up of components that are not difficult and / or costly to manufacture. This is particularly advantageous if the use of disposable components is intended, for example to prevent (cross) contamination.

[0091] As can be seen from figure 2, only the transfer plate 17 and the diaphragm structures 19, 20 come into contact with the fluid flowing through the fluid lines, and these components can be particularly simply manufactured, all other components are not in contact with the fluid flowing through the fluid lines, and these components can be reused without special cleaning efforts.

[0092] According to the second teaching, a valve switching system is claimed per se, comprising the proposed valve switching cassette 1 and the proposed actuator block 25 assigned to the valve switching cassette 1. Reference is made to all the explanations given with regard to the preceding teachings.

[0093] According to the third teaching, a bioprocessing installation 2 is claimed per se. The bioprocessing installation 2 comprises components to be selectively interconnected, in this case preferably a chromatography device 5 with a number of chromatography columns 9-16, which are connected to a valve switching cassette 1, for example in order to carry out a simulated moving bed (SMB) chromatography process. Reference is made to all the explanations given with regard to the preceding teachings.

[0094] According to the fourth teaching, a valve switching system and a method for operating the valve switching cassette 1 are respectively claimed per se. In this case, the above-mentioned valve diaphragm m x,y But, valve unit n x,y 1. Essentially, the switching action is provided by diaphragm structures 19, 20 which are selectively engaged to switch between the active and passive states. Again, reference is made to the above discussion for the teachings set forth above.

[0095] Finally, it can be pointed out that the valve switching cassette 1 according to the various teachings can be scaled up to different levels of batch size without the need to introduce structural modifications.

Claims

1. A valve switching cassette (1) for selectively interconnecting components of a bioprocessing facility (2), the valve switching cassette (1) having at least one fluid flow system (7, 8) consisting of ports and fluid lines, the fluid flow system including a primary fluid line (L ｐ ) in communication with the primary port (P ｐ ) and a secondary fluid line (L ｓ ) in communication with the secondary port (P ｓ ) and the valve switching cassette (1) includes the primary fluid line (L ｐ ) to the secondary fluid line (L ｓ ) via a transfer fluid line (T), ｘ，ｙ ) in a valve switching cassette having an array of The valve switching cassette (1) has a transfer plate (17) with an opening (18) and elastically deformable diaphragm structures (19, 20) on each flat surface (21, 22) of the transfer plate (17), and the primary fluid line (L ｐ ) and the secondary fluid line (L ｓ ) extends between the transfer plate (17) and one of the diaphragm structures (19, 20), and the transfer fluid line (T) is at least partially provided by the opening (18).

2. The at least one fluid flow system (7, 8) comprises a first fluid flow system (7) consisting of ports and fluid lines, the first fluid flow system (7) comprising the primary fluid line (L ｐ ) communicating with the primary port (P ｐ ) and the secondary fluid line (L ｓ ) communicated with the secondary port (P ｓ ), and the at least one fluid flow system (7, 8) includes an additional second fluid flow system (8) consisting of ports and fluid lines, the second fluid flow system (8) including a primary fluid line (1 ｐ ) communicated with the primary port (p ｐ ) and a secondary fluid line (l ｓ ) communicated with the secondary port (p ｓ ) and preferably includes a valve unit (n ｘ，ｙ ) are connected to the fluid lines of the first fluid flow system (7), preferably to the secondary fluid lines (L ｓ ) into the fluid line of said second fluid flow system (8), preferably into said primary fluid line (1 ｐ 2. The valve switching cassette of claim 1, further operable to selectively interconnect a valve switching element to a valve switching element.

3. The primary fluid line (L ｐ , l ｐ ) and the secondary fluid line (L ｓ , l ｓ 3. The valve switching cassette according to claim 1, wherein the transfer fluid lines (T) extend transversely to the respective flat surfaces (21, 22) of the transfer plate (17).

4. The fluid flow (F) is ｐ , l ｐ ) to the secondary fluid line (L ｓ , l ｓ 3. The valve switching cassette according to claim 1, wherein the valve is oriented toward the valve shaft.

5. The valve unit (n ｘ，ｙ ) are the valve diaphragms (m ｘ，ｙ ) and the valve unit (n ｘ，ｙ ) of the valve diaphragm (m ｘ，ｙ ) is provided by at least one of the diaphragm structures (19, 20), and preferably by the valve diaphragm (m ｘ，ｙ ) relative movement of the valve units (n ｘ，ｙ 3. The valve switching cassette according to claim 1, wherein the valve is opened or closed.

6. The valve unit (n ｘ，ｙ ) are the valve seats (s ｘ，ｙ ), and the valve diaphragm (m) is provided by one of the diaphragm structures (19, 20). ｘ，ｙ ) is the valve unit (n ｘ，ｙ ) to switch the valve seat (s ｘ，ｙ ) and preferably can selectively engage the assigned valve seat (s ｘ，ｙ ) relative to each of the valve diaphragms (m ｘ，ｙ ) by the movement of the valve unit (n ｘ，ｙ 6. The valve switching cassette of claim 5, wherein selective engagement of the valve diaphragm for switching the valve is provided.

7. Each valve unit (n ｘ，ｙ ) for the fluid line (L ｐ , l ｐ , L ｓ , l ｓ ), preferably one of the secondary fluid lines (L ｓ , l ｓ ) and one of the transfer fluid lines (T) are connected to the valve seat (s ｘ，ｙ ) and the valve diaphragm (m) provided by the diaphragm structure (19, 20) ｘ，ｙ 7. The valve switching cassette of claim 6, wherein the valve switching cassette is capable of interacting and sealing with the valve.

8. Each valve unit (n ｘ，ｙ ) for the valve seat (s ｘ，ｙ ) is arranged in each of said transport fluid lines (T), and preferably each transport fluid line (T) has at least one assigned valve seat (s ｘ，ｙ 7. The valve switching cassette of claim 6, further comprising:

9. 3. The valve switching cassette according to claim 1, wherein the diaphragm structures (19, 20) each have at least one diaphragm (23, 24) extending along one flat surface (21, 22) of the transfer plate (17), and preferably the diaphragms (23, 24) are made of fluorocarbon-based fluoroelastomer (FKM).

10. The valve switching cassette (1) interacts with an actuator block (25), which acts on the diaphragm structure (20) for the actuator block to actuate each of the valve seats (s ｘ，ｙ 8. A valve switching cassette according to claim 7, wherein the actuator block (25) selectively engages the diaphragm structure (20), and preferably the actuator block (25) has a plunger system (26) with at least one plunger (27) for acting on the diaphragm structure (20).

11. The primary fluid line (L ｐ , l ｐ ) and / or the secondary fluid line (L ｓ , l ｓ 3. The valve switching cassette according to claim 1, wherein the diaphragm structure (19, 20) is capable of assuming a first expanded state configured to form a fluid connection in each of the fluid lines and a second contracted state configured to terminate a fluid connection in each of the fluid lines, and preferably the expanded state is formed by fluid pressure generated by the presence of fluid inflow in each of the fluid lines and elastic deformation of the diaphragm structure (19, 20), and the contracted state is formed by the absence of fluid inflow and elastic restoring force of the diaphragm structure (19, 20).

12. 3. The valve switching cassette according to claim 1, wherein the valve switching cassette has at least one holding frame that covers one of the diaphragm structures with a flat surface facing the transfer plate, the holding frame providing a releasable or non-releasable fluid-tight connection between the diaphragm structure and the transfer plate.

13. The valve switching cassette (1) has at least one passage plate (30, 31) covering the diaphragm structure (19, 20), the passage plate having a hole (43) that allows the plunger (27) to engage with the deformed diaphragm structure (19, 20), the passage plate (30, 31) having a plurality of passages (32-35), the passages being connected to a primary fluid line (L ｐ , l ｐ ) and into the secondary fluid line (L ｓ , l ｓ ) on the passage plates (30, 31), and preferably, in a properly assembled state, the fluid lines (L ｐ , l ｓ ) is arranged horizontally, and the fluid line (L ｓ / l ｐ 3. The valve switching cassette according to claim 1, wherein the valves are arranged vertically.

14. The port (P ｐ , p ｐ , P ｓ , p ｓ ) are connected to or within the transfer plate (17) through a common interface conduit (C ｐ , c ｐ , C ｓ , c ｓ ), and the interface pipe (C ｐ , c ｐ , C ｓ , c ｓ ) extends from one of the narrow faces (36) of the transfer plate (17) to the fluid line (L ｐ , l ｐ , L ｓ , l ｓ ) and preferably extends to one of the interface conduits (C ｐ , c ｐ , C ｓ , c ｓ ) and each of the fluid lines (L ｐ , l ｐ , L ｓ , l ｓ 3. The valve switching cassette according to claim 1, wherein a joint (J) between the diaphragm structure (19, 20) and the valve diaphragm structure (19, 20) provides an interface valve seat (K), and a valve diaphragm provided by the diaphragm structure (19, 20) can engage with the valve seat (K), thereby providing a pressure valve.

15. 3. The valve switching cassette (1) according to claim 1 or 2, wherein the valve switching cassette (1) comprises at least one cassette enclosure (37, 38) assigned to one of the diaphragm structures (19, 20), the cassette enclosure defining a sealed internal space (39, 40) between the cassette enclosure (37, 38) and the diaphragm structure (19, 20), preferably the passage plate (30, 31) being arranged between the diaphragm structure (19, 20) and the cassette enclosure (37, 38), and further preferably the cassette enclosure (37, 38) comprising a cassette enclosure inlet (41, 42) configured to introduce pressure, preferably gas or liquid pressure, into the sealed internal space (39, 40), preferably thereby purging liquid out of the at least one fluid flow system (7, 8).

16. 2. A valve switching system comprising a valve switching cassette (1) according to claim 1, the valve switching system having an actuator block (25) assigned to the valve switching cassette (1), the actuator block (25) including: ｘ，ｙ ) for selectively engaging a diaphragm structure (20) for the actuator block of the valve switching cassette, and preferably the actuator block (25) has a plunger system (26) with at least one plunger (27) for acting on the diaphragm structure (20) of the assigned valve switching cassette.

17. 17. A bioprocessing installation comprising a valve switching system according to claim 16 and components to be selectively interconnected by a valve switching cassette (1) of said valve switching system.

18. 18. The bioprocessing installation according to claim 17, wherein the bioprocessing installation (2) comprises, as a component to be selectively interconnected, a chromatography device (5) with a plurality of chromatography columns (9 to 16) connected to the valve switching cassette (1) of the valve switching system according to claim 16 in order to perform a simulated moving bed chromatography (SMB) process.

19. 17. A method for operating a valve switching system according to claim 16, comprising the steps of: ｘ，ｙ ) into the valve unit (n ｘ，ｙ ) by a diaphragm structure (19, 20) selectively engaged to switch.

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